Toxic epidermal necrolysis, DRESS, AGEP: Do overlap cases exist?

Abstract

BackgroundSevere cutaneous adverse reactions to drugs (SCARs) include acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) and epidermal necrolysis (Stevens-Johnson syndrome–toxic epidermal necrolysis [SJS-TEN]). Because of the varied initial presentation of such adverse drug reactions, diagnosis may be difficult and suggests overlap among SCARs. Overlapping SCARs are defined as cases fulfilling the criteria for definite or probable diagnosis of at least 2 ADRs according to scoring systems for AGEP, DRESS and SJS-TEN. We aimed to evaluate the prevalence of overlap among SCARs among cases in the referral hospital in France.MethodsWe retrospectively analyzed data for 216 patients hospitalized in the referral centre over 7 years with a discharge diagnosis of AGEP (n = 45), DRESS (n = 47), SJS-TEN (n = 80) or “drug rash” (n = 44). Each case with detailed clinical data and a skin biopsy specimen was scored for AGEP, DRESS and SJS-TEN by use of diagnostic scores elaborated by the RegiSCAR group.ResultsIn total, 45 of 216 cases (21%) had at least 2 possible diagnoses: 35 had a single predominant diagnosis (definite or probable), 7 had several possible diagnoses and 3 (2.1% of 145 confirmed SCARs) were overlap SCARs.ConclusionsDespite ambiguities among SCARs, confirmed overlap cases are rare. This study did not avoid pitfalls linked to its retrospective nature and selection bias. In the acute stage of disease, early identification of severe ADRs can be difficult because of clinical or biologic overlapping features and missing data on histology, biology and evolution. Retrospectively analyzing cases by use of diagnostic algorithms can lead to reliable discrimination among AGEP, DRESS and SJS-TEN.

Reactivation of Human Herpes Virus-6 in the Renal Tissue of a Patient with Drug-induced Hypersensitivity Syndrome/Drug Rash with Eosinophilia and Systemic Symptoms (DIHS/DRESS)

“…The syndrome is included in drug-induced severe eruptions as well as acute generalized exanthematous pustulosis, StevensJohnson syndrome and toxic epidermal necrolysis (10). DIHS/DRESS can be distinguished from these diseases according to the dermatologic findings, delayed onset, persis- However, the clinical manifestations of these conditions occasionally overlap (11), and DIHS/DRESS remains a challenging disease for clinicians to diagnose. The incidence rate is estimated to range from 0.1 to 1 in 1,000 drug exposures (12), however, its mortality rate is approximately 5 to 10% (2,13,14).…”

Sequential appearance of four clinical delayed drug hypersensitivity in the same patient

“…3 The diagnosis is sometime difficult due to overlap in their clinical presentations. Overlapping SCARs are defined as fulfilling the criteria for definite or probable diagnosis of at least 2 severe adverse drug reactions (DRESS, AGEP, and SJS-TEN).…”

“…4 The common causative drugs for DRESS were aromatic anticonvulsants, followed by allopurinol, sulphonamides, and other antibiotics. [3][4][5] Rifampicin and levofloxacin have been reported to be causative drugs. 5 Thus, all of the suspected drugs were discontinued resulting in a significant clinical improvement of our patient.…”

HLA and Delayed Drug-Induced Hypersensitivity

“…Although there are typical patterns of the mucocutaneous signs of DDAR (fig. 1), the diagnosis of these conditions is further complicated by the existence of concomitant syndromes, which lack a single diagnostic procedure [15] and are characterized by the coexistence of diagnostic features from different entities [16]. …”