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| ==Typhus fever==
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| *Typhus refers to a group of zoonotic diseases caused by bacteria that are spread to humans by fleas, lice, and chiggers.
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| *Typhus fevers include scrub typhus, murine typhus, and epidemic typhus.
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| *The most common symptoms are fever, headaches, and sometimes rash.
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| ==Historical perspective==
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| *In 1083, Typhus was first identified as a disease in Spain.
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| *In 1489, during the Spanish siege of Moorish Granada, the first reliable description of the disease was made.
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| *In 1546, Fracastoro extensively described the disease and distinguished it from plague in his book Contagione.
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| *In 1676, Von Zavorziz wrote a book on typhus called The Infection of Military Camps.
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| *In 1739, Huxham stated typhus and typhoid as two different entities, later in the same year Boissier de Sauvages confirmed this and called it exanthematic typhus.
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| *In 1829, Louis, French clinician clearly differentiated Typhus Fever from Typhoid Fever.
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| *In 1836, Gerhard(United States) clearly distinguished the two diseases from each other based on pathologic findings.
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| *In 1909, Charles Nicolle for the first time described the role of lice bite in transmission of typhus. In 1928, he was awarded the Nobel Prize for his discovery.
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| *In 1916, Weil and Felix reported the isolation of a Proteus that was agglutinated by the sera of patients with typhus, which was the basis for the first serological test for the disease.
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| *In 1916, DaRocha-Lima isolated and identified Rickettsia prowazeki.
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| *In 1926, Maxcy described the various forms of typhus.
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| *In 1938, Starzyk demonstrated that patients are infected by the feces and not the bite of the louse.
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| *In 1922, Wolbach described the human histopathology of R prowazekii infection.<ref name="pmid4997497">{{cite journal |vauthors=Woodward TE |title=Typhus verdict in American history |journal=Trans. Am. Clin. Climatol. Assoc. |volume=82 |issue= |pages=1–8 |year=1971 |pmid=4997497 |pmc=2441062 |doi= |url=}}</ref>
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| *In 1938, Cox was successful in growing cell cultures of R prowazekii in embryonated eggs.<ref name="Cox1938">{{cite journal|last1=Cox|first1=Herald R.|title=Use of Yolk Sac of Developing Chick Embryo as Medium for Growing Rickettsiae of Rocky Mountain Spotted Fever and Typhus Groups|journal=Public Health Reports (1896-1970)|volume=53|issue=51|year=1938|pages=2241|issn=00946214|doi=10.2307/4582741}}</ref>
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| *In 1940, Cox and Bell prepared an Epidemic Typhus vaccine based upon the use of tissue culture.
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| *In 1943–1944, during World war II DDT (a pesticide) was employed to control lice and typhus.
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| *In 1998, Andersson et al, sequenced the entire genome after much study of the fundamental mechanisms of R prowazekii's intracellular life and its effects on host cells.<ref name="pmid9823893">{{cite journal |vauthors=Andersson SG, Zomorodipour A, Andersson JO, Sicheritz-Pontén T, Alsmark UC, Podowski RM, Näslund AK, Eriksson AS, Winkler HH, Kurland CG |title=The genome sequence of Rickettsia prowazekii and the origin of mitochondria |journal=Nature |volume=396 |issue=6707 |pages=133–40 |year=1998 |pmid=9823893 |doi=10.1038/24094 |url=}}</ref>
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| ==Pathophysiology==
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| Typhus fever is a zoonotic disease, Humans could be infected by bites from ticks, lice, inhalation of the bacteria, and direct contact of bacteria with skin wounds or mucous membranes. Following transmission, white blood cells phagocyte the pathogen and transports it via hematologic or lymphatic route to different organs, specially to those of the reticuloendothelial system. The pathophysiology of typhus fever can be described in the following steps.
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| ===Transmission===
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| *Rickettsial pathogens are harboured by parasites such as fleas, lice, mites, and ticks.
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| *Organisms are transmitted by the bites from these parasites or by the inoculation of infectious fluids or feces from the parasites into the skin.
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|
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| class="wikitable"
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| {|
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|
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| !Disease
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| !Etiological agent
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| !Vector
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| |-
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| |Epidemic typhus
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| |''Rickettsia prowazekii''
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| |Human body louse
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| |-
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| |Murine typhus
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| |''Rickettsia typhi''
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| |Infected fleas
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| |-
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| |Scrub typhus
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| |''Orientia tsutsugamushi''
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| |Larval mites
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| |}
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|
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| ===Dissemination===
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| *Scratching a louse-bite site allows the rickettsia-laden excrement to be inoculated into the bite wound.
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| *Following transmission, rickettsia are ingested by [[macrophages]] and [[Polymorphonuclear cells|polymorphonuclea]]<nowiki/>r cells. On ingestion, they replicate intracellularly inside the lysed cells and disseminate systemically.
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| ===Incubation===
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| Incubation period of Typhus fever varies from one to two weeks.
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| ===Pathogenesis===
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| *On transmission, Rickettsia is actively phagocytosed by the endothelial cells of the small venous, arterial, and capillary vessels.
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| *It is followed by systemic hematogenous spread resulting in multiple localizing vasculitis. The major pathology is caused by vasculitis and its complications.
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| *This process of inflammatory response (aggregation of leukocytes, macrophages, and platelets) along with occlusion of small blood vessels results in formation of nodules.
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| *Occlusion of supplying blood vessels also causes gangrene of the distal portions of the extremities, nose, ear lobes, and genitalia.
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| *This vasculitic process also results destruction of the endothelial cells and leakage of the blood leading to volume depletion and subsequently leading to decreased tissue perfusion and, possibly, organ failure.
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| *Endothelial damage lead to activation of clotting system
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|
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| ==Natural history==
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| Without treatment, fever may last 2 weeks, followed by a prolonged recovery time and a significantly greater chance of developing complications. Delay in treatment may result in advanced disease, including neurologic manifestations such as confusion, seizures, or coma, and widespread vasculitis (damage to the endothelial cells that line blood vessels).
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| ===Complications===
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| *Hearing loss
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| *Myocarditis
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| *Vasculitis
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| *Aseptic meningitis
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| ===Prognosis===
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| Prognosis depends on age and immunization status of the individual. With prompt, appropriate treatment, most individuals recover completely.The fatality rate for epidemic typhus varies from 1% to 20%.
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|
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| ==History==
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| *History of travel to endemic areas
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| *History of tick bite
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|
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| ==Symptoms==
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| {| class="wikitable"
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| !Typhus fever
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| !Rash
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| |-
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| |Scrub typhus
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| |About 25–50% of scrub typhus patients develop a rash. The rash is usually macular or maculopapular. Typically, it will begin on the abdomen of an infected individual and then spread to the extremities. Petechiae are uncommon
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| |-
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| |Murine Typhus
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| |The rash typically occurs at the end of the first week of the illness and lasts 1–4 days. It generally starts as a maculopapular eruption on the trunk and spreads peripherally, sparing the palms of the hands and soles of the feet. Rash may vary among individuals, or may be absent altogether and should not be relied upon for diagnosis.
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| |-
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| |Epidemic Typhus
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| |The rash usually begins a couple of days after the onset of symptoms. It typically begins as a maculopapular eruption on the trunk of the body and spreads to the extremities, usually sparing the palms of hands and soles of feet. When the disease is severe, petechiae may develop. The rash may be variable among individuals and stage of infection, or may be absent altogether and should not be relied upon for diagnosis
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| |}
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| About 25–50% of scrub typhus patients develop a rash. The rash is usually macular or maculopapular. Typically, it will begin on the abdomen of an infected individual and then spread to the extremities. Petechiae are uncommon.
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| Murine Typhus
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| The rash typically occurs at the end of the first week of the illness and lasts 1–4 days. It generally starts as a maculopapular eruption on the trunk and spreads peripherally, sparing the palms of the hands and soles of the feet. Rash may vary among individuals, or may be absent altogether and should not be relied upon for diagnosis.
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| Epidemic Typhus
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| The rash usually begins a couple of days after the onset of symptoms. It typically begins as a maculopapular eruption on the trunk of the body and spreads to the extremities, usually sparing the palms of hands and soles of feet. When the disease is severe, petechiae may develop. The rash may be variable among individuals and stage of infection, or may be absent altogether and should not be relied upon for diagnosis.
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| '''Most common symptoms'''
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| *Fever
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| *Headache
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| *Malaise
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| *Maculopapular, vesicular, or petechial rash
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| *Eschar
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| *Nausea and vomiting.
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| '''Less common symptoms'''
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| *Abdominal pain
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| *Cough
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| *Prostration
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| *Confusion
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| *Photophobia
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| *Diarrhea
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|
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| ==Lab diagnosis==
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| *Laboratory studies are not particularly helpful in confirming a diagnosis of typhus.
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| *They assess the degree of severity of the illness and in help in excluding other diseases.
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| *The diagnosis of typhus is clinically suggested when the appropriate historical elements are elicited from a patient who presents with the characteristic symptoms and signs.
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| *Antibiotic therapy should begin promptly when the diagnosis is suspected; thereafter, appropriate laboratory studies can be serially performed as needed.
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| *Diagnosis may be confirmed using laboratory tests; however, more than one week may pass before patients mount a demonstrable immune response that can be measured serologically.
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| *Typhus is a vasculitic process, any organ may be affected, and multiorgan system dysfunction or failure may occur if the illness is not diagnosed and treated in the early stages.
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| *Renal - Azotemia/proteinuria
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| *Hematologic
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| *Leukopenia (common in the early stages of disease)
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| *WBC count normal/mildly elevated later
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| *Thrombocytopenia
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| *Hepatic - Mild transaminase elevations
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| *Metabolic - Hypoalbuminemia/electrolyte abnormalities (particularly hyponatremia)
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| *Indirect immunofluorescence assay (IFA) or enzyme immunoassay (EIA) testing can be used to evaluate for a rise in the immunoglobulin M (IgM) antibody titer, which indicates an acute primary disease.
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| *Brill-Zinsser disease can be confirmed in a patient with a history of primary epidemic typhus who has recurrent symptoms and signs of typhus and a rise in the immunoglobulin G (IgG) antibody titer, which indicates a secondary immune response.
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| *IFA and EIA tests can be used to confirm a diagnosis of typhus, but they do not identify the various rickettsial species.
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| *Polymerase chain reaction (PCR) amplification of rickettsial DNA of serum or skin biopsy specimens can be used for diagnosing typhus. [9]
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| *The complement fixation (CF) test is a serological test that can be used to demonstrate which specific rickettsial organism is causing disease by detection of specific antibodies.
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| ===Histologic Findings===
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| *Rickettsia may be observed in tissue sections using Giemsa or Gimenez staining techniques.
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|
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| ==Xray chest==
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| *No imaging studies are specifically indicated to aid in diagnosing typhus.
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| *Imaging studies are indicated only on a case-by-case basis to evaluate potential complications or as needed.
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| *Chest radiography may be a complementary tool to evaluate the clinical course of scrub typhus.
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| *Chest radiographic examinations should be obtained during the first week after the onset of illness.
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| ==Differential==
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| {| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
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| |+
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| ! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|Disease}}
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| ! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Findings}}
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| | style="padding: 5px 5px; background: #DCDCDC;" | '''[[Ebola]]'''
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| | style="padding: 5px 5px; background: #F5F5F5;" | Presents with [[fever]], [[chills]] [[vomiting]], [[diarrhea]], generalized [[pain]] or [[malaise]], and sometimes [[Internal bleeding|internal]] and external [[bleeding]], that follow an [[incubation period]] of 2-21 days.
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| |-
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| | style="padding: 5px 5px; background: #DCDCDC;" | '''[[Typhoid fever]]'''
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| | style="padding: 5px 5px; background: #F5F5F5;" | Presents with [[fever]], [[headache]], [[rash]], gastrointestinal symptoms, with [[lymphadenopathy]], relative [[bradycardia]], [[cough]] and [[leucopenia]] and sometimes [[sore throat]]. [[Blood]] and [[stool culture]] can confirm the presence of the causative bacteria.
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| |-
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| | style="padding: 5px 5px; background: #DCDCDC;" |'''[[Malaria]]'''
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| | style="padding: 5px 5px; background: #F5F5F5;" |Presents with acute [[fever]], [[headache]] and sometimes [[diarrhea]] (children). A [[blood smear]]s must be examined for malaria parasites. The presence of [[parasites]] does not exclude a concurrent viral infection. An [[antimalarial]] should be prescribed as an [[empiric therapy]].
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| |-
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| | style="padding: 5px 5px; background: #DCDCDC;" | '''[[Lassa fever]]'''
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| | style="padding: 5px 5px; background: #F5F5F5;" |Disease onset is usually gradual, with [[fever]], [[sore throat]], [[cough]], [[pharyngitis]], and [[facial edema]] in the later stages. [[Inflammation]] and exudation of the [[pharynx]] and [[conjunctiva]] are common.
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| |-
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| | style="padding: 5px 5px; background: #DCDCDC;" | '''[[Yellow fever]] and other [[Flaviviridae]] '''
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| | style="padding: 5px 5px; background: #F5F5F5;" | Present with [[hemorrhage|hemorrhagic]] complications. [[Epidemiological]] investigation may reveal a pattern of disease [[transmission]] by an insect vector. Virus isolation and serological investigation serves to distinguish these [[viruses]]. Confirmed history of previous [[yellow fever]] [[vaccination]] will rule out [[yellow fever]].
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| |-
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| | style="padding: 5px 5px; background: #DCDCDC;" | '''[[Shigellosis]] & other bacterial enteric infections'''
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| | style="padding: 5px 5px; background: #F5F5F5;" | Presents with [[diarrhea]], possibly [[Dysentery|bloody]], accompanied by [[fever]], [[nausea]], and sometimes [[toxemia]], [[vomiting]], [[cramps]], and [[tenesmus]]. [[Stool]]s contain [[blood]] and mucous in a typical case. A search for possible sites of bacterial infection, together with cultures and [[blood smear]]s, should be made. Presence of [[leucocytosis]] distinguishes bacterial infections from [[viral infections]].
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| |-
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| | style="padding: 5px 5px; background: #DCDCDC;" | '''Others'''
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| | style="padding: 5px 5px; background: #F5F5F5;" |[[Leptospirosis]], [[viral hepatitis]], [[rheumatic fever]], and [[mononucleosis]] can produce [[signs]] and [[symptoms]] that may be confused with [[Ebola]] in the early stages of [[infection]].
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| |-
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| |}
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| {| class="wikitable"
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| !Diseases
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| ! colspan="5" |Clinical features
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| ! colspan="2" |Diagnosis
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| |-
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| |Fever
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| |Rash
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| |Diarrhea
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| |Cough
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| |Specific
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| |-
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| |Ebola
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| |-
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| |Typhoid fever
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| |-
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| |Malaria
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| |-
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| |Lassa fever
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| |-
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| |'''[[Yellow fever]] and'''
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| '''other [[Flaviviridae]] '''
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| |-
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| |'''[[Shigellosis]] &'''
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| '''other bacterial enteric infections'''
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| |}
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|
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| ==Labs==
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| Serologic assays are the most frequently used methods for confirming cases of scrub typhus. The indirect immunofluorescence assay (IFA) is generally considered the reference standard, but is usually not available in developing countries where this disease is endemic. Other serological tests include ELISA and indirect immunuoperoxidase (IIP) assays. Weil-Felix OX-K agglutination assays may be used in some international settings but lack sensitivity and specificity and are not generally used in the United States. These assays can detect either IgG or IgM antibodies. Diagnosis is typically confirmed by documenting a four-fold rise in antibody titer between acute and convalescent samples. Acute specimens are taken during the first week of illness and convalescent samples are taken 2–4 weeks later. IgG antibodies are considered more accurate than IgM, but detectable levels of IgG antibody generally do not appear until 7–10 days after the onset of illness.
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|
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| Because antibody titers may persist in some individuals for years after the original exposure, only demonstration of recent changes in titers between paired specimens can be considered reliable confirmation of an acute scrub typhus infection. The most rapid and specific diagnostic assays for scrub typhus rely on molecular methods like polymerase chain reaction (PCR), which can detect DNA in a whole blood, eschar swab, or tissue sample. Immunostaining procedures can also be performed on formalin-fixed tissue samples. Since scrub typhus is not common in the United States, confirmatory tests are not typically available at state and local health departments; nonetheless, IFA, culture, and PCR assays can all be performed at the CDC through submission from state health departments.
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| ===Murine typhus===
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| Rickettsia typhi can be detected via indirect immunofluorescence antibody (IFA) assay, immunohistochemistry (IHC), polymerase chain reaction (PCR) assays using blood, plasma, or tissue samples, or culture isolation. PCR is most sensitive on samples taken during the first week of illness, but prior to the start of doxycycline.
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|
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| Serologic tests (typically using IFA) are the most common means of confirming murine typhus and can be used to detect either IgG or IgM antibodies. Diagnosis is usually confirmed by demonstrating a four-fold rise in antibody titer between acute and convalescent samples. Acute specimens are taken during the first week of illness and convalescent samples are taken 2–4 weeks later. IgG antibodies are considered more accurate than IgM. Detectable levels of IgG antibody generally do not appear until 7–10 days after the onset of illness.
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|
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| Because antibody titers may persist in some individuals for years after the original exposure, only demonstration of recent changes in titers between paired specimens can be considered reliable serological confirmation of an acute murine typhus infection. R. typhi antigens frequently cross-react with those of R. prowazekii and R. felis, and less often with R. rickettsii. When possible, species-specific assays for R. typhi, R. prowazekii, R. felis, and R. rickettsii should be run in parallel. IHC can be used to detect infection with typhus group Rickettsia (including R. prowazekii and R. typhi) in formalin-fixed tissue samples. PCR of whole blood or tissue can distinguish between infection with R. typhi and R. prowazekii although the sensitivity of these assays varies considerably based on the sample type, timing of sample collection, and the severity of disease.
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| ===Epidimic===
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| Rickettsia prowazekii can be detected via indirect immunofluorescence antibody (IFA) assay, immunohistochemistry (IHC), polymerase chain reaction (PCR) assay of blood, plasma, or tissue samples, or culture isolation. Serologic tests are the most common means of confirmation and can be used to detect either IgG or IgM antibodies. Diagnosis is typically confirmed by documenting a four-fold rise in antibody titer between acute and convalescent samples. Acute specimens are taken during the first week of illness and convalescent samples are taken 2–4 weeks later. Detectable levels of IgG or IgM antibodies generally do not appear until 7–10 days after the onset of illness.
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|
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| Because IgG antibody titers may persist in some individuals for years after the original exposure, only demonstration of recent changes in titers between paired specimens can be considered reliable serological confirmation of an acute epidemic typhus infection. R. prowazekii antigens may cross react with those of R. typhi, and occasionally with R. rickettsii. When possible, species-specific serological assays for R. prowazekii, R. typhi, and R. rickettsii should be run in parallel. Persons with Brill-Zinsser disease generally show a rise in IgG but not IgM antibodies to R. prowazekii. IHC can be used to detect infection with typhus group Rickettsia (including R. prowazekii and R. typhi) in formalin-fixed tissue samples. PCR of whole blood or tissue can distinguish between infection with R. typhi and R. prowazekii although the sensitivity of these assays vary considerably based on the sample type, timing of sample collection, and the severity of disease. Since epidemic typhus is not common in the United States, testing is not typically available at state and local health departments. IFA, culture, and PCR can all be performed at the CDC, through submission from state health departments.
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| ==Epidemiology and Demographics==
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| All age groups are at risk for rickettsial infections during travel to endemic areas. Both short and long-term travelers are at risk for infection. Transmission is increased during outdoor activities in the spring and summer months when ticks and fleas are most active. However, infection can occur throughout the year. Because of the 5- to 14-day incubation period for most rickettsial diseases, tourists may not necessarily experience symptoms during their trip, and onset may coincide with their return home or develop within a week after returning. Although the most commonly diagnosed rickettsial diseases in travelers are usually in the spotted fever or typhus groups, travelers may acquire a wide range of rickettsioses, including emerging and newly recognized species.
