Toxic epidermal necrolysis (TEN) is a life-threatening mucocutaneous reaction characterized by rapidly progressive epidermal necrosis within hours to days, extensive skin detachment, and high mortality. Rarely, patients present with TEN-like eruptions that evolve slowly, over days to weeks, and have skin changes mostly confined to photodistributed areas, with possible mucosal involvement. The latter scenario is compatible with TEN-like lupus erythematosus. We report a 65-year-old man without prior lupus history who developed a widespread, photodistributed erythematous patchy eruption within 24 h of initiating donepezil for Parkinsonism-associated aphasia. The erythema rapidly progressed to erosions, bullae, and detachment involving 81% total body surface area (TBSA) and a Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) of 2. Initial differential diagnoses included TEN/Stevens Johnson Syndrome (SJS), bullous pemphigoid, generalized bullous fixed drug eruption, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), and reactive infectious mucocutaneous eruption (RIME). Histopathology revealed interface dermatitis with diffuse basilar apoptosis, focal full-thickness epidermal necrosis and robust dermal mucin deposits. Direct immunofluorescence study was negative. Serologies showed strongly positive anti-Ro/SSA and ANA titers. COVID-19 testing was positive. The constellation of clinical, pathologic and laboratory features supported a diagnosis of TEN-like subcutaneous lupus erythematosus (SCLE), likely triggered by donepezil and complicated by a concurrent COVID-19 infection. To our knowledge, this is a novel case of TEN-like SCLE associated with donepezil initiation.

Generalized bullous fixed drug eruption (GBFDE) is a rare variant of fixed drug eruption that is known to clinically mimic Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). Numerous medications have been reported to cause GBFDE, including antiplatelet agents like ticagrelor, but few reports exist linking this reaction to clopidogrel specifically. We report a case of a medically complex 80-year-old male who was found to have clopidogrel hypersensitivity manifesting as GBFDE based on clinical characteristics and pathology. He was successfully treated using the Jefferson desensitization protocol, which was developed by cardiologists to enable continuation of clopidogrel. While clopidogrel hypersensitivity reactions are well-reported, there is a shortage of dermatology literature characterizing the clinical characteristics of these rashes and highlighting the use of the Jefferson desensitization protocol. This case reports on an etiology for GBFDE that is rarely observed and emphasizes the importance of histopathology when differentiating this entity from SJS/TEN. It also reports the successful use of the Jefferson protocol for GBFDE secondary to clopidogrel hypersensitivity.

Concurrent NSAID therapy can pharmacologically mask early scrotal abscess, generating a presentation that fulfills clinical and historical criteria for fixed drug eruption. Ibuprofen simultaneously acts as a recognized causative agent and suppresses infectious inflammatory signs. Normal inflammatory markers and absent fluctuation do not exclude an abscess. Early scrotal ultrasound is mandatory.

Generalized bullous fixed drug eruption (GBFDE) is a rare and severe adverse drug reaction characterized by widespread blisters and erosions involving at least 10% of the body surface. GBFDE can mimic Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), both clinically and histologically. We present the case of a 76-year-old woman with extensive painful blisters and erosions affecting approximately 70% of her skin, including the oral and genital mucosa, accompanied by an impaired general condition, strongly suggesting TEN. However, the absence of Nikolsky's sign, together with slate-gray hyperpigmentation, pointed toward GBFDE, later supported by histopathological analysis. Paracetamol was identified as the most likely causative agent. Following discontinuation of the culprit drug, the patient was treated with high-dose corticosteroids and antibiotics within a multidisciplinary care approach. After 3 weeks of hospitalization, the skin lesions healed with residual hyperpigmentation, and her condition stabilized. Our case highlights the challenge of differentiating between two uncommon severe disorders with overlapping clinical and histopathological features, including extensive epidermal necrosis and subepidermal blistering. Clinical and pathological correlation by experienced physicians is essential for distinguishing GBFDE from TEN because their management strategies differ, impacting both patient outcomes and healthcare costs.

