The clinical manifestations are divided into early and late stages. Early infection may be localized or disseminated. Early localized disease develops 7 to 14 days after a tick bite as the site forms an erythematous papule that expands to form a red, raised border, often with central clearing. The lesion, erythema migrans, harbors B. burgdorferi and may be 15 cm wide, pruritic, or painful. Systemic manifestations may include malaise, lethargy, fever, headache, arthralgias, stiff neck, myalgias, and lymphadenopathy. The skin lesions and early manifestations resolve without treatment over 2 to 4 weeks. Not all patients with Lyme disease recall a tick bite or develop erythema migrans.
Approximately 20% of patients develop early disseminated disease with multiple secondary skin lesions, aseptic meningitis, pseudotumor, papilledema, cranioneuropathies including Bell palsy, polyradiculitis, peripheral neuropathy, mononeuritis multiplex, or transverse myelitis. Carditis with various degrees of heart block rarely may develop during this stage. Neurologic manifestations usually resolve by 3 months but may recur or become chronic.
Late disease begins weeks to months after infection. Arthritis is the usual manifestation and may develop in 50% to 60% of untreated patients. The male to female ratio is 7:1. The knee is involved in greater than 90% of cases, but any joint may be affected. Symptoms may resolve over 1 to 2 weeks but often recur in other joints. If untreated most cases resolve, but chronic erosive arthritis persists in 10% of patients as the episodes increase in duration and severity. Cardiac abnormalities occur in approximately 10% of untreated patients. Neuroborreliosis, the late manifestations of Lyme disease involving the central nervous system (CNS), is rarely reported in children.
Antibody tests during early, localized Lyme disease may be negative and are not useful. The diagnosis of late disease is confirmed by serologic tests specific for B. burgdorferi. Thesensitivity and specificity of serologic tests for Lyme disease vary substantially. A positive enzyme-linked immunosorbent assay or immunofluorescence assay result must be confirmed by immunoblot showing antibodies against at least either two to three (for IgM) or five (for IgG) proteins of B. burgdorferi(at least one of which is one of the more specific, low-molecular-weight, outer-surface proteins).
In late disease, the erythrocyte sedimentation rate is elevated and complement may be reduced. The joint fluid shows an inflammatory response with total white blood cell count of 25,000 to 125,000 cells/mm3, often with a polymorphonuclear predominance (see Table 118-2). The rheumatoid factor and antinuclear antibody are negative, but the Venereal Disease Research Laboratory test may be falsely positive. With CNS involvement, the cerebrospinal fluid shows a lymphocytic pleocytosis with normal glucose and slightly elevated protein.
A history of a tick bite and the classic rash is helpful but is not always present. Erythema migrans of early, localized disease may be confused with nummular eczema, tinea corporis, granuloma annulare, an insect bite, or cellulitis. Southern tick-associated rash illness, which is similar to erythema migrans, occurs in southeastern and south central states and is associated with the bite of Amblyomma americanum, the lone star tick, and infection with Borrelia lonestari.