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| Tickborne spotted fever rickettsioses are the most frequently reported travel-associated rickettsial infections. Game hunting and traveling to southern Africa from November through April are risk factors for African tick-bite fever, and this consistently remains the most commonly reported rickettsial infection acquired during travel. Mediterranean spotted fever infections are less commonly reported but occur over an even larger region, including (but not limited to) much of Europe, Africa, India, and the Middle East. Rocky Mountain spotted fever (also known as Brazilian spotted fever, as well as other local names) is reported throughout much of the Western Hemisphere, including Canada, the United States, Mexico, and various countries in Central and South America. Contact with dogs (in both rural and urban settings) and outdoor activities such as hiking, hunting, fishing, and camping increase the risk of infection.
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|
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| Scrub typhus, which is transmitted by mites encountered in high grass and brush, is endemic in northern Japan, Southeast Asia, the western Pacific Islands, eastern Australia, China, maritime areas and several parts of south-central Russia, India, and Sri Lanka. More than 1 million cases occur annually. Most travel-acquired cases of scrub typhus occur during visits to rural areas in endemic countries for activities such as camping, hiking, or rafting, but urban cases have also been described.
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|
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| R. typhi and R. felis, which are transmitted by fleas, are widely distributed, especially throughout the tropics and subtropics and in port cities and coastal regions with rodents. Humans exposed to flea-infested cats, dogs, and peridomestic animals while traveling in endemic regions, or who enter or sleep in areas infested with rodents, are at most risk for fleaborne rickettsioses. Murine typhus has been reported among travelers returning from Asia, Africa, and the Mediterranean Basin and has also been reported from Hawaii, California, and Texas in the United States.
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|
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| R. akari, the causative agent of rickettsialpox, is transmitted by house-mouse mites, and circulates in mainly urban centers in Ukraine, South Africa, Korea, the Balkan states, and the United States. Outbreaks of rickettsialpox most often occur after contact with infected rodents and their mites, especially during natural die-offs or exterminations of infected rodents that cause the mites to seek out new hosts, including humans. The agent may spill over and occasionally be found in other wild rodent populations.
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|
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| Epidemic typhus is rarely reported among tourists but can occur in communities and refugee populations where body lice are prevalent. Outbreaks often occur during the colder months when infested clothing is not laundered. Travelers at most risk for epidemic typhus include those who may work with or visit areas with large homeless populations, impoverished areas, refugee camps, and regions that have recently experienced war or natural disasters. Active foci of epidemic typhus are known in the Andes regions of South America and some parts of Africa (including but not limited to Burundi, Ethiopia, and Rwanda). Louseborne epidemic typhus does not regularly occur in the United States, but a zoonotic reservoir occurs in the southern flying squirrel, and sporadic sylvatic epidemic typhus cases are reported. Tick-associated reservoirs of R. prowazekii have been described in Ethiopia, Mexico, and Brazil, but documented human cases are rare.
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|
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| Ehrlichiosis and anaplasmosis are tickborne infections most commonly reported in the United States. A variety of species are implicated in infection, but E. chaffeensis and A. phagocytophilum are most common. Infections with various Ehrlichia and Anaplasma spp. have also been reported in Europe, Asia, and South America. Neoehrlichia mikurensis is a tickborne pathogen that occurs in Europe and Asia. Sennetsu fever, caused by Neorickettsia sennetsu, occurs in Japan, Malaysia, and possibly other parts of Asia. This disease can be contracted from eating raw infected fish.
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|
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| ==Physical examination==
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| ===Vitals===
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| *Fever
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| *Relative bradycardia with the fever.
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| *Tachypnea and cough
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|
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| ===Skin===
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| *Rash
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| The macular, maculopapular, or petechial rash initially occurs on the trunk and axilla and spreads to involve the rest of the body except for the face, palms, and soles.
| |
| Rash may be petechial in patients with epidemic or murine typhus.
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| *Eschar
| |
| This is found in the scrub form of typhus and is essential in confirming a clinical diagnosis. It occurs in up to 60% of cases.
| |
| Eschar occurs at the site of the arthropod bite. It starts as a painless papule, and the lesion becomes indurated and enlarged. The center of the lesion becomes necrotic and develops into a black scab.
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| Other features
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| ===Lymph nodes===
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| Regional lymphadenopathy
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| Lymph nodes are often tender and enlarged.
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| Generalized lymphadenopathy
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| ===Abdomnen===
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| *Hepatomegaly
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| *Splenomegaly
| |
| ===HEENT===
| |
| Conjunctival suffusion occurs in scrub typhus.
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| ==Medical Therapy==
| |
| ===Pharmacotherapy===
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| ===Typhus, louse-borne===
| |
| * '''Louse born typhus, Rickettsia prowazekii''' (epidemic typhus, sylvatic typhus and Brill–Zinsser typhus''' <ref name="pmid23253320">{{cite journal| author=Botelho-Nevers E, Socolovschi C, Raoult D, Parola P| title=Treatment of Rickettsia spp. infections: a review. | journal=Expert Rev Anti Infect Ther | year= 2012 | volume= 10 | issue= 12 | pages= 1425-37 | pmid=23253320 | doi=10.1586/eri.12.139 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23253320 }} </ref>'''
| |
| :* Pathogen-directed antimicrobial therapy
| |
| ::* In adults
| |
| :::* Preferred regimen (1): [[Doxycycline]] 200 mg PO for 5 days or 2-3 days after defervescence
| |
| :::* Preferred regimen (2): [[Doxycycline]] 100-200 mg PO single dose in outbreak situation
| |
| :::* Alternative regimen: [[Chloramphenicol]] 60 to 75 mg/kg/day PO in four divided doses
| |
| ::* In children
| |
| :::* Preferred regimen (1): [[Doxycycline]] 100-200 mg PO single dose
| |
| ::* In pregnant women
| |
| :::* Preferred regimen: [[Doxycycline]] 100-200 mg PO single dose
| |
|
| |
| ===Typhus, murine===
| |
| * '''Murine typhus,Rickettsia typhi''' (flea-borne infection) <ref name="pmid23253320">{{cite journal| author=Botelho-Nevers E, Socolovschi C, Raoult D, Parola P| title=Treatment of Rickettsia spp. infections: a review. | journal=Expert Rev Anti Infect Ther | year= 2012 | volume= 10 | issue= 12 | pages= 1425-37 | pmid=23253320 | doi=10.1586/eri.12.139 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23253320 }} </ref>
| |
| :* Pathogen-directed antimicrobial therapy
| |
| ::* 1. '''Adults'''
| |
| :::* Preferred regimen : [[Doxycycline]] 100 mg PO bid continued for 3 days after the symptoms have resolved, [[Doxycycline]] 100-200 mg, PO single dose
| |
| :::* Alternative regimen (1): [[Oxacillin]] 2-12 g/24 hr IV q4-6h IV (maximum dose: 12 g/24)
| |
| :::* Alternative regimen (2): [[Chloramphenicol]] 60 to 75 mg/kg/day PO in qid
| |
| ::* 2. '''Children'''
| |
| :::* Preferred regimen: [[Doxycycline]] 100-200 mg, PO for 3-7 days
| |
| :::* Alternative regimen: [[Chloramphenicol]] 50-75 mg/kg/24 hr IV/PO q 6-8 hr
| |
| ::* 3. '''Pregnant women'''
| |
| :::* Preferred regimen: [[Doxycycline]] 100-200 mg, PO single dose ( late trimester)
| |
| :::* Alternative regimen (1): [[Erythromycin]] Base: 333 mg PO tid or estolate/stearate/ base: 250-500 mg PO qid
| |
| :::* Alternative regimen (2): [[Chloramphenicol]] 50 mg/kg/24 hr IV/PO q6h (maximum dose: 4 g/24 hr) (early trimester: first and second trimesters)
| |
| ===Typhus, scrub===
| |
| * '''Scrub typhus, Orientia tsutsugamushi''' (previously called Rickettsia tsutsugamushi- mite-borne infectious disease) <ref name="pmid12137646">{{cite journal| author=Panpanich R, Garner P| title=Antibiotics for treating scrub typhus. | journal=Cochrane Database Syst Rev | year= 2002 | volume= | issue= 3 | pages= CD002150 | pmid=12137646 | doi=10.1002/14651858.CD002150 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12137646 }} </ref>
| |
| :* Pathogen-directed antimicrobial therapy
| |
| ::* Preferred regimen (1): [[Doxycycline]] 100 mg PO/IV q12h for 3 days
| |
| ::* Preferred regimen (2): [[Chloramphenicol]] 500 mg PO/IV q6h
| |
| ::* Alternative regimen: [[Azithromycin]] 500 mg PO day 1 followed by 250 mg for 4 days
| |
| ==Prevention==
| |
| ==Primary Prevention==
| |
|
| |
| Avoid areas where you might encounter rat fleas or lice. Good sanitation and public health measures reduce the rat population. Measures to get rid of lice when an infection has been found include:
| |
| * Bathing
| |
| * Boiling clothes or avoiding infested clothing for at least 5 days (lice will die without feeding on blood)
| |
| * Using insecticides (10% DDT, 1% malathion, or 1% permethrin)
| |
|
| |
| ===Vaccine===
| |
| The first major step in the development of the [[vaccine]] was [[Charles Nicolle]]'s 1909 discovery that [[lice]] were the [[Vector (biology)|vectors]] for epidemic typhus. This made it possible to isolate the bacteria causing the disease and develop a vaccine; he was awarded the 1928 [[Nobel Prize in Physiology or Medicine]] for this work. Nicolle attempted a vaccine but was not successful in making one that worked on a large enough scale.<ref>Gross, Ludwik (1996) [http://www.pnas.org/cgi/reprint/93/20/10539.pdf ''How Charles Nicolle of the Pasteur Institute discovered that epidemic typhus is transmitted by lice: reminiscences from my years at the Pasteur Institute in Paris''] Proc. Natl. Acad. Sci. Vol. 93, pp. 10539-10540.</ref>
| |
|
| |
| [[Henrique da Rocha Lima]] in 1916 then proved that the bacteria ''Rickettsia prowazekii'' was the agent responsible for typhus; he named bacteria after H. T. Ricketts and [[Stanislaus von Prowazek]], two zoologists who died investigating a typhus epidemic in a prison camp in 1915. Once these crucial facts were recognized, Rudolf Weigl in 1930 was able to fashion a practical and effective vaccine production method by grinding up the guts of infected lice that had been drinking blood. It was, however, very dangerous to produce, and carried a high likelihood of infection to those who were working on it.
| |
|
| |
| A safer mass-production-ready method using egg yolks was developed by [[H. R. Cox|Herald R. Cox]] in 1938.<ref name="Mazal1">[http://www.mazal.org/archive/nmt/01/NMT01-T508.htm ''Nuernberg Military Tribunal, Volume I''] pp. 508-511</ref> This vaccine was used heavily by 1943.
| |
|
| |
| ==Colonic abscess==
| |
| A colonic abscess develops as a complication of diverticulitis. A colonic abscess is a localized collection of pus within the wall of the colon that may cause swelling and destroy tissue. If the abscess is small and remains within the wall of the colon, it may clear up with antibiotics alone. If the abscess is large > 5cms, or unresponsive to medical treatment, it must be drained using a catheter facilitated by sonography or x-ray.
| |
| ===Causes===
| |
| Colon abscess is a rare entity and arises as a compliecation of diseases such as IBD, colorectal cancer, diverticulosis or diverticulitis. Natural gut flora which includes [[Gram-negative bacteria|gram negative]] and [[anaerobic bacteria]] play a major role in the development of colonic abscess.<ref name="pmid20034345">{{cite journal| author=Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA, Goldstein EJ, Baron EJ et al.| title=Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2010 | volume= 50 | issue= 2 | pages= 133-64 | pmid=20034345 | doi=10.1086/649554 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20034345 }} </ref>
| |
|
| |
| ====Most common causes====
| |
| * [[Enterococcus]]
| |
| * [[Escherichia coli]]
| |
| * [[Staphylococcus aureus]]
| |
| * [[Bacteroides fragilis]]
| |
| * [[Clostridium perfringens]]
| |
|
| |
| ====Less common causes====
| |
| * [[Klebsiella pneumoniae]]
| |
| * [[Pseudomonas aeruginosa]]
| |
| * [[Proteus]]
| |
|
| |
| ===Pathophysiology===
| |
| *The primary process is thought to be an erosion of the diverticular wall by increased intraluminal pressure or inspissated food particles.
| |
| *Inflammation and focal necrosis ensue, resulting in the abscess formation.
| |
| ====Gross Pathology====
| |
| *The serosal surface of the [[colon]] looks pale with rough edges and yellowish [[exudate]] along with [[hyperemia]]
| |
|
| |
| ====Microscopic findings====
| |
| *A focally [[necrotic]] debris is seen in the [[Mucosa|mucosal]] wall.
| |
| *[[Intravascular|Intravascular fibrin]] is seen in medium-sized [[blood vessels]].
| |
| *Clusters of [[neutrophils]] are seen on the [[Serosa|serosal]] aspect.
| |
|
| |
| ===Risk factors===
| |
| Risk factors in the development of colonic abscess include same as that of diverticular diseases of the colon, such as advanced age, chronic constipation, connective tissue diseases (such as Marfan syndrome or Ehlers-Danlos syndrome), low dietary fiber intake, high intake of fat and red meat, and obesity.
| |
| ===Screening===
| |
| Screening for colonic abscess is not recommended in the general population.
| |
| ===Epidemiology and Demographics===
| |
| ====Prevalance====
| |
| *The prevalence of diverticulosis is age-dependent.
| |
| *The prevalence increases from fewer than 20% at age 40 to approximately 60% by age 60.<ref name="pmid1109818">{{cite journal |vauthors=Painter NS, Burkitt DP |title=Diverticular disease of the colon, a 20th century problem |journal=Clin Gastroenterol |volume=4 |issue=1 |pages=3–21 |year=1975 |pmid=1109818 |doi= |url=}}</ref><ref name="pmid">{{cite journal |vauthors=Peery AF, Barrett PR, Park D, Rogers AJ, Galanko JA, Martin CF, Sandler RS |title=A high-fiber diet does not protect against asymptomatic diverticulosis |journal=Gastroenterology |volume=142 |issue=2 |pages=266–72.e1 |year=2012 |pmid= |doi=10.1053/j.gastro.2011.10.035 |url=}}</ref>
| |
| ====Incidence====
| |
| *Incidence rates among age groups 18 to 44 is 0.151 to 0.251 per 1000 population.
| |
| *Incidence rates among age groups 45 to 64 years of age is 0.659 to 0.777 per 1000 population.
| |
|
| |
| ====Gender====
| |
| *At young age (<50 years), males are more commonly affected with diverticulosis than females.
| |
| *At older age, women are more frequently affected with diverticulosis than males.<ref name="pmid17299613">{{cite journal |vauthors=Warner E, Crighton EJ, Moineddin R, Mamdani M, Upshur R |title=Fourteen-year study of hospital admissions for diverticular disease in Ontario |journal=Can. J. Gastroenterol. |volume=21 |issue=2 |pages=97–9 |year=2007 |pmid=17299613 |pmc=2657668 |doi= |url=}}</ref>
| |
| ====Race====
| |
| *There is a slight racial predilection to the development of diverticulosis.
| |
| *Caucasian individuals are at higher risk of developing diverticulosis compared with Asian and non-African Black individuals.<ref name="pmid21448352">{{cite journal |vauthors=Golder M, Ster IC, Babu P, Sharma A, Bayat M, Farah A |title=Demographic determinants of risk, colon distribution and density scores of diverticular disease |journal=World J. Gastroenterol. |volume=17 |issue=8 |pages=1009–17 |year=2011 |pmid=21448352 |pmc=3057143 |doi=10.3748/wjg.v17.i8.1009 |url=}}</ref>
| |
| ===Natural history===
| |
| If left untreated colonic abscess will rupture through the wall, and this may eventually lead to death if peritonitis develops.
| |
|
| |
| ===Complications===
| |
| *Peritonitis
| |
| *Septicemia
| |
| *Hemorrhage
| |
| *Death
| |
| ===Prognosis===
| |
| *Majority of the patients with colonic abscess recover quickly with drain and IV antibiotics, but complications can occur if treatment is delayed or if peritonitis occurs.[3][4]
| |
| *It usually takes between 10 and 28 days to recover completely.
| |
| *Typical abscess responds quickly to antibiotics and percutaneous drain and resolves spontaneously.
| |
| ===History and symptoms===
| |
| The most common symptom of colonic abscess is left lower quadrant abdominal pain along with fever and chills. The most common sign is tenderness around the left side of the lower abdomen. Nausea, vomiting, chills, cramping, diarrhea and constipation may occur as well. The severity of symptoms depends on the extent of the infection.
| |
| ===Differentiating Colonic abscess from other diseases===
| |
| {| class="wikitable"
| |
| ! rowspan="3" align="center" style="background:#4479BA; color: #FFFFFF;" |Diseases
| |
| ! colspan="5" align="center" style="background:#4479BA; color: #FFFFFF;" |Clinical features
| |
| ! colspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" |Diagnosis
| |
| ! rowspan="3" align="center" style="background:#4479BA; color: #FFFFFF;" |Associated findings
| |
| |-
| |
| ! colspan="4" align="center" style="background:#4479BA; color: #FFFFFF;" |Symptoms
| |
| ! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" |Signs
| |
| ! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" |Laboratory fingdings
| |
| ! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" |Radiological findings
| |
| |-
| |
| | style="background:#4479BA; color: #FFFFFF" |'''Fever'''
| |
| | style="background:#4479BA; color: #FFFFFF" |'''Abdominal pain'''
| |
| | style="background:#4479BA; color: #FFFFFF" |'''Nausea'''
| |
| '''vomiting'''
| |
| | style="background:#4479BA; color: #FFFFFF" |'''Diarrhea'''
| |
| |-
| |
| | style="background:#4479BA; color: #FFFFFF" |'''Crohn's disease'''
| |
| | '''+'''
| |
| |
| |
| LLQ continuous localized [[pain]]
| |
| | '''+'''
| |
| |
| |
| Bloody
| |
| |
| |
| Fullness or a discrete [[mass]] in the LLQ of the [[abdomen]]
| |
| |
| |
| [ASCA]) are found in [[Crohn disease]]
| |
| |
| |
| Transmural [[ulcerations]] are seen on colonoscopy
| |
| |
| |
| * H/O [[weight loss]],
| |
| * Extra [[intestinal]] manifestaions
| |
| * [[Endoscopic]] [[biopsy]] for diagnosis
| |
| |-
| |
| | style="background:#4479BA; color: #FFFFFF" |'''Gastroenteritis'''
| |
| (Bacterial and viral)
| |
| | '''+'''
| |
| |
| |
| Diffuse crampy intermittent [[abdominal pain]]
| |
| | '''+'''
| |
| |
| |
| Bloody or watery
| |
| |
| |
| [[Rebound tenderness]], [[rash]]
| |
| |
| |
| * Fecal [[leukocytes]]
| |
| * [[Stool culture]]
| |
| * [[Stool]] [[toxin]] assay
| |
| |No specific findings
| |
| |
| |
| * H/O [[food poisoning]], travel
| |
| |-
| |
| | style="background:#4479BA; color: #FFFFFF" |'''Primary peritonitis'''
| |
| | '''+'''
| |
| |
| |
| Abrupt diffuse abdominal pain
| |
| | '''+'''
| |
| |
| |
| Bloody/watery
| |
| |
| |
| [[Abdominal distension]], rebound tenderness
| |
| |
| |
| [[Peritoneal fluid]] shows >500/microliter count and >25% polymorphonuclear [[leukocytosis]].
| |
| |
| |
| * X-ray [[abdomen]] identifies free air under the [[diaphragm]]
| |
| * CT demonstrates [[abscess]] or [[fluid]] in [[abdomen]]
| |
| |
| |
| * History of advanced [[cirrhosis]] or [[nephrosis]]
| |
| * Peritoneal fluid analysis confirms the diagnosis
| |
| |-
| |
| | style="background:#4479BA; color: #FFFFFF" |'''Pelvic inflammatory disease'''
| |
| | '''+'''
| |
| |
| |
| Bilateral lower quadrant pain
| |
| | '''+'''
| |
| | '''-'''
| |
| |
| |
| * [[Purulent]] discharge from cervical os.
