Histopathologic Features of Maculopapular Drug Eruption

Abstract

Background: Cutaneous adverse drug reaction (CADR) is common in both inpatient and outpatient clinical settings and has been associated with a large variety of medications. Drug reactions represent a significant burden to the healthcare system due to increased hospital stay durations and associated costs. Moreover, some of these reactions may be life-threatening. The most common clinical manifestation of a CADR is a maculopapular drug eruption (MDE). Due to its many clinical mimics and associations with a variety of histopathologic patterns, maculopapular drug eruption is difficult to definitively diagnose from both a clinical and histopathological perspective. Summary: We reviewed the clinical and histopathologic features of 327 cases of MDE from several studies in the literature and summarized characteristic histopathologic findings and their frequencies of occurrence. We found that the most common and suggestive histopathologic features of MDE were epidermal spongiosis, lymphocytic infiltrate, and occasional necrotic keratinocytes; interface change at the DEJ; superficial perivascular and interstitial lymphocytic infiltrate with or without eosinophils and neutrophils in the mid-to-deep dermis and mild papillary dermal edema; and dilation of superficial vessels. The presence of multiple histopathologic patterns within the same tissue specimen is also suggestive of MDE. This review and analysis suggest that a biopsy may improve the diagnostic accuracy by both establishing common and uncommon features associated with MDE and reviewing features that help to exclude other causes of maculopapular eruption. Key Message: Histopathologic criteria for the diagnosis of MDE, while not entirely specific, may aid in establishing a differential that includes a drug eruption. Thus, a biopsy can be a helpful diagnostic tool when MDE is suspected by demonstrating findings suggestive of MDE or by ruling out clinical mimics. However, biopsy results cannot be used in isolation as clinical-pathologic correlation is paramount in MDE.

Functional heterogeneity of human skin‐resident memory T cells in health and disease

“…162,167 This is in line with a different clinical and histological presentation without any blister formation and dermal rather than epidermal lymphocytic infiltration. 167 In allergic contact dermatitis (ACD), active lesions contain a mixed CD4 + /CD8 + lymphocytic infiltrate with persisting T cells preferentially expressing CD4 and CCR10. 168 Long-term immunological memory in murine hapten-induced ACD was shown to be mediated by CD4 + T RM and initially confined to sensitized body areas until re-challenge.…”

“…Although this ‘two‐hit’ mechanism has also been demonstrated for amoxicillin‐induced maculopapular rash in association with EBV infection, 166 the T‐cell infiltrate comprise CD4 + Th1 and Th2 effector memory T cells and smaller percentages of cytotoxic T cells in contrast to T RM in TEN lesions 162,167 . This is in line with a different clinical and histological presentation without any blister formation and dermal rather than epidermal lymphocytic infiltration 167 . In allergic contact dermatitis (ACD), active lesions contain a mixed CD4 + /CD8 + lymphocytic infiltrate with persisting T cells preferentially expressing CD4 and CCR10 168 .…”

“…The presence of specific HLA alleles followed by a “second hit” with viral skin infections is discussed as a potential mechanism leading to generalized drug hypersensitivity conditions 164,165 . Although this ‘two‐hit’ mechanism has also been demonstrated for amoxicillin‐induced maculopapular rash in association with EBV infection, 166 the T‐cell infiltrate comprise CD4 + Th1 and Th2 effector memory T cells and smaller percentages of cytotoxic T cells in contrast to T RM in TEN lesions 162,167 . This is in line with a different clinical and histological presentation without any blister formation and dermal rather than epidermal lymphocytic infiltration 167 .…”

Urticaria: A Narrative Overview of Differential Diagnosis

“…The lesions usually appear 5–14 days after the administration of the culprit drug, but tend to appear earlier in the case of rechallenge. Iatrogenic eruption can present as an isolated finding or in association with pruritus and a low-grade fever [ 80 ]; mucous membranes are typically spared. Resolution may occur spontaneously over a period of one to two weeks after the culprit drug has been discontinued; desquamation and post-inflammatory hyperpigmentation are common sequelae [ 80 ].…”

Considerations in geriatric dermatopathology

“…Notably, polypharmacy and increased age tend to have a strong association with cutaneous drug reactions. Generally, the more medications a patient takes, the more likely there may be metabolic or drug–drug interaction that could precipitate a CADR 37 . In addition, underlying viral infections and specific genetic markers are risk factors that may be present in this population 37,38 …”