Jarisch-Herxheimer reaction in complement-depleted rabbits. Histological and immunofluorescence studies of early cutaneous lesions.

Abstract

SUMMARYThe possible role of complement in the pathogenesis of the Jarisch-Herxheimer reaction was assessed in cutaneous syphilitic lesions in two groups of rabbits treated with penicillin; in one group complement was depleted before penicillin therapy. Serial biopsy specimens were similar histologically in both groups. The activation of the complement pathways did not seem to play a role in the pathogenesis of early cutaneous syphilitic lesions in rabbits during the Jarisch-Herxheimer reaction.

Fulminant proliferative vitreoretinopathy in syphilitic uveitis

“…3 ), which may underlie the rapid fibroglial proliferation seen in our cases. This pattern is consistent with that seen in the histopathology of Jarisch-Herxheimer reaction following antibiotic therapy [ 13 ]. It is likely that such intraocular inflammation in our cases may have served as a trigger for PVR.…”

Pathophysiology and Immunology of the Jarisch-Herxheimer-Like Reaction in Louse-Borne Relapsing Fever: Comparison of Tetracycline and Slow-Release Penicillin

“…Borrelia turicatae from the blood as effectively as normal controls [30]. In the rabbit model of the Jarisch-Herxheimer-like reaction of early syphilis, histologic appearances of the cutaneous lesions were identical in controls and in animals depleted of complement before penicillin treatment [31]. Taken together, these findings in human and animal spirochetal infections strongly deny a role for complement activation in the pathogenesis of the Jarisch-Herxheimer-like reaction.…”

Delayed Onset of the Jarisch–Herxheimer Reaction in Doxycycline-Treated Disease

“…The detection of spirochetes by immunohistochemistry and B. burgdorferi DNA by polymerase chain reaction in lesional EM skin supports this contention that she experienced delayed and attenuated JHR. [14][15][16] This histopathologic pattern is considered to be the most specific finding for JHR rather than any clinical and/or laboratory finding 10 ( Table 2). Epidermis was spared* Pinkus 7 Syphilis Marked cellular dermal infiltration, congested vessels, and edema of the epidermis (ie, spongiotic dermatitis) Frieboes 8 Syphilis Dermal vascular congestion, edema, and infiltration by neutrophils † Lloyd 9 Syphilis Increased intensity of inflammatory changes with congestion, edema, and infiltration by lymphocytes and plasma cells* Sheldon and Heyman 10 1-, 2-, and 3-degree syphilis Histology similar for all stages of syphilis From 5 to 18 hr after Rx a transient acute inflammatory response characterized by vascular congestion, followed by edema, diapedesis of neutrophils, dermal neutrophilic infiltration, then clearing of neutrophils in ,24 hr † 3-degree syphilis had suppurative granulomas No eosinophils, vasculitis, thrombosis or spirochetes observed Rosen et al 11 2-degree syphilis Edema with sub-or intra-epidermal vesiculation, congestion of capillaries and veins, and endothelial cell swelling accompanied by infiltration of dermis by neutrophils, lymphocytes, and plasma cells* Chung et al 12 3-degree syphilis (gumma) Dense dermal, lichenoid, and nodular infiltrates composed of lymphocytes, macrophages, multinucleated cells, and plasma cells with granulomas † Singh and Jalpota 13 1-and 2-degree latent syphilis Edema, vascular congestion, and diapedesis of inflammatory cells into lesional tissue, neutrophils, and lymphocytes* Rabbit model [14][15][16] 1-degree syphilis Histology similar to human JHR 10 Vascular congestion, followed by edema, diapedesis of neutrophils, dermal neutrophilic infiltration, then clearing of inflammatory cells from 4 to 18 hr after antibiotic Rx or administration of immune serum † hypersensitivity (type 4 Gell and Coomb reaction), which occurs days rather than hours after antigen exposure.…”

“…1,2,14,27 The most accepted theory is that antibiotic treatment causes a discharge of endotoxins or endotoxin-like material from injured or dead sphirochetes. 1,2,14,27 The most accepted theory is that antibiotic treatment causes a discharge of endotoxins or endotoxin-like material from injured or dead sphirochetes.…”

“…1,3 In addition, a growing number of case reports and small series exist of JHR occurring in variety of other bacterial, fungal, protozoal, and parasitic infections such as tularemia, pneumocystosis, malaria, and strongyloidosis, highlighting that JHR is not organism specific but related to unique host-infectious agent interactions and/or organism load. [14][15][16] Herein, we report the clinicopathologic findings of a woman with EM, who experienced a delayed and attenuated JHR during doxycycline therapy and discuss the pathogenesis of this phenomenon. 2 For treated Lyme disease, the frequency of JHR averages around 15%, varying in North America from 12% to 18% and in Europe, from 1% to 21%.…”