Clinical Case: Drug-Induced Sweet Syndrome Presenting with Systemic Symptoms in Primary Care
This case highlights a dermatologic condition with systemic implications that should be considered in the context of Primary Care.
A 55-year-old female patient, with a medical history of hypertension and chronic obstructive pulmonary disease (COPD), presented to the Primary Care clinic with dermatologic symptoms. She reported no known drug allergies and had a smoking habit of 10 cigarettes per day. Her regular medications included enalapril for six years and inhaled formoterol for two years. Due to a recent worsening of her pulmonary symptoms, her pulmonologist modified her treatment plan, replacing formoterol with a combination of indacaterol and glycopyrronium inhaled capsules.
On the second day following the initiation of this new inhalation therapy, the patient developed painful, erythematous patches on her cheeks and neck, along with a low-grade fever (see Fig. 1). She denied recent use of new cosmetics, changes in her diet, or experiencing catarrhal symptoms. Although she had been exposed to the sun, she reported using adequate sun protection.
Given the acute onset and appearance of the lesions, an urgent referral to Dermatology was made. The dermatology team advised discontinuation of the new inhaled therapy and initiated diagnostic procedures including a skin biopsy and comprehensive blood tests (CBC, autoantibodies, lupus anticoagulant, and infectious serologies). The patient was started on oral corticosteroids.
Within 24–48 hours, the lesions showed marked improvement and pain subsided. Blood test results revealed leukocytosis with neutrophilia. Autoimmune and infectious panels, including lupus anticoagulant and serologies, were negative.
Twenty days later, the skin biopsy results confirmed the diagnosis of Sweet syndrome (acute febrile neutrophilic dermatosis).
Overview of Sweet Syndrome
Sweet syndrome is a neutrophilic dermatosis, defined histopathologically by dense infiltration of neutrophils in the dermis without evidence of vasculitis[^1]. Clinically, it presents with the sudden onset of painful, erythematous papules or plaques—often asymmetrically distributed—typically affecting the face, neck, upper trunk, and extremities. Systemic features such as fever and leukocytosis with neutrophilia are frequently present[^1,^2,^3].
Diagnostic criteria include:
| Major Criteria | Minor Criteria |
|---|---|
| Sudden onset of painful erythematous or violaceous plaques/nodules | Fever or preceding infection |
| Neutrophilic dermal infiltrate without vasculitis | Leukocytosis |
| Arthralgia, conjunctivitis, or associated neoplasia | |
| Positive response to systemic corticosteroids | |
| Elevated ESR |
Pathogenesis and Etiology
The precise cause of Sweet syndrome remains unclear. Evidence suggests an exaggerated immune response involving cytokine-mediated chemotaxis and activation of neutrophils and histiocytes[^4,^5]. It may be triggered by preceding infections, paraneoplastic syndromes, autoimmune conditions, or medications[^2,^6,^7].
Sweet syndrome can also serve as a clinical marker of underlying systemic diseases, including hematologic malignancies, inflammatory bowel disease, and autoimmune connective tissue disorders. Drug-induced forms are more common in women[^2], with frequently implicated agents including oral contraceptives, antiepileptics, antibiotics, antihypertensives, colony-stimulating factors, and vaccines[^6].
Clinical Relevance of This Case
This patient’s presentation followed a clear temporal association with the initiation of a new inhaled therapy. Although no prior cases of Sweet syndrome have been reported in relation to inhaled indacaterol/glycopyrronium, the rapid onset of symptoms and improvement following drug discontinuation support a diagnosis of drug-induced Sweet syndrome.
This case underscores the importance of considering Sweet syndrome in the differential diagnosis of sudden-onset, painful cutaneous eruptions—particularly when systemic symptoms are present and there is recent drug exposure. Differential diagnoses initially included urticaria, contact dermatitis, drug eruption, and cutaneous lupus erythematosus, all of which were excluded through clinical history, laboratory evaluation, and confirmatory biopsy.
Management and Implications for Primary Care
First-line treatment for Sweet syndrome is systemic corticosteroids, which typically produce rapid resolution of systemic symptoms and cutaneous lesions within days[^2]. While Sweet syndrome is rare, Primary Care physicians play a critical role in its recognition, referral, and early management, especially in cases triggered by commonly used medications.
Because Sweet syndrome may indicate a more serious underlying systemic condition, it is essential that further evaluation be conducted after diagnosis to rule out malignancies, infections, or autoimmune diseases.
Ethical and Legal Considerations
- Ethical Approval: No experimental procedures involving humans or animals were conducted for this case.
- Confidentiality: All patient data were handled according to institutional confidentiality protocols.
- Informed Consent: Written informed consent was obtained from the patient for the publication of this case.
