by Brian Schwartz, M.D., M.S.
The classic presentation of early Lyme disease is the appearance of a characteristic rash, termed erythema migrans (previously named erythema chronicum migrans). This rash begins as a small red papule at the site of a tick bite, generally 3-30 days after a tick bite of sufficient duration to transmit the bacteria, but most patients (68-86%) do not recall a tick bite at the site. Over several days to weeks, it can grow in size, with red expanding borders and often a clearing center. Several concentric rings of redness may appear, resembling a target. The rash can grow to over 20 cm in diameter, and the specificity of this sign for the diagnosis of Lyme disease is probably improved with increasing diameter of the rash (a minimum diameter of 5 cm is suggested by the Centers for Disease Control for diagnosis). B. burgdorferi can be detected (by culture or polymerase chain reaction) at the leading edge of the rash.
While the vast majority of patients develop a rash (60 to 80%), the classic, target-shaped rash is probably not the most common appearance of this rash, however. Central clearing probably occurs in less than 40% of cases, and solid red rashes are probably most common. Vesicular eruptions have been uncommonly reported, but scaling lesions are not likely to be Lyme disease. Multiple lesions occur in approximately 20% of cases. Up to 80% of patients have associated symptoms. Specific respiratory or gastrointestinal complaints (other than anorexia) are rare and the presence of these symptoms argues against a diagnosis of Lyme disease.
Table 2. Table of Symptoms
(days to weeks after tick bite)
|Erythema migrans probably over 80%|
Flu-like symptoms – %gt;50%
Stiff neck 30-40%
(weeks to months later)
|Meningitis overall central nervous system (CNS) or peripheral nervous system (PNS) involvement in 10-20%|
Cranial neuropathy overall CNS or PNS involvement in 10-20%
Radiculoneuropathy overall CNS or PNS involvement in 10-20%
Atroventricular nodal block overall cardiac involvement in 4-10%
Pericarditis overall cardiac involvement in 4-10%
Myopericarditis overall cardiac involvement in 4-10%
Eye involvement probably uncommon
(months to years later)
|Arthritis up to 60% of untreated patients, most often monoarticular and large joint|
Encephalopathy subtle cognitive dysfunction probably uncommon
Polyneuropathy distal paresthesias or radicular pain probably uncommon
Are all target-shaped rashes from Lyme disease?
It was previously thought that all target-shaped rashes (i.e., circular-shaped with red border and clearing center) were erythema migrans, and that the appearance of this rash was pathognomonic for Lyme disease. There is increasing clinical suspicion that many rashes that patients report as resembling erythema migrans are probably not Lyme disease. Furthermore, as discussed above, most Lyme disease skin rashes are not target-shaped. It appears increasingly likely that immune responses to tick salivary gland antigens and reactions to spider bites can result in rashes that may be mistakenly presumed to be erythema migrans by the patient or the physician.
What is the clinical presentation of the later minifestations of Lyme disease?
Within weeks to months of becoming infected, early disseminated Lyme disease may occur (formerly termed stage 2). Approximately 4-10% of patients in the U.S. develop cardiac manifestations, including conduction defects (e.g., atrioventricular block, complete heart block, bundle branch block, fascicular block), tachyarrhythmias (e.g., atrial due to pericarditis, uncommonly ventricular as an escape rhythm), myopericarditis, and mild myocardial dysfunction. Involvement of the central or peripheral nervous systems may occur in up to 10 to 20% of cases, may be manifested by headache, fatigue, stiff neck, and malaise, and includes such diagnoses as Lyme meningitis, neuroborreliosis, cranial neuropathies (especially facial nerve palsy, which can be bilateral), peripheral neuropathy, radiculitis, myelopathy, or brachial plexopathy. Lyme disease may also involve the eye (e.g., follicular conjunctivitis, keratitis, and rarely uveitis or vitritis). Musculoskeletal manifestations of Lyme disease are very common. During early infection, migratory arthralgias and pain in bursae, tendon, muscle, or bone occur in the majority of patients. Weeks to months later, frank arthritis, most commonly mono- or oligoarticular and involving large joints (most commonly knees, but also shoulders, ankles, elbows, and other sites), may develop. Lyme arthritis is one manifestation of persistent or late Lyme disease (previously termed state 3).
In the United States, approximately 60% of untreated patients will develop intermittent episodes of joint pain and swelling, months to years after the infecting tick bite. The most common presentation is a single involved knee, but both large and small joints may be affected, and usually only one or two joints at a time. Over time, the frequency and severity of attacks can decline, and, on average, the proportion of patients with recurrent attacks declines by 10-20% annually. Approximately 10% of untreated patients may develop chronic arthritis, defined as one year or more of continuous joint inflammation. Lyme arthritis patients have evidence of prominent cellular and humoral immune responses. Some patients with Lyme arthritis have no resolution of symptoms even after long-term antibiotic therapy, and have been termed by Steere, et al. as having antibiotic treatment-resistant Lyme arthritis. It is thought that this condition may represent an autoimmune phenomenon. Increasing evidence suggests that certain HLA haplotypes increase the risk of this condition, and that antibodies directed at outer surface protein A (OspA) of the spirochete may cross-react with an adhesion molecule on T lymphocytes that binds with macrophages and endothelial cells. This molecular mimicry may explain the persistence of symptoms after eradication of spirochetes from the joint.