| |
| * Cervical motion tenderness
| |
| |
| |
| *Abundant white blood cells ([[White blood cell (WBC) count|WBCs]]) on saline microscopy of [[vaginal]] secretions
| |
| *Laboratory evidence of cervical infection with ''[[N gonorrhoeae]]'' or ''[[Chlamydia trachomatis|C trachomatis]]''(via culture or DNA probe)
| |
| |
| |
| Transvaginal ultrasonographic scanning or magnetic resonance imaging (MRI) shows thickened fluid-filled tubes with or without free pelvic fluid or [[tubo-ovarian abscess]] (TOA).
| |
| |
| |
| [[Laparoscopy]] helps in confirmation of the diagnosis
| |
| |-
| |
| | style="background:#4479BA; color: #FFFFFF" |'''Ruptured ectopic pregnancy'''
| |
| | '''+'''
| |
| |
| |
| Diffuse abdominal pain
| |
| | '''+'''
| |
| | '''-'''
| |
| |
| |
| * Unilateral or bilateral abdominal tenderness
| |
| * [[Abdominal]] rigidity, guarding
| |
| * On pelvic examination, the [[uterus]] may be slightly enlarged and soft, and cervical motion tenderness
| |
| |
| |
| [[HCG|BHCG]] [[hormone]] level is high in serum and in urine
| |
| |
| |
| Ultrasound reveals presence of mass in [[fallopian tubes]].
| |
| |
| |
| * Triad of [[amenorrhea]], [[abdominal pain]] and [[vaginal bleeding]]
| |
| * SIgns of [[hypotension]]
| |
| * Transvaginal ultrasound with [[BHCG]] levels are the gold standard for diagnosis
| |
| |}
| |
|
| |
| ==Laboratory findings==
| |
| Hematologic parameters suggestive of [[infection]] like, [[leukocytosis]], [[anemia]], [[Thrombosis|abnormal platelet counts]], and [[Abnormal liver function test|abnormal liver function]] frequently are present in patients with colonic abscess, although patients who are debilitated or elderly often fail to mount reactive [[leukocytosis]] or [[Fever|fever]]. [[Blood cultures]] indicating persistent polymicrobial [[bacteremia]] strongly implicate the presence of an abscess.
| |
| ==CT Abdomen==
| |
|
| |
| *Colonic and paracolic inflammation in the presence of underlying diverticula (diverticula are identified on CT scans as outpouchings of the colonic wall).
| |
| *Symmetric thickening of the colonic of approximately 4-5 mm is common.
| |
| * Enhancement of the colonic wall is commonly noted. This usually has inner and outer high-attenuation layers, with a thick middle layer of low attenuation.
| |
| * Free diverticular perforation results in the extravasation of air and fluid into the pelvis and peritoneal cavity.
| |
| * Air in the bladder in the presence of a nearby segment of diverticulitis is suggestive of a colovesical fistula.
| |
|
| |
| ==Medical therapy==
| |
| [[Antibiotics]] should be started immediately once the diagnosis of abscess is made. Preoperative antibiotics have been associated with lower rates of [[wound]] and [[Intra-abdominal infection|intra-abdominal infections]].<ref name="pmid20034345">{{cite journal| author=Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA, Goldstein EJ, Baron EJ et al.| title=Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2010 | volume= 50 | issue= 2 | pages= 133-64 | pmid=20034345 | doi=10.1086/649554 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20034345 }} </ref> <ref name="SartelliViale2013">{{cite journal|last1=Sartelli|first1=Massimo|last2=Viale|first2=Pierluigi|last3=Catena|first3=Fausto|last4=Ansaloni|first4=Luca|last5=Moore|first5=Ernest|last6=Malangoni|first6=Mark|last7=Moore|first7=Frederick A|last8=Velmahos|first8=George|last9=Coimbra|first9=Raul|last10=Ivatury|first10=Rao|last11=Peitzman|first11=Andrew|last12=Koike|first12=Kaoru|last13=Leppaniemi|first13=Ari|last14=Biffl|first14=Walter|last15=Burlew|first15=Clay Cothren|last16=Balogh|first16=Zsolt J|last17=Boffard|first17=Ken|last18=Bendinelli|first18=Cino|last19=Gupta|first19=Sanjay|last20=Kluger|first20=Yoram|last21=Agresta|first21=Ferdinando|last22=Di Saverio|first22=Salomone|last23=Wani|first23=Imtiaz|last24=Escalona|first24=Alex|last25=Ordonez|first25=Carlos|last26=Fraga|first26=Gustavo P|last27=Junior|first27=Gerson Alves Pereira|last28=Bala|first28=Miklosh|last29=Cui|first29=Yunfeng|last30=Marwah|first30=Sanjay|last31=Sakakushev|first31=Boris|last32=Kong|first32=Victor|last33=Naidoo|first33=Noel|last34=Ahmed|first34=Adamu|last35=Abbas|first35=Ashraf|last36=Guercioni|first36=Gianluca|last37=Vettoretto|first37=Nereo|last38=Díaz-Nieto|first38=Rafael|last39=Gerych|first39=Ihor|last40=Tranà|first40=Cristian|last41=Faro|first41=Mario Paulo|last42=Yuan|first42=Kuo-Ching|last43=Kok|first43=Kenneth Yuh Yen|last44=Mefire|first44=Alain Chichom|last45=Lee|first45=Jae Gil|last46=Hong|first46=Suk-Kyung|last47=Ghnnam|first47=Wagih|last48=Siribumrungwong|first48=Boonying|last49=Sato|first49=Norio|last50=Murata|first50=Kiyoshi|last51=Irahara|first51=Takayuki|last52=Coccolini|first52=Federico|last53=Lohse|first53=Helmut A Segovia|last54=Verni|first54=Alfredo|last55=Shoko|first55=Tomohisa|title=2013 WSES guidelines for management of intra-abdominal infections|journal=World Journal of Emergency Surgery|volume=8|issue=1|year=2013|pages=3|issn=1749-7922|doi=10.1186/1749-7922-8-3}}</ref>
| |
| :*'''1 Emperic therapy:'''
| |
| ::*'''1.1 Single agent:'''
| |
| :::*Preferred regimen (1): [[Imipenem-Cilastatin]] 500 mg IV q6h {{or}} 1 g q8h
| |
| :::*Preferred regimen (2): [[Meropenem]] 1 g IV q8h
| |
| :::*Preferred regimen (3): [[Doripenem]] 500 mg IV q8h
| |
| :::*Preferred regimen (4): [[Piperacillin-tazobactam]] 3.375 g IV q6h
| |
|
| |
| ::*'''1.2 Combination:'''
| |
| :::*Preferred regimen (1): [[Cefepime]] 2 g q8–12 h {{and}} [[Metronidazole]] 500 mg IV q8–12 h or 1500 mg q24h
| |
| :::*Preferred regimen (2): [[Ceftazidime]] 2 g q8h {{and}} [[Metronidazole]] 500 mg IV q8–12 h or 1500 mg q24h
| |
| :::*Preferred regimen (3): [[Ciprofloxacin]] 400 mg q12h {{and}} [[Metronidazole]] 500 mg IV q8–12 h or 1500 mg q24h
| |
| :::*Preferred regimen (4): [[Levofloxacin]] 750 mg q24h {{and}} [[Metronidazole]] 500 mg IV q8–12 h or 1500 mg q24h
| |
| :::*Note: Antimicrobial therapy of established infection should be limited to 4–7 days, unless it is difficult to achieve adequate source control. Longer durations of therapy have not been associated with improved outcome.
| |
|
| |
| ==Surgery==
| |
| Percutaneous drainage can be performed under ultrasound or CT guidance, using either the Seldinger or trocar technique. Ultrasound is limited if the abscess is small, obscured by other structures, or if precise placement is required because of nearby vessels or organs. In these cases, CT is the optimal imaging modality. When an abscess is deep in the pelvis, depending on the specific location of the fluid collection, access may be obtained via transgluteal, transvaginal, or transrectal approaches. If the fluid collection is sterile, a transgluteal approach is preferred because it allows for sterile technique. Depending on the location of abscess, patient is placed in prone or supine position on the CT table. Localization scan using CT allows in selecting a safe window of access into the collection. A coaxial micropuncture introducer set is advanced into the abscess under CT guidance. An Amplatz guidewire is advanced through the sheath and coiled within the abscess. After serial dilatation of the tract with a dilator, an pigtail drain is advanced over the guidewire and deployed.
| |
| {{#ev:youtube|f5KvsjHaOnI}}
| |
| ==Prevention==
| |
| Dietary fiber and a vegetarian diet may reduce the incidence of symptomatic diverticular disease by decreasing intestinal [[inflammation]] and altering the intestinal microbiota.<ref name="pmid7942584">{{cite journal |vauthors=Aldoori WH, Giovannucci EL, Rimm EB, Wing AL, Trichopoulos DV, Willett WC |title=A prospective study of diet and the risk of symptomatic diverticular disease in men |journal=Am. J. Clin. Nutr. |volume=60 |issue=5 |pages=757–64 |year=1994 |pmid=7942584 |doi= |url=}}</ref>.
| |
| Vigorous physical activity appears to reduce the risk of [[diverticulitis]] and diverticular bleeding.<ref name="pmid7883230">{{cite journal |vauthors=Aldoori WH, Giovannucci EL, Rimm EB, Ascherio A, Stampfer MJ, Colditz GA, Wing AL, Trichopoulos DV, Willett WC |title=Prospective study of physical activity and the risk of symptomatic diverticular disease in men |journal=Gut |volume=36 |issue=2 |pages=276–82 |year=1995 |pmid=7883230 |pmc=1382417 |doi= |url=}}</ref>.
| |
| ==Acute kidney injury in cancer patients==
| |
| ===Types of Acute Kidney Injury in Patients with Hematologic Cancers===
| |
| ====Cancer-related injury====
| |
| *Tumor infiltration of the kidneys
| |
| *Obstructive nephropathy related to retroperitoneal lymphadenopathy
| |
| *Lysozymuria (CMML or AML) with direct tubular injury
| |
| *Hemophagocytic lymphohistiocytosis with acute interstitial disease
| |
| *Vascular occlusion associated with DIC and hyperleukocytosis (rare)
| |
| *Hypercalcemia with hemodynamic acute kidney injury and acute nephrocalcinosis
| |
| *Glomerular diseases (minimal change disease, focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, membranous
| |
| nephropathy, amyloidosis, immuno-tactoid glomerulonephritis, fibrillary glomerulonephritis, crescentic glomerulonephritis)
| |
| ====Therapy-related injury====
| |
| *Nephrotoxicity (including thrombotic microangiopathy, acute tubular injury, tubulointerstitial nephritis, and glomerular disease)
| |
| *Tumor lysis syndrome with acute uric acid nephropathy (may occur spontaneously)
| |
| *Intratubular obstruction from medications (e.g., methotrexate)
| |
| ====Other types of injuries====
| |
| *Volume depletion
| |
| *Sepsis and septic shock
| |
| *Nephrotoxicity of radiocontrast agents
| |
| *Nephrotoxicity of common medications, such as NSAIDs, ACE inhibitors,
| |
| *ARBs, and antibiotics
| |
| ===Cancers and association===
| |
| *MM
| |
| *RCC
| |
| *
| |
| ==Types of Haemophilus influenzae Infections==
| |
| H. influenzae, including Hib, can cause many different kinds of infections. These infections can range from mild ear infections to severe diseases, like bloodstream infections. When the bacteria invade parts of the body that are normally free from germs, like spinal fluid or blood, this is known as "invasive disease." Invasive disease is usually severe and can sometimes result in death.<br>
| |
| The most common types of invasive disease caused by H. influenzae are:
| |
| *Pneumonia
| |
| *Bacteremia
| |
| *Meningitis (infection of the covering of the brain and spinal cord)
| |
| *Epiglottitis (swelling of the windpipe that can cause breathing trouble)
| |
| *Cellulitis (skin infection)
| |
| *Infectious arthritis (inflammation of the joint)
| |
| H. influenzae can also be a common cause of ear infections in children and bronchitis in adults.
| |
|
| |
| ==Causes==
| |
| *Haemophilus influenzae disease is caused by the bacterium Haemophilus influenzae.
| |
| *There are six identifiable types of H. influenzae (a through f) and other non-identifiable types (called nontypeable). The one that people are most familiar with is H. influenzae type b, or Hib.
| |
| *These bacteria live in the nose and throat, and usually cause no harm. However, the bacteria can sometimes move to other parts of the body and cause infection. Some of these infections are considered “invasive” and can be very serious and sometimes even deadly.
| |
|
| |
| ==Incubation period==
| |
| The incubation period (time between exposure and first symptoms) of H. influenzae disease is not certain, but could be as short as a few days.
| |
| .
| |
|
| |
| ==Natural history==
| |
| *Between 3% to 6% of Hib cases in children are fatal; up to 20% of patients who survive Hib meningitis have permanent hearing loss or other long-term neurological sequelae.
| |
| *Patients ≥65 years of age with invasive H. influenzae disease (Hib, non-b, and nontypeable) have higher case-fatality ratios than children and young adults.
| |
| ==Epidemiology==
| |
| ===Incidence===
| |
| *Before vaccine became available in 1988, the annual attack rate of invasive Hib disease was estimated at 64-129 cases per 100,000 children younger than 5 years.
| |
| *The estimated annual incidence of Hib infection is 0.04 cases per 100,000 general population.
| |
| *The estimated annual incidence of non-Hib infection is 0.36 cases per 100,000 general population.
| |
| ===Gender===
| |
| *Hib disease has no sexual predilection
| |
| ===Age===
| |
| *Hib infections are rare in patients older than 6 years.
| |
| *Hib infections are most common in children aged 6 months to 6 years.
| |
| ==Risk factors==
| |
| *Unimmunized children younger than 4 years of age, as well as household contacts and daycare classmates of a person with Hib disease are at increased risk of Hib disease.
| |
| *Close contacts of patients with non-b or nontypeable H. influenzae has not been identified.
| |
| *Patients with sickle cell disease, asplenia, HIV, and certain immunoglobulin and complement component deficiencies, as well as recipients of hematopoietic stem cell transplant and chemotherapy or radiation therapy for malignant neoplasms are at increased risk for invasive H. influenzae disease.
| |
| *Immigrants
| |
| ==Complications==
| |
| *Complications depend on the type of invasive infection caused the bacteria.
| |
| *Meningitis can result in hearing loss.
| |
| *Bacteremia (blood infection) can result in loss of limb(s).
| |
| *Invasive H. influenzae infections can sometimes result in death. Even with antibiotic treatment, about 3 to 6 out of every 100 children with meningitis caused by Hib die from the disease.
| |
| *When H. influenzae cause a non-invasive infection, like bronchitis or an ear infection, complications are rare and typically not severe. If appropriate, antibiotics can be given to prevent complications
| |
| ==Medical therapy==
| |
| A number of medical treatments are utilized with the goal of putting and keeping the disease in [[remission (medicine)|remission]]. These include [[mesalazine|5-aminosalicylic acid]] (5-ASA) formulations (Pentasa capsules, Asacol tablets, Lialda tablets, Rowasa retention enemas), [[prednisone|steroid]] medications, immunomodulators (such as [[azathioprine]], [[mercaptopurine]] (6-MP), and [[methotrexate]]), and newer [[biological therapy for inflammatory bowel disease|biological]] medications, such as [[infliximab]] (Remicade) and [[adalimumab]] (Humira).<ref name="Podolsky">{{Cite journal|last=Podolsky|first= Daniel K.|title=Inflammatory bowel disease|journal=New England Journal of Medicine|month=August|year=2002|volume=346|issue=6|pages=417-29
| |
| |url=http://content.nejm.org/cgi/content/extract/347/6/417|accessdate=2006-07-02|id=PMID 12167685}}</ref>Also in January 2008 the U.S. Food and Drug Administration approved a new biological medication known as [[natalizumab]] (Tysabri) for both induction of remission and maintenance of remission in moderate and severe Crohn's Disease.
| |
| Treatment is only needed for people exhibiting symptoms. The therapeutic approach to Crohn's disease is sequential: to treat [[acute (medical)|acute]] disease and then to maintain [[remission]]. Treatment initially involves the use of medications to treat any infection and to reduce inflammation. This usually involves the use of aminosalicylate anti-inflammatory drugs and corticosteroids, and may include antibiotics.
| |
|
| |
| Once remission is induced, the goal of treatment becomes maintaining remission and avoiding flares. Because of side-effects, the prolonged use of corticosteroids must be avoided. Although some people are able to maintain remission with aminosalicylates alone, many require immunosuppressive drugs.
| |
| On 14 January 2008 the U.S. Food and Drug Administration approved [[natalizumab]] (Tysabri) for both induction of remission and maintenance of remission in Crohns. Natalizumab is humanized monoclonal antibody (MAb), and the first alpha-4 antagonist in a new class of agents called selective adhesion-molecule (SAM) inhibitors. Alpha-4 integrin is required for [[leukocyte]]s to adhere to the walls of blood vessels and migrate into the gut; natalizumab prevents leukocytes from doing that. Natalizumab was previously approved for [[multiple sclerosis]]. However, because it suppresses the [[immune system]], natalizumab has been linked to a very rare adverse effect that is usually fatal if undetected. Leukocytes also protect the body from viruses, and 2 patients on natalizumab, who were also receiving other immuno-suppressive drugs ([[Interferon beta-1a|Avonex]] and Immuran), died of a rare brain infection, [[progressive multifocal leukoencephalopathy]]. Because of this danger, patients must be in a special monitoring program, and natalizumab is given as a mono-therapy.<ref name="FDA-Tysbari">{{cite press release|title=FDA Approves Tysabri to Treat Moderate-to-Severe Crohn's Disease|publisher=U.S. Food and Drug Administration|date=2008-01-14|url=http://www.fda.gov/bbs/topics/NEWS/2008/NEW01775.html|accessdate=2008-01-16
| |
| }}</ref> As of late December 2007, more than 21,000 MS patients were receiving natalizumab mono-therapy without a single incidence of PML occurring.<ref>.http://www.elan.com/News/full.asp?ID=1091942</ref>
| |
|
| |
| [[Surgery]] may be required for complications such as obstructions, fistulas and/or abscesses, or if the disease does not respond to drugs within a reasonable time. For patients with an obstruction due to a stricture, two options for treatment are strictureplasty and resection of that portion of bowel. According to a retrospective review at the Cleveland Clinic, there is no [[statistical significance]] between strictureplasty alone versus strictureplasty and resection specifically in cases of duodenal involvement. In these cases, re-operation rates were 31% and 27%, respectively, indicating that strictureplasty is a safe and effective treatment for selected patients with duodenal involvement.<ref name="pmid8918424">{{cite journal | author = Ozuner G, Fazio VW, Lavery IC, Milsom JW, Strong SA | title = Reoperative rates for Crohn's disease following strictureplasty. Long-term analysis | journal = Dis. Colon Rectum | volume = 39 | issue = 11 | pages = 1199-203 | year = 1996 | pmid = 8918424 | doi = }}</ref>
| |
|
| |
| Recent studies using [[Helminthic therapy]] or [[hookworm]]s to treat Crohn's Disease and other (non-viral) auto-immune diseases seem to yield promising results.<ref>British Medical Journal [http://gut.bmj.com/cgi/content/full/55/1/136 A proof of concept study establishing Necator americanus in Crohn’s patients and reservoir donors]</ref><ref name="Daily Mail">Daily Mail. [http://www.dailymail.co.uk/pages/live/articles/technology/technology.html?in_article_id=481875&in_page_id=1965 The bloodsucking worm that fights allergies from inside your tummy] 14-09-2007.</ref><ref>[http://www.kuro5hin.org/story/2006/4/30/91945/8971 How to cure your asthma or hayfever using hookworm - a practical guide]. 01-05-2006.</ref>
| |
|
| |
| ==Pathophysiology of Sepsis==
| |
| *Sepsis is defined as a collection of physiologic responses by the immune system in response to an infectious agent.
