Venetoclax‐Induced Symmetrical Drug‐Related Intertriginous and Flexural Exanthema (SDRIFE): Implications for Diagnosis and Treatment Continuation

ABSTRACT

Symmetrical drug‐related intertriginous and flexural exanthema (SDRIFE) is an uncommon type of cutaneous drug eruption, most frequently associated with antibiotics such as amoxicillin. Reports of SDRIFE induced by anticancer agents remain limited. We describe a case of SDRIFE in a 77‐year‐old man treated with venetoclax for acute myeloid leukemia. The eruption developed shortly after drug initiation and resolved rapidly following drug withdrawal without systemic involvement. Notably, venetoclax was continued for a certain period after onset without progression of symptoms. This case highlights the importance of recognizing SDRIFE in patients receiving chemotherapy and suggests that continuation of the causative agent may be feasible in selected cases.

1. Introduction

Symmetrical drug‐related intertriginous and flexural exanthema (SDRIFE) is a distinctive drug eruption characterized by well‐demarcated erythema in intertriginous and flexural areas without systemic involvement [1]. Although SDRIFE has been reported in association with various drugs, it is most reported with antibiotics. To date, there have been no case reports of SDRIFE related to venetoclax. Here, we describe the first case of SDRIFE induced by venetoclax.

2. Case Report

A 77‐year‐old man with a history of acute myeloid leukemia was treated with azacitidine and venetoclax. Two days after initiation, he developed symmetrical erythematous eruptions in the groins and axillae without mucosal involvement and systemic distribution (Figure 1). Laboratory findings showed no significant abnormalities. Other medications included polymyxin B, famotidine, and rebamipide. Dermatologic evaluation on day 13 suggested SDRIFE based on the characteristic distribution and symmetry. Topical corticosteroids and antihistamines were initiated. Venetoclax was discontinued 3 days after dermatology consultation, as disease control had been achieved. Following withdrawal of venetoclax, the eruption resolved within 3 days without recurrence; although concomitant medications, including polymyxin B, famotidine, and rebamipide, were continued. Venetoclax and azacitidine were initiated on the same day, while polymyxin B, famotidine, and rebamipide had been stated 1 day earlier. The eruption progressed despite temporary withdrawal of azacitidine and subsequently improved only after discontinuation of venetoclax; venetoclax was considered the most likely culprit drug.

FIGURE 1.

Clinical images at the first visit. (A) Symmetrical, well‐demarcated erythematous macules involving the intertriginous and flexural area of the right axilla to the lateral chest. (B) Similar symmetrical findings extending from the left axilla to the lateral chest. (C) The eruption was accentuated in flexural and lateral areas with relative sparing of the midline back. (D) Similar erythema extending from the abdomen to groin. (E) Similar symmetrical findings on the inner thighs.

3. Discussion

Venetoclax is a selective BCL‐2 inhibitor that induces apoptosis in malignant cells and is used to treat chronic lymphocytic leukemia and acute myeloid leukemia. Cutaneous adverse events such as rash have been reported in approximately 5%–15% of patients receiving venetoclax. However, distinctive patterns such as SDRIFE have rarely been reported. SDRIFE is diagnosed based on the five criteria: (1) exposure to a systemically administered drug at the time of first or repeated doses (contact allergens excluded); (2) sharply demarcated erythema of the gluteal/perianal area and/or V‐shaped erythema of the inguinal/perigenital area; (3) involvement of at least one other intertriginous/flexural fold; (4) symmetry of affected areas; and (5) absence of systemic symptoms and signs [1]. This case fulfilled all of these criteria for SDRIFE and was therefore diagnosed as SDRIFE.

Toxic erythema of chemotherapy (TEC), as described by Bolognia et al., encompasses a spectrum of painful cutaneous eruptions induced by chemotherapeutic agents, with hand–foot syndrome being a representative manifestation. This condition is thought to result from the accumulation and excretion of cytotoxic agents via eccrine sweat glands [2]. Among the differential diagnoses, both TEC and SDRIFE are categorized as intertriginous eruptions associated with chemotherapy, and careful differentiation between the two conditions is required. From a histopathological perspective, Bolognia reported that TEC is characterized by features such as epidermal dysmaturation and eccrine squamous syringometaplasia [2]. These findings are typically absent in SDRIFE [3], making them useful criteria for distinguishing between the two entities. Given the absence of characteristic histopathological findings in SDRIFE [3], skin biopsy was not actively performed in this case.

Clinically, TEC is more often associated with tenderness and pain, whereas SDRIFE is typically characterized by pruritus [1, 2]. As noted by Smith et al., differences in the timing of onset after drug exposure also aid in differentiation: TEC usually develops over several days to weeks, while SDRIFE typically occurs within hours to a few days. This difference in latency from drug exposure to eruption is a helpful distinguishing feature [4]. While TEC cannot be entirely ruled out in this case, the conceptual overlap between TEC and SDRIFE raises the possibility that SDRIFE may be subsumed within the spectrum of TEC, potentially leading to misclassification.

SDRIFE has an excellent prognosis, with resolution in most cases after discontinuation of the offending drug and lacks systemic organ involvement [5]. A previous report by Tanaka et al. described SDRIFE induced by paclitaxel, in which continuation of paclitaxel was possible with concomitant oral prednisolone [6]. In the present case, venetoclax was continued for 18 days after the onset of the eruption, without progression to severe cutaneous or systemic manifestations. This observation suggests that immediate discontinuation of the causative agent may not always be necessary in cases of SDRIFE, particularly when the underlying disease requires ongoing treatment. Although not systematically reported, we have encountered several cases of SDRIFE during chemotherapy, including with agents such as paclitaxel, in which no severe progression occurred and treatment could be continued without modification. These observations further support the notion that SDRIFE associated with anticancer agents may follow a benign clinical course.

We report the first case of venetoclax‐induced SDRIFE. Recognition of this entity is important to avoid misdiagnosis and unnecessary discontinuation of essential anticancer therapy.

Funding

The authors have nothing to report.

Ethics Statement

The authors have nothing to report.

Consent

Written informed consent for publication of this case report and accompanying images was obtained from the patient.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.