Immunohistopathological Findings of Severe Cutaneous Adverse Drug Reactions

Abstract

Diagnosis of severe cutaneous adverse drug reactions should involve immunohistopathological examination, which gives insight into the pathomechanisms of these disorders. The characteristic histological findings of erythema multiforme (EM), Stevens–Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) provide conclusive evidence demonstrating that SJS/TEN can be distinguished from EM. Established SJS/TEN shows full-thickness, extensive keratinocyte necrosis that develops into subepidermal bullae. Drug-induced hypersensitivity syndrome (DIHS) and exanthema in drug reaction with eosinophilia and systemic symptoms (DRESS) each display a variety of histopathological findings, which may partly correlate with the clinical manifestations. Although the histopathology of DRESS is nonspecific, the association of two or more of the four patterns—eczematous changes, interface dermatitis, acute generalized exanthematous pustulosis- (AGEP-) like patterns, and EM-like patterns—might appear in a single biopsy specimen, suggesting the diagnosis and severe cutaneous manifestations of DRESS. Cutaneous dendritic cells may be involved in the clinical course. AGEP typically shows spongiform superficial epidermal pustules accompanied with edema of the papillary dermis and abundant mixed perivascular infiltrates. Mutations in IL36RN may have a definite effect on pathological similarities between AGEP and generalized pustular psoriasis.

Coupled Plasma Filtration Adsorption for Treatment of Capillary Leak Syndrome Superimposed to Acute Generalized Exanthematous Pustolosis: A Case Report

“…Our patient developed a cutaneous reaction suggestive for hydroxychloroquineinduced AGEP, and the skin biopsy had all the histological hallmarks of the disease confirming the clinical hypothesis ( Fig. 1) [17]. Despite being a severe drug reaction, AGEP is usually a self-limiting condition that typically resolves within 2 weeks after drug discontinuation and steroids administration [6].…”

Severe cutaneous adverse drug reactions: diagnostic approach and genetic study in a Brazilian case series

“…The skin rash biopsy may be helpful because it presents typical findings in the cases of SJS/TEN and AGEP, however it is non-specific in DRESS/DIHS (21). In this study, it was useful in an overlapping phenotype (DRESS/AGEP) in a patient with DRESS criteria.…”

GenotypingHLAalleles to predict the development of Severe cutaneous adverse drug reactions (SCARs): state-of-the-art

“…SJS and TEN cases show histological features of massive epidermal necrosis (including all layers of the epidermis), focal adnexal necrosis, necrotic keratinocytes, mild mononuclear cell dermal infiltrate, and negative direct immunofluorescence test. In DRESS, the histological findings are described as nonspecific lichenoid or eczematous lesions, focal necrotic keratinocytes, dense and diffuse dermal-epidermal infiltrates with lymphocytic exocytosis, dermal edema, and superficial perivascular infiltrate of mostly lymphocytes with or without eosinophils [11][12][13].…”