Adverse Antibiotic-Induced Eruptions Associated With Epstein Barr Virus Infection and Showing Kikuchi-Fujimoto Disease-Like Histology

Abstract

The antibiotic-induced eruption of infectious mononucleosis is a well-known clinical phenomenon. Latent viral infection with herpesviridae (eg, human herpes virus 6 (HHV-6) and Epstein-Barr virus (EBV)) is suspected to play a role in the drug hypersensitivity syndrome. The cutaneous pathologic findings have not been reported in the former, and are infrequently reported in the latter entity. Herein, we describe the biopsy findings of a cefprozil-induced rash in infectious mononucleosis and a minocycline-associated drug hypersensitivity syndrome. Biopsy of these exanthematous eruptions revealed an acute vacuolar interface superficial and deep perivascular and interstitial lymphocytic dermatitis. CD8(+) lymphocytes predominated and were associated with non-neutrophilic nuclear (karyorrhectic) debris and numerous small CD68(+) and CD123(+) monocytes. These aforementioned features have been described in cutaneous lesions of Kikuchi-Fujimoto disease, an entity whose clinicopathologic findings overlap with both infectious mononucleosis and lupus erythematosus. Serologic evidence of active and chronic active EBV infection was found in both patients, respectively. No evidence of EBV or HHV6 was found in the cutaneous lesions. Plasmacytoid monocytes (CD68(+)/CD123(+) cells), which produce type I interferon, are believed to play a role in viral immunity by protecting other cells from viral infections and promoting survival of antigen-activated T cells. Their presence in these two putative examples of viral-drug immune dysregulation could be a clue to pathogenesis and represent a common cellular component of some adverse cutaneous drug eruptions.

The Link between Hypersensitivity Syndrome Reaction Development and Human Herpes Virus-6 Reactivation

“…The presence of HHV-6 was not assessed in this study [82]. HHV-6 reactivation was observed in two patients with sulfasalazine severe hypersensitivity [83].…”

Epstein–Barr Virus in Cutaneous Pathology

“…80,90,91 The rash usually remits and is not associated with recurrence, even with subsequent administration of the same antibiotic on other occasions (unless the patient shows hypersensitivity to the drug or atopic symptoms). 93 Carlson et al 94 reported an adverse drug reaction in 2 patients with EBV infection (one with IM and the other with chronic active EBV) in which the morphologic changes were similar to the ones observed in cutaneous involvement by the Kikuchi disease (KD). Rarer accompanying manifestations are edema of the lips and eyelids, diarrhea, or arthralgias.…”

Plasmacytoid (CD68+CD123+) Monocytes May Play a Crucial Role in the Pathogenesis of Hydroa Vacciniforme: A Case Report

“…Similar, but less extensive deposition of nuclear debris associated with PM has been described in adverse antibiotic eruptions occurring during acute and latent EBV infection. 19 In this latter scenario, the antibiotic is believed to act as an antigen stimulating T-lymphocyte proliferation that secondarily potentiates active or triggers transition from latent to active EBV infection.…”