The clinical spectrum of early lyme borreliosis in patients with culture-confirmed erythema migrans

• Published in: The American journal of medicine Vol. 100; no. 5; pp. 502 - 508
• Main Authors: Nadelman, Robert B., Nowakowski, John, Forseter, Gilda, Goldberg, Neil S., Bittker, Susan, Cooper, Denise, Aguero-Rosenfeld, Maria, Wormser, Gary P.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.1996; Elsevier; Elsevier Sequoia S.A
• Subjects: Adolescent; Adult; Aged; Bacteria; Bacterial diseases; Bacteriological Techniques; Biological and medical sciences; Blood - microbiology; Borrelia burgdorferi Group - isolation & purification; Borrelia infections; Enzyme-Linked Immunosorbent Assay; Erythema Chronicum Migrans - diagnosis; Female; Human bacterial diseases; Humans; Infectious diseases; Linear Models; Lyme disease; Lyme Disease - diagnosis; Male; Medical research; Medical sciences; Middle Aged; Polymerase Chain Reaction; Prospective Studies; Time Factors; Tropical bacterial diseases; Infection; Human; Erythema chronicum migrans; Lyme disease; Skin disease; Borrelia infection; Diseases of the osteoarticular system; Bacteriosis; Biological marker; Diagnosis; Spirachaetosis
• ISSN: 0002-9343; 1555-7162
• DOI: 10.1016/S0002-9343(95)99915-9

The diagnosis of erythema migrans (EM), the characteristic rash of early Lyme borreliosis, is based primarily on its clinical appearance since it often occurs prior to the development of a specific antibody response. Other skin disorders, however, may be confused with EM. Between June 1991 and September 1993, a prospective study was conducted at the Lyme Disease Diagnostic Center of the Westchester County Medical Center to isolate Borrelia burgdorferi systematically from patients with EM, and to characterize the clinical manifestations of patients with culture-documented infection. Skin biopsies and/or needle aspirates of the advancing margin of primary lesions, and blood specimens from adult patients were cultured for B burgdorferi in modified Barbour-Stoenner-Kelly medium at 33 °C. B burgdorferi was recovered from 79 patients (49 [62%] males) ranging in age from 16 to 76 years old (mean, 43 ± 14 years old). Maximum EM diameter (mean, 16 ± 10 cm; range, 6–73 cm) was a function of EM duration (mean 6.7 ± 6.4 days; range, 1–39 days)(correlation coefficient = 0.7; P <0.001). Twenty (25%) patients had noted a tick bite at the site of the primary lesion a mean of 10 days (range, 1–27 days) before onset. Multiple EM lesions (range, 2–70) were present in 14 (18%) patients. Systemic symptoms were present at the time of culture in 54 patients (68%) including fatigue (54%), arthralgia (44%), myalgia (44%), headache, (42%), fever and/or chills (39%), stiff neck (35%), and anorexia (26%). Thirty-three patients (42%) had at least one objective finding on physical examination in addition to EM, including 18 (23%) with localized lymphadenopathy, 13 (16%) with fever (T ≥ 37.8 °C), seven (9%) with tender neck flexion, six (8%) with joint tenderness, and 1 each with joint swelling, nuchal rigidity, and facial nerve palsy. No patient had new electrocardiogram evidence of atrioventricular block. Liver function assays were abnormally elevated in 37% of patients. Thirty-four percent of patients were seropositive by enzyme-linked immunosorbent assay at presentation. Most others rapidly seroconverted so that 69 of 78 evaluable patients (88%) were seropositive at some point during the first month after diagnosis. We describe the largest group of culture-positive patients with EM from the United States to date. Although systemic symptoms were present in most patients, objective evidence of advanced disease was uncommon. Our patients with culture-confirmed EM were less sick than those described in the days before culture confirmation was possible. The ability to isolate B burgdorferi from lesional skin of large numbers of patients with EM should make culture-positive patients the standard by which to define manifestations of early Lyme borreliosis associated with this rash. Microbiologic documentation of Lyme borreliosis will help delineate the manifestations of this illness, and should form the framework for research directed at pathophysiology, diagnosis, treatment, and prevention.