Fever of unknown origin differential diagnosis: Difference between revisions

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| style="vertical-align: middle; padding: 5px;" align=center | [[File:Siren.gif|30px|link=Fever of unknown origin resident survival guide]]
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| style="vertical-align: middle; padding: 5px;" align=center | [[Fever of unknown origin resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
| style="vertical-align: middle; padding: 5px;" align="center" |[[Fever of unknown origin resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
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{{Fever of unknown origin}}
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==Overview==
==Overview==
[[Fever]] of unknown origin must be differentiated from other causes that present with [[fever]] as the primary symptom.
 
#[[Fever]] can be the presenting symptom with many diseases, it is therefore important to differentiate fever of unknown origin from all those diseases which present with fever.
#Because of the broad range of differential diagnosis they can be grouped into four categories based on their etiology.
 
*Infectious
*[[Malignant]]
*[[Inflammatory]]
*Miscellaneous<ref name="Cunha2007">{{cite journal|last1=Cunha|first1=Burke A.|title=Fever of Unknown Origin: Focused Diagnostic Approach Based on Clinical Clues from the History, Physical Examination, and Laboratory Tests|journal=Infectious Disease Clinics of North America|volume=21|issue=4|year=2007|pages=1137–1187|issn=08915520|doi=10.1016/j.idc.2007.09.004}}</ref><ref name="CunhaLortholary2015">{{cite journal|last1=Cunha|first1=Burke A.|last2=Lortholary|first2=Olivier|last3=Cunha|first3=Cheston B.|title=Fever of Unknown Origin: A Clinical Approach|journal=The American Journal of Medicine|volume=128|issue=10|year=2015|pages=1138.e1–1138.e15|issn=00029343|doi=10.1016/j.amjmed.2015.06.001}}</ref>


==Differential diagnosis==
==Differential diagnosis==
Various differential diagnosis of fever of unknown origin include<ref> name="pmid28672419">{{cite journal| author=Kümmerle-Deschner JB| title=[Autoinflammatory Diseases as a Differential Diagnosis of Fever of Unknown Origin]. | journal=Dtsch Med Wochenschr | year= 2017 | volume= 142 | issue= 13 | pages= 969-978 | pmid=28672419 | doi=10.1055/s-0043-103468 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28672419  }} </ref>
===Infectious===
**Autoinflammatory diseases
These patients mostly have a history of hospitalization, surgical procedures, contact with infected person or travel to an endemic place.<ref name="CunhaLortholary20152">{{cite journal|last1=Cunha|first1=Burke A.|last2=Lortholary|first2=Olivier|last3=Cunha|first3=Cheston B.|title=Fever of Unknown Origin: A Clinical Approach|journal=The American Journal of Medicine|volume=128|issue=10|year=2015|pages=1138.e1–1138.e15|issn=00029343|doi=10.1016/j.amjmed.2015.06.001}}</ref><ref name="pmid23111594">{{cite journal| author=Salzberger B, Schneidewind A, Hanses F, Birkenfeld G, Müller-Schilling M| title=[Fever of unknown origin. Infectious causes]. | journal=Internist (Berl) | year= 2012 | volume= 53 | issue= 12 | pages= 1445-53; quiz 1454-5 | pmid=23111594 | doi=10.1007/s00108-012-3173-8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23111594  }}</ref>
 
Examples include:
 
*[[Histoplasmosis]]
*Abscess
*Subacute bacterial endocarditis
*[[Q fever]]
*[[Brucellosis]]
*[[Toxoplasmosis]]
*[[Leptospirosis]]
*[[Ehrlichiosis]]
*[[Anaplasmosis]]
*[[Tuberculosis]]
*[[Infectious mononucleosis]].
 
<br />
 
===Malignant===
They are mostly accompanied by loss of weight, decrease in appetite, lymph node enlargement and aquagenic pruritic mostly occurring after  hot shower.
 
Examples include:
 
*[[Hodgkin lymphoma]]
*[[Myeloproliferative disease|myeloproliferative disorders]]
*[[Colorectal carcinoma]]
*[[Hepatocellular carcinoma (hepatoma)|Hepatocellular carcinoma]]
*[[Renal cell carcinoma]]
*[[carcinoma of CNS]]  etc.
 
