Diagnostic challenges of early Lyme disease: lessons from a community case series

Abstract

Background: Lyme disease, the most common vector-borne infection in North America, is increasingly reported. When the characteristic rash, erythema migrans, is not recognized and treated, delayed manifestations of disseminated infection may occur. The accuracy of diagnosis and treatment of early Lyme disease in the community is unknown.

Methods: A retrospective, consecutive case series of 165 patients presenting for possible early Lyme disease between August 1, 2002 and August 1, 2007 to a community-based Lyme referral practice in Maryland. All patients had acute symptoms of less than or equal to 12 weeks duration. Patients were categorized according to the Centers for Disease Control and Prevention criteria and data were collected on presenting history, physical findings, laboratory serology, prior diagnoses and prior treatments.

Results: The majority (61%) of patients in this case series were diagnosed with early Lyme disease. Of those diagnosed with early Lyme disease, 13% did not present with erythema migrans; of those not presenting with a rash, 54% had been previously misdiagnosed. Among those with a rash, the diagnosis of erythema migrans was initially missed in 23% of patients whose rash was subsequently confirmed. Of all patients previously misdiagnosed, 41% had received initial antibiotics likely to be ineffective against Lyme disease.

Conclusion: For community physicians practicing in high-risk geographic areas, the diagnosis of Lyme disease remains a challenge. Failure to recognize erythema migrans or alternatively, viral-like presentations without a rash, can lead to missed or delayed diagnosis of Lyme disease, ineffective antibiotic treatment, and the potential for late manifestations.

Figure 1

Classification of 165 patients referred for possible acute Lyme disease. * Presenting objective findings include: 2 patients with radiculopathy, 2 with VII nerve palsy, 1 with carditis, 1 with arthritis. ^† Percentages in this row represent proportion of all referred acute patients. ^‡ 2 patients were excluded from this analysis because no confirmatory serology was drawn after antibiotics were initiated.

Figure 2

Atypical EM with previous misdiagnosis and treatment failure. A 26 year old woman was diagnosed with a brown recluse spider bite and treated with oral cephalexin and prednisone for an erythematous lesion with a central eschar (panel A). Ten days later, she has persistent malaise and generalized aches and was seen by one of the authors (JA). She was found to have healing of the primary EM lesion with the appearance of new secondary lesions (panel B). Serology showed ELISA reactivity with positive confirmatory IgM and IgG western blots. Treatment with oral doxycycline resulted in a prompt response and resolution of the lesions and symptoms.

Figure 3

Disseminated cutaneous EM lesions. A 57 year old man was seen by his primary care physician for fever, fatigue, headache, and arthralgia and no specific diagnosis was made. He presented for re-evaluation to one of the authors (JA) four days later, after his wife noticed a rash. On examination, he had multiple target lesions. Serology showed ELISA reactivity with positive confirmatory IgM and IgG western blots. Treatment with oral doxycycline resulted in a prompt response and resolution of the lesions and symptoms.

Figure 4

Typical disseminated EM lesions with VII nerve palsy. An 18 year old man was seen for new VII nerve palsy. A complete physical exam showed multiple lesions consistent with disseminated cutaneous Lyme disease. Serology for Lyme disease showed ELISA and IgM reactivity. Treatment with oral doxycycline resulted in a prompt resolution of the rash, with recovery of the VII nerve palsy over the next several weeks.

Figure 5

Misdiagnosis of flu-like illness with typical, non-bull's eye EM. A 45 year old man was seen for 'flu-like' symptoms and was diagnosed with a viral syndrome. Several days later he presented to one of the authors (JA) for re-evaluation of persistent symptoms. Complete physical exam showed a round, red, non-tender skin lesion over the later aspect of his knee. Serology for Lyme disease was negative on ELISA testing. He was treated with oral doxycycline with prompt resolution of his rash and symptoms.

Figure 6

Classic bull's eye EM with initial misdiagnosis as urinary tract infection. A 78 year old women presented to an urgent care center with 3 days of fever, mild headache and the absence of rhinitis, cough or typical upper respiratory viral symptoms. The physical exam showed a temperature of 102 degrees Fahrenheit and a skin rash was not noted. Urinalysis showed 5–10 WBCs, a diagnosis of pylonephritis was made, and ciprofloxacin was initiated. The patient returned the following day when she noticed a large, red rash on her side. The patient was referred to one of the authors (JA) who confirmed the diagnosis of Lyme disease. Ciprofloxacin was discontinued, doxycycline initiated and the rash resolved. Serology returned with a positive ELISA and confirmatory western blot.