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Sweet syndrome (acute febrile neutrophilic dermatosis) is an uncommon dermatological condition with potential systemic involvement. Though primarily idiopathic, it can be triggered by infections, malignancies, autoimmune diseases, and certain medications. Prompt diagnosis is essential to prevent complications and identify any underlying systemic conditions. We present a rare case of drug-induced Sweet syndrome following a change in inhaled therapy for chronic obstructive pulmonary disease (COPD)—a case of particular relevance to primary care physicians due to its atypical presentation and implications for early intervention.
Case Presentation
A 55-year-old female presented to her Primary Care clinic with acute dermatological symptoms. Her medical history included well-controlled arterial hypertension and chronic obstructive pulmonary disease (COPD). She had no known drug allergies and was a chronic smoker, averaging 10 cigarettes per day.
She had been on enalapril (10 mg daily) for six years and using inhaled formoterol for the past two years as part of her COPD management. Recently, due to worsening pulmonary function, her pulmonologist replaced formoterol with a combination of indacaterol and glycopyrronium in capsule form for inhalation.
Within 48 hours of initiating the new inhalation regimen, the patient developed painful, erythematous plaques on both cheeks and the anterior neck, accompanied by low-grade fever. She denied recent upper respiratory infections, dietary changes, or the use of new skincare products. While she reported sun exposure, she had used adequate photoprotection. No prior catarrