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Revision as of 20:59, 31 July 2017

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2], Ilan Dock, B.S.

Overview

Lyme disease is divided into 3 stages and symptoms are stage specific. Initial symptoms include "bulls-eye" rash, with accompanying constitutional symptoms. It can progress to cardiovascular or neurological complications.

History

The incubation period from infection to the onset of symptoms is usually 1–2 weeks, but can be much shorter (days), or much longer (months to years). Symptoms most often occur from May through September because the nymphal stage of the tick is responsible for most cases. ^[1]Asymptomatic infection exists, but is uncommon.^[2]
The specific areas of focus when obtaining the history, are outlined below:
- Tick bite
- Vacation, living, or working environment in endemic areas
- Spending time outdoor (especially in woody or grassy area).

Symptoms

Lyme disease is divided into 3 stages and symptoms are stage specific.

Stage 1 - Early localized disease
Stage 2 - Early disseminated disease
Stage 3 - Late disseminated disease

Stage 1 - Early localized disease

Features of early localized disease includes erythema migrans and constitutional symptoms.

Erythema migrans (EM) also known as Erythema chronicum migrans, "bull’s-eye" rash, or Lyme rash develops in around 70% - 80% of patients.^[3]
- EM begins at the site of a tick bite after a delay of 3 to 30 days (average is about 7 days).
- EM gradually expands over a period of days reaching up to 12 inches(30 cm)or more across.
- EM may feel warm to touch but is rarely itchy or painful.
- EM clears as it enlarges, resulting in a target or “bull’s-eye” appearance.
- EM may appear on any area of the body but majority of times present in areas including axilla, inguinal region, popliteal fossa, or along belt line.
- The rash does not represent an allergic reaction to the bite, but rather a skin infection with the Lyme bacteria, Borrelia burgdorferi sensu lato.
- An infection resulting from a B. mayonii infection may cause a diffuse rash, erupting in "red spots," spanning the entire body.
Constitutional symptoms includes:^[4]
- Fatigue
- Arthralgia
- Myalgia
- Headache
- Fever and/or chills
- Stiff neck
- Anorexia

Lyme disease, expamding rash with central clearing

Stage 2 - Early disseminate disease

Features of early disseminated disease can be divided system wise and includes:

Neurological symptoms: The triad of neurologic manifestation of Lyme disease includes meningitis, cranial neuritis, and radiculoneuritis.^[5]
- Lymphocytic meningitis (most common neurological symptom)
- Cranial neuropathies (particularly facial nerve palsy)
- Painful radiculitis
- Mononeuritis multiplex^[6]
- Altered mental status^[7]
- Pseudotumor cerebri
- Myelitis
- Chorea
- Cerebellar ataxia
Cardiac manifestations
- Palpitations
- Atrio-ventricular block
- Myopericarditis
- Sudden cardiac death
- Chronic cardiomyopathy
Dermatological manifestations^[8]
- Borrelial lymphocytoma: Most common site is earlobe.
Ocular manifestations^[9]
- Primary ocular symptoms occurs due to inflammation of ocular tissue. These symptoms includes conjunctivitis, keratitis, iridocyclitis, retinal vasculitis, chorioiditis, and optic neuropathy (extremely rarely episcleritis, panuveitis, panophthalmitis)

Secondary ocular symptoms occurs due to extraocular manifestations. These symptoms includes pareses of cranial nerves and orbital myositis.

Stage 3 - Late disseminated disease

Features of late disseminated disease can take months to years to manifest after the onset of infection.
Lyme arthritis is dominant months later but chronic neurologic involvement becomes more obvious years later.
The symptoms of late disseminated lyme disease includes:
- Musculoskeletal manifestation:
  - Lyme arthritis
    - Lyme arthritis is the hallmark of stage 3 Lyme disease.
    - Most frequently presented symptom in late disseminated Lyme disease.
    - Commonly affects knee joint.
- Neurological manifestations:
  - These neurological symptoms may take months to years to manifest after the infection. In addition to acute symptoms, Neuroborrerliosis can be manifested by a wide-range of neurological disorders, either central or peripheral including:
    - Encephalopathy (sub-acute): Affects memory, mood, sleep, and sometimes with subtle language disturbances.
    - Polyneuropathy or Paresthesia
    - Leukoencephalitis^[10]
    - Muscle twitching
    - Otolaryngologic manifestations: Neck pain, odynophagia, head and neck dysesthesia, otalgia, tinnitus, hearing loss, vertigo, temporomandibular joint pain, lymphadenopathy, dysgeusia.^[11]^[12]
  - Neuropsychiatric symptoms often develop much later in the disease progression, much like tertiary neurosyphilis.^[13]
  - In rare cases, frank psychosis have been attributed to chronic Lyme disease effects, including misdiagnoses of schizophrenia and bipolar disorder.
  - Panic attack and anxiety can occur, also delusional behavior, including somatoform delusions, sometimes accompanied by a depersonalization or derealization syndrome similar to what was seen in the past in the prodromal or early stages of general paresis.^[14]
- Dermatological manifestation^[8]
  - Acrodermatitis chronica atrophicans

Symptoms differentiated on the basis of frequency^[15]
Common symptoms	Less common symptoms
Erythema migrans(Erythema chronicum migrans) Constitutional symptoms Arthritis	Cardiac manifestations Neurological manifestations

Difference in clinical features in Europe and North America^[16]
Features	Europe	North America
Erythema migrans	Single lesion more frequently	Multiple lesions occurs more freuqently
Heterogenous dissemination	Less common	More common
Borrelial lymphocytoma	Present	Absent
ACA	Present	Absent
Meningoradiculoneuritis	More common	Less common
Lyme arthritis	Rarely preceded by Erythema migrans	Commonly preceded by Erythema migrans

Frequency of Lyme disease symptoms, 2001-2015

Lyme Carditis

Cardiac involvement occurs in about 5—10% of untreated Lyme disease and patients usually have symptoms related to fluctuating degrees of atrioventricular block (first-degree block to complete heart block) including lightheadedness, palpitations, shortness of breath, chest pain, and syncope.^[17]
Less commonly, patients may present with an acute picture of left ventricular dysfunction, cardiomegaly, perimyocarditis, or pancarditis without noticeable cardiac murmurs.^[18]
Lyme carditis can occur independently, it is usually accompanied by other cutaneous, joint, or neurologic features of Lyme disease.^[19]

Manifestations of Lyme Disease by Stage

**Manifestations of Lyme Disease by Stage^[18]**
System	Stage 1 (Localized Infection)	Stage 2 (Early Disseminated Infection)	Stage 3 (Late Persistent Infection)
Skin	Erythema migrans	Secondary annular lesions Malar rash Diffuse erythema or urticaria Evanescent lesions Lymphocytoma	Acrodermatitis chronica atrophicans Localized scleroderma-like lesions
Musculoskeletal	—	Migratory arthralgia Brief arthritis attacks Myositis Osteomyelitis Panniculitis	Prolonged arthritis attacks Chronic arthritis Peripheral enthesopathy Periostitis or joint subluxations below acrodermatitis
Neurologic	—	Meningitis Cranial neuritis or Bell's palsy Motor or sensory radiculoneuritis Encephalitis Mononeuritis multiplex Pseudotumor cerebri Myelitis Chorea Cerebellar ataxia	Chronic encephalomyelitis Spastic parapareses Ataxic gait Mental disorders Chronic axonal polyradiculopathy Dementia
Lymphatic	Regional lymphadenopathy	Regional or generalized lymphadenopathy Splenomegaly	—
Heart	—	Atrioventricular block Myopericarditis Pancarditis	—
Eyes	—	Conjunctivitis Iritis Choroiditis Retinal hemorrhage or retinal detachment Panophthalmitis	Keratitis
Liver	—	Mild or recurrent hepatitis	—
Respiratory	—	Nonexudative sore throat Nonproductive cough Adult respiratory distress syndrome	—
Kidney	—	Microscopic hematuria or proteinuria	—
Genitourinary	—	Orchitis	—
Constitutional systems	Fatigue Arthralgia Myalgia Headache Fever and/or chills Stiff neck Anorexia	Severe malaise and fatigue	Fatigue

Adapted from Steere AC. Lyme disease. N Engl J Med. 1989;321:586.

References

↑ Falco RC, McKenna DF, Daniels TJ, Nadelman RB, Nowakowski J, Fish D; et al. (1999). "Temporal relation between Ixodes scapularis abundance and risk for Lyme disease associated with erythema migrans". Am J Epidemiol. 149 (8): 771–6. PMID 10206627.
↑ Steere AC, Sikand VK, Schoen RT, Nowakowski J (2003). "Asymptomatic infection with Borrelia burgdorferi". Clin. Infect. Dis. 37 (4): 528–32. PMID 12905137.
↑ Steere AC, Sikand VK (2003). "The presenting manifestations of Lyme disease and the outcomes of treatment". N Engl J Med. 348 (24): 2472–4. doi:10.1056/NEJM200306123482423. PMID 12802042.
↑ Nadelman RB, Nowakowski J, Forseter G, Goldberg NS, Bittker S, Cooper D; et al. (1996). "The clinical spectrum of early Lyme borreliosis in patients with culture-confirmed erythema migrans". Am J Med. 100 (5): 502–8. PMID 8644761.
↑ Halperin JJ (2008). "Nervous system Lyme disease". Infect Dis Clin North Am. 22 (2): 261–74, vi. doi:10.1016/j.idc.2007.12.009. PMID 18452800.
↑ England JD, Bohm RP, Roberts ED, Philipp MT (1997). "Mononeuropathy multiplex in rhesus monkeys with chronic Lyme disease". Ann Neurol. 41 (3): 375–84. doi:10.1002/ana.410410313. PMID 9066359.
↑ Chabria SB, Lawrason J (2007). "Altered mental status, an unusual manifestation of early disseminated Lyme disease: A case report". 1 (1): 62. doi:10.1186/1752-1947-1-62. PMID 17688693.
↑ ^8.0 ^8.1 Mullegger RR (2004). "Dermatological manifestations of Lyme borreliosis". Eur J Dermatol. 14 (5): 296–309. PMID 15358567.
↑ Stanek G, Strle F (2003). "Lyme borreliosis". Lancet. 362 (9396): 1639–47. doi:10.1016/S0140-6736(03)14798-8. PMID 14630446.
↑ Halperin JJ, Volkman DJ, Wu P (1991). "Central nervous system abnormalities in Lyme neuroborreliosis". Neurology. 41 (10): 1571–82. PMID 1922798.
↑ Rosenhall U, Hanner P, Kaijser B (1988). "Borrelia infection and vertigo". Acta Otolaryngol. 106 (1–2): 111–6. PMID 3421091.
↑ Moscatello AL, Worden DL, Nadelman RB, Wormser G, Lucente F (1991). "Otolaryngologic aspects of Lyme disease". Laryngoscope. 101 (6 Pt 1): 592–5. PMID 2041438.
↑ Logigian, Eric L.; Kaplan, Richard F.; Steere, Allen C. (1990). "Chronic Neurologic Manifestations of Lyme Disease". New England Journal of Medicine. 323 (21): 1438–1444. doi:10.1056/NEJM199011223232102. ISSN 0028-4793.
↑ Fallon BA, Nields JA (1994). "Lyme disease: a neuropsychiatric illness". The American journal of psychiatry. 151 (11): 1571–83. PMID 7943444.Hess A, Buchmann J, Zettl UK; et al. (1999). "Borrelia burgdorferi central nervous system infection presenting as an organic schizophrenialike disorder". Biol. Psychiatry. 45 (6): 795. PMID 10188012.)
↑ Ciesielski CA, Markowitz LE, Horsley R, Hightower AW, Russell H, Broome CV (1989). "Lyme disease surveillance in the United States, 1983-1986". Rev. Infect. Dis. 11 Suppl 6: S1435–41. PMID 2682955.
↑ Stanek G, Strle F (2008). "Lyme disease: European perspective". Infect Dis Clin North Am. 22 (2): 327–39, vii. doi:10.1016/j.idc.2008.01.001. PMID 18452805.
↑ . doi:10.7326/0003-4819-157-3-20120807-01002. Missing or empty |title= (help)
↑ ^18.0 ^18.1 Steere, AC. (1989). "Lyme disease". N Engl J Med. 321 (9): 586–96. doi:10.1056/NEJM198908313210906. PMID 2668764. Unknown parameter |month= ignored (help)
↑ Fish, AE.; Pride, YB.; Pinto, DS. (2008). "Lyme carditis". Infect Dis Clin North Am. 22 (2): 275–88, vi. doi:10.1016/j.idc.2007.12.008. PMID 18452801. Unknown parameter |month= ignored (help)

Template:WikiDoc Sources

[pmid10206627-1] Falco RC, McKenna DF, Daniels TJ, Nadelman RB, Nowakowski J, Fish D; et al. (1999). "Temporal relation between Ixodes scapularis abundance and risk for Lyme disease associated with erythema migrans". Am J Epidemiol. 149 (8): 771–6. PMID 10206627.

[pmid12905137-2] Steere AC, Sikand VK, Schoen RT, Nowakowski J (2003). "Asymptomatic infection with Borrelia burgdorferi". Clin. Infect. Dis. 37 (4): 528–32. PMID 12905137.

[pmid12802042-3] Steere AC, Sikand VK (2003). "The presenting manifestations of Lyme disease and the outcomes of treatment". N Engl J Med. 348 (24): 2472–4. doi:10.1056/NEJM200306123482423. PMID 12802042.

[pmid8644761-4] Nadelman RB, Nowakowski J, Forseter G, Goldberg NS, Bittker S, Cooper D; et al. (1996). "The clinical spectrum of early Lyme borreliosis in patients with culture-confirmed erythema migrans". Am J Med. 100 (5): 502–8. PMID 8644761.

[pmid184528002-5] Halperin JJ (2008). "Nervous system Lyme disease". Infect Dis Clin North Am. 22 (2): 261–74, vi. doi:10.1016/j.idc.2007.12.009. PMID 18452800.

[pmid9066359-6] England JD, Bohm RP, Roberts ED, Philipp MT (1997). "Mononeuropathy multiplex in rhesus monkeys with chronic Lyme disease". Ann Neurol. 41 (3): 375–84. doi:10.1002/ana.410410313. PMID 9066359.

[7] Chabria SB, Lawrason J (2007). "Altered mental status, an unusual manifestation of early disseminated Lyme disease: A case report". 1 (1): 62. doi:10.1186/1752-1947-1-62. PMID 17688693.

[pmid15358567-8] 8.0 ^8.1 Mullegger RR (2004). "Dermatological manifestations of Lyme borreliosis". Eur J Dermatol. 14 (5): 296–309. PMID 15358567.

[pmid14630446-9] Stanek G, Strle F (2003). "Lyme borreliosis". Lancet. 362 (9396): 1639–47. doi:10.1016/S0140-6736(03)14798-8. PMID 14630446.

[pmid192279822-10] Halperin JJ, Volkman DJ, Wu P (1991). "Central nervous system abnormalities in Lyme neuroborreliosis". Neurology. 41 (10): 1571–82. PMID 1922798.

[11] Rosenhall U, Hanner P, Kaijser B (1988). "Borrelia infection and vertigo". Acta Otolaryngol. 106 (1–2): 111–6. PMID 3421091.

[12] Moscatello AL, Worden DL, Nadelman RB, Wormser G, Lucente F (1991). "Otolaryngologic aspects of Lyme disease". Laryngoscope. 101 (6 Pt 1): 592–5. PMID 2041438.

[LogigianKaplan1990-13] Logigian, Eric L.; Kaplan, Richard F.; Steere, Allen C. (1990). "Chronic Neurologic Manifestations of Lyme Disease". New England Journal of Medicine. 323 (21): 1438–1444. doi:10.1056/NEJM199011223232102. ISSN 0028-4793.

[14] Fallon BA, Nields JA (1994). "Lyme disease: a neuropsychiatric illness". The American journal of psychiatry. 151 (11): 1571–83. PMID 7943444.Hess A, Buchmann J, Zettl UK; et al. (1999). "Borrelia burgdorferi central nervous system infection presenting as an organic schizophrenialike disorder". Biol. Psychiatry. 45 (6): 795. PMID 10188012.)

[Ciesielski_198922-15] Ciesielski CA, Markowitz LE, Horsley R, Hightower AW, Russell H, Broome CV (1989). "Lyme disease surveillance in the United States, 1983-1986". Rev. Infect. Dis. 11 Suppl 6: S1435–41. PMID 2682955.

[pmid18452805-16] Stanek G, Strle F (2008). "Lyme disease: European perspective". Infect Dis Clin North Am. 22 (2): 327–39, vii. doi:10.1016/j.idc.2008.01.001. PMID 18452805.

[17] . doi:10.7326/0003-4819-157-3-20120807-01002. Missing or empty |title= (help)

[Steere-1989-18] 18.0 ^18.1 Steere, AC. (1989). "Lyme disease". N Engl J Med. 321 (9): 586–96. doi:10.1056/NEJM198908313210906. PMID 2668764. Unknown parameter |month= ignored (help)

[Fish-2008-19] Fish, AE.; Pride, YB.; Pinto, DS. (2008). "Lyme carditis". Infect Dis Clin North Am. 22 (2): 275–88, vi. doi:10.1016/j.idc.2007.12.008. PMID 18452801. Unknown parameter |month= ignored (help)

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@@ Line 45: / Line 45: @@
 ===Stage 2 - Early disseminate disease===
 Features of early disseminated disease can be divided system wise and includes:
-*Neurological symptoms:<ref name="pmid18452800">{{cite journal| author=Halperin JJ| title=Nervous system Lyme disease. | journal=Infect Dis Clin North Am | year= 2008 | volume= 22 | issue= 2 | pages= 261-74, vi | pmid=18452800 | doi=10.1016/j.idc.2007.12.009 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18452800  }} </ref>
+*Neurological symptoms: The triad of neurologic manifestation of [[Lyme disease]] includes [[meningitis]], [[cranial]] [[neuritis]], and radiculoneuritis.<ref name="pmid184528002">{{cite journal|author=Halperin JJ|title=Nervous system Lyme disease.|journal=Infect Dis Clin North Am|year=2008|volume=22|issue=2|pages=261-74, vi|pmid=18452800|doi=10.1016/j.idc.2007.12.009|pmc=|url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18452800}}</ref>
-**Lymphocytic meningitis (most common neurological symptom)
+**[[Lymphocyte|Lymphocytic]] [[meningitis]] (most common neurological symptom)
-**Cranial neuropathies(particularly facial nerve palsy)
+**[[Cranial nerve palsies|Cranial neuropathies]] (particularly facial nerve palsy)
-**Painful radiculitis
+**Painful [[radiculitis]]
-**Mononeuritis multiplex<ref name="pmid9066359">{{cite journal| author=England JD, Bohm RP, Roberts ED, Philipp MT| title=Mononeuropathy multiplex in rhesus monkeys with chronic Lyme disease. | journal=Ann Neurol | year= 1997 | volume= 41 | issue= 3 | pages= 375-84 | pmid=9066359 | doi=10.1002/ana.410410313 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9066359  }} </ref>
+**[[Mononeuritis multiplex]]<ref name="pmid9066359">{{cite journal| author=England JD, Bohm RP, Roberts ED, Philipp MT| title=Mononeuropathy multiplex in rhesus monkeys with chronic Lyme disease. | journal=Ann Neurol | year= 1997 | volume= 41 | issue= 3 | pages= 375-84 | pmid=9066359 | doi=10.1002/ana.410410313 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9066359  }} </ref>
-**Altered mental status<ref>{{cite journal|author=Chabria SB, Lawrason J|title=Altered mental status, an unusual manifestation of early disseminated Lyme disease: A case report|journal=|volume=1|issue=1|pages=62|year=2007|pmid=17688693|doi=10.1186/1752-1947-1-62}}</ref>
+**[[Altered mental status]]<ref>{{cite journal|author=Chabria SB, Lawrason J|title=Altered mental status, an unusual manifestation of early disseminated Lyme disease: A case report|journal=|volume=1|issue=1|pages=62|year=2007|pmid=17688693|doi=10.1186/1752-1947-1-62}}</ref>
-**Pseudotumor cerebri
+**[[Pseudotumor cerebri]]
-**Myelitis
+**[[Myelitis]]
-**Chorea
+**[[Chorea]]
-**Cerebellar ataxia
+**[[Cerebellar ataxia]]
-**The triad of neurologic manifestation of Lyme disease includes meningitis, cranial neuritis, and radiculoneuritis.
+*[[Cardiac]] manifestations
-*Cardiac manifestations
+**[[Palpitation|Palpitations]]
-**Palpitations
+**[[Atrioventricular block|Atrio-ventricular block]]
-**Atrio-ventricular block
+**[[Myopericarditis]]
-**Myopericarditis
+**[[Sudden cardiac death]]
-**Sudden cardiac death
+**Chronic [[cardiomyopathy]]
-**Chronic cardiomyopathy
+*[[Dermatological]] manifestations<ref name="pmid15358567">{{cite journal| author=Mullegger RR| title=Dermatological manifestations of Lyme borreliosis. | journal=Eur J Dermatol | year= 2004 | volume= 14 | issue= 5 | pages= 296-309 | pmid=15358567 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15358567  }} </ref>
-*Dermatological manifestations<ref name="pmid15358567">{{cite journal| author=Mullegger RR| title=Dermatological manifestations of Lyme borreliosis. | journal=Eur J Dermatol | year= 2004 | volume= 14 | issue= 5 | pages= 296-309 | pmid=15358567 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15358567  }} </ref>
+**Borrelial lymphocytoma: Most common site is [[earlobe]].
-**Borrelial lymphocytoma
+*[[Ocular]] manifestations<ref name="pmid14630446">{{cite journal| author=Stanek G, Strle F| title=Lyme borreliosis. | journal=Lancet | year= 2003 | volume= 362 | issue= 9396 | pages= 1639-47 | pmid=14630446 | doi=10.1016/S0140-6736(03)14798-8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14630446  }}</ref>
-*Ocular manifestations
+**Primary [[ocular]] symptoms occurs due to [[inflammation]] of [[ocular]] tissue. These symptoms includes [[conjunctivitis]], [[keratitis]], [[iridocyclitis]], [[retinal]] [[vasculitis]], chorioiditis, and [[optic neuropathy]] (extremely rarely [[episcleritis]], panuveitis, panophthalmitis)
+*Secondary [[ocular]] symptoms occurs due to extraocular manifestations. These symptoms includes [[Cranial nerve palsies|pareses of cranial nerves]] and [[Orbit (anatomy)|orbital]] [[myositis]].
 ===Stage 3 - Late disseminated disease===
@@ Line 70: / Line 72: @@
 *Lyme arthritis is dominant months later but chronic neurologic involvement becomes more obvious years later.
 * The symptoms of late disseminated lyme disease includes:
-**Musculoskeletal manifestation:
+**[[Musculoskeletal]] manifestation:
 ***Lyme arthritis
-****Lyme arthritis is the hallmark of stage 3 Lyme disease.
+****Lyme arthritis is the hallmark of stage 3 [[Lyme disease]].
-****Commonly affects knee joint
+****Most frequently presented symptom in late disseminated [[Lyme disease]].
-**Neurological manifestations:
+****Commonly affects [[Knee|knee joint]].
-***These neurological symptoms may take months to years to manifest after the infection. In addition to acute symptoms, Neuroborrerliosis can be manifested by a wide-range of neurological disorders, either [[Central nervous system|central]] or [[Peripheral nervous system|peripheral]] including:
+**[[Neurology|Neurological]] manifestations:
-**** Encephalopathy(sub-acute): Affects  memory, mood, sleep, and sometimes with subtle language disturbances.
+***These [[neurological]] symptoms may take months to years to manifest after the [[infection]]. In addition to acute symptoms, Neuroborrerliosis can be manifested by a wide-range of [[Neurology|neurological]] disorders, either [[Central nervous system|central]] or [[Peripheral nervous system|peripheral]] including:
-**** Polyneuropathy or  [[Paresthesia]]
+**** [[Encephalopathy]] (sub-acute): Affects  [[memory]], [[Mood (psychology)|mood]], [[sleep]], and sometimes with subtle [[language]] disturbances.
+**** [[Polyneuropathy]] or  [[Paresthesia]]
 **** Leukoencephalitis<ref name="pmid192279822">{{cite journal|year=1991|title=Central nervous system abnormalities in Lyme neuroborreliosis.|url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1922798|journal=Neurology|volume=41|issue=10|pages=1571-82|doi=|pmc=|pmid=1922798|author=Halperin JJ, Volkman DJ, Wu P}}</ref>
 **** [[Fasciculation|Muscle twitching]]
-**** [[Otolaryngology|Otolaryngologic]] manifestations: Neck pain, odynophagia, head and neck dysesthesia, otalgia, tinnitus, hearing loss, vertigo, temporomandibular pain, lymphadenopathy, dysgeusia.<ref>{{cite journal|year=1988|title=Borrelia infection and vertigo|journal=Acta Otolaryngol.|volume=106|issue=1-2|pages=111-6|pmid=3421091|author=Rosenhall U, Hanner P, Kaijser B}}</ref><ref>{{cite journal|author=Moscatello AL, Worden DL, Nadelman RB, Wormser G, Lucente F|title=Otolaryngologic aspects of Lyme disease|journal=Laryngoscope|volume=101|issue=6 Pt 1|pages=592-5|year=1991|pmid=2041438}}</ref>
+**** [[Otolaryngology|Otolaryngologic]] manifestations: [[Neck pain]], [[odynophagia]], head and neck [[dysesthesia]], [[otalgia]], [[tinnitus]], [[hearing loss]], [[vertigo]], [[temporomandibular joint pain]], [[lymphadenopathy]], [[dysgeusia]].<ref>{{cite journal|year=1988|title=Borrelia infection and vertigo|journal=Acta Otolaryngol.|volume=106|issue=1-2|pages=111-6|pmid=3421091|author=Rosenhall U, Hanner P, Kaijser B}}</ref><ref>{{cite journal|author=Moscatello AL, Worden DL, Nadelman RB, Wormser G, Lucente F|title=Otolaryngologic aspects of Lyme disease|journal=Laryngoscope|volume=101|issue=6 Pt 1|pages=592-5|year=1991|pmid=2041438}}</ref>
 ***[[Neuropsychiatric]] symptoms often develop much later in the disease progression, much like tertiary [[neurosyphilis]].<ref name="LogigianKaplan1990">{{cite journal|last1=Logigian|first1=Eric L.|last2=Kaplan|first2=Richard F.|last3=Steere|first3=Allen C.|title=Chronic Neurologic Manifestations of Lyme Disease|journal=New England Journal of Medicine|volume=323|issue=21|year=1990|pages=1438–1444|issn=0028-4793|doi=10.1056/NEJM199011223232102}}</ref>
 *** In rare cases, frank [[psychosis]] have been attributed to chronic [[Lyme disease]] effects, including misdiagnoses of [[schizophrenia]] and [[bipolar disorder]].
-*** [[Panic attack]] and [[anxiety]] can occur, also [[delusional]] [[behavior]], including somataform [[delusions]], sometimes accompanied by a [[depersonalization]] or [[derealization]] syndrome similar to what was seen in the past in the prodromal or early stages of general paresis.<ref>{{cite journal|year=1994|title=Lyme disease: a neuropsychiatric illness|journal=The American journal of psychiatry|volume=151|issue=11|pages=1571-83|pmid=7943444|author=Fallon BA, Nields JA}}{{cite journal|author=Hess A, Buchmann J, Zettl UK, ''et al''|title=Borrelia burgdorferi central nervous system infection presenting as an organic schizophrenialike disorder|journal=Biol. Psychiatry|volume=45|issue=6|pages=795|year=1999|pmid=10188012}})</ref>
+*** [[Panic attack]] and [[anxiety]] can occur, also [[delusional]] [[behavior]], including somatoform [[delusions]], sometimes accompanied by a [[depersonalization]] or [[derealization]] syndrome similar to what was seen in the past in the prodromal or early stages of general paresis.<ref>{{cite journal|year=1994|title=Lyme disease: a neuropsychiatric illness|journal=The American journal of psychiatry|volume=151|issue=11|pages=1571-83|pmid=7943444|author=Fallon BA, Nields JA}}{{cite journal|author=Hess A, Buchmann J, Zettl UK, ''et al''|title=Borrelia burgdorferi central nervous system infection presenting as an organic schizophrenialike disorder|journal=Biol. Psychiatry|volume=45|issue=6|pages=795|year=1999|pmid=10188012}})</ref>
 **Dermatological manifestation<ref name="pmid15358567">{{cite journal| author=Mullegger RR| title=Dermatological manifestations of Lyme borreliosis. | journal=Eur J Dermatol | year= 2004 | volume= 14 | issue= 5 | pages= 296-309 | pmid=15358567 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15358567  }} </ref>
 ***Acrodermatitis chronica atrophicans
@@ Line 137: / Line 140: @@
 ==Lyme Carditis==
-*Cardiac involvement occurs in about 5—10% of untreated Lyme disease and patients usually have symptoms related to fluctuating degrees of [[atrioventricular block]] ([[First degree AV block|first-degree block]] to [[complete heart block]]) including [[lightheadedness]], [[palpitations]], [[shortness of breath]], [[chest pain]], and [[syncope]].<ref>{{cite journal|doi=10.7326/0003-4819-157-3-20120807-01002}}</ref>
+*[[Cardiac]] involvement occurs in about 5—10% of untreated [[Lyme disease]] and patients usually have symptoms related to fluctuating degrees of [[atrioventricular block]] ([[First degree AV block|first-degree block]] to [[complete heart block]]) including [[lightheadedness]], [[palpitations]], [[shortness of breath]], [[chest pain]], and [[syncope]].<ref>{{cite journal|doi=10.7326/0003-4819-157-3-20120807-01002}}</ref>
 *Less commonly, patients may present with an acute picture of [[left ventricular dysfunction]], [[cardiomegaly]], [[perimyocarditis]], or pancarditis without noticeable [[cardiac murmurs]].<ref name="Steere-1989">{{Cite journal  | last1 = Steere | first1 = AC. | title = Lyme disease. | journal = N Engl J Med | volume = 321 | issue = 9 | pages = 586-96 | month = Aug | year = 1989 | doi = 10.1056/NEJM198908313210906 |PMID = 2668764 }}</ref>
-*Lyme [[carditis]] can occur independently, it is usually accompanied by other [[cutaneous]], [[joint]], or neurologic features of Lyme disease.<ref name="Fish-2008">{{Cite journal  | last1 = Fish | first1 = AE. | last2 = Pride | first2 = YB. | last3 = Pinto | first3 = DS. | title = Lyme carditis. | journal = Infect Dis Clin North Am | volume = 22 | issue = 2 | pages = 275-88, vi | month = Jun | year = 2008 | doi = 10.1016/j.idc.2007.12.008 | PMID = 18452801 }}</ref>
+*Lyme [[carditis]] can occur independently, it is usually accompanied by other [[cutaneous]], [[joint]], or [[Neurology|neurologic]] features of [[Lyme disease]].<ref name="Fish-2008">{{Cite journal  | last1 = Fish | first1 = AE. | last2 = Pride | first2 = YB. | last3 = Pinto | first3 = DS. | title = Lyme carditis. | journal = Infect Dis Clin North Am | volume = 22 | issue = 2 | pages = 275-88, vi | month = Jun | year = 2008 | doi = 10.1016/j.idc.2007.12.008 | PMID = 18452801 }}</ref>
 ==Manifestations of Lyme Disease by Stage==
@@ Line 147: / Line 150: @@
 | style="background:LightSlateGray; width:15%;" | '''System''' || style="background: #efefef; width:25%;" | '''Stage 1 (Localized Infection)''' || style="background: #efefef; width:25%;" | '''Stage 2 (Early Disseminated Infection)''' || style="background: #ffdead; width:35%" | '''Stage 3 (Late Persistent Infection)'''
