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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. Symptoms include "bulls-eye" rash, with accompanying fever, malaise, and musculoskeletal pain (arthralgia or myalgia). 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. Asymptomatic infection exists, but is uncommon.
• 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.

1. Early localized disease
2. Early disseminated disease
3. Late disseminated disease

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.
  • EM egins 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:
  • Fatigue
  • Arthralgia
  • Myalgia
  • Headache
  • Fever and/or chills
  • Stiff neck
  • Anorexia

Early disseminate disease

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

• Neurological symptoms:
  • Lymphocytic meningitis (most common neurological symptom)
  • Cranial neuropathies(particularly facial nerve palsy)
  • Painful radiculitis
  • Mononeuritis multiplex
  • Altered mental status
  • Pseudotumor cerebri
  • Myelitis
  • Chorea
  • Cerebellar ataxia
  • The triad of neurologic manifestation of Lyme disease includes meningitis, cranial neuritis, and radiculoneuritis.
• Cardiac manifestations
  • Palpitations
  • Atrio-ventricular block
  • Myopericarditis
  • Sudden cardiac death
  • Chronic cardiomyopathy
• Dermatological manifestations
  • Borrelial lymphocytoma
• Ocular manifestations

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:
  • Arthritis
    • Commonly affects knee joint

• • Neurological: These neurological symptoms may take months to years to manifest after the infection. Neuropsychiatric symptoms often develop much later in the disease progression, much like tertiary neurosyphilis.
    • Sub-acute encephalopathy: Affects memory, mood, sleep, and sometimes with subtle language disturbances.
    • Polyneuropathy
    • Leukoencephalitis
  • Dermatological manifestation
• Acrodermatitis chronica atrophicans

Symptoms differentiated on the basis of frequency 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 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

Chronic Disease

• Untreated or persistent cases may progress to a chronic form most commonly characterized by meningoencephalitis
• Cardiac inflammation (myocarditis)
• Frank arthritis
• It should be noted, however, that chronic Lyme disease can have a multitude of symptoms affecting numerous physiological systems.
• The symptoms appear heterogeneous in the affected population, which may be due to innate immunity or variations in Borrelia bacteria.
• Late symptoms of Lyme disease can appear months or years after initial infection and often progress in cumulative fashion over time.
• Neuropsychiatric symptoms often develop much later in the disease progression, much like tertiary neurosyphilis.

Chronic neurological disorders

• In addition to the acute symptoms, chronic Lyme disease can be manifested by a wide-range of neurological disorders, either central or peripheral including:
  • Encephalitis or Encephalomyelitis
  • Muscle twitching
  • Polyneuropathy or Paresthesia
  • Vestibular symptoms
  • Otolaryngologic
• Neuropsychiatric disturbances can occur (possibly from a low-level encephalitis), which may lead to symptoms of memory loss, sleep disturbances, or changes in mood or affect.
• 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.

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.
• Less commonly, patients may present with an acute picture of left ventricular dysfunction, cardiomegaly, perimyocarditis, or pancarditis without noticeable cardiac murmurs.
• Lyme carditis can occur independently, it is usually accompanied by other cutaneous, joint, or neurologic features of Lyme disease.

Manifestations of Lyme Disease by Stage

Manifestations of Lyme Disease by Stage

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	▸ Minor	▸ Severe malaise and fatigue	▸ Fatigue

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

References

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