A 55-year-old woman with a history of well-controlled hypertension and chronic obstructive pulmonary disease (COPD) sought medical attention after developing sudden, painful skin eruptions on her face and neck. Her symptoms were accompanied by low-grade fever, fatigue, and general malaise. Until this episode, her conditions had been stable on enalapril for blood pressure management and formoterol as maintenance therapy for COPD.
Two days before the onset of symptoms, her respiratory treatment was adjusted to a dual long-acting bronchodilator combination containing indacaterol and glycopyrronium. She denied recent infections, exposure to new skincare products or cosmetics, dietary changes, or any personal history of allergies or autoimmune disease. Due to the rapid evolution and severity of her symptoms, she was promptly referred for dermatologic evaluation.
Physical examination revealed multiple well-demarcated, raised, erythematous plaques involving the cheeks, forehead, and cervical area. The lesions were markedly tender and painful to touch. Given the close temporal association between the initiation of the new inhaled medication and symptom onset, a drug-related inflammatory reaction was strongly suspected.
The newly introduced inhaler was discontinued immediately, and systemic corticosteroid therapy was initiated. Laboratory testing demonstrated leukocytosis with pronounced neutrophilia, consistent with an acute inflammatory response. Extensive serologic studies ruled out infectious etiologies, autoimmune disorders, and connective tissue disease.
The patient showed rapid clinical improvement within 48 hours of starting corticosteroids. Fever resolved, pain subsided, and the skin lesions began to regress. A punch biopsy obtained from an affected area confirmed the diagnosis of Sweet syndrome, also referred to as acute febrile neutrophilic dermatosis.
Sweet syndrome is an uncommon inflammatory condition characterized by the sudden appearance of painful erythematous plaques or nodules, often accompanied by fever and systemic symptoms. Histopathological findings classically demonstrate dense neutrophilic infiltration of the dermis without evidence of vasculitis. The condition most frequently affects middle-aged women and may be associated with infections, malignancies—particularly hematologic cancers—autoimmune diseases, pregnancy, or exposure to certain medications.
Drug-induced Sweet syndrome represents a minority of cases and has most commonly been linked to agents such as granulocyte colony-stimulating factor, antibiotics, antiepileptic drugs, and chemotherapy. To date, there is little documented evidence associating inhaled bronchodilators, including indacaterol or glycopyrronium, with the development of this syndrome, making this case especially noteworthy.
Several differential diagnoses were considered during evaluation. Urticaria was excluded due to the fixed and painful nature of the lesions. Contact dermatitis was unlikely given the absence of new topical exposures. Toxic drug reactions and cutaneous lupus were also ruled out based on clinical presentation, laboratory findings, and histological analysis.
This case highlights the need for clinicians to maintain a broad diagnostic perspective when assessing acute dermatologic reactions, particularly following changes in medication. Although inhaled therapies are generally considered safe with minimal systemic effects, rare immune-mediated reactions can still occur.
Timely recognition of Sweet syndrome is essential, as the condition typically responds quickly to systemic corticosteroids and may be associated with underlying systemic disease. Patients diagnosed with Sweet syndrome should undergo appropriate evaluation to exclude malignancy, autoimmune conditions, and other potential triggers.
For primary care clinicians, this case emphasizes the importance of early dermatology referral and interdisciplinary collaboration when managing unusual adverse drug reactions. Increased awareness of rare dermatologic entities can lead to faster diagnosis, reduced morbidity, and improved patient outcomes.
In summary, while extremely uncommon, Sweet syndrome should be included in the differential diagnosis for patients presenting with acute painful erythematous lesions and systemic symptoms following medication changes — even when the implicated agent is an inhaled bronchodilator. Ongoing reporting of such cases will enhance clinical understanding and improve diagnostic accuracy in the future.