| |
| *The clinical course of sepsis depends on the type and resistance of the infectious organism, the site and size of the infecting insult, and the genetically determined or acquired properties of the host's immune system.
| |
| *The pathogenesis of sepsis can be discussed as follows
| |
|
| |
| ===Immune system activation===
| |
| *The immune system is activated by pathogen entry which is facilitated by contamination of tissue either by surgery or infection, foreign body insertion (catheters) and in an immunocompromised state.
| |
| *Products of activation include
| |
| **Bacterial cell wall products such as lipopolysaccharide
| |
| **Binding to host receptors, including Toll-like receptors (TLRs).
| |
| *Toll-like receptors are found in leukocytes and macrophages, and endothelial cells.
| |
| *These have specificity for different bacterial, fungal, or viral products.
| |
| *TLRs are associated with a predisposition to shock with gram-negative organisms.
| |
| *Activation of the innate immune system results in a complex series of cellular and humoral responses.
| |
|
| |
| ===Immune repsonse===
| |
| *Immune response includes the release of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha and interleukins 1 and 6 along with reactive oxygen species, nitric oxide (NO), proteases, and pore-forming molecules, which bring about activation of immune cells and bacterial killing.
| |
| *Nitrous oxide is responsible for vasodilatation and increased capillary permeability and has been implicated in sepsis-induced mitochondrial dysfunction.
| |
| *The complement system also gets activated which mediates activation of leukocytes, attracting them to the site of infection (phagocytes, cytotoxic T lymphocytes),
| |
| *Complement system also helps as a mediator for antigen-presenting cells and B lymphocytes
| |
| *This response by complement system helps the B lymphocyte to produce memory cells in case of future infection and is responsible for the increased production and chemotaxis of more T helper cells.
| |
|
| |
| ===The endothelium and coagulation system===
| |
| *The vascular endothelium plays a major role in the host's defense to an invading organism, but also in the development of sepsis.
| |
| *Activated endothelium not only allows the adhesion and migration of stimulated immune cells but becomes porous to large molecules such as proteins, resulting in the tissue edema.
| |
| *Alterations in the coagulation systems include an increase in procoagulant factors, such as plasminogen activator inhibitor type I and tissue factor, and reduced circulating levels of natural anticoagulants, including antithrombin III and activated protein C (APC), which also carry anti-inflammatory and modulatory roles.
| |
| ===Inflammation and organ dysfunction===
| |
| *Through vasodilatation (causing reduced systemic vascular resistance) and increased capillary permeability (causing extravasation of plasma), sepsis results in relative and absolute reductions in circulating volume.
| |
| *A number of factors combine to produce multiple organ dysfunctions.
| |
| *Relative and absolute hypovolemia are compounded by reduced left ventricular contractility to produce hypotension.
| |
| *Initially, through an increased heart rate, cardiac output increases to compensate and maintain perfusion pressures, but as this compensatory mechanism becomes exhausted, hypoperfusion and shock may result.
| |
| *Impaired tissue oxygen delivery is exacerbated by pericapillary edema.
| |
| *It makes oxygen to diffuse a greater distance to reach target cells.
| |
| *There is a reduction of capillary diameter due to mural edema and the procoagulant state results in capillary microthrombus formation.
| |
| ===Additional contributing factors===
| |
| *Disordered blood flow through capillary beds, resulting from a combination of shunting of blood through collateral channels and an increase in blood viscosity secondary to loss of red cell flexibility.
| |
| *As a result, organs become hypoxic, even with increase blood flow.
| |
| *These abnormalities leads to lactic acidosis, cellular dysfunction, and multiorgan failure.
| |
| *Cellular energy levels fall as metabolic activity begins to exceed production.
| |
| *However, cell death appears to be uncommon in sepsis, implying that cells shut down as part of the systemic response.
| |
| *This could explain why relatively few histologic changes are found at autopsy, and the eventual rapid resolution of severe symptoms, such as complete anuria and hypotension, once the systemic inflammation resolves.
| |
| ==H influenza infection==
| |
| ===Overview===
| |
| H.influenzae is a type of bacteria that can cause infections in people of all ages ranging from mild, such as an ear infection, to severe, such as a bloodstream infection.
| |
| ===Causes===
| |
| *Haemophilus influenza disease is caused by the bacterium Haemophilus influenza.
| |
| *There are six identifiable types of H.influenza (a through f) and other non-identifiable types (called nontypeable).
| |
| *The most common type of H.influeza that is most familiar is H. influenza type b, or Hib.
| |
| *These bacteria are a normal commensal of throat and nose. However, the bacteria can sometimes move to other parts of the body and cause infection.
| |
| *Some of these infections are considered “invasive” and can be very serious.
| |
|
| |
| ===Classification===
| |
| H. influenzae, including Hib, can cause many different kinds of infections. These infections can range from mild ear infections to severe diseases, like bloodstream infections. When the bacteria invade parts of the body that are normally free from germs, like spinal fluid or blood, this is known as "invasive disease." Invasive disease is usually severe and can sometimes result in death.<br>
| |
| The most common types of invasive disease caused by H.influenza are:
| |
| *Pneumonia
| |
| *Bacteremia
| |
| *Meningitis (infection of the covering of the brain and spinal cord)
| |
| *Epiglottitis (swelling of the windpipe that can cause breathing trouble)
| |
| *Cellulitis (skin infection)
| |
| *Infectious arthritis (inflammation of the joint)
| |
| The most common types of Non-invasive disease caused by H.influenza are:
| |
| *Otitis media
| |
| *Conjuctivitis
| |
|
| |
| {{Family tree/start}}
| |
| {{Family tree | | | | | | | | | | | | | | | | | | | | | | | A01 | | | | | | | | | | | | |A01= '''[[H influenza infection]]'''}}
| |
| {{Family tree | | | | | | | | | | |,|-|-|-|-|-|-|-|-|-|-|-|-|^|-|-|-|-|-|-|-|-|-|-|-|-|-|.| | }}
| |
| {{Family tree | | | | | | | | | | C01 | | | | | | | | | | | | | | | | | | | | | | | | | C02 |C01= Infection due to capsulated [[H influenza]]| C02= Infection due to non-capsulated [[H influenza]]}}
| |
| {{Family tree | | |,|-|-|-|v|-|-|-|^|-|-|-|v|-|-|-|v|-|-|-|v|-|-|-|.| | | | | |,|-|-|-|-|^|-|-|-|-|.|}}
| |
| {{Family tree | | D01 | | D02 | | | | | | D03 | | D04 | | D05 | | D06 | | | | D07 | | | | | | | | D08 |D01= [[Meningitis]] |D02=[[Cellulitis]]|D03=[[Epiglottitis]] |D04= [[Pneumonia]]|D05=[[Pericarditis]]|D06=[[Septic arthritis]]|D07=[[otitis media]]|D08=[[Conjunctivitis]]}}
| |
| {{Family tree/end}}
| |
|
| |
| ==Pathophysiology==
| |
| ===Transmission===
| |
| *Transmission is by direct contact or by inhalation of respiratory tract droplets.
| |
| *Neonates can acquire the infection by aspiration of amniotic fluid or contact with genital tract secretions containing the bacteria.
| |
| ===Incubation period===
| |
| The incubation period (time between exposure and first symptoms) of H. influenzae disease is not certain, but could be as short as a few days.
| |
| ===Seeding===
| |
| *A larger bacterial load or the presence of a concomitant viral infection can potentiate the infection.
| |
| *The colonizing bacteria invade the mucosa and enter the bloodstream.
| |
| *The spread of bacteria by direct extension to the eustachian tubes causes otitis media.
| |
| *Spread to the sinuses leads to sinusitis.
| |
| *Spread down the respiratory tract results in bronchitis and pneumonia.
| |
| *Eustachian tube dysfunction, antecedent viral upper respiratory tract infection (URTI), foreign bodies, and mucosal irritants, including smoking, can promote infection.
| |
| *In patients with underlying chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF), NTHi frequently colonizes the lower respiratory tract and can exacerbate the disease.
| |
| ===Pathogenesis===
| |
| *The capsule of H influenza plays a key role in the pathogenesis of the all the capsulated H influenza infections.
| |
| *The antiphagocytic nature of the Hib capsule makes it resistant to natural host phagocytic defense mechanisms and facilitating bacterial proliferation.
| |
| *After proliferation, the bacterial load disseminates to various sites, including meninges, subcutaneous tissue, joints, pleura, pericardiam, and lungs triggering an inflammatory response and subsequently activating the complement system.
| |
| *Capsulated H influenza can penetrate the normal epithelium and are therefore responsible for invasive infections.
| |
| *Non-capsulated are non-invasive but can still induce the inflammatory response similar to that of capsulated organisms
| |
| *The Hib conjugate vaccine induces protection by inducing antibodies against the PRP capsule.
| |
| *The Hib conjugate vaccine does not provide protection against Non-typable H influenza strains. Since the widespread use of the Hib conjugate vaccine, Non-typable H influenza strains has become more of a pathogen
| |
| ==Toxoplasmosis==
| |
| ==== Transmission ====
| |
|
| |
| Transmission may occur through:
| |
| * Ingestion of raw or partly cooked meat, especially pork, lamb, or venison containing Toxoplasma cysts. Infection prevalence in countries where undercooked meat is traditionally eaten, such as France, has been related to this transmission method. Oocysts may also be ingested during hand-to-mouth contact after handling undercooked meat, or from using knives, utensils, or cutting boards contaminated by raw meat.<ref name="CDC">{{cite web
| |
|
| |
| | url=http://www.dpd.cdc.gov/DPDx/HTML/Toxoplasmosis.htm
| |
| | title=Toxoplasmosis
| |
| | publisher=Centers of Disease Control and Prevention
| |
| | date=2004-11-22 }}</ref>
| |
|
| |
| * Ingestion of contaminated cat faeces. This can occur through hand-to-mouth contact following gardening, cleaning a cat's litter box, contact with children's sandpits, or touching anything that has come into contact with cat faeces.
| |
| * Drinking water contaminated with Toxoplasma.
| |
| * Transplacental infection [[Uterus|in utero]].
| |
| * Receiving an infected [[organ transplant]] or [[blood transfusion]], although this is extremely rare.<ref name="CDC" />
| |
| * Accidental inoculation of tachyzoites
| |
|
| |
| ====[[Transplacental]] Transmission====
| |
|
| |
| *infection in [[1st trimester]] - incidence of transplacental infection is low (15%) but disease in neonate is most severe.
| |
| *Infection in [[3rd trimester]] - incidence of transplacental infection is high (65%) but infant is usually asymptomatic at birth.
| |
|
| |
| The cyst form of the parasite is extremely hardy, capable of surviving exposure to freezing down to −12 degrees Celsius, moderate temperatures and chemical disinfectants such as bleach, and can survive in the environment for over a year. It is, however, susceptible to high temperatures—above 66 degrees Celsius, and is thus killed by thorough cooking, and would be killed by 24 hours in a typical domestic freezer.<ref>[http://www.ncagr.com/vet/ToxoplasmosisTxt.htm]</ref>
| |
|
| |
| Cats excrete the [[pathogen]] in their faeces for a number of weeks after contracting the disease, generally by eating an infected rodent. Even then, cat faeces are not generally contagious for the first day or two after excretion, after which the cyst 'ripens' and becomes potentially pathogenic. Studies have shown that only about 2% of cats are shedding oocysts at any one time, and that oocyst shedding does not recur even after repeated exposure to the parasite. Although the pathogen has been detected on the fur of cats, it has not been found in an infectious form, and direct infection from handling cats is generally believed to be very rare.
| |
| ===Pathophysiology===
| |
| ====Life cycle of Toxoplasma gondii====
| |
| *T gondii has 2 distinct life cycles.
| |
| *The sexual cycle occurs only in cats, the definitive host.
| |
| *The asexual cycle occurs in other mammals (including humans) and various strains of birds.
| |
| *It consists of 2 forms: tachyzoites (the rapidly dividing form observed in the acute phase of infection) and bradyzoites (the slowly growing form observed in tissue cysts).
| |
| *A cat becomes infected with T gondii by eating contaminated raw meat, wild birds, or mice.
| |
| *The organism’s sexual cycle then begins in the cat’s gastrointestinal (GI) tract. Macrogametocytes and microgametocytes develop from ingested bradyzoites and fuse to form zygotes.
| |
| *The zygotes then become encapsulated within a rigid wall and are shed as oocysts.
| |
| *The zygote sporulates and divides to form sporozoites within the oocyst.
| |
| *Sporozoites become infectious 24 hours or more after the cat sheds the oocyst via feces.
| |
| *During a primary infection, the cat can excrete millions of oocysts daily for 1-3 weeks.
| |
| *The oocysts are very strong and may remain infectious for more than one year in warm humid environments.
| |
| *T gondii oocysts, tachyzoites, and bradyzoites can cause infection in humans.
| |
| ====Transmission====
| |
| *Infection can occur by ingestion of oocysts following the handling of contaminated soil or cat litter or through the consumption of contaminated water or food sources (eg, unwashed garden vegetables).
| |
| *Transmission of tachyzoites to the fetus can occur via the placenta following primary maternal infection.
| |
| *Rarely, infection by tachyzoites occurs from ingestion of unpasteurized milk or by direct entry into the bloodstream through a blood transfusion or laboratory accident.
| |
| *Transmission can also occur via ingestion of tissue cysts (bradyzoites) in undercooked or uncooked meat or through transplantation of an organ that contains tissue cysts. (Slaughterhouse workers and butchers may be at increased risk of infection.)
| |
| ====Seeding====
| |
| *T gondii oocysts are ingested in material contaminated by feces from infected cats.
| |
| *When T gondii is ingested, bradyzoites are released from cysts or sporozoites are released from oocysts, and the organisms enter gastrointestinal cells. *Host cell receptors consisting of laminin, lectin, and SAG1 are involved in T gondii tachyzoite attachment and penetration.
| |
| *Tachyzoites multiply, rupture cells, and infect contiguous cells.
| |
| *The ability of T gondii to actively penetrate host cells results in formation of a parasitophorous vacuole that is derived from the plasma membrane, which is entirely distinct from a normal phagocytic or endocytic compartment.
| |
| *Following apical attachment, the parasite rapidly enters the host cell in a process that is significantly faster than phagocytosis.
| |
| *The vacuole is formed primarily by invagination of the host cell plasma membrane, which is pulled over the parasite through the concerted action of the actin-myosin cytoskeleton of the parasite.
| |
| *During invasion, the host cell is essentially passive and no change is detected in membrane ruffling, the actin cytoskeleton, or phosphorylation of host cell proteins.
| |
| ====Dissemination====
| |
| *They are transported via the lymphatics and are disseminated hematogenously throughout the tissues.
| |
| ====Immune response====
| |
| *Tachyzoites proliferate, producing necrotic foci surrounded by a cellular reaction.
| |
| *Upon the development of a normal immune response, tachyzoites disappear from tissues.
| |
| *In immunodeficient individuals and in some apparently immunologically healthy patients, the acute infection progresses, resulting in potentially lethal consequences such as pneumonitis, myocarditis, and necrotizing encephalitis.
| |
| ====Changes in T-lymphocyte levels====
| |
| *Alterations in subpopulations of T lymphocytes are profound and prolonged during acute acquired T gondii infection.
| |
| *These have been correlated with disease syndromes but not with disease outcome.
| |
| *Some patients with prolonged fever and malaise have lymphocytosis, increased suppressor T-cell counts, and a decreased helper-to-suppressor T-cell ratio.
| |
| *In some patients with lymphadenopathy, helper-cell counts are diminished for more than 6 months after infection onset.
| |
| *Ratios of T-cell subpopulations may also be abnormal in asymptomatic patients.
| |
| *Some patients with disseminated toxoplasmosis have a very marked reduction in T cells and a marked depression in the ratio of helper to suppressor T lymphocytes.
| |
| *Depletion of inducer T lymphocytes in patients with AIDS may contribute to the severe manifestations of toxoplasmosis observed in these patients.
| |
|
| |
| ===Retinochoroiditis===
| |
| *Retinochoroiditis usually results from reactivation of congenital infection, although cases have been recorded that were part of acute infection.
| |
| *There are 5 hypotheses related to the inflammatory process of ocular toxoplasmosis, as follows
| |
| **Infection and inflammatory response after spontaneous cyst rupture
| |
| **Parasitic toxic mediators released from T gondii
| |
| **Lytic effect of inflammatory mediators
| |
| **Delayed-type hypersensitivity reaction to antigens of T gondii
| |
| **Cell-mediated immunity against retinal antigens
| |
| *When the organism reaches the eye through the bloodstream, depending on the host's immune status, a clinical or subclinical focus of infection begins in the retina.
| |
| *As the host's immune system responds and the tachyzoites convert themselves into bradyzoites, the cyst forms.
| |
| *The cyst is extremely resistant to the host's defenses, and a chronic, latent infection ensues.
| |
| *If a subclinical infection is present, no funduscopic changes are observed.
| |
| *The cyst remains in the normal-appearing retina. Whenever the host's immune function declines for any reason, the cyst wall may rupture, releasing organisms into the retina, and the inflammatory process restarts.
| |
| *If an active clinical lesion is present, healing occurs as a retinochoroidal scar.
| |
| *The cyst often remains inactive within or adjacent to the scar.
| |
| ==Strongyloidiasis==
| |
| Strongyloidiasis is a disease caused by a nematode, or a roundworm, in the genus Strongyloides. Though there are over 40 species within this genus that can infect birds, reptiles, amphibians, livestock and other primates, Strongyloides stercoralis is the primary species that accounts for human disease. The larvae are small; the longest reach about 1.5mm in length -- the size of a mustard seed or a large grain of sand.
| |
| ===Classification===
| |
| '''Acute strongyloidiasis'''<br>
| |
| '''Chronic strongyloidiasis'''<br>
| |
| '''Hyperinfection syndrome and disseminated strongyloidiasis'''
| |
|
| |
| ===Pathogenesis===
| |
| Strongyloides is classified as a soil-transmitted helminth. This means that the primary mode of infection is through contact with soil that is contaminated with free-living larvae. When the larvae come in contact with skin, they are able to penetrate it and migrate through the body, eventually finding their way to the small intestine where they burrow and lay their eggs. Unlike other soil-transmitted helminths such as hookworm and whipworm whose eggs do not hatch until they are in the environment, the eggs of Strongyloides hatch into larvae in the intestine. Most of these larvae will be excreted in the stool, but some of the larvae may molt and immediately re-infect the host either by burrowing into the intestinal wall, or by penetrating the perianal skin. This characteristic of Strongyloides is termed auto-infection. The significance of auto-infection is that unless treated for Strongyloides, persons may remain infected throughout their lifetime.
| |
| ====Transmission====
| |
| *Contact with soil and auto-infection, there have been rare cases of person-to-person transmission in:
| |
| *Organ transplantation
| |
| *Institutions for the development nfeclly disabled
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| *Long-term care facilities
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| *Daycare centers
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| ====Incubation period====
| |
| Most people do not know when their exposure occurred. For those who do, a local rash can occur immediately. The cough usually occurs several days later. Abdominal symptoms typically occur approximately 2 weeks later, and larvae can be found in the stool about 3 to 4 weeks later.
| |
| ====Life cycle====
| |
| *The Strongyloides life cycle is more complex than that of most nematodes with its alternation between free-living and parasitic cycles, and its potential for autoinfection and multiplication within the host.
| |
| *Two types of cycles exist:
| |
| '''Free-living cycle''':
| |
| *The rhabditiform larvae passed in the stool can either become infective filariform larvae (direct development) or free living adult males and females
| |
| *These adult forms mate and produce eggs from which rhabditiform larvae hatch, eventually become infective filariform larvae.
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| *The filariform larvae penetrate the human host skin to initiate the parasitic cycle.
