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Delayed Onset of the Jarisch–Herxheimer Reaction in Doxycycline-Treated Disease: A Case Report and Review of its Histopathology and Implications for Pathogenesis

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By P. Kadam  et al.


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.
Source: Kadam P, Gregory NA, Zelger B, Carlson JA. Delayed Onset of the Jarisch–Herxheimer Reaction in Doxycycline-Treated Disease:  A Case Report and Review of its Histopathology and Implications for Pathogenesis. American Journal of Dermatopathology. 2015 Jun;37(6):e68-74. 

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