 
===Autoinflammatory/Rheumatologic===
Mostly they have multi organ involvement and lymphadenopathy along with joint symptoms may be present.<ref name="pmid28672419">{{cite journal| author=Kümmerle-Deschner JB| title=[Autoinflammatory Diseases as a Differential Diagnosis of Fever of Unknown Origin]. | journal=Dtsch Med Wochenschr | year= 2017 | volume= 142 | issue= 13 | pages= 969-978 | pmid=28672419 | doi=10.1055/s-0043-103468 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28672419  }}</ref><ref name="pmid27964789">{{cite journal| author=Mulders-Manders CM, Simon A, Bleeker-Rovers CP| title=Rheumatologic diseases as the cause of fever of unknown origin. | journal=Best Pract Res Clin Rheumatol | year= 2016 | volume= 30 | issue= 5 | pages= 789-801 | pmid=27964789 | doi=10.1016/j.berh.2016.10.005 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27964789  }}</ref>
 
Examples include:
 
*[[Systemic lupus erythematosus]]
*[[Takayasu Arteritis]]
*[[Polyarteritis nodosa]]
*[[Polymyalgia rheumatica]]
*[[Sarcoidosis]] etc.
 
===Miscellaneous===
Mostly does not belong to any of the above.
 
Examples include:
 
*[[Familial mediterranean fever|Familial Mediterranean fever]]
*[[Drug fever]]
*[[Thyroiditis]]
*[[Hypertriglyceridemia]] etc.
 
*
 
{| style="border: 0px; font-size: 85%; margin: 3px; width:1000px;" align="center"
! style="background: #4479BA; color:#FFF;  width: 150px;" |Disease
! style="background: #4479BA; color:#FFF;  width: 200px;" |History
! style="background: #4479BA; color:#FFF;  width: 200px;" |Physical examination
! style="background: #4479BA; color:#FFF;  width: 200px;" |Laboratory or radiological findings
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Bacterial endocarditis|Subacute Bacterial endocartitis]]
| style="padding: 5px 5px; background: #F5F5F5;" |Recent dental procedures, Joint pain, decrease weight, Night sweats, back pain
 
*
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Heart murmur, [[Splinter hemorrhage|splinter hemorrhages]], [[Janeway lesion|Janeway lesions]], [[Roth's spot|Roth spots]], enlarged spleen.
 
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Elevated WBCs, decreased platelets, Elevated [[ESR]] , presence of [[Cryoglobulins]]
*
*
*
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Abscess]]
| style="padding: 5px 5px; background: #F5F5F5;" |GI, genitourinary, Pelvic procedure or infection , fever, chills, decrease weight, night sweats.
 
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |RUQ tenderness ( subphrenic Abscess),[[hepatomegaly]] (hepatic abscess), [[splenomegaly]] ( splenic abscess), tenderness on DRE ( pelvic abscess).
 
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Elevated WBCs and [[ESR]], elevated platelets, Positive CT/MRI findings
 
*
*
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Tuberculosis]] of CNS
| style="padding: 5px 5px; background: #F5F5F5;" |Previous tuberculosis, [[Altered mental status]], Headace
 
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Morning temperature spikes[[Relative bradycardia|, relative bradycardia]], [[Abducens nerve palsy|Abducens palsy]].
 
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |[[CSF]]: Increased lymphocytes, increased RBCs,  decreased glucose, increased lactate, positive [[Acid-fast|AFB stain]] and Culture.
 
*
*
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[EBV infection]]
| style="padding: 5px 5px; background: #F5F5F5;" |Exposure to saliva ( [[kissing disease]] ) , [[upper respiratory tract infection]]
*
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |[[Lymphadenopathy|Enlarged lymph nodes]], palatal [[Petechia|petechiae]], enlarged tonsils, enlarged spleen.
 
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Positive monospot test, decreased WBCs, decreased lymphocytes, [[Atypical lymphocyte|atypical lymphocytosis]], positive [[PCR]], positive IgM EBV VCA titers, enlarged spleen, increased [[LFTs|LFT]]<nowiki/>s.
 
*
*
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[CMV infection]]
| style="padding: 5px 5px; background: #F5F5F5;" |Exposure to body fluids or blood transfusion
 
*
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Enlarged lymph nodes, palatal petechiae, enlarged tonsils, enlarged spleen.
 
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Negative monospot test, decreased WBCs, decreased lymphocytes, [[Atypical lymphocyte|atypical lymphocytosi]]<nowiki/>s, positive [[PCR|PCR,]] increased IgM, increased [[Liver function tests|LFTs]]
*
*
*
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[HIV AIDS|HIV infection]]
| style="padding: 5px 5px; background: #F5F5F5;" |Exposure to body fluids (blood, breast milk, semen and vaginal secretions), IV drug abuse, weight loss, night sweats .
 
*
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Generalized lymphadenopathy, pharyngeal and palatal petechiae.
 
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Decreased lymphocytes, decreased platelets, positive [[Human Immunodeficiency Virus (HIV)|HIV]] serology and [[PCR]] , increased viral load.
 
*
*
*
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Toxoplasmosis]]
| style="padding: 5px 5px; background: #F5F5F5;" |Exposure to cat feces or consumption of uncooked meat, joint pain.
 
*
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |[[Chorioretinitis]], enlarged lymph nodes, enlarged spleen.
 
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |[[Atypical lymphocyte|Atypical lymphocytes]], increased IgM titers ( toxoplasma serology), Positive MRI/CT scan finding in brain ( ring enhancing lesions ).
 
*
*
*
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Ehrlichiosis]]/ [[Anaplasmosis]]
| style="padding: 5px 5px; background: #F5F5F5;" |Recent insect (Tick) exposure, Headache, muscle aches, fatigue,
 
*
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Relative bradycardia, enlarged spleen.
 
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Decreased WBCs, decreased platelets, inclusions in Monocytes (Ehrlichiosis ) and Granulocytes (Anaplasmosis ), positive serology.
 
*
*
*
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Leptospirosis]]
| style="padding: 5px 5px; background: #F5F5F5;" |Exposure to water contaminated with animal (Rodents) urine, common in surfers, Flu like symptoms, Headache.
 
*
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Calf tenderness, [[Photophobia]], Jaundice, [[Conjunctival disease|conjunctival suffusion]] without exudate, enlarged liver.
 
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Increased WBCs, Decreased platelets, increased LFTs, Increased [[Creatine kinase|creatinine kinase]], positive serology. 
 
*
*
*
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Brucellosis]]
| style="padding: 5px 5px; background: #F5F5F5;" |Exposure to animals or contaminated dairy products (milk, cheese), Headache, muscle aches, fatigue,
 
*
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Muscle (Thigh) tenderness, Spine tenderness, enlarged lymph nodes, enlarged spleen.
 
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Positive serology, increased [[LFTs]] , [[Atypical lymphocyte|Atypical lymphocytes]], positive blood culture.
 
*
*
*
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Histoplasmosis]]
| style="padding: 5px 5px; background: #F5F5F5;" |Cave exploration, Mississippi and Ohio river valleys location, weight loss, night sweats
 
*
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Palatal/tongue ulcers, enlarged spleen, enlarged liver.
 
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Decreased WBCs, decreased platelets, increased LFTs, positive serum and urine antigen test.
 
*
*
*
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Q fever]]
| style="padding: 5px 5px; background: #F5F5F5;" |Exposure to cattle/sheep amniotic fluid, night sweats, weight loss, [[Prosthetic heart valve|prosthetic heart valve.]]
*
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Relative bradycardia, heart murmur, enlarged spleen.
 
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Decreased platelets, increased [[Liver function tests|LFTs]], positive [[PCR]]
*
*
*
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[SLE]]
| style="padding: 5px 5px; background: #F5F5F5;" |Young female, joint pain, recurrent infections, fatigue, headache, hair loss, [[anemia]]
*
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Multiple mucosal ulcers, [[malar rash]], enlarged lymph nodes, enlarged spleen, [[Osler's Disease|Osler nodes]], [[Roth's spot|Roth spots]], heart murmur ([[endocarditis]]),
 
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |[[Pancytopenia]], increased [[ANA]], increased [[C-reactive protein|C reactive protein]], increased [[ferritin]], positive ds DNA, decreased complement.
 
*
*
*
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Giant cell arteritis|Giant cell temporal arteritis]]
| style="padding: 5px 5px; background: #F5F5F5;" |Old age, [[amaurosis fugax]], jaw pain, headache (unilateral), muscle aches. .
 
*
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |[[temporal artery]] nodules and tenderness, jaw tenderness, pallor of [[optic disc]].
 