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| '''Parasitic cycle:'''
| |
| *Filariform larvae in contaminated soil penetrate the human skin and by various, often random routes, migrate into the small intestine.
| |
| *Historically it was believed that the larvae migrate via the bloodstream to the lungs, where they are eventually coughed up and swallowed.
| |
| *However, there is also evidence that larvae can migrate directly to the intestine via connective tissues.
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| *In the small intestine they molt twice and become adult female worms.
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| *The females live threaded in the epithelium of the small intestine and by parthenogenesis produce eggs which yield rhabditiform larvae.
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| *The rhabditiform larvae can either be passed in the stool or can cause autoinfection.
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| *In autoinfection, the rhabditiform larvae become infective filariform larvae, which can penetrate either the intestinal mucosa (internal autoinfection) or the skin of the perianal area (external autoinfection); in either case, the filariform larvae may disseminate throughout the body.
| |
| *To date, occurrence of autoinfection in humans with helminthic infections is recognized only in Strongyloides stercoralis and Capillaria philippinensis infections.
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| *In the case of Strongyloides, autoinfection may explain the possibility of persistent infections for many years in persons who have not been in an endemic area and of hyperinfections in immunosuppressed individuals.
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| [[Image:Strongyloides LifeCycle.gif|center|Life cycle of Strongyloides stercoralis]]
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| ==Microscopic findings==
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|
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| {{#ev:youtube|TSwN602mcn4}}
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| ===Signs and Symptoms===
| |
| The majority of people infected with Strongyloides are without symptoms.The symptomatic spectrum of Strongyloides ranges from subclinical in acute and chronic infection to severe and fatal in hyperinfection syndrome and disseminated strongyloidiasis, which have case-fatality rates that approach 90%. In either case, patients’ symptoms are a result of the parasite’s larval form migrating through various organs of the body. Those who do develop symptoms tend to have non-specific, or generalized complaints. Some people develop abdominal pain, bloating, heartburn, intermittent episodes of diarrhea and constipation, a dry cough, and rashes. Rarely people will develop arthritis, kidney problems, and heart conditions.
| |
| Strongyloidiasis can be severe and life-threatening in persons who:
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| *People who use oral or intravenous steroids -- such as those with asthma or chronic obstructive pulmonary disease (COPD) exacerbations, lupus, gout, or in persons using steroids for immunosuppression or symptomatic relief
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| *HTLV-1 infection
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| *Have hematologic malignancies such as leukemia or lymphoma
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| *Transplant recipients.
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|
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| ===Acute strongyloidiasis===
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| *The initial sign of acute strongyloidiasis, if noticed at all, is a localized pruritic, erythematous rash at the site of skin penetration.
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| *Patients may then develop tracheal irritation and a dry cough as the larvae migrate from the lungs up through the trachea.
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| *After the larvae are swallowed into the gastrointestinal tract, patients may experience diarrhea, constipation, abdominal pain, and anorexia.
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| ===Chronic strongyloidiasis===
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| *Chronic strongyloidiasis is generally asymptomatic, but in patients with clinical disease gastrointestinal and cutaneous manifestations are the most common. *Of the gastrointestinal complaints, epigastric pain, postprandial fullness, heartburn, and brief episodes of intermittent diarrhea and constipation are the most frequent.
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| *Less commonly, patients may present with fecal occult blood, or massive colonic and gastric hemorrhage.
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| *Presentations resembling inflammatory bowel disease, specifically ulcerative colitis, are rare. Also rare, but documented, are endoscopic exams revealing pathology similar to pseudopolyposis.
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| *Cutaneous symptoms include chronic urticaria and the pathognomonic larva currens- a recurrent serpiginous maculopapular or urticarial rash along the buttocks, perineum, and thighs due to repeated auto-infection.
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| *It has been described as advancing as rapidly as 10cm/hr.
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| *Rarely, patients with chronic strongyloidiasis have complained of arthritis, cardiac arrhythmias, and signs and symptoms consistent with chronic malabsorption, duodenal obstruction, nephrotic syndrome, and recurrent asthma.
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| *Up to 75% of people with chronic strongyloidiasis have mild peripheral eosinophilia or elevated IgE levels.
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|
| |
| ===Hyperinfection syndrome and disseminated strongyloidiasis===
| |
| *Hyperinfection syndrome and disseminated strongyloidiasis are most frequently associated with subclinical infection in patients receiving high-dose corticosteroids for the treatment of asthma or chronic obstructive pulmonary disease (COPD) exacerbations.
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| *Subsequent impaired host immunity leads to accelerated autoinfection and an overwhelming number of migrating larvae.
| |
| *Whereas in chronic strongyloidiasis and in hyperinfection syndrome the larvae are limited to the GI tract and the lungs, in disseminated strongyloidiasis the larvae invade numerous organs.
| |
| *Left untreated, the mortality rates of hyperinfection syndrome and disseminated strongyloidiasis can approach 90%.
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| The following are signs and symptoms that can be seen with hyperinfection syndrome and disseminated strongyloidiasis:
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|
| |
| '''Gastrointestinal manifestations'''
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| *Abdominal pain, nausea, vomiting, diarrhea, ileus, bowel edema, intestinal obstruction, mucosal ulceration, massive hemorrhage, and subsequent peritonitis or bacterial sepsis
| |
| '''Pulmonary manifestations and findings'''
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| *Cough, wheezing, dyspnea, hoarseness, pneumonitis, hemoptysis, respiratory failure, diffuse interstitial infiltrates or consolidation on chest radiographs
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| '''Neurologic findings'''
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| *Aseptic or gram-negative meningitis
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| *Larvae have been reported in the CSF, meningeal vessels, dura, epidural, subdural, and subarachnoid spaces
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| '''Systemic signs and symptoms'''
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| *Peripheral edema and ascites secondary to hypoalbuminemia from protein losing enteropathy
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| *Recurrent gram negative bacteremia/sepsis from larvae carrying bacteria that penetrate mucosal walls
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| *Syndrome of inappropriate secretion of anti-diuretic hormone (SIADH)
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| *Peripheral eosinophilia is frequently absent
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| '''Cutaneous manifestations'''
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| *Recurrent maculopapular or urticarial rash most commonly found along the buttocks, perineum, and thighs due to repeated auto-infection, but can be found anywhere on the skin
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| *Larva currens - pathognomonic serpiginous or urticarial rash that advances as rapidly as 10cm/hr.
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|
| |
| ==Physical examination==
| |
| ==Overview==
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| The physical examination findings in ascariasis vary and it is usually dependent on the worm burden and the involved organ.
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| ==Physical Examination==
| |
| ===General appearance===
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| Most patients generally appear well with minimal or no symptoms on physical examination.
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| ===Vital signs===
| |
| A low-grade [[fever]] may occur in some patients with ascariasis.A high grade [[fever]] may be seen when there are complications such as acute [[cholangitis]], [[hepatic abscess]], etc.
| |
| ===HEENT===
| |
| An icteric sclera due to [[Jaundice|obstructive jaundice]] from biliary ascariasis may be seen.
| |
|
| |
| ===Chest===
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| * [[Dyspnea]]
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| * Dry [[rales]]
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| * [[Wheezing]] resulting from [[bronchospasms]]
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|
| |
| ===Abdomen===
| |
| * Abdominal tenderness- Abdominal tenderness can be secondary to [[intestinal obstruction]], [[appendicitis]], [[biliary colic]], acute [[cholangitis]], [[acute cholecystitis]], [[hepatic abscess]], etc
| |
| * [[Abdominal distension]]
| |
| * Signs of acute [[bowel obstruction]]
| |
| ===Skin===
| |
| The patients with ascariasis can present with [[urticaria]].
| |
| ==Natural history, Complications and Prognosis==
| |
| ===Natural history===
| |
| If left untreated, the subclinical strongyloidiasis can disseminate and transform into hyper infection syndrome with a mortality rate of 90%.
| |
| ===Complications===
| |
| * Disseminated strongyloidiasis
| |
| * Eosinophilic pneumonia
| |
| * [[Malnutrition]] due to problems absorbing nutrients from the gastrointestinal tract ([[malabsorption]])
| |
| ===Prgonosis===
| |
| With good treatment, people should make a full recovery and the parasites should be removed. Sometimes treatment needs to be repeated. Infections that are severe or widespread often have a poor outcome, especially in people with a weakened immune system.
| |
| ===Laboratory findings===
| |
| *The gold standard for the diagnosis of Strongyloides is serial stool examination.
| |
| *However, traditional stool examinations are insensitive and require up to seven stool exams to reach a sensitivity of 100%.
| |
| *Specialized stool exams include Baermann concentration, Horadi-Mori filter paper culture, quantitative acetate concentration technique, and nutrient agar plate cultures.
| |
| *Duodenal aspirate is more sensitive than stool examination, and duodenal biopsy may reveal parasites in the gastric crypts, in the duodenal glands, or eosinophilic infiltration in the lamina propria.
| |
| *Frequently, larvae can be seen by a simple wet-mount in fluid from a bronchoalveolar lavage (BAL).
| |
| *Many of the serologic tests that are available are quite sensitive, but cross-react with other filarial parasites, schistosomes, and Ascaris lumbricoides, decreasing the specificity of the tests.
| |
| *Furthermore, it can be difficult to distinguish between active cases and historical cases as traditional antibodies can persist for some time.
| |
| * More sensitive and specific serologic tests using recombinant antigens have been, and are being developed, and are available at specific laboratories.
| |
| *An additional advantage to these serologic tests is that there is typically a significant drop in titer by 6 months after parasite eradication, which may make it possible to use these tests as a "test of cure."raph
| |
|
| |
| ===Epidimeology and Demographics===
| |
| ====Geographic distrubution====
| |
| *Strongyloides is known to exist on all continents except for Antarctica, but it is most common in the tropics, subtropics, and in warm temperate regions.
| |
| ==== Incidence and Prevalance====
| |
| *The global prevalence of Strongyloides is unknown, but experts estimate that there are between 30–100 million infected persons worldwide.
| |
| *In the United States, a series of small studies in select populations have shown that between 600-1000 per 100,000 persons sampled were infected.
| |
| *Studies in immigrant populations have shown a much higher percentage of infected persons ranging from 460-1000 per 100.000 persons.
| |
| ===Risk Factors===
| |
| *Strongyloides is found more frequently in the socioeconomically disadvantaged, in institutionalized populations, and in rural areas. It is often associated with agricultural activities.
| |
| *The most common way of becoming infected with Strongyloides is by contacting soil that is contaminated with Strongyloides larvae. Therefore, activities that increase contact with the soil increase the risk of becoming infected, such as:
| |
| **Walking with bare feet
| |
| **Contact with human waste or sewage
| |
| **Occupations that increase contact with contaminated soil such as farming and coal mining.
| |
| **Association with Strongyloides and infection with Human T-Cell Lymphotropic Virus-1 (HTLV-1).
| |
| ===differentiating strongyloidosis ===
| |
| {| class="wikitable"
| |
| ! colspan="7" |Differentiating Ascaris lumbricoides infection from other Nematode infections<ref name="Principles and Practice">Durand, Marlene (2015). "Chapter 288:Intestinal Nematodes (Roundworms)". Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases Updated Edition, Eighth Edition. Elsevier. pp. 3199–3207. ISBN 978-1-4557-4801-3.</ref><ref name="Murray and Nadel's Textbook of Respiratory Medicine">{{cite book |last1=Kim |first1=Kami |last2=Weiss |first2=Louis |last3=Tanowitz |first3=Herbert |title=Murray and Nadel's Textbook of Respiratory Medicine Sixth Edition |publisher=Elsevier |date=2016 |pages=682-698 |chapter=Chapter 39:Parasitic Infections |isbn=978-1-4557-3383-5}}</ref>
| |
| |-
| |
| |Nematode
| |
| |Transmission
| |
| |Direct Person-Person Transmission
| |
| |Duration of Infection
| |
| |Pulmonary Manifestation
| |
| |Location of Adult worm(s)
| |
| |Treatment
| |
| |-
| |
| |[[Ascaris lumbricoides]]
| |
| |Ingestion of infective ova
| |
| |No
| |
| |1-2 years
| |
| |
| |
| * [[Löffler's syndrome]] (usually about 9-12 days after exposure to ova)
| |
| * [[Cough]]
| |
| * Substernal discomfort
| |
| * [[Crackles]]
| |
| * [[Wheezing]]
| |
| * Transient opacities
| |
| |Free in the lumen of the small bowel
| |
| (primarily jejunum)
| |
| |
| |
| * [[Albendazole]]
| |
|
| |
| * [[Mebendazole]]
| |
|
| |
| * [[Pyrantel pamoate]]
| |
|
| |
| * [[Ivermectin]]
| |
|
| |
| * [[Levamisole]]
| |
|
| |
| * [[Piperazine]]
| |
| |-
| |
| |[[Trichuris trichiura]]
| |
| (whipworm)
| |
| |Ingestion of infective [[ova]]
| |
| |No
| |
| |1-3 years
| |
| |No pulmonary migration, therefore, no pulmonary manifestation
| |
| |Anchored in the superficial mucosa of cecum and colon
| |
| |
| |
| * [[Albendazole]]
| |
|
| |
| * [[Mebendazole]]
| |
| |-
| |
| |[[Hookworm]] ([[Necator americanus]] and [[Ancylostoma duodenale]])
| |
| |Skin penetration by filariform larvae
| |
| |No
| |
| |
| |
| * 3-5 years (Necator)
| |
| * 1 year (Ancylostoma)
| |
| |
| |
| * [[Löffler's syndrome]]
| |
| * Transient opacities
| |
| |Attached to the mucosa of mid-upper portion of the [[small bowel]]
| |
| |
| |
| * [[Albendazole]]
| |
|
| |
| * [[Mebendazole]]
| |
|
| |
| * [[Levamisole]]
| |
|
| |
| * [[Pyrantel pamoate]]
| |
| |-
| |
| |[[Strongyloides stercoralis]]
| |
| |Filariform larvae penetrates skin or bowel mucosa
| |
| |Yes
| |
| |Lifetime of the host
| |
| |
| |
| * [[Löffler's syndrome]]
| |
| * Chronic [[cough]]
| |
| * [[Pneumonia]] or [[sepsis]] in hyperinfection
| |
| |Embedded in the mucosa of the [[duodenum]], [[jejunum]]
| |
| |
| |
| * [[Ivermectin]]
| |
| * [[Albendazole]]
| |
| * [[Thiabendazole]]
| |
| |-
| |
| |[[Enterobius vermicularis]] ([[pinworm]])
| |
| |Ingestion of infective [[ova]]
| |
| |Yes
| |
| |1 month
| |
| |Extraintestinal migration is very rare<ref name="pmid21879805">{{cite journal| author=Serpytis M, Seinin D| title=Fatal case of ectopic enterobiasis: Enterobius vermicularis in the kidneys. | journal=Scand J Urol Nephrol | year= 2012 | volume= 46 | issue= 1 | pages= 70-2 | pmid=21879805 | doi=10.3109/00365599.2011.609834 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21879805 }} </ref>
| |
| |Free in the lumen of [[cecum]], [[appendix]], adjacent [[colon]]
| |
| |
| |
| * [[Albendazole]]
| |
| * [[Mebendazole]]
| |
| * [[Pyrantel pamoate]]
| |
| * [[Ivermectin]]
| |
| * [[Levamisole]]
| |
| * [[Piperazine]]
| |
| |}
| |
| ===Historical Perspective===
| |
| *In 1876, Louis Alexis Normand, a French physician discovered strongyloides for the first time.
| |
| *Later in the same year, Professor Arthur Réné Jean Baptiste Bavay at the French Conseil Supérieur de Santé, gave a detailed description of the worm.
| |
| *In 1883, Karl Georg Friedrich Rudolf Leuckart German parasitologist discovered the alternation of generations involving parasitic and free-living phases. *The discovery that infection occurred through the skin was made by a Belgian physician, Paul Van Durme, whose studies were based on the work of Looss.
| |
| *In 1940, detailed studies on disseminated infections of strongyloides in immunosuppressed patients were described.
| |
| ==Treatment==
| |
| ===Acute and chronic strongyloidiasis===
| |
| *First line therapy: Ivermectin, in a single dose, 200 µg/kg orally for 1-2 days
| |
| *Alternative Albendazole: 400 mg orally two times a day for 7 days.
| |
|
| |
|
| |
|
| |
| In patients with positive stool examination for Strongyloides and persistent symptoms, follow-up stool exams should be performed 2-4 weeks after treatment to confirm clearance of infection. If recrudescence of larvae is observed, retreatment is indicated.
| |
|
| |
| Hyperinfection syndrome/Disseminated strongyloidiasis
| |
|
| |
| If possible, immunosuppressive therapy should be stopped or reduced, and:
| |
|
| |
| Ivermectin, 200 µg/kg per day orally until stool and/or sputum exams are negative for 2 weeks.
| |
|
| |
| For patients unable to tolerate oral therapy, such as those with ileus, obstruction, or known or suspected malabsorption, published case reports have demonstrated efficacy with rectal administration.
| |
|
| |
| If oral and/or rectal administrations are not possible, there have been instances where Investigational New Drug (IND) exemptions for the veterinary subcutaneous formulation of ivermectin have been granted by the FDA.
| |
|
| |
| ==Sepsis Differential==
| |
| {| align="center"
| |
| |-
| |
| |
| |
| {| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
| |
| ! style="background:#4479BA; color: #FFFFFF;" |Disease
| |
| ! style="background:#4479BA; color: #FFFFFF;" |Symptoms and signs
| |
| ! style="background:#4479BA; color: #FFFFFF;" |Labs
| |
| ! style="background:#4479BA; color: #FFFFFF;" |Other findings
| |
| |-
| |
| | align="center" style="background:#DCDCDC;" |Heat stroke
| |
| | style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| |
| * CNS dysfunction ([[disorientation]], [[headache]], irrational behavior, irritability, emotional instability, [[Confusion|confusion,]] [[coma]], or [[seizure]])
| |
| * [[Hypotension]] and [[tachycardia]]
| |
| * [[Hyperventilation]]
| |
| * [[Weakness]], [[nausea and vomiting]], profuse sweating, [[dehydration]].
| |
| | style="padding: 5px 5px; background: #F5F5F5;" align="left" |Electrolyte disturbances, increased [[Creatine kinase|CK]], [[Aspartate transaminase|AST]], and [[Alanine transaminase|ALT]]
| |
| | style="padding: 5px 5px; background: #F5F5F5;" align="left" |Relevant history of excessive exercise and lack of water access
| |
| |-
| |
| | align="center" style="background:#DCDCDC;" |[[Sepsis]]
| |
| | style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| |
| * Altered mental status ([[confusion]], altered consciousness, [[coma]], or [[seizure]])
| |
| * Respiratory rate ≥22/minute
| |
| * Systolic blood pressure ≤100 mmHg
| |
| | style="padding: 5px 5px; background: #F5F5F5;" align="left" |[[Thrombocytopenia]], [[leukocytosis]], [[leukopenia]], elevated [[Creatinine|Cr]]
| |
| | style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| |
| |-
| |
| | align="center" style="background:#DCDCDC;" |[[Malignant hyperthermia]]
| |
| | style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| |
| * [[Masseter muscle|Masseter]] [[muscle rigidity]] (early)
| |
| * Generalized muscle rigidity
| |
| * [[Sinus tachycardia]]
| |
| * [[Arrhythmias|Arrhythmia]]
| |
| | style="padding: 5px 5px; background: #F5F5F5;" align="left" |[[Hypercarbia]] (PaCO2) >65 mmHg, [[hyperkalemia]]
| |
| | style="padding: 5px 5px; background: #F5F5F5;" align="left" |History of receiving anaesthetic agent
| |
| |-
| |
| | align="center" style="background:#DCDCDC;" |[[Neuroleptic malignant syndrome]]
| |
| | style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| |
| * Change in mental status
| |
| * [[Muscle rigidity]]
| |
| * Autonomic instability (labile [[BP]], [[tachypnea]], profuse sweating)
| |
| | style="padding: 5px 5px; background: #F5F5F5;" align="left" |Electrolyte disturbances, increased [[Creatine kinase|CK]], [[Lactate dehydrogenase|LDH]], [[ALP]], [[Aspartate transaminase|AST]], and [[Alanine transaminase|ALT]], [[leukocytosis]], [[myoglobinuria]].
