title: Delayed onset of the Jarisch-Herxheimer reaction in doxycycline-treated disease: a case report and review of its histopathology and implications for pathogenesis.
abstract: The Jarisch-Herxheimer reaction (JHR) is a transient inflammatory syndrome triggered hours after the start of antibiotic treatment of spirochete infections, namely syphilis. Clinically, JHR manifests as an abrupt onset of constitutional symptoms and exacerbation of cutaneous lesions that resolve without intervention. JHR's pathogenesis is unclear and it is histopathologically rarely reported. Herein, the authors report a 47-year-old woman, with solitary erythema migrans and positive Lyme disease serology, who presented for medical care 14 days after commencement of doxycycline therapy. She complained of malaise, facial flushing, gingival erythema, and acquisition of additional plaques characterized by swelling, increased erythema, pruritus, and exfoliative scale. Punch biopsies demonstrated subacute to chronic spongiotic psoriasiform reaction patterns with a superficial lymphocytic infiltrate. By Borrelia-specific immunohistochemistry, spirochetes were found in the deep dermis, unassociated with inflammation, and focally in the upper spinous layer, associated with spongiosis. Borrelia burgdorferi DNA was detected by nested polymerase chain reaction. Doxycycline was discontinued, and symptoms and signs resolved within a few days. Liberation of endotoxin-like materials (eg, lipoproteins) from degenerating spirochetes and concomitant cytokine production is the suspected cause of JHR and supported by the finding of lesional spirochetes. Alternatively, a reversal reaction with a delayed-type hypersensitivity reaction is also a plausible cause based on spirochetes found in the lymphocytic spongiotic dermatitis.
authors.affiliation: *Department of Pathology, Divisions of Dermatology and Dermatopathology, Albany Medical College, Albany, NY; †Upper Hudson Valley Dermatology, Castleton, NY; and ‡Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Pooja
authors.initials: P
authors.lastname: Kadam
authors.forename: Neal A
authors.initials: NA
authors.lastname: Gregory
authors.forename: Bernhard
authors.initials: B
authors.lastname: Zelger
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Carlson
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D004318:Doxycycline / Q000009:adverse effects*; D003875:Drug Eruptions / Q000209:etiology* / Q000473:pathology*; D015787:Erythema Chronicum Migrans / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008875:Middle Aged
chemical_list: D000900:Anti-Bacterial Agents; D004318:Doxycycline