Symmetric drug‐related intertriginous and flexural exanthema: Clinicopathologic study of 19 cases and review of literature

Abstract

Background: Symmetric drug-related intertriginous and flexural exanthema (SDRIFE) is a cutaneous drug reaction characterized by gluteal/anogenital erythema and symmetric involvement of other intertriginous location(s) without systemic signs. Clinicopathologic characterization has been limited to case reports and small series. We describe 19 new cases and review the literature to better define the clinical and histopathologic spectrum of SDRIFE.Methods: Pathology archives were searched for "SDRIFE" and "baboon syndrome."Cases meeting clinical criteria were included. Clinical and histopathologic features were recorded. Previous reports of SDRIFE with histopathologic descriptions were reviewed. Results: Nineteen new cases were included, over half triggered by antibiotics. Six new causative medications were identified. Median onset was 7 days. Typical lesions were erythematous plaques or papules with or without scale. The most common histopathologic finding was superficial perivascular lymphocytic infiltrate followed by dermal eosinophils, spongiosis, and orthokeratosis. Basal vacuolization and apoptotic keratinocytes were less common. Interstitial histiocytes were present in almost half of our cases. Other findings included atypical lymphocytes and "flame figure." Conclusions: Appreciation of the range of inciting medications and clinicopathologic features in SDRIFE will improve recognition of this condition. Although many histopathologic features overlap with other common dermatitides, biopsy may assist in excluding key clinical mimics. K E Y W O R D S baboon syndrome, drug reaction with eosinophilia and systemic symptoms, histopathology, symmetric drug-related intertriginous and flexural exanthema, toxic erythema of chemotherapy 1 | INTRODUCTION Symmetric drug-related intertriginous and flexural exanthema (SDRIFE) is a rare cutaneous drug reaction characterized clinically by marked erythema of the gluteal/perianal area and/or V-shaped erythema of the inguinal/perigenital area, symmetric involvement of at least one other intertriginous or flexural area, and the absence of systemic signs or symptoms. 1 It is induced by administration of a systemic agent at first or repeated exposure. 1 Contact allergens should be excluded. Latency between exposure to the offending agent and development of the rash varies but is usually within hours to days. 2

A flexural exanthem following postexposure prophylaxis

“…A variety of histopathological appearances of SDRIFE has been reported. Commonly, a superficial perivascular infiltrate of mononuclear cells is observed 6 . Epidermal changes such as spongiosis and acanthosis are also seen.…”

“…[2][3][4][5] The primary morphology is variable, and can include plaques, papules or patches with or without scale, and colour varying from erythematous to dusky, hyperpigmented or violaceous. 6 The latency between drug exposure and clinical manifestations in SDRIFE is also variable, from hours to days. 1 The most commonly associated medications include aminopenicillins, b-lactam antibacterials, chemotherapeutic agents, hydroxyzine and itraconazole.…”

“…A number of diagnostic criteria for SDRIFE have been proposed, including sharply demarcated, symmetrically distributed erythema of the gluteal/perianal/inguinal/perigenital area, following exposure to a systemic medication and absence of systemic symptoms and signs 2–5 . The primary morphology is variable, and can include plaques, papules or patches with or without scale, and colour varying from erythematous to dusky, hyperpigmented or violaceous 6 . The latency between drug exposure and clinical manifestations in SDRIFE is also variable, from hours to days 1 .…”

“…AGEP may be distinguished from SDRIFE by a disseminated eruption comprised of nonfollicular pustules, often with systemic features such as fever and facial oedema, peripheral neutrophilia, and predominantly neutrophilic histology. DRESS may be distinguished from SDRIFE by systemic symptoms, other organ involvement and peripheral eosinophilia; however, histological differentiation from SDRIFE can be difficult and therefore, awareness of culprit medications, in combination with identification of suggestive clinical features and histological findings, is important in differentiating between SDRIFE and other common dermatoses 2,6 …”

“…DRESS may be distinguished from SDRIFE by systemic symptoms, other organ involvement and peripheral eosinophilia; however, histological differentiation from SDRIFE can be difficult and therefore, awareness of culprit medications, in combination with identification of suggestive clinical features and histological findings, is important in differentiating between SDRIFE and other common dermatoses. 2,6 In contrast to classic Type IV-mediated delayed hypersensitivity reactions, SDRIFE has been reported to occur following exposure to a systemically administered drug at either the first or a repeat dose. SDRIFE may represent a distinct subgroup of Type IV drug eruption; however, theories relating to predisposing factors, such as local factors in flexures including increased density of apocrine/eccrine apparatus, friction or humidity, are unproven.…”