| |
| | style="padding: 5px 5px; background: #F5F5F5;" align="left" |Relevant history of recent use of anti-psychotics
| |
| |-
| |
| | align="center" style="background:#DCDCDC;" |[[Serotonin syndrome]]
| |
| | style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| |
| * Mental status changes ([[anxiety]], agitated [[delirium]], [[restlessness]], and [[disorientation]])
| |
| * Autonomic instability ([[diaphoresis]], [[tachycardia]],, [[hypertension]], [[vomiting]], and diarrhea)
| |
| * Neuromuscular hyperactivity ([[tremor]], [[myoclonus]], [[hyperreflexia]], and bilateral [[Babinski sign]])
| |
| | style="padding: 5px 5px; background: #F5F5F5;" align="left" |Elevated [[Creatine kinase|CK]], [[Lactate dehydrogenase|LDH]], [[Alkaline phosphatase|ALP]], [[Aspartate transaminase|AST]], and [[Alanine transaminase|ALT]]
| |
| | style="padding: 5px 5px; background: #F5F5F5;" align="left" |History of recent use of [[Selective serotonin reuptake inhibitor|SSRIs]], [[Serotonin-norepinephrine reuptake inhibitor|SNRIs]] , or [[Monoamine oxidase inhibitor|MAOIs]].
| |
| |}
| |
| ==Fibromyalgia==
| |
| ===Historical perspective===
| |
| *In 1800s, the first case study of fibromyalgia was reported. It was known by other names such as muscular rheumatism and fibrosita.
| |
| *In 1904, Sir William Gowers coined the term “fibrositis”.
| |
| *In 1906, later the term Fibromyalgia was coined.
| |
| *In 1981, Dr. Muhammad B. Yunus published the "first controlled study of the clinical characteristics" of the fibromyalgia syndrome, for which he is considered "the father of our modern view of fibromyalgia."<ref name="Winfield">John B. Winfield (2007), "Fibromyalgia and Related Central Sensitivity Syndromes: Twenty-five Years of Progress", ''Seminars in Arthritis and Rheumatism'' '''36''' (6): 335-338.</ref><ref name="sciencedaily">[http://www.sciencedaily.com/releases/2007/06/070625095756.htm Further Legitimization Of Fibromyalgia As A True Medical Condition], ''[[Science Daily]]'', June 25, 2007.</ref>
| |
| *In 1986, [[serotonergic]] and norepinephric [[drug]]s were proved to be effective for fibromyalgia.<ref name="Inanici">F. Fatma Inanici and Muhammad B. Yunus (2004), "History of fibromyalgia: Past to present", '''8''' (5): 369-378.</ref>
| |
| *In 1987, American Medical Association recognized fibromyalgia as an illness and a cause of disability.
| |
| *In 1984, he proposed the important concept that the fibromyalgia syndrome and other similar conditions are interconnected.
| |
| *In 1990, the ACR published criteria for fibromyalgia and developed [[Neurohormone|neurohormonal]] mechanisms with central [[sensitization]].
| |
|
| |
| ===Classification===
| |
| DSM 5 divides fibromyalgia into four groups based on the differences in psychological and autonomic nervous system profiles among affected individuals
| |
| *Extreme sensitivity to pain but no associated psychiatric conditions
| |
| *Fibromyalgia and comorbid, pain-related depression
| |
| *Depression with concomitant fibromyalgia syndrome
| |
| *Fibromyalgia due to somatization
| |
| ===Risk Factors===
| |
| The possible risk factors for fibromyalgia include:
| |
| *Sex. Women are twice as likely to have fibromyalgia as men
| |
| *Stressful or traumatic events, such as car accidents, post-traumatic stress disorder (PTSD)
| |
| *Repetitive injuries. Injury from repetitive stress on a joint, such as frequent knee bending
| |
| *Illness (such as viral infections)
| |
| *Family history
| |
| *Obesity
| |
| ===Differential===
| |
| It is a clinical diagnosis and all other conditions that present with muscular pain and stiffness all over the body such as polymyalgia rheumatica, myofascial pain syndrome (MPS), chronic fatigue syndrome, myositis, malingering
| |
| ===Epidemiology and Demographics===
| |
| ====Incidence and Prevalance====
| |
| *The Prevalence of Fibromyalgia in the United States was reported to range from 500-5000 per 100,000 persons.
| |
| ====Gender====
| |
| *Females are more commonly affected than males.
| |
| ====Age====
| |
| 20-50 year age group is more commonly affected
| |
| ====Race====
| |
| Fibromyalgia has no racial predilication.
| |
| ===Natural History===
| |
| If left untreated, chronic pain could cause permanent changes in how the body perceives pain.
| |
| ===Complications===
| |
| Complications that can develop as a result of Fibromyalgia are
| |
| *Marked functional impairment
| |
| *Depression
| |
| *Anxiety
| |
| *Insomnia
| |
| *Obesity
| |
| *Allodynia
| |
| ===Prognosis===
| |
| Fibromyalgia is a long-term disorder. Various factors play a key role in the outcomes<br>
| |
| '''Factors associated with poor outcomes'''
| |
| *Female gender
| |
| *Low socioeconomic status
| |
| *Being unemployed
| |
| Even with appropriate treatment, symptoms of fibromyalgia improve other times, the pain may get worse and continue for months or years.
| |
| ==Diagnosis==
| |
| The most widely accepted set of diagnostic criteria for fibromyalgia was elaborated in 2010 by the Multicenter Criteria Committee of the the American College of Rheumatology.
| |
| ===Criteria===
| |
| A patient satisfies diagnostic criteria for fibromyalgia if the following 3 conditions are met:
| |
| *1) Widespread pain index (WPI) > 7 and symptom severity (SS) scale score >5 or WPI 3–6 and SS scale score >9.
| |
| *2) Symptoms have been present at a similar level for at least 3 months.
| |
| *3) The patient does not have a disorder that would otherwise explain the pain.
| |
| ===Ascertainment===
| |
| 1) WPI: note the number areas in which the patient has had pain over the last week. In how many areas has the patient had pain?
| |
| *Score will be between 0 and 19.
| |
| *Shoulder girdle, left Hip (buttock, trochanter), left Jaw, left Upper back, Shoulder girdle, right Hip (buttock, trochanter), right Jaw, right Lower back, Upper arm, left Upper leg, left Chest Neck, Upper arm, right Upper leg, right Abdomen, Lower arm, left Lower leg, left, Lower arm, right Lower leg, right
| |
| 2) SS scale score:
| |
| *Fatigue
| |
| *Waking unrefreshed
| |
| *Cognitive symptoms
| |
| For the each of the 3 symptoms above, indicate the level of severity over the past week using the following scale:
| |
| *0 = no problem
| |
| *1 = slight or mild problems, generally mild or intermittent
| |
| *2 = moderate, considerable problems, often present and/or at a moderate level
| |
| *3 = severe: pervasive, continuous, life-disturbing problems
| |
| Considering somatic symptoms in general, indicate whether the patient has:
| |
| *0 = no symptoms
| |
| *1 = few symptoms
| |
| *2 = moderate number of symptoms
| |
| *3 = Severe symptoms
| |
| The SS scale score is the sum of the severity of the 3 symptoms (fatigue, waking unrefreshed, cognitive symptoms) plus the
| |
| extent (severity) of somatic symptoms in general. The final score is between 0 and 12.
| |
| ==History and symtpoms==
| |
| The defining symptoms of fibromyalgia are chronic, widespread pain and tenderness to light touch. Other symptoms include
| |
| {| class="wikitable"
| |
| !Organ system
| |
| !Symptoms
| |
| |-
| |
| |Systemic
| |
| |
| |
| * Weight gain
| |
| * Cold symptoms
| |
| * Severe fatigue
| |
| |-
| |
| |CNS
| |
| |
| |
| * Headaches
| |
| * Sleep disorders
| |
| * Dizziness
| |
| * Cognitive impairment
| |
| * Memory impairment
| |
| * Anxiety- Depression
| |
| * Tingling of the skin
| |
| |-
| |
| |Musculoskeletal
| |
| |
| |
| * Myofascial pain
| |
| * Twitches
| |
| * Achiness in the muscle tissues
| |
| * Prolonged muscle spasms
| |
| * Muscle weakness
| |
| * Allodynia
| |
| |-
| |
| |Abdominal
| |
| |
| |
| *Nausea
| |
| *Pain
| |
| |-
| |
| |Eyes
| |
| |
| |
| *Blurred vision
| |
| *Photosensitivity
| |
| |}
| |
|
| |
| ==Laboratory findings==
| |
| Fibromyalgia is a diagnosed clinically by careful history and examination. Blood and urine tests are usually normal. However, tests may be done to rule out other conditions that may have similar symptoms.
| |
| ==Medical therapy==
| |
| ===Single agent therapy===
| |
| *Preferred regimen (1): Amitriptyline 10-70 mg orally once daily at bedtime
| |
| *Preferred regimen (2): Cyclobenzaprine 5-30 mg orally once daily at bedtime
| |
| *Preferred regimen (3): Duloxetine : 30-60 mg orally once daily
| |
| *Preferred regimen (4): Milnacipran 12.5 mg orally once daily initially, followed by 12.5 mg twice daily for 2 days, followed by 25 mg twice daily for 4 days, then 50-100 mg twice daily thereafter
| |
| *Preferred regimen (5): Pregabalin 75-225 mg orally twice daily, maximum 450 mg/day
| |
| ===Combination Thereapy===
| |
| *Preferred regimen (1): Amitriptyline 10-70 mg orally once daily at bedtime '''(OR)'''
| |
| *Preferred regimen (2): Cyclobenzaprine 5-30 mg orally once daily at bedtime
| |
| '''AND'''
| |
| *Preferred regimen (3): Duloxetine 30-60 mg orally once daily; higher doses have been used, consult specialist for guidance '''(OR)'''
| |
| *Preferred regimen (4): Milnacipran 12.5 mg orally once daily initially, followed by 12.5 mg twice daily for 2 days, followed by 25 mg twice daily for 4 days, then 50-100 mg twice daily thereafter
| |
| '''AND'''
| |
| *Preferred regimen (5): Pregabalin 75-225 mg orally twice daily, maximum 450 mg/day '''(OR)'''
| |
| *Preferred regimen (6): Gabapentin 300 mg orally once daily on first day, followed by 300 mg twice daily on second day, followed by 300 mg three times daily on third day, then titrate dose according to response up to 1800-2400 mg/day given in 3 divided doses
| |
| ==Pathophysiology==
| |
| The cause of fibromyalgia is unknown. In fact it is not be due to a singular factor at all, but r due to a multiplicity of causes. Fibromyalgia can, but most often does not, start as a result of some [[Physical trauma|trauma]] such as a traffic accident, major surgery, or disease. Some evidence shows that [[Lyme Disease]] may be a trigger of fibromyalgia symptoms.<ref>{{cite web | url = http://www.immunesupport.com/library/showarticle.cfm/ID/3579 | title = Late and Chronic Lyme Disease: Symptom Overlap with Chronic Fatigue Syndrome & Fibromyalgia}}</ref> Another study suggests that more than one clinical entity may be involved, ranging from a mild, idiopathic [[inflammation|inflammatory]] process to [[clinical depression]]<ref>http://www.springerlink.com/content/1271314042w8405g/ Mueller W, et al. The classification of fibromyalgia syndrome. Rheumatol Int. 2007 Jul 25</ref>
| |
|
| |
| === Genetics ===
| |
| By using self-reported "Chronic Widespread Pain" (CWP) as a surrogate marker for fibromyalgia, the [http://www.meb.ki.se/twinreg/index_en.html Swedish Twin Registry] found that a modest genetic contribution may exist:<ref name="PMID16646040">{{cite journal |author=Kato K, Sullivan P, Evengård B, Pedersen N |title=Importance of genetic influences on chronic widespread pain |journal=Arthritis Rheum. |volume=54 |issue=5 |pages=1682-6 |year=2006 | doi=10.1002/art.21798 |pmid=16646040}}</ref><ref name="PMID16908799">{{cite journal |author=Kato K, Sullivan P, Evengård B, Pedersen N |title=Chronic widespread pain and its comorbidities: a population-based study |journal=Arch. Intern. Med. |volume=166 |issue=15 |pages=1649-54 |year=2006 | url=http://archinte.ama-assn.org/cgi/content/full/166/15/1649 |pmid=16908799}}</ref>
| |
| * [[Monozygotic twins]] with CWP have a 15% chance that their twin sibling has CWP
| |
| * Dizygotic [[twins]] with CWP have a 7% chance that their twin sibling has CWP
| |
|
| |
| === Stress ===
| |
| *[[Stress (medicine)|Stress]] is a significant precipitating factor in the development of fibromyalgia.<ref>{{cite journal | author = Anderberg UM, Marteinsdottir I, Theorell T, von Knorring L | title=The impact of life events in female patients with fibromyalgia and in female healthy controls. | journal=Eur Psychiatry | month=Aug| year=2000 | pages=33-41 | volume=15 | issue=5 | id=PMID 10954873 }}</ref><ref>{{cite journal | author= Amital D, Fostick L, Polliack ML, Segev S, Zohar J, Rubinow A, Amital H | title=Posttraumatic stress disorder, tenderness, and fibromyalgia syndrome: are they different entities? | journal=J Psychosom Res | month=Nov | year=2006 | pages=663-9 | volume=61 | issue=5 | id=PMID 17084145}}</ref><ref>{{cite journal | author= Raphael KG, Janal MN, Nayak S | title=Comorbidity of fibromyalgia and posttraumatic stress disorder symptoms in a community sample of women. | journal=Pain Med. | month=Mar| year=2004 | pages=33-41 | volume=5 | issue=1 | id=PMID 14996235}}</ref>
| |
| *A non-mainstream hypothesis that fibromyalgia may be a [[psychosomatic illness]] has been described by John E. Sarno's "[[tension myositis syndrome]]".
| |
| * He believes many cases of [[chronic pain]] result from changes in the body caused by the mind's subconscious strategy of distracting painful or dangerous emotions.
| |
| *Education, attitude change, (and in some cases, psychotherapy) are treatments proposed to stop the brain from using that strategy.<ref>{{cite book |last=Sarno|first=Dr. John E,|authorlink=John E. Sarno|title=The Mindbody Prescription: Healing the Body, Healing the Pain |year=1998 |isbn=0-446-67515-6 |pages=76-78}}</ref><ref>{{cite book |last=Sarno|first=Dr. John E. et al,| title=The Divided Mind: The Epidemic of Mindbody Disorders |year=2006 |isbn=0-06-085178-3 |pages=21-22,235-237,294-298}}</ref>
| |
| *Robert G. Schwartz, MD has proposed an alternative view where in mind-body connections may play an important role in chronic disease (not just fibromyalgia). Through his program strategies to align incentives are offered.
| |
|
| |
| ===Dopamine abnormality===
| |
| *[[Dopamine]] is a [[catecholamine]] [[neurotransmitter]] known for its role in the pathology of [[schizophrenia]], [[Parkinson's disease]] and [[addiction]].
| |
| *Fibromyalgia has been commonly referred to as a "stress-related disorder" due to its frequent onset and worsening of symptoms in the context of stressful events.<ref>[http://www.ncbi.nlm.nih.gov/pubmed/16174484?ordinalpos=18&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum The role of life stress in fibromyalgia. [Curr Rheumatol Rep. 2005] - PubMed Result<!-- Bot generated title -->]</ref><ref>[http://www.ncbi.nlm.nih.gov/pubmed/12849719?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Chronic widespread pain and fibromyalgia: what we ...[Best Pract Res Clin Rheumatol. 2003] - PubMed Result<!-- Bot generated title -->]</ref>
| |
| *It was therefore proposed that fibromyalgia may represent a condition characterized by low levels of central dopamine that likely results from a combination of genetic factors and exposure to environmental stressors, including psychosocial distress, physical trauma, systemic viral infections or inflammatory disorders (e.g. [[rheumatoid arthritis]], systemic [[lupus erythematosus]]).<ref>[http://www.ncbi.nlm.nih.gov/pubmed/14975515?ordinalpos=10&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Stress and dopamine: implications for the pathophy...[Med Hypotheses. 2004] - PubMed Result<!-- Bot generated title -->]</ref>
| |
| *This conclusion was based on three key observations: (1) fibromyalgia is associated with stress; (2) chronic exposure to stress results in a disruption of dopamine-related neurotransmission and (3) dopamine plays a critical role in modulating pain perception and central [[analgesia]] in such areas as the [[basal ganglia]];including the [[nucleus accumbens]], [[insular cortex]], [[anterior cingulate cortex]] [[thalamus]], [[periaqueductal gray]], and [[spinal cord]]<ref>[http://www.ncbi.nlm.nih.gov/pubmed/6314870?ordinalpos=113&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Dopamine-containing neurons in the spinal cord: an...[Ann Neurol. 1983] - PubMed Result<!-- Bot generated title -->]</ref> <ref>[http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=15975975 Direct inhibition of substantia gelatinosa neurones in the rat spinal cord by activation of dopamine D2-like receptors<!-- Bot generated title -->]</ref><ref>[http://www.ncbi.nlm.nih.gov/pubmed/9355111?ordinalpos=27&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum The effects of stress on central dopaminergic neur...[Neurochem Res. 1997] - PubMed Result<!-- Bot generated title -->]</ref><ref>[http://www.ncbi.nlm.nih.gov/pubmed/7715939?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum The role of the basal ganglia in nociception and p...[Pain. 1995] - PubMed Result<!-- Bot generated title -->]</ref> <ref>[http://www.ncbi.nlm.nih.gov/pubmed/10597883?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum The role of dopamine in the nucleus accumbens in a...[Life Sci. 1999] - PubMed Result<!-- Bot generated title -->]</ref><ref>[http://www.jneurosci.org/cgi/content/full/19/10/4169 Dopamine Reuptake Inhibition in the Rostral Agranular Insular Cortex Produces Antinociception - Burkey et al. 19 (10): 4169 - Journal of Neuroscience<!-- Bot generated title -->]</ref> <ref>[http://www.ncbi.nlm.nih.gov/pubmed/15327817?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Dopamine and NMDA systems modulate long-term nocic...[Pain. 2004] - PubMed Result<!-- Bot generated title -->]</ref><ref>[http://www.ncbi.nlm.nih.gov/pubmed/1611515?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Neurophysiological, pharmacological and behavioral...[Brain Res. 1992] - PubMed Result<!-- Bot generated title -->]</ref><ref>[http://www.ncbi.nlm.nih.gov/pubmed/15275769?ordinalpos=6&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Opiate anti-nociception is attenuated following le...[Pain. 2004] - PubMed Result<!-- Bot generated title -->]</ref>
| |
| *As is the case with several of the neurotransmitters, there is evidence for a role of dopamine in [[restless leg syndrome]], which is a common co-morbid condition in patients with fibromyalgia. <ref>[http://www.bmj.com/cgi/content/full/312/7042/1339 Restless legs syndrome and leg cramps in fibromyalgia syndrome: a controlled study - Yunus and Aldag 312 (7042): 1339 - BMJ<!-- Bot generated title -->]</ref><ref>[http://www.ncbi.nlm.nih.gov/pubmed/16816393?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Support for dopaminergic hypoactivity in restless ...[Brain. 2006] - PubMed Result<!-- Bot generated title -->]</ref>
| |
| *Patients with restless legs syndrome have also been demonstrated to have [[hyperalgesia]] to static mechanical stimulation.<ref>[http://brain.oxfordjournals.org/cgi/content/full/127/4/773 Static mechanical hyperalgesia without dynamic tactile allodynia in patients with restless legs syndrome - Stiasny-Kolster et al. 127 (4): 773 - Brain<!-- Bot generated title -->]</ref>
| |
|
| |
| ===Serotonin===
| |
| *[[Serotonin]] is a [[neurotransmitter]] that is known to play a role in regulating sleep patterns, mood, feelings of well-being, concentration and descending inhibition of pain.
