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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. 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. 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. Stage 1 - Early localized disease
2. Stage 2 - Early disseminated disease
3. 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. 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: Fatigue Arthralgia Myalgia Headache Fever and/or chills Stiff neck Anorexia

Classic Lyme disease rash 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.
  • 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
• Cardiac manifestations
  • Palpitations
  • Atrio-ventricular block
  • Myopericarditis
  • Sudden cardiac death
  • Chronic cardiomyopathy
• Dermatological manifestations
  • Borrelial lymphocytoma: Most common site is earlobe.
• 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 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
      • Muscle twitching
      • Otolaryngologic manifestations: Neck pain, odynophagia, head and neck dysesthesia, otalgia, tinnitus, hearing loss, vertigo, temporomandibular joint pain, lymphadenopathy, dysgeusia.
    • Neuropsychiatric symptoms often develop much later in the disease progression, much like tertiary neurosyphilis.
    • 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.
  • 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 Acrodermatitis chronica atrophicans 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.
• 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	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

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