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Elevated [[ESR]], positive imaging findings, positive biopsy ([[granulomatous]] inflammatory).
 
*
*
*
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Polyarteritis nodosa|Poly arteritis nodosa]]
| style="padding: 5px 5px; background: #F5F5F5;" |Fever, weight loss, fatigue, abdominal pain, black stools, rashes, [[livedo reticularis]], neurologic problems, [[edema]].
 
*
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Increased blood pressure, skin [[purpura]].
 
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Elevated ESR, increased creatinine, positive [[hepatitis B]] serology, [[fibrinoid necrosis]] on biopsy.
 
*
*
*
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Takayasu's arteritis|Takayasu arteritis]]
| style="padding: 5px 5px; background: #F5F5F5;" |Headache, joint pain, weight loss, edematous face, [[claudication]], skin nodules, neurologic deficits
 
*
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Unequal B.P in arms, bruits over larger arteries.
 
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Elevated [[ESR|ESR,]] positive imaging findings, positive biopsy (granulomatous inflammatory).
 
*
*
*
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Sarcoidosis]]
| style="padding: 5px 5px; background: #F5F5F5;" |[[Arthritis]], headache, eye problems, hearing problems, [[Peripheral neuropathy|peripheral neuropathy,]] [[parotitis]], skin nodules.
 
*
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Enlarged lymph nodes, [[erythema nodosum]], [[Bell's palsy|facial nerve palsy]], [[Argyll Robertson pupil]],  [[uveitis]], enlarged liver.
 
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Decreased WBCs, decreased platelets, increase [[Eosinophils]], hypercalcemia, hypercalciuria,  increased ACE levels in blood.
 
*
*
*
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Hodgkin's lymphoma|Hodgkin lymphoma]]
| style="padding: 5px 5px; background: #F5F5F5;" |Radiation exposure, fever, night sweats, fatigue, bone pain, pruritis.
 
*
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Enlarged lymph nodes, enlarged liver, enlarged spleen,
 
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |lymphopenia, eosinophilia, increased basophils, increased LDH, positive CT/MRI, [[Reed-Sternberg cell|Reed Sternberg]] cells on lymph node biopsy.
 
*
*
*
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[CNS Disease|CNS Malignancies]]
| style="padding: 5px 5px; background: #F5F5F5;" |Headache, vomiting, [[altered mental status]], [[Seizure|seizures]].
 
*
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Cranial nerves abnormalities, [[Optic disc|optic disc swelling]]
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Positive CT/ MRI of brain, CSF increased protein and RBcs
 
*
*
*
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Hepatocellular carcinoma|Hepatocellular Carcinoma]]
| style="padding: 5px 5px; background: #F5F5F5;" |Abdominal pain, family history, [[Alpha 1 antitrypsin deficiency|alpha 1 anti trypsin deficiency]], [[Cirrhosis]], [[Chronic Hepatitis B]]<nowiki/>and C infection. 
 
*
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Enlarged Liver, [[ascites]], abdominal tenderness
 
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Increased [[LFTs|LFT]]<nowiki/>s, Increased [[Alpha-fetoprotein|AFP]], increased [[ALP]], Malignant cells on biopsy, positive imaging.
 
*
*
*
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Chronic lymphocytic leukemia]]
| style="padding: 5px 5px; background: #F5F5F5;" |fever, weight loss, night sweats
 
*
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Enlarged lymph nodes, enlarged spleen.
 
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |Elevated [[ESR]], positive [[coombs test]], [[Smudge cells]] on blood smear, Leukocytosis.
 
*
*
*
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*
*
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |
*
*
*
|-
|}
 
*


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}


 
{{WH}}
[[Category:Ailments of unknown etiology]]
{{WS}}
[[Category: (name of the system)]]

Latest revision as of 17:12, 15 February 2021

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: febris continua e causa ignota; febris e causa ignota; febris E.C.I.; FUO; PUO; pyrexia of unknown origin

Overview

  1. Fever can be the presenting symptom with many diseases, it is therefore important to differentiate fever of unknown origin from all those diseases which present with fever.
  2. Because of the broad range of differential diagnosis they can be grouped into four categories based on their etiology.

Differential diagnosis

Infectious

These patients mostly have a history of hospitalization, surgical procedures, contact with infected person or travel to an endemic place.[3][4]

Examples include:


Malignant

They are mostly accompanied by loss of weight, decrease in appetite, lymph node enlargement and aquagenic pruritic mostly occurring after hot shower.