| |
| *Accordingly, it has been hypothesized that the [[pathophysiology]] underlying the symptoms of fibromyalgia may be a dysregulation of serotonin metabolism, which may explain (in part) many of the symptoms associated with the disorder. <ref>[http://www.ncbi.nlm.nih.gov/pubmed/1313504?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Platelet 3H-imipramine uptake receptor density and...[J Rheumatol. 1992] - PubMed Result<!-- Bot generated title -->]</ref><ref>[http://www.ncbi.nlm.nih.gov/pubmed/1374252?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Cerebrospinal fluid biogenic amine metabolites in ...[Arthritis Rheum. 1992] - PubMed Result<!-- Bot generated title -->]</ref>
| |
| *However, [[selective serotonin reuptake inhibitors]] (SSRIs) have met with limited success in alleviating the symptoms of the disorder.
| |
|
| |
| ===Sleep disturbance===
| |
| *The sleep disturbance hypothesis states that any event such as a trauma or illness causes sleep disturbance and also chronic pain that may initiate the disorder.
| |
| *According to the hypothesis stage 4 sleep is critical for normal functioning of the [[nervous system]], as it is during that stage that certain neurochemical processes in the body 'reset'.
| |
| *It is during that stage 4 sleep, pain causes the release of the [[neuropeptide]] [[substance P]] in the [[spinal cord]] which has the effect of amplifying pain and causing nerves to become more sensitive to pain.
| |
| *If pain becomes chronic and body-wide this process can run out of control.
| |
| *The sleep disturbance hypothesis holds that deep sleep is critical to reset the substance P mechanism and prevent this out-of-control effect.
| |
| *The sleep disturbance/substance P hypothesis could explain "tender points" that are characteristic of fibromyalgia but which are otherwise enigmatic since their positions don't correspond to any particular set of nerve junctions or other obvious body structures.
| |
| *The hypothesis proposes that these locations are more sensitive because the sensory nerves that serve them are positioned in the spinal cord to be most strongly affected by substance P.
| |
| *This hypothesis could also explain some of more general neurological features of fibromyalgia, since substance P is active in many other areas of the nervous system.
| |
| *The sleep disturbance hypothesis could also provide a possible connection between fibromyalgia, [[chronic fatigue syndrome]] (CFS) and [[post-polio syndrome]] through damage to the ascending reticular activating system of the [[reticular formation]].
| |
| *This area of the brain, in addition to apparently controlling the sensation of fatigue, is known to control sleep behaviors and is also believed to produce some neuropeptides, and thus injury or imbalance in this area could cause both CFS and sleep-related fibromyalgia.
| |
| *[[Electroencephalography]] studies have shown that people with fibromyalgia lack [[slow-wave sleep]] and circumstances that interfere with stage four sleep (pain, depression, serotonin deficiency, certain medications or [[anxiety]]) may cause or worsen the condition.
| |
|
| |
| ===Human growth hormone===
| |
| *An alternate hypothesis suggests that stress-induced problems in the [[hypothalamus]] may lead to reduced sleep and reduced production of [[human growth hormone]] (HGH) during [[slow-wave sleep]].
| |
| *People with fibromyalgia tend to produce inadequate levels of HGH.
| |
| *Most patients with fibromyalgia with low IGF-I levels failed to secrete HGH after stimulation with clonidine and l-dopa.
| |
| *This view is supported by the fact that those hormones under the direct or indirect control of HGH, including [[IGF-1]], [[cortisol]], [[leptin]] and [[neuropeptide Y]] are abnormal in people with fibromyalgia.
| |
| *In addition, treatment with exogenous HGH or growth hormone secretagogue reduces fibromyalgia related pain and restores slow wave sleep though there is disagreement about the proposition.<ref>{{cite journal | last = McCall-Hosenfeld | first = JS | coauthors = Goldenberg DL, Hurwitz S, Adler GK. | title = Growth hormone and insulin-like growth factor-1 concentrations in women with fibromyalgia | journal = Journal of Rheumatology | volume = 30 | issues = 4 | pages = 809-14 | pmid = 12672204 }}</ref><ref>{{cite journal | last = Anderberg | first = UM | coauthors = Liu Z, Berglund L, Nyberg F | pmid = 10700334 | title = Elevated plasma levels of neuropeptide Y in female fibromyalgia patients. | journal = European Journal of Pain | volume = 3 | issue = 1 | year = 1999 | pages = 19-30}}</ref><ref>{{cite journal | last = Jones | first = KD | coauthors = Deodhar P, Lorentzen A, Bennett RM, Deodhar AA | title = Growth hormone perturbations in fibromyalgia: a review. | journal = Seminars in Arthritis and Rheumatism | year = 2007 | volume = 36 | issue = 6 | pages = 357-79 | pmid = 17224178 }}</ref><ref>{{cite journal | last = Shuer | first = ML | title = Fibromyalgia: symptom constellation and potential therapeutic options | journal = Endocrine | volume = 22 | issue = 1 | pages = 67-76 | pmid = 14610300 }}</ref><ref>{{cite journal | last = Yuen | first = KC | coauthors = Bennett RM, Hryciw CA, Cook MB, Rhoads SA, Cook DM | journal = Growth hormone & IGF research | title = Is further evaluation for growth hormone (GH) deficiency necessary in fibromyalgia patients with low serum insulin-like growth factor (IGF)-I levels? | volume = 17 | issue = 1 | year = 2007 | pages = 82-8 | pmid = 17289417 }}</ref><ref>{{cite journal | last = Bennett | first = RM | coauthors = Cook DM, Clark SR, Burckhardt CS, Campbell SM. | pmid = 9228141 | title = Hypothalamic-pituitary-insulin-like growth factor-I axis dysfunction in patients with fibromyalgia | | Journal of Rheumatology | volume = 24 | issue = 7 | pages = 1384-9 }}</ref>
| |
|
| |
| ===Deposition disease===
| |
| *The 'deposition hypothesis of fibromyaglia' poses that fibromyalgia is due to intracellular [[phosphate]] and [[calcium]] accumulations that eventually reaches levels sufficient to impede the [[Adenosine triphosphate|ATP]] process, possibly caused by a [[kidney]] defect or missing [[enzyme]] that prevents the removal of excess phosphates from the blood stream.
| |
| *Accordingly, proponents of this hypothesis suggest that fibromyalgia may be an inherited disorder, and that phosphate build-up in cells is gradual but can be accelerated by trauma or illness.
| |
| *Calcium is required for the excess phosphate to enter the cells. The additional phosphate slows down the ATP process; however the excess calcium prods the cell to continue producing ATP.
| |
| *The phosphate build-up hypothesis explains many of the symptoms present in fibromyalgia and proposes an underlying cause.
| |
|
| |
| ===Other hypotheses===
| |
| *Other hypotheses have been proposed related to various [[toxin]]s from the patient's environment, [[virus|viral]] causes such as the [[Epstein-Barr Virus]], [[growth hormone]] deficiencies possibly related to an underlying (maybe autoimmune) disease affecting the hypothalamus gland, an aberrant immune response to [[intestinal bacteria]], [[neurotransmitter]] disruptions in the [[central nervous system]], and erosion of the protective chemical coating around sensory nerves.<ref name="ClinExpDermatol2004-KendallSN">{{cite journal | author=Kendall SN | title=Remission of rosacea induced by reduction of gut transit time. | journal=Clin Exp dermatol. | month=May | year=2004 | pages=297-9 | volume=29 | issue=3 | pmid=15115515}}</ref><ref name="AnnRheumDis2004-PimentalM">{{cite journal | author=Pimental M, Wallace D, Hallegua D et .al | title=A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing. | journal=Ann Rheum Dis. | month=April | year=2004 | pages=450-2 | volume=63 | issue=4 |pmid=15020342}}</ref>
| |
| *A 2001 study suggested an increase in fibromyalgia among women with extracapsular silicone gel leakage, compared to women whose implants were not broken or leaking outside the capsule.<ref name="Brown2001">{{cite journal | author=Brown SL, Pennello G, Berg WA, Soo MS, Middleton MS | title=Silicone gel breast implant rupture, extracapsular silicone, and health status in a population of women | journal=J Rheumatol | year=2001 | pages=996-1003 | volume=28 | issue=5 | pmid=11361228}}</ref><ref>{{cite web |title=Study of Silicone Gel Breast Implant Rupture, Extracapsular Silicone, and Health Status in a Population of Women |url=http://www.fda.gov/cdrh/breastimplants/extracapstudy.html |date=May 29, 2001 |publisher=FDA}}</ref> <ref>{{cite web |title=FDA Breast Implant Consumer Handbook 2004 |url=http://www.fda.gov/cdrh/breastimplants/handbook2004/diseases.html#1 |date=June 8, 2004 |publisher=FDA}}</ref><ref name="Lipworth">{{cite journal | author=Lipworth L, Tarone RE, McLaughlin JK.| title=Breast implants and fibromyalgia: a review of the epidemiological evidence.| journal=Ann Plast Surg. | year=2004 | pages=284-7| volume=52 | issue=3 |pmid=15156983}}</ref>
| |
| *Another hypothesis on the cause of symptoms in fibromyalgia states that patients suffer from [[vasomotor]] dysregulation causing improper [[Blood vessel|vascular]]flow and [[hypoperfusion]] (decreased blood flow to a given tissue or organ).<ref name="pmid17376601">{{cite journal |author=Katz DL, Greene L, Ali A, Faridi Z |title=The pain of fibromyalgia syndrome is due to muscle hypoperfusion induced by regional vasomotor dysregulation |journal=Med Hypotheses. |volume=(Epub ahead of print) |issue= |pages= |year=2007 |month=19 Mar |pmid=17376601 |doi=10.1016/j.mehy.2005.10.037}}</ref>
| |
|
| |
| ===Associated Conditions===
| |
| *Fibromyalgia is always a [[comorbidity|comorbid]] disorder, occurring in combination with some other disorder that likely served to trigger the fibromyalgia in the first place.
| |
| *Two possible triggers are [[gluten sensitivity]] and/or irritable bowel.
| |
| *Irritable bowel is found at high frequency in fibromyalgia and a large celiac support group survey of adult celiacs revealed that 7% had fibromyalgia and also has a co-occurrence with chronic fatique.<ref name="pmid16042909">{{cite journal | author = Frissora CL, Koch KL | title = Symptom overlap and comorbidity of irritable bowel syndrome with other conditions | journal = Current gastroenterology reports | volume = 7 | issue = 4 | pages = 264-71 | year = 2005 | pmid = 16042909 | doi = }}</ref> <ref name="pmid12741468">{{cite journal | author = Zipser RD, Patel S, Yahya KZ, Baisch DW, Monarch E | title = Presentations of adult celiac disease in a nationwide patient support group | journal = Dig. Dis. Sci. | volume = 48 | issue = 4 | pages = 761-4 | year = 2003 | pmid = 12741468 | doi = }}</ref>
| |
| *In some cases, the original disorder abates on its own or is separately treated and cured, but the fibromyalgia remains. This is especially apparent when fibromyalgia seems triggered by major surgery.
| |
| *In other cases the two disorders coexist. Since it can be extremely complex to treat the source of fibromyalgia, and since it is most probably a multifactoral disorder that is different from one afflicted patient to the next, the concept of has been proposed.
| |
| *In this instance the total number of things that does not allow a patient to get well is treated, one at a time, taking into consideration the unique conditions of that individual patient.[http://wehelpwhathurts.homestead.com/diseasemanagement.html Reducing Total Load]
| |
|
| |
| ==Fibromyalgia Differential==
| |
| {| class="wikitable"
| |
| !Disease
| |
| !Differentiating signs and symptoms
| |
| !Diifferentiating labs
| |
| !
| |
| |-
| |
| |Rheumatoid arthritis
| |
| |
| |
| * Multiple joint swelling
| |
| * Morning stiffness
| |
| * Rheumatoid nodules
| |
| |
| |
| * RF or anti-cyclic citrullinated protein (CCP) antibody is positive.
| |
|
| |
| * Markers of systemic inflammation (ESR, CRP) are typically elevated.
| |
| |
| |
| |-
| |
| |SLE
| |
| |
| |
| * Maculo-papular rash
| |
| * Multi system involvement
| |
| |
| |
| |
| |
| |-
| |
| |[[Chronic fatigue syndrome]]
| |
| |
| |
| *Fatigue plus 4 of the following symptoms
| |
| *(1) Short-term memory loss
| |
| *(2) Sore throat
| |
| *(3) tender lymph nodes in the neck or armpit
| |
| *(4) muscle pain
| |
| *(5) joint pain without swelling or redness
| |
| *(6) headaches
| |
| *(7) unrefreshing sleep
| |
| *(8) malaise
| |
| |
| |
| *Diagnosis of exclusions
| |
| *Symptoms must present for more than 6 months
| |
| |
| |
| |-
| |
| |Spondyloarthritis
| |
| |
| |
| * Axial skeletal pain and stiffness
| |
| * Restricted spinal motion
| |
| |
| |
| * Elevated ESR or CRP
| |
| * Negtive RF
| |
|
| |
| * Bamboo spine on X-ray
| |
| |
| |
| |-
| |
| |Polymyalgia rheumatica
| |
| |
| |
| * Older at onset
| |
| * Generalized stiffness
| |
| |
| |
| * An elevated erythrocyte sedimentation rate (ESR) OR C-reactive protein (CRP
| |
| * Response to corticosteroids
| |
| |
| |
| |-
| |
| |Osteoarthritis
| |
| |
| |
| * Localized joint pain
| |
| * Restricted to affect joints
| |
| * Older at onset
| |
| |
| |
| * Xray of the involved joints demonstrate degenerative changes
| |
| |
| |
| |-
| |
| |Hypothyroidism
| |
| |
| |
| *Systemic symptoms such as weight gain, constipation, dry skin
| |
| *Muscular aching and prominent fatigue that improves on replacement of thyroid hormone.
| |
| |
| |
| *TSH is elevated and free T4 is low.
| |
| |
| |
| |-
| |
| |Myopathaies(polymyositis and dermatomyositis)
| |
| |
| |
| *Pelvic and shoulder girdle muscle weakness
| |
| *Rash
| |
| |
| |
| *Muscle biopsy confirms the diagnosis
| |
| *Elevated CPK enzyme
| |
| |
| |
| |-
| |
| |Neuropathy
| |
| |
| |
| *Numbness and tingling
| |
| *Paresthesia
| |
| |
| |
| *Abnormal EMG
| |
| |}
| |
| ==Physical examination==
| |
| ===General appearance===
| |
| *Patient looks tired
| |
| *Fatigue unrelieved by rest
| |
| ===Musculoskeletal===
| |
| *Diffuse tenderness on multiple points
| |
| [[Image:Tender points fibromyalgia.png|center|300px]]
| |
|
| |
| ===Neurological===
| |
| *Sleep disturbance
| |
| *Mood disturbance
| |
| *Cognitive dysfunction
| |
| *Headaches
| |
| *Numbness/tingling sensations
| |
| *Stiffness
| |
| *Sensitivity to sensory stimuli such as bright lights, odors, noises
| |
| ===Extremites===
| |
| *Fluid retention
| |
| However, a steady interest in the disorder on the part of academic researchers as well as pharmaceutical interests has led to improvements in its treatment, which ranges from symptomatic prescription medication to [[alternative medicine|alternative]] and [[complementary medicine]].
| |
|
| |
| The European League Against Rheumatism (EULAR) issued the first guidelines for the treatment of fibromyalgia syndrome (FMS) and published them in the September 17th On-line First issue of the Annals of the Rheumatic Diseases.
| |
|
| |
| Many medications are used to treat specific symptoms of fibromyalgia, such as muscle pain and insomnia.
| |
|
| |
| [[Image:Fibromyalgia_treatment.png|left|400px]]
| |
|
| |
| ==== Pain Relief ====
| |
|
| |
| A number of pain relievers have been prescribed for fibromyalgia. This includes [[NSAID]] medications over the counter, COX-2 inhibitors, and [[tramadol]] in prescription form for more advanced cases. Recently, [[pregabalin]] (marketed as Lyrica) has been given FDA approval for the treatment of diagnosed Fibromyalgia.
| |
|
| |
| ====Muscle Relaxants====
| |
|
| |
| Muscle relaxants, such as [[cyclobenzaprine]] (Flexeril) or [[tizanidine]] (Zanaflex), may be used to treat the muscle pain associated with the disorder.
| |
|
| |
| ====Tricyclic antidepressants (TCAs)====
| |
| Traditionally, low doses of sedating antidepressants (e.g. [[amitriptyline]] and [[trazodone]]) have been used to reduce the sleep disturbances that are associated with fibromyalgia and are believed by some practitioners to alleviate the symptoms of the disorder. Because depression often accompanies chronic illness, these antidepressants may provide additional benefits to patients suffering from depression. [[Amitriptyline]] is often favoured as it can also have the effect of providing relief from neuralgenic or [[Neuropathy|neuropathic pain]]. It is to be noted that Fibromyalgia is not considered a depressive disorder; antidepressants are used for their sedating effect to aid in sleep.
| |
|
| |
| ====Selective serotonin reuptake inhibitors (SSRIs)====
| |
| Research data consistently contradict the utility of agents with specificity as serotonin reuptake inhibitors for the treatment of core symptoms of fibromyalgia. <ref>[http://www.ncbi.nlm.nih.gov/pubmed/7478688?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum A randomized controlled trial of citalopram in the...[Pain. 1995] - PubMed Result<!-- Bot generated title -->]</ref><ref>[http://www.ncbi.nlm.nih.gov/pubmed/10833553?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus Citalopram in patients with fibromyalgia-a random...[Eur J Pain. 2000] - PubMed Result<!-- Bot generated title -->]</ref><ref>[http://www.ncbi.nlm.nih.gov/pubmed/17466657?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum A randomized, controlled, trial of controlled rele...[Am J Med. 2007] - PubMed Result<!-- Bot generated title -->]</ref> Moreover, SSRIs are known to aggravate many of the comorbidities that commonly affect patients with fibromyalgia including restless legs syndrome and sleep bruxism<ref>[http://www.ncbi.nlm.nih.gov/pubmed/9416386?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Extrapyramidal reactions and the selective seroton...[Ann Pharmacother. 1997] - PubMed Result<!-- Bot generated title -->]</ref><ref>[http://www.ncbi.nlm.nih.gov/pubmed/8909330?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Movement disorders associated with the serotonin s...[J Clin Psychiatry. 1996] - PubMed Result<!-- Bot generated title -->]</ref><ref>[http://www.ncbi.nlm.nih.gov/pubmed/9640489?ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Selective serotonin-reuptake inhibitor-induced mov...[Ann Pharmacother. 1998] - PubMed Result<!-- Bot generated title -->]</ref>.
| |
|
| |
| ====Anti-seizure drugs====
| |
| Anti-seizure drugs are also sometimes used, such as [[gabapentin]]<ref>Arnold LM, Goldenberg DL, Stanford SB, et. al. Gabapentin in the treatment of fibromyalgia: a randomized, double-blind, placebo-controlled, multicenter trial.
| |
| Arthritis Rheum. 2007 Apr;56(4):1336-44</ref> and [[pregabalin]] (Lyrica). [[Pregabalin]], originally used for the nerve pain suffered by diabetics, has been approved by the American [[Food and Drug Administration]] for treatment of fibromyalgia. A [[randomized controlled trial]] of [[pregabalin]] 450 mg/day found that a [[number needed to treat]] of 6 patients for one patient to have 50% reduction in pain.<ref name="pmid15818684">{{cite journal |author=Crofford LJ, Rowbotham MC, Mease PJ, ''et al'' |title=Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial |journal=Arthritis Rheum. |volume=52 |issue=4 |pages=1264-73 |year=2005 |pmid=15818684 |doi=10.1002/art.20983}}</ref>
| |
|
| |
| ====Dopamine agonists====
| |
| [[Dopamine agonists]] (e.g. [[pramipexole]] (Mirapex) and [[ropinirole]] (ReQuip)) have been studied for use in the treatment of fibromyalgia with good results. <ref>{{cite journal |author=Andrew J. Holman and Robin R. Myers |title=A Randomized, Double-Blind, Placebo-Controlled Trial of Pramipexole, a Dopamine Agonist, in Patients With Fibromyalgia Receiving Concomitant Medications |journal=Arthritis and Rheumatism |volume=52 |issue=8 |pages=2495-2505 |year=2005}}</ref> A trial of transdermal [[rotigotine]] is currently on going <ref>[http://clinicaltrials.gov/ct2/show/NCT00464737 A Double-Blind Multicenter Proof of Concept Trial to Assess the Efficacy and Safety of Rotigotine in Subjects With Fibromyalgia Syndrome - Full Text View - ClinicalTrials.gov<!-- Bot generated title -->]</ref>.
