Clinical Case: Sweet Syndrome Triggered by Inhaled Medication – A Rare but Important Diagnosis in Primary Care
This case highlights a rare dermatological condition with systemic implications—Sweet syndrome—that should be considered in Primary Care, particularly when new medications are introduced.
A 55-year-old woman with a medical history of hypertension and chronic obstructive pulmonary disease (COPD) presented to her Primary Care physician with an acute dermatological reaction. She had no known allergies, was a current smoker (10 cigarettes/day), and had been on enalapril for six years and inhaled formoterol for two years. Due to a recent worsening of her pulmonary condition, her pulmonologist modified her treatment by replacing formoterol with a combination of indacaterol and glycopyrronium in inhaled capsule form.
Just two days after starting the new medication, the patient developed painful, red patches on her cheeks and neck, accompanied by a low-grade fever (see Fig. 1). She denied any recent changes in diet, skincare products, or exposure to respiratory infections. She did report some sun exposure but claimed to have used proper sun protection.
Due to the sudden and unusual nature of her symptoms, she was urgently referred to Dermatology. The specialists recommended immediate discontinuation of the new inhaler. A skin biopsy and a comprehensive set of blood tests were ordered—including complete blood count, autoantibody profile, lupus anticoagulant, and serologies. Oral corticosteroids were initiated.
Within 24 to 48 hours, her skin lesions began to fade, and the pain significantly diminished. Lab results revealed leukocytosis with neutrophilia, positive lupus anticoagulant, but otherwise negative serology findings.
Twenty days later, the biopsy confirmed the diagnosis: Sweet syndrome (acute febrile neutrophilic dermatosis).
About Sweet Syndrome
Sweet syndrome is a rare neutrophilic dermatosis marked by sudden-onset, painful, erythematous papules or plaques, often with systemic symptoms such as fever and elevated neutrophils. These lesions typically appear on the face, neck, upper trunk, and hands, often asymmetrically.
Histologically, the condition is defined by dense infiltrates of neutrophils in the upper dermis, without vasculitis. The exact etiology remains unclear, but immune dysregulation, particularly involving cytokines, is thought to drive the recruitment and activation of neutrophils. Triggers include infections, malignancies (particularly hematologic), autoimmune diseases, and certain medications.
Drug-Induced Sweet Syndrome: A Diagnostic Challenge
Drug-induced Sweet syndrome is more common in women and has been associated with various agents, including:
- Antibiotics
- Anticonvulsants
- Oral contraceptives
- Antihypertensives
- Colony-stimulating factors
- Vaccines
However, this is the first reported case of Sweet syndrome triggered by inhaled indacaterol-glycopyrronium therapy, highlighting the need to remain vigilant for adverse drug reactions—even with medications not previously implicated.
Clinical Implications and Differential Diagnosis
The rapid appearance of papular erythematous lesions in this patient necessitated differentiation from other dermatologic conditions such as:
- Urticaria
- Contact dermatitis
- Drug-induced toxicoderma
- Cutaneous lupus erythematosus
Thanks to the combination of thorough clinical history, blood work, and a confirmatory skin biopsy, these were ruled out, and Sweet syndrome was diagnosed.
Treatment and Outcome
Oral corticosteroids remain the first-line treatment for Sweet syndrome, typically producing a dramatic response within hours to days. In this case, treatment led to rapid symptom resolution.
Given Sweet syndrome’s potential links to systemic illnesses, a broader diagnostic workup is essential after confirmation. In particular, clinicians should investigate possible underlying neoplasms, autoimmune disorders, or infections.
Lessons for Primary Care
Although rare, Sweet syndrome should be part of the differential when systemic symptoms accompany new dermatologic findings—especially in the context of recent medication changes. Early recognition in Primary Care, paired with timely referrals, can lead to accurate diagnosis and effective treatment.
Ethical Considerations
- Ethical Approval: No animal or human experiments were conducted for this case report.
- Confidentiality: The authors adhered to all institutional protocols regarding the protection and publication of patient data.
- Informed Consent: Informed consent was obtained from the patient; documentation is held by the corresponding author.