Macrolides are widely prescribed antibiotics in pediatric practice and are commonly used as alternatives in children with suspected or confirmed beta-lactam allergy. Although generally considered safe and associated with low allergenic potential, hypersensitivity reactions to macrolides do occur and may lead to inappropriate drug avoidance. This review critically appraises the current evidence on macrolide-induced hypersensitivity reactions in the pediatric population, focusing on clinical manifestations, diagnostic approaches, cross-reactivity, and management strategies. Hypersensitivity reactions to macrolides are estimated to occur in 0.4–3% of treatments, with immediate reactions such as urticaria and angioedema being the most frequently reported. Anaphylaxis is exceedingly rare, while delayed reactions, particularly maculopapular exanthema, represent the most common non-immediate presentations. Severe cutaneous adverse reactions, including Stevens–Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, and fixed drug eruptions, have been reported but remain exceptional in children. The diagnostic workup of suspected macrolide allergy is challenging due to the limited sensitivity and poor predictive value of skin tests and the lack of validated in vitro assays. Current evidence supports the use of drug provocation tests as the gold standard for diagnosis, particularly in children with non-severe, skin-limited reactions. Recent guidelines increasingly favor direct oral challenge without prior skin testing in low-risk pediatric patients. Studies consistently demonstrate that most children with suspected macrolide allergy tolerate re-exposure, confirming that true allergy is uncommon. Cross-reactivity among macrolides appears to be infrequent in children but may occur, especially in severe reactions. Desensitization protocols, although not standardized, have been successfully applied in selected pediatric cases when macrolides are indispensable. Overall, accurate diagnosis through appropriate testing is essential to avoid unnecessary antibiotic restrictions, ensure optimal antimicrobial therapy, and reduce the burden of incorrect allergy labeling in pediatric patients.

Cutaneous adverse drug reactions (CADRs) are a common and significant concern, arising from both immunological and non-immunological mechanisms. Therefore, it is of interest to identify the incidence, patterns and drug associations of CADRs at a tertiary care hospital in Vidisha, Madhya Pradesh. A total of 56 cases were observed with fixed drug eruptions (FDEs) caused by NSAIDs being the most frequent. The findings highlight the prevalent role of self-medication and the need for strict regulations, with improved pharmacovigilance to mitigate these adverse reactions.

Fixed drug eruption (FDE) is a dermatological manifestation characterized by well-circumscribed erythematous-violaceous lesions that recur at identical anatomical sites upon re-exposure to the offending medication. We present a 39-year-old male who developed symmetric erythematous-violaceous macules in bilateral axillary, inguinal, and popliteal regions within 48 hours of initiating concurrent ciprofloxacin and metronidazole therapy for acute infectious diarrhea. Physical examination revealed six well-demarcated, tender, pruritic macules without mucosal involvement or systemic manifestations. Dermoscopic examination demonstrated a homogeneous violaceous background with fine pigment granularity throughout all affected areas. Due to resource limitations in the private clinic setting, skin biopsy and definitive drug causality testing were not performed. Both antibiotics were discontinued upon recognition of the cutaneous reaction. Treatment consisted of systemic corticosteroids (prednisone 20 mg daily for seven days), oral antihistamines (desloratadine 5 mg daily), and topical therapy including fluticasone propionate 0.05% nightly and calamine-based emollients. Symptomatic improvement was achieved with initial emergency treatment. Near-complete resolution of erythema occurred by day nine with residual post-inflammatory hyperpigmentation at previously affected sites. This case highlights the diagnostic challenge when multiple potential culprits are administered simultaneously, and confirmatory testing is unavailable. Dermoscopy proved valuable as a non-invasive diagnostic tool when histopathology was inaccessible. This report emphasizes the importance of clinical vigilance when prescribing commonly used antibiotics and demonstrates the utility of alternative diagnostic approaches in resource-limited settings. Primary care physicians and dermatologists should maintain awareness of FDE presentations and counsel patients to avoid re-exposure to implicated medications.

Generalized Bullous Fixed Drug Eruption (GBFDE) is a severe variant of Fixed Drug Eruption (FDE) characterized by widespread dusky erythematous plaques and blistering, often mimicking Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN). Early distinction is critical, as misdiagnosis can lead to delayed or inappropriate management. We report a case of nimesulide-induced GBFDE in a 32-year-old male who developed rapidly progressing dusky plaques and flaccid bullae within 24 hours of self-medicating with an over-the-counter Nimesulide formulation. A prior similar episode following exposure to the same drug strongly supported the diagnosis. Prompt withdrawal of the drug, systemic corticosteroids, and supportive care led to rapid clinical improvement. This case highlights the diagnostic challenges, the dangers of over-the-counter NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) use, and the importance of pharmacovigilance reporting, given that only three cases of nimesulide-associated GBFDE have been documented to date. Increased awareness among clinicians is essential to prevent morbidity and recognize this rare but potentially life-threatening adverse reaction.