| |
|
| |
| ====Combination therapy====
| |
| A controlled clinical trial of [[amitriptyline]] and [[fluoxetine]] demonstrated utility when used in combination.<ref name="pmid8912507">{{cite journal |author=Goldenberg D, Mayskiy M, Mossey C, Ruthazer R, Schmid C |title=A randomized, double-blind crossover trial of fluoxetine and amitriptyline in the treatment of fibromyalgia |journal=Arthritis Rheum. |volume=39 |issue=11 |pages=1852-9 |year=1996 |pmid=8912507 |doi=}}</ref>
| |
|
| |
| ====Cannabis and cannabinoids====
| |
| Fibromyalgia patients frequently self-report using [[cannabis (drug)|cannabis]] therapeutically to treat symptoms of the disorder.<ref name="pmid16202145">{{cite journal |author=Swift W, Gates P, Dillon P |title=Survey of Australians using cannabis for medical purposes |journal=Harm reduction journal |volume=2 |issue= |pages=18 |year=2005 |pmid=16202145 |doi=10.1186/1477-7517-2-18 |url=http://www.biomedcentral.com/content/pdf/1477-7517-2-18.pdf |format=PDF}}</ref> Writing in the July 2006 issue of the journal Current Medical Research and Opinion, investigators at Germany's University of Heidelberg evaluated the analgesic effects of oral THC ([[tetrahydrocannabinol|∆<sup>9</sup>-tetrahydrocannabinol]]) in nine patients with fibromyalgia over a 3-month period. Subjects in the trial were administered daily doses of 2.5 to 15 mg of THC, but received no other pain medication during the trial. Among those participants who completed the trial, all reported a significant reduction in daily recorded pain and electronically induced pain.<ref name="pmid16834825">{{cite journal |author=Schley M, Legler A, Skopp G, Schmelz M, Konrad C, Rukwied R |title=Delta-9-THC based monotherapy in fibromyalgia patients on experimentally induced pain, axon reflex flare, and pain relief |journal=Current medical research and opinion |volume=22 |issue=7 |pages=1269–76 |year=2006 |pmid=16834825 |doi=10.1185/030079906X112651}}</ref> Previous clinical and preclinical trials have shown that both naturally occurring and endogenous cannabinoids hold analgesic qualities,<ref>{{cite journal |author=Burnes TL, Ineck JR |title=Cannabinoid Analgesia as a Potential New Therapeutic Option in the Treatment of Chronic Pain |journal=Annals of Pharmacotherapy |year= |volume=40 |issue=2 |pages=251-60 |doi=10.1345/aph.1G217 |url=http://www.theannals.com/cgi/content/full/40/2/251}}</ref> particularly in the treatment of cancer pain and neuropathic pain,<ref name="pmid15757410">{{cite journal |author=Radbruch L, Elsner F |title=Emerging analgesics in cancer pain management |journal=Expert opinion on emerging drugs |volume=10 |issue=1 |pages=151–71 |year=2005 |pmid=15757410 |doi=}}</ref><ref name="pmid15096238">{{cite journal |author=Notcutt W, Price M, Miller R, ''et al'' |title=Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34 'N of 1' studies |journal=Anaesthesia |volume=59 |issue=5 |pages=440–52 |year=2004 |pmid=15096238 |doi=10.1111/j.1365-2044.2004.03674.x}}</ref> both of which are poorly treated by conventional opioids. As a result, some experts have suggested that cannabinoid agonists would be applicable for the treatment of chronic pain conditions unresponsive to opioid analgesics such as fibromyalgia, and they propose that the disorder may be associated with an underlying clinical deficiency of the [[endocannabinoid system]].<ref name="pmid15159679">{{cite journal |author=Russo EB |title=Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? |journal=Neuro Endocrinol. Lett. |volume=25 |issue=1-2 |pages=31–9 |year=2004 |pmid=15159679 |doi=}}</ref>
| |
| ====Topical Remedies====
| |
|
| |
| Users of Epsom Salts in the gel form ([[Magnesium Sulfate]]), have reported significant and lasting relief from pain associated with fibromyalgia. Epsom Salts have long been touted for its ability to reduce pain and swelling.
| |
| ====Injection Therapy====
| |
| Interventional therapy can ease pain by blocking nerve conduction between specific areas of the body and the brain. Approaches range from injections of local anesthetics, steroids, proliferative agents ([[Prolotherapy]]) into affected soft tissues, joints, or nerve roots to more complex nerve blocks. Chronic use of steroid injections may lead to increased functional impairment.
| |
| ====Physical treatments====
| |
| Studies have found exercise improves fitness and sleep and may reduce pain and fatigue in some people with fibromyalgia.<ref name="pmid12137713">{{cite journal |author=Busch A, Schachter CL, Peloso PM, Bombardier C |title=Exercise for treating fibromyalgia syndrome |journal=Cochrane database of systematic reviews (Online) |volume= |issue=3 |pages=CD003786 |year=2002 |pmid=12137713 |doi=}}</ref> Many patients find temporary relief by applying heat to painful areas. Those with access to [[physical therapy]], [[massage]], or acupuncture may find them beneficial.<ref name="pmid10086765">{{cite journal |author=Berman BM, Ezzo J, Hadhazy V, Swyers JP |title=Is acupuncture effective in the treatment of fibromyalgia? |journal=The Journal of family practice |volume=48 |issue=3 |pages=213–8 |year=1999 |pmid=10086765 |doi=}}</ref> Most patients find exercise, even low intensity exercise to be extremely helpful.<ref name="pmid14770100">{{cite journal |author=Gowans SE, deHueck A |title=Effectiveness of exercise in management of fibromyalgia |journal=Current opinion in rheumatology |volume=16 |issue=2 |pages=138–42 |year=2004 |pmid=14770100 |doi=}}</ref> [[Osteopathic Manipulative Medicine|Osteopathic manipulative therapy]] can also temporarily relieve pain due to fibromyalgia.<ref name="pmid12090649">{{cite journal |author=Gamber RG, Shores JH, Russo DP, Jimenez C, Rubin BR |title=Osteopathic manipulative treatment in conjunction with medication relieves pain associated with fibromyalgia syndrome: results of a randomized clinical pilot project |journal=The Journal of the American Osteopathic Association |volume=102 |issue=6 |pages=321–5 |year=2002 |pmid=12090649 |doi= |url=http://www.jaoa.org/cgi/reprint/102/6/321.pdf |format=PDF}}</ref>
| |
|
| |
| Transcutaneous electrical nerve stimulation (TENS) is administered by a battery-powered device that sends mild electric pulses along nerve fibers to block pain signals to the brain. Small electrodes placed on the skin at or near the site of pain generate nerve impulses that block incoming pain signals from the peripheral nerves. TENS may also help stimulate the brain’s production of endorphins (chemicals that have pain-relieving properties).
| |
|
| |
| A holistic approach—including managing diet, sleep, stress, activity, and pain—is used by many patients. Dietary supplements, massage, chiropractic care, managing blood sugar levels, and avoiding known triggers when possible means living as well as it is in the patient's power to do.
| |
| ====Dietary treatment====
| |
| In a 2001 review of four case studies, symptom alleviation was found by minimizing consumption of [[monosodium glutamate]].<ref>Smith et al, Relief of fibromyalgia symptoms following discontinuation of dietary excitotoxins, Ann Pharmacother. 2001 Jun;35(6):702-6.</ref>
| |
| ==Historty and sysmtoms==
| |
| Persons with echinococcosis often remain asymptomatic. The clinical presentation of echinococcosis infection depends upon the site of the cysts and their size. Cysts grow large in size to cause discomfort, pain, nausea, and vomiting. The cysts grow over the course of several years before reaching maturity and the rate at which symptoms appear typically depend on the location of the cyst. The cysts are mainly found in the liver and lungs but can also appear in the [[brain]], [[eyes]], [[spleen]], [[kidney]]s, [[heart]], [[bone]], and [[central nervous system]]. A liver cyst may produce no symptoms for 10 - 20 years until it is large enough to be felt by physical examination.In the lungs, ruptured cyst membranes may be coughed up through the bronchi, resulting in a cure. Cyst rupture is most frequently caused by trauma and may cause mild to severe [[anaphylactic reaction]]s, even [[death]], as a result of the release of cystic fluid.
| |
|
| |
| Alveolar echinococcosis is characterized by parasitic cysts in the [[liver]] and other organs including the [[lungs]] and brain. AE in humans is similar to that in the natural hosts but differs in that the larval cyst is inhibited from completing development by the host. The cysts invade and destroy surrounding tissues and cause discomfort or [[pain]], [[weight loss]], and [[malaise]]. AE is a dangerous disease resulting in a mortality rate between 50% and 75% and is made worse because of the remote locations and poor health care where cases are found.
| |
|
| |
| Symptoms include:
| |
| * Pain in the upper right part of the abdomen
| |
| * Bloody [[sputum]]
| |
| * [[Chest pain]]
| |
| * [[Cough]]
| |
| * [[Fever]]
| |
| * Severe skin [[itching]]
| |
| *[[Nausea]]
| |
| * [[Vomiting]]
| |
| ===History and symptoms===
| |
|
| |
|
| |
| Small and/or calcified cysts may remain asymptomatic indefinitely. However, symptoms due to mass effect within organs, obstruction of blood or lymphatic flow, or complications such as rupture or secondary bacterial infections can result.
| |
|
| |
| Cysts typically increase in diameter at a rate of one to five centimeters per year. However, cyst growth rates and time courses are highly variable [1,2]. Hydatid cysts may be found in almost any site of the body, either from primary inoculation or via secondary spread. The liver is affected in approximately two-thirds of patients, the lungs in approximately 25 percent, and other organs including the brain, muscle, kidneys, bone, heart, and pancreas in a small proportion of patients. Single-organ involvement occurs in 85 to 90 percent of patients with E. granulosus infection, and only one cyst is observed in more than 70 percent of cases (image 1).
| |
|
| |
| Liver involvement — E. granulosus infection of the liver frequently produces no symptoms. The right lobe is affected in 60 to 85 percent of cases. Significant symptoms are unusual before the cyst has reached at least 10 cm in diameter. If the cysts become large, hepatomegaly with or without associated right upper quadrant pain, nausea, and vomiting can result (picture 1).
| |
|
| |
| E. granulosus cysts can rupture into the biliary tree and produce biliary colic, obstructive jaundice, cholangitis, or pancreatitis. (See "Endoscopic diagnosis and management of biliary parasitosis".)
| |
|
| |
| Pressure or mass effects on the bile ducts, portal and hepatic veins, or on the inferior vena cava can result in cholestasis, portal hypertension, venous obstruction, or the Budd-Chiari syndrome. (See "Etiology of the Budd-Chiari syndrome".)
| |
|
| |
| Liver cysts can also rupture into the peritoneum, causing peritonitis, or transdiaphragmatically into the pleural space or bronchial tree, causing pulmonary hydatidosis or a bronchial fistula. Secondary bacterial infection of the cysts can result in liver abscesses. (See "Pyogenic liver abscess".)
| |
|
| |
| Lung involvement — The most common symptoms of pulmonary cystic echinococcosis (CE) described in the literature include cough (53 to 62 percent), chest pain (49 to 91 percent), dyspnea (10 to 70 percent), and hemoptysis (12 to 21 percent). Less frequent symptoms include malaise, nausea and vomiting, and thoracic deformations [3,4]. The majority of children and adolescents with lung lesions are asymptomatic despite having lesions of impressive size, assumedly because of a weaker immune response and the relatively higher elasticity of the lung parenchyma relative to older patients [3,5].
| |
|
| |
| Cysts can break or develop secondary bacterial infection. The presence of these complications changes the clinical presentation, either by causing new symptoms or by increasing the severity of existing symptoms. The principal complication is cyst rupture, with spilling of cyst material containing fragments of larval tissue and protoscolices into the bronchial tree or the pleural cavity. Bronchial tree involvement can lead to cough, chest pain, hemoptysis, or emesis; pleural cavity involvement can cause pneumothorax, pleural effusion, or empyema. Secondary bacterial infection of the cyst can manifest as a pulmonary abscess with poorly defined margins [6-8].
| |
|
| |
| Approximately 60 percent of pulmonary hydatid disease affects the right lung, and 50 to 60 percent of cases involve the lower lobes [9]. Multiple cysts are common. Approximately 20 percent of patients with lung cysts also have liver cysts [10]. The ratio of lung to liver involvement is higher in children than in adults [10].
| |
|
| |
| Other organs — Involvement of organs outside of the liver or lung is unusual but can lead to significant morbidity and mortality.
| |
|
| |
| ●Infection of the heart can result in mechanical rupture with widespread dissemination or pericardial tamponade [11-13].
| |
| ●Central nervous system involvement can lead to seizures or signs of raised intracranial pressure; infection of the spinal cord can result in spinal cord compression [14].
| |
| ●Cysts in the kidney can cause hematuria or flank pain [15]. Immune complex-mediated disease, glomerulonephritis leading to the nephrotic syndrome, and secondary amyloidosis have also been described [16,17].
| |
| ●Bone cysts are usually asymptomatic until a pathologic fracture develops; the spine, pelvis, and long bones are most frequently affected [18].
| |
| ●Ocular cysts also occur [19,20].
| |
| ●Subcutaneous cyst has been described [21,22].
| |
|
| |
| ==Lab diagnosis==
| |
| Blood cell count
| |
|
| |
| Hypereosinophilia is a rare feature of disease (< 10%).
| |
| Lymphopenia develops in 45% of cases.
| |
| Immunoglobulin concentrations
| |
|
| |
| Increase in levels of gammaglobulins is common, primarily resulting from an increase in immunoglobulin G (IgG) levels and, to a lesser degree, levels of immunoglobulin
| |
| Increased immunoglobulin E (IgE) levels are uncommon.
| |
| Inflammatory proteins
| |
|
| |
| Tests usually show increased levels of haptoglobin, alpha1 acid glycoprotein, C3 and C4, and ceruloplasmin despite the absence of increased C-reactive protein (CRP) levels.
| |
| CRP levels increase in cases complicated by bacterial superinfection.
| |
| Hepatic function
| |
|
| |
| Results may be normal in asymptomatic cases.
| |
| Gamma-glutamyl transferase (GGT) levels usually increase before the patient is symptomatic. GGT levels also increase if bile ducts are obstructed. levels can reach 20 times the reference range.
| |
| Alkaline phosphatase levels increase later than GGT levels and are observed only in symptomatic patients.
| |
| Conjugated bilirubin levels increase in symptomatic patients who are diagnosed with jaundice.
| |
| levels of aminotransferases increase only when associated with necrosis. Aspartate aminotransferase (AST) is equal to alanine aminotransferase (ALT).
| |
| Prothrombin time decreases because of cholestasis, which can usually be corrected with vitamin K supplementation.
| |
| Factor V levels decrease in rare cases of hepatic failure (eg, secondary biliary cirrhosis, Budd-Chiari syndrome).
| |
| Specific serology
| |
|
| |
| |- suspected based on ultrasonography or CT scanning findings obtained in a clinical setting. These studies are also used for mass screenings.
| |
| Results from routine tests using heterologous antigen (E granulosus cyst fluid) are positive for indirect hemagglutination in 75-80% of cases with a threshold value at 1/300 dilution and 94% of cases with a threshold value at 1/80 (with a very poor specificity, often positive in other helminth infections). Immunofluorescence using protoscoleces as an antigen yields similar results but is rarely performed.
| |
| Immunoelectrophoresis using Echinococcus crude extract yield low sensitivity and specificity and is currently rarely performed. Arc 5, considered typical of E granulosus, is observed in nearly 60% of patients with alveolar echinococcosis.
| |
| Enzyme-linked immunosorbent assay (ELISA) results using heterologous antigen (E granulosus cyst fluid) are positive in 97% of cases, positive in abortive cases, and positive before species-specific tests in cases that recur after radical surgery or transplantation. ELISA results may also be positive in other types of cestode infections, especially cysticercosis (Taenia solium infection in humans) and, although less frequently, in other helminth infections. Considerations are as follows:
| |
| ELISA results using homologous antigen ( E multilocularis extract) are positive in 95% of cases but may be positive in other cestode infections.
| |
| ELISA results using recombinant and purified antigens of E multilocularis (Em2+ or recombinant Em18) are positive in 95% of cases and have better specificity. The EM2+ test is commercially available.
| |
| Combined ELISA for the diagnosis of echinococcosis and discrimination between E granulosus and E multilocularis, as a rapid test that does not require laboratory facilities, is commercially available in the People's Republic of China.
| |
| ELISA using the purified alkaline phosphatase of E multilocularis is both highly sensitive and specific (nearly 100%) but is not commercially available.
| |
| Western blot tests using combined extracts of E granulosus and E multilocularis or E multilocularis alone result in patterns specific for alveolar echinococcosis. Two narrow bands at 18 kDa are associated with 1 band at 26-27 kDa or only 1 band at 26-28 kDa. A pattern consisting of 1 band at 7 kDa and 1 band at 26-28 kDa without an intermediate band cannot differentiate E multilocularis infection from that of E granulosus. Western blot tests are highly sensitive (97%), and cross-reactions resulting in a similar pattern are observed only with sera from patients with neurocysticercosis. Western blot tests are commercially available. Specific Western blot using Em18 antigen or Em18 recombinant protein has comparable diagnostic value but is not commercially available.
| |
| Specific IgE are present in the serum of 50% of patients and cannot be used for diagnosis.
| |
|
| |
|
| |
| ==Strongy==
| |
| __NOTOC__
| |
| {{Strongyloidiasis}}
| |
| {{CMG}} ; {{AE}} {{ADG}}
| |
|
| |
| ==Overview==
| |
| The prevention of strongyloidiasis is best achieved through improvements in personal hygiene and environmental sanitation.<ref name="pmid17940124">{{cite journal |vauthors=Segarra-Newnham M |title=Manifestations, diagnosis, and treatment of Strongyloides stercoralis infection |journal=Ann Pharmacother |volume=41 |issue=12 |pages=1992–2001 |year=2007 |pmid=17940124 |doi=10.1345/aph.1K302 |url=}}</ref>
| |
|
| |
| ==Prevention==
| |
| The prevention of strongyloidiasis is best achieved by:
| |
| *Avoiding ingesting soil that may be contaminated with human feces, including where human fecal matter ("night soil") or wastewater is used to fertilize crops.
| |
| *Washing hands with soap and warm water before handling food.
| |
| *Teaching children the importance of washing hands to prevent infection.
| |
| *Washing, peeling, or cooking all raw vegetables and fruits before eating, particularly those that have been grown in soil that has been fertilized with manure.
| |
| *Avoiding defecating outdoors.
| |
| *The use of effective sewage disposal systems.
| |
|
| |
| ==References==
| |
|
| |
| {{Reflist|2}}
| |
|
| |
| [[Category:Needs content]]
| |
| [[Category:Disease]]
| |
| [[Category:Infectious disease]]
| |
|
| |
| {{WH}}
| |
| {{WS}}
| |
|
| |
| ==treatment==
| |
| * [[Metronidazole]] 400-600mg
| |
| * [[Albendazole]]
| |
| * [[Mebendazole]] to prevent recurrence
| |
|
| |
| ==References==
| |
| {{reflist|2}}
| |
| |}
| |
| |}
| |