Cutaneous drug eruptions, including morbilliform drug eruption (MDE) and the less-common symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), are characterized by an erythematous rash after medication exposure, often to beta-lactam antibiotics. Whereas MDE is thought to involve tissue-resident memory T cells, the immunopathogenesis of SDRIFE remains poorly understood. We sought to define the inflammatory patterns in SDRIFE compared with that of MDE and to elucidate the spatial localization of immune cells within the skin. To address these questions, we performed single-cell RNA sequencing, exploratory spatial transcriptomics, and immunohistochemistry to compare skin from patients with MDE and SDRIFE. MDE lesions featured a predominance of CD8[+] cytotoxic T cells and T helper 1-type CD4[+] T cells, high expression of CXCL9-11, and upregulation of IFN-responsive genes. In contrast, SDRIFE showed limited CD8[+] infiltration, enrichment for CD4[+] T cells with modest T helper 2 skewing, and macrophages with an immunomodulatory profile. Exploratory spatial transcriptomics revealed substantial T-cell and macrophage presence in the superficial dermis in both conditions. We conclude that MDE and SDRIFE display distinct immune landscapes: MDE is characterized by cytotoxic and INF-mediated inflammation, whereas SDRIFE involves an immunomodulatory, nonclassical response. These findings reveal inflammatory patterns in SDRIFE and highlight potential diagnostic and therapeutic targets.

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.

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is an interesting phenomenon of drug response characterized by symmetrical, exuberant skin reactions often seen in flexural and intertriginous areas. This report describes a 35-year-old gentleman with no relevant clinical history who developed SDRIFE subsequent to the use of oral fluconazole. His skin examination showed non-scaly, erythematous to violaceous patches within the genital, antecubital, axillary, neck, and inframammary folds. The diagnosis was made based on the clinical picture. Discontinuation of fluconazole and a tapering course of oral prednisolone led to complete resolution of symptoms. This case underlines the importance of maintaining a low threshold of suspicion for rare drug reactions such as SDRIFE, even with medications that are not commonly viewed as requiring dermatological follow-up, so that the condition can be directly managed and hopefully prevented in the future.

Symmetric drug-related intertriginous and flexural exanthema, also known as baboon syndrome, is a rare cutaneous adverse drug reaction that is classified as a delayed type IV hypersensitivity reaction mediated by T lymphocytes and characterized by a sharply demarcated, symmetric erythematous rash predominantly involving intertriginous and flexural areas, typically without systemic involvement.

Acute generalized exanthematous pustulosis (AGEP) is a rare, severe type IV hypersensitivity reaction, most commonly triggered by antibiotics, calcium channel blockers, or antifungal agents, while fluconazole-induced AGEP is exceptionally reported. Early recognition and prompt management are essential to prevent complications. We report the case of a 21-year-old female with no personal or family history of psoriasis who developed a sudden-onset, pruritic, erythematous pustular rash six days after a single 150 mg dose of fluconazole prescribed for vaginal candidiasis. On examination, she was febrile (39°C) and asthenic, with widespread non-follicular pustules initially involving intertriginous areas and subsequently extending to the trunk and limbs. The Nikolsky sign was negative, and mucosal surfaces were spared. Laboratory investigations revealed leukocytosis (10,400/mm[3]) with neutrophilia (7,800/mm[3]), and pustular cultures were sterile. Histopathological examination showed intraepidermal pustules associated with dermal neutrophilic and eosinophilic infiltrates. The European Study of Severe Cutaneous Adverse Reactions (EuroSCAR) score was 11, confirming the diagnosis of fluconazole-induced AGEP. Rapid clinical improvement was observed following discontinuation of fluconazole and supportive treatment with antihistamines and emollients; desquamation occurred within four days, and no systemic complications were noted. Although rare, fluconazole should be considered a potential cause of AGEP, and early diagnosis with prompt withdrawal of the offending drug remains essential to ensure a favorable prognosis.

Paraphenylenediamine (PPD) is an aromatic amine that was first manufactured in Germany by Hofmann in 1833. It is primarily employed for its antioxidant and staining properties and is found in rubber goods, printer ink, photographic supplies, textiles and footwear, henna tattoos, and hair dyes. As it is a prehapten that can cross the skin barrier easily, it can be detected in plasma, urine, and faeces after application of hair dye within half an hour. The molecular properties of PPD allow hair dye to effectively permeate the skin, resulting in sensitisation and the eventual development of allergic contact dermatitis. Redness, pain, pruritus, dryness, prickling sensation, burning or tingling sensation, and discomfort are some of the symptoms of hair dye dermatitis. Clinically, allergic reactions to PPD may vary from localised lesions, such as eyelid eczema, nummular eczema, or hand eczema, to disseminated forms, such as airborne contact dermatitis, prurigo-nodularis-like, or erythroderma-like. Systemic contact dermatitis (SCD) is a severe, delayed immune-mediated reaction (type IV hypersensitivity reaction) to PPD, a common ingredient in hair dyes and temporary "black henna" tattoos, causing widespread eczema, intense itching, redness, swelling, and sometimes even asthma-like symptoms or lymph node swelling, occurring far beyond the direct contact area after initial sensitization, and requires strict avoidance of PPD in all forms. This is a case of a woman who presented with symmetrical drug-related intertriginous and flexural exanthema (SDRIFE)-like features, a type of SCD post hairdye application, but without any history of drug intake that is relevant for Baboon syndrome (synonymous with SDRIFE).