 |-
-| ''Skin'' || valign="top" | ▸ [[Erythema migrans]] || valign="top" | ▸ Secondary annular lesions <BR> ▸ [[Malar rash]] <BR> ▸ Diffuse [[erythema]] or [[urticaria]] <BR> ▸ Evanescent lesions <BR> ▸ Lymphocytoma || valign="top" | ▸ [[Acrodermatitis chronica atrophicans]] <BR> ▸ Localized [[scleroderma]]-like lesions
+| ''Skin'' || valign="top" |
+* [[Erythema migrans]]
+| valign="top" |
+* Secondary annular lesions
+* [[Malar rash]]
+* Diffuse [[erythema]] or [[urticaria]]
+* Evanescent lesions
+* Lymphocytoma
+| valign="top" |
+* [[Acrodermatitis chronica atrophicans]]
+* Localized [[scleroderma]]-like lesions
 |-
-| ''Musculoskeletal'' || — || valign="top" | ▸ Migratory [[arthralgia]] <BR> ▸ Brief [[arthritis]] attacks <BR> ▸ [[Myositis]] <BR> ▸ [[Osteomyelitis]] <BR> ▸ [[Panniculitis]]|| valign="top" | ▸ Prolonged [[arthritis]] attacks <BR> ▸ Chronic [[arthritis]] <BR> ▸ Peripheral [[enthesopathy]] <BR> ▸ [[Periostitis]] or joint subluxations below acrodermatitis
+|
+* ''Musculoskeletal''
+|
+* —
+| valign="top" |
+* Migratory [[arthralgia]]
+* Brief [[arthritis]] attacks
+* [[Myositis]]
+* [[Osteomyelitis]]
+* [[Panniculitis]]
+| valign="top" |
+* Prolonged [[arthritis]] attacks
+* Chronic [[arthritis]]
+* Peripheral [[enthesopathy]]
+* [[Periostitis]] or joint subluxations below acrodermatitis
 |-
-| ''Neurologic'' || — || valign="top" | ▸ [[Meningitis]] <BR> ▸ Cranial [[neuritis]] or [[Bell's palsy]] <BR> ▸ Motor or sensory radiculoneuritis <BR> ▸ [[Encephalitis]] <BR>▸ [[Mononeuritis multiplex]] <BR> ▸ [[Pseudotumor cerebri]] <BR> ▸ [[Myelitis]] <BR> ▸ [[Chorea]] <BR> ▸ [[Cerebellar ataxia]] || valign="top" | ▸ Chronic [[encephalomyelitis]] <BR> ▸ Spastic parapareses <BR> ▸ [[Ataxic gait]] <BR> ▸ Mental disorders <BR> ▸ Chronic axonal polyradiculopathy <BR> ▸ [[Dementia]]
+| ''Neurologic'' || — || valign="top" |
+* [[Meningitis]]
+* Cranial [[neuritis]] or [[Bell's palsy]]
+* Motor or sensory radiculoneuritis
+* [[Encephalitis]]
+* [[Mononeuritis multiplex]]
+* [[Pseudotumor cerebri]]
+* [[Myelitis]]
+* [[Chorea]]
+* [[Cerebellar ataxia]]
+| valign="top" |
+* Chronic [[encephalomyelitis]]
+* Spastic parapareses
+* [[Ataxic gait]]
+* Mental disorders
+* Chronic axonal polyradiculopathy
+* [[Dementia]]
 |-
-| ''Lymphatic'' || valign="top" | ▸ Regional [[lymphadenopathy]] || valign="top" | ▸ Regional or generalized [[lymphadenopathy]] <BR> ▸ [[Splenomegaly]] || —
+| ''Lymphatic'' || valign="top" |
+* Regional [[lymphadenopathy]]
+| valign="top" |
+* Regional or generalized [[lymphadenopathy]]
+* [[Splenomegaly]]
+| —
 |-
-| ''Heart'' || — || valign="top" | ▸ [[Atrioventricular block]] <BR> ▸ [[Myopericarditis]] <BR> ▸ Pancarditis || —
+| ''Heart'' || — || valign="top" |
+* [[Atrioventricular block]]
+* [[Myopericarditis]]
+* Pancarditis
+| —
 |-
-| ''Eyes'' || — || valign="top" | ▸ [[Conjunctivitis]] <BR> ▸ [[Iritis]] <BR> ▸ [[Choroiditis]] <BR> ▸ Retinal hemorrhage or [[retinal detachment]] <BR> ▸ Panophthalmitis|| valign="top" | ▸ [[Keratitis]]
+| ''Eyes'' || — || valign="top" |
+* [[Conjunctivitis]]
+* [[Iritis]]
+* [[Choroiditis]]
+* Retinal hemorrhage or [[retinal detachment]]
+* Panophthalmitis
+| valign="top" |
+* [[Keratitis]]
 |-
-| ''Liver'' || — || ▸ Mild or recurrent [[hepatitis]] || —
+|
+* ''Liver''
+|
+* —
+|
+* Mild or recurrent [[hepatitis]]
+| —
 |-
-| ''Respiratory'' || — || valign="top" | ▸ Nonexudative [[sore throat]] <BR> ▸ Nonproductive [[cough]] <BR> ▸ [[Adult respiratory distress syndrome]] || —
+| ''Respiratory'' || — || valign="top" |
+* Nonexudative [[sore throat]]
+* Nonproductive [[cough]]
+* [[Adult respiratory distress syndrome]]
+| —
 |-
-| ''Kidney'' || — || valign="top" | ▸ Microscopic [[hematuria]] or [[proteinuria]] || —
+| ''Kidney'' || — || valign="top" |
+* Microscopic [[hematuria]] or [[proteinuria]]
+| —
 |-
-| ''Genitourinary'' || — || ▸ [[Orchitis]] || —
+| ''Genitourinary'' || — ||
+* [[Orchitis]]
+| —
 |-
-| ''Constitutional systems'' || ▸ Minor || ▸ Severe [[malaise]] and [[fatigue]] || ▸ [[Fatigue]]
+| ''Constitutional systems'' ||
+* [[Fatigue]]
+* [[Arthralgia]]
+* [[Myalgia]]
+* [[Headache]]
+* [[Fever]] and/or [[chills]]
+* [[Stiff neck]]
+* [[Anorexia]]
+|
+* Severe [[malaise]] and [[fatigue]]
+|
+* [[Fatigue]]
 |}
 <SMALL><span style="align=center">''Adapted from Steere AC. Lyme disease. N Engl J Med. 1989;321:586.''</span></SMALL>