Examples include:


Autoinflammatory/Rheumatologic

Mostly they have multi organ involvement and lymphadenopathy along with joint symptoms may be present.[5][6]

Examples include:

Miscellaneous

Mostly does not belong to any of the above.

Examples include:

Disease History Physical examination Laboratory or radiological findings
Subacute Bacterial endocartitis Recent dental procedures, Joint pain, decrease weight, Night sweats, back pain
Heart murmur, splinter hemorrhages, Janeway lesions, Roth spots, enlarged spleen.
Elevated WBCs, decreased platelets, Elevated ESR , presence of Cryoglobulins
Abscess GI, genitourinary, Pelvic procedure or infection , fever, chills, decrease weight, night sweats.
RUQ tenderness ( subphrenic Abscess),hepatomegaly (hepatic abscess), splenomegaly ( splenic abscess), tenderness on DRE ( pelvic abscess).
Elevated WBCs and ESR, elevated platelets, Positive CT/MRI findings
Tuberculosis of CNS Previous tuberculosis, Altered mental status, Headace
Morning temperature spikes, relative bradycardia, Abducens palsy.
CSF: Increased lymphocytes, increased RBCs, decreased glucose, increased lactate, positive AFB stain and Culture.
EBV infection Exposure to saliva ( kissing disease ) , upper respiratory tract infection
Enlarged lymph nodes, palatal petechiae, enlarged tonsils, enlarged spleen.
Positive monospot test, decreased WBCs, decreased lymphocytes, atypical lymphocytosis, positive PCR, positive IgM EBV VCA titers, enlarged spleen, increased LFTs.
CMV infection Exposure to body fluids or blood transfusion
Enlarged lymph nodes, palatal petechiae, enlarged tonsils, enlarged spleen.
Negative monospot test, decreased WBCs, decreased lymphocytes, atypical lymphocytosis, positive PCR, increased IgM, increased LFTs
HIV infection Exposure to body fluids (blood, breast milk, semen and vaginal secretions), IV drug abuse, weight loss, night sweats .
Generalized lymphadenopathy, pharyngeal and palatal petechiae.
Decreased lymphocytes, decreased platelets, positive HIV serology and PCR , increased viral load.
Toxoplasmosis Exposure to cat feces or consumption of uncooked meat, joint pain.
Chorioretinitis, enlarged lymph nodes, enlarged spleen.
Atypical lymphocytes, increased IgM titers ( toxoplasma serology), Positive MRI/CT scan finding in brain ( ring enhancing lesions ).
Ehrlichiosis/ Anaplasmosis Recent insect (Tick) exposure, Headache, muscle aches, fatigue,
Relative bradycardia, enlarged spleen.
Decreased WBCs, decreased platelets, inclusions in Monocytes (Ehrlichiosis ) and Granulocytes (Anaplasmosis ), positive serology.
Leptospirosis Exposure to water contaminated with animal (Rodents) urine, common in surfers, Flu like symptoms, Headache.
Calf tenderness, Photophobia, Jaundice, conjunctival suffusion without exudate, enlarged liver.
Increased WBCs, Decreased platelets, increased LFTs, Increased creatinine kinase, positive serology.
Brucellosis Exposure to animals or contaminated dairy products (milk, cheese), Headache, muscle aches, fatigue,
Muscle (Thigh) tenderness, Spine tenderness, enlarged lymph nodes, enlarged spleen.
Positive serology, increased LFTs , Atypical lymphocytes, positive blood culture.
Histoplasmosis Cave exploration, Mississippi and Ohio river valleys location, weight loss, night sweats
Palatal/tongue ulcers, enlarged spleen, enlarged liver.
Decreased WBCs, decreased platelets, increased LFTs, positive serum and urine antigen test.
Q fever Exposure to cattle/sheep amniotic fluid, night sweats, weight loss, prosthetic heart valve.
Relative bradycardia, heart murmur, enlarged spleen.
Decreased platelets, increased LFTs, positive PCR
SLE Young female, joint pain, recurrent infections, fatigue, headache, hair loss, anemia
Multiple mucosal ulcers, malar rash, enlarged lymph nodes, enlarged spleen, Osler nodes, Roth spots, heart murmur (endocarditis),
Pancytopenia, increased ANA, increased C reactive protein, increased ferritin, positive ds DNA, decreased complement.
Giant cell temporal arteritis Old age, amaurosis fugax, jaw pain, headache (unilateral), muscle aches. .
temporal artery nodules and tenderness, jaw tenderness, pallor of optic disc.
Elevated ESR, positive imaging findings, positive biopsy (granulomatous inflammatory).
Poly arteritis nodosa Fever, weight loss, fatigue, abdominal pain, black stools, rashes, livedo reticularis, neurologic problems, edema.
Increased blood pressure, skin purpura.
Elevated ESR, increased creatinine, positive hepatitis B serology, fibrinoid necrosis on biopsy.
Takayasu arteritis Headache, joint pain, weight loss, edematous face, claudication, skin nodules, neurologic deficits
Unequal B.P in arms, bruits over larger arteries.
Elevated ESR, positive imaging findings, positive biopsy (granulomatous inflammatory).
Sarcoidosis Arthritis, headache, eye problems, hearing problems, peripheral neuropathy, parotitis, skin nodules.
Enlarged lymph nodes, erythema nodosum, facial nerve palsy, Argyll Robertson pupil, uveitis, enlarged liver.
Decreased WBCs, decreased platelets, increase Eosinophils, hypercalcemia, hypercalciuria, increased ACE levels in blood.
Hodgkin lymphoma Radiation exposure, fever, night sweats, fatigue, bone pain, pruritis.
Enlarged lymph nodes, enlarged liver, enlarged spleen,
lymphopenia, eosinophilia, increased basophils, increased LDH, positive CT/MRI, Reed Sternberg cells on lymph node biopsy.
CNS Malignancies Headache, vomiting, altered mental status, seizures.
Cranial nerves abnormalities, optic disc swelling
Positive CT/ MRI of brain, CSF increased protein and RBcs
Hepatocellular Carcinoma Abdominal pain, family history, alpha 1 anti trypsin deficiency, Cirrhosis, Chronic Hepatitis Band C infection.
Enlarged Liver, ascites, abdominal tenderness
Increased LFTs, Increased AFP, increased ALP, Malignant cells on biopsy, positive imaging.
Chronic lymphocytic leukemia fever, weight loss, night sweats
Enlarged lymph nodes, enlarged spleen.
Elevated ESR, positive coombs test, Smudge cells on blood smear, Leukocytosis.

References

  1. ↑ Cunha, Burke A. (2007). "Fever of Unknown Origin: Focused Diagnostic Approach Based on Clinical Clues from the History, Physical Examination, and Laboratory Tests". Infectious Disease Clinics of North America. 21 (4): 1137–1187. doi:10.1016/j.idc.2007.09.004. ISSN 0891-5520.
  2. ↑ Cunha, Burke A.; Lortholary, Olivier; Cunha, Cheston B. (2015). "Fever of Unknown Origin: A Clinical Approach". The American Journal of Medicine. 128 (10): 1138.e1–1138.e15. doi:10.1016/j.amjmed.2015.06.001. ISSN 0002-9343.
  3. ↑ Cunha, Burke A.; Lortholary, Olivier; Cunha, Cheston B. (2015). "Fever of Unknown Origin: A Clinical Approach". The American Journal of Medicine. 128 (10): 1138.e1–1138.e15. doi:10.1016/j.amjmed.2015.06.001. ISSN 0002-9343.
  4. ↑ Salzberger B, Schneidewind A, Hanses F, Birkenfeld G, Müller-Schilling M (2012). "[Fever of unknown origin. Infectious causes]". Internist (Berl). 53 (12): 1445–53, quiz 1454-5. doi:10.1007/s00108-012-3173-8. PMID 23111594.
  5. ↑ Kümmerle-Deschner JB (2017). "[Autoinflammatory Diseases as a Differential Diagnosis of Fever of Unknown Origin]". Dtsch Med Wochenschr. 142 (13): 969–978. doi:10.1055/s-0043-103468. PMID 28672419.
  6. ↑ Mulders-Manders CM, Simon A, Bleeker-Rovers CP (2016). "Rheumatologic diseases as the cause of fever of unknown origin". Best Pract Res Clin Rheumatol. 30 (5): 789–801. doi:10.1016/j.berh.2016.10.005. PMID 27964789.

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