Lyme disease history and symptoms

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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 the symptoms are stage specific. Initial symptoms include bullseye rash called erythema migrans, with accompanying flu-like symptoms. Lyme disease can progress to cardiovascular, neurological, dermatological and/or musculoskeletal manifestations. Multiple erythema migrans develops as disease disseminates throughout the body. Most common neurological manifestation includes lymphocytic meningitis and cranial nerve palsies (usually facial nerve palsy). Dermatological manifestation includes borrelial lymphocytoma and acrodermatitis chronica atrophicans appearing in stage 2 and stage 3 Lyme disease respectively. Cardiac manifestation include Lyme carditis. Musculoskeletal manifestation include Lyme arthritis. There is a difference in clinical features of Lyme disease in patients living in different geographical regions depending on the genospecies of Borrelia burgdorferi sensu lato complex causing it.

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 can happen, but is uncommon.
• The specific areas of focus when obtaining patient history are outlined below:
  • Tick bite
  • Vacation, living, or working environment in endemic areas
  • Spending time outdoors (especially in woody or grassy areas)

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 flu-like symptoms. Erythema migrans (EM) also known as erythema chronicum migrans, bullseye 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 bullseye appearance. EM may appear on any area of the body but is usually present on areas including the axilla, inguinal region, popliteal fossa, or along the 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. Flu-like symptoms including: Fatigue Arthralgia Myalgia Headache Fever and/or chills Stiff neck Anorexia

Classic Lyme disease rash - Source: CDC.gov Lyme disease, expanding rash with central clearing - Source: CDC.gov

Stage 2 - Early disseminate disease

Features of early disseminated disease can be divided by organ system and include: Multiple erythema migrans 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

Disseminated Lyme disease, multiple rash - Source: CDC.gov

• 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 occur due to inflammation of ocular tissue. These symptoms include conjunctivitis, keratitis, iridocyclitis, retinal vasculitis, chorioiditis, and optic neuropathy (and, extremely rarely, episcleritis, panuveitis, panophthalmitis).
  • Secondary ocular symptoms occur 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 include:
  • Musculoskeletal manifestations:
    • 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, neuroborreliosis can manifest as 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, and dysgeusia
    • Neuropsychiatric symptoms often develop much later in the disease's progression, much like tertiary neurosyphilis
    • In rare cases, frank psychoses have been attributed to chronic Lyme disease effects, including misdiagnoses of schizophrenia and bipolar disorder
    • Panic attack and anxiety can occur, as well as 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 manifestations:
    • Acrodermatitis chronica atrophicans

Symptoms differentiated on the basis of frequency Common symptoms Less common symptoms Erythema migrans (erythema chronicum migrans) Flu-like symptoms Fatigue Arthralgia Myalgia Headache Fever and/or chills Stiff neck Anorexia Lyme arthritis Neurological manifestations Cardiac manifestations Ocular manifestations Hepatitis

Frequency of Lyme disease symptoms, 2001-2015 - Source: CDC.gov/

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

Erythema Migrans

Erythema migrans (EM), also known as erythema chronicum migrans, bullseye rash, or Lyme rash, develops in around 70% - 80% of patients. EM is the pathognomonic rash of Lyme disease. The majority of patients with the rash do not recall a tick bite. EM begins at the site of a tick bite after a delay of 3 to 30 days (average is about 7 days). EM is classically 5 to 6.8 cm in diameter and appears as an annular homogenous erythema (59%), central erythema (30%), central clearing (9%), or central purpura (2%). 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 bullseye appearance. EM may appear on any area of the body but is usually present in areas including the axilla, inguinal region, or popliteal fossa. The rash does not represent an allergic reaction to the bite, but rather a skin infection with the Lyme bacteria, Borrelia burgdorferi sensu lato. EM resolves in approximately 28 days in untreated patients. The characteristic bullseye rash with central clearing is present in about 20% of endemic cases in the United States, whereas in Europe and the non-endemic United States, 80% of rashes have central clearing. In endemic areas of the United States, homogeneously red rashes are more frequent. Serologic testing is not recommended in patients with EM. Initially, the majority of patients are seronegative. Multiple erythema migrans are present in disseminated disease. Mini erythema migrans: sometimes, erythema migrans may be less than 5 cm in diameter. It is an important and atypical sign of early localized Lyme disease.

Erythema chronicum migrans - Source: Dermatology Atlas. Bulls eye lesion - Source: WIKICOMMONS

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, but it is usually accompanied by other cutaneous, joint, or neurologic features of Lyme disease.

Lyme Arthritis

• Lyme arthritis is the hallmark of stage 3 Lyme disease.
• Lyme arthritis is most frequently presented symptom in late disseminated Lyme disease.
• Lyme arthritis is not necessarily preceded by erythema migrans.
• Lyme arthritis may occur due to hematogenous spread of B. burgdorferi to multiple joints during early infection. This might explain migratory arthralgia during early stages of Lyme disease.
• It usually takes months to years for Lyme disease to progress to Lyme arthritis.
• Lyme arthritis symptoms range from intermittent attacks of monoarthritis/oligoarthritis to persistent arthritis.
• Intermittent attacks of Lyme arthritis range from 3 days to 11.5 months in duration with a mean of 3 months.
• During early years of illness, attacks of Lyme arthritis are more frequent and longer in duration. Both frequency and duration of attacks subsequently decrease.
• There may months or years of complete remission between each attack of Lyme arthritis.
• Most of the time, Lyme arthritis involves large joints. The most commonly affected joint is the knee joint, but any joint can be affected including the shoulder, ankle, elbow, temporomandibular joint, and wrist.
• Tendonitis and/or bursitis may also be present in some patients. Most of the time, joints involved are the shoulder, knee, or elbow.
• Most patients have little/no joint dysfunction after remission of attack. Some patients with persistent arthritis may show erosion and permanent damage to joint.

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	—
Flu-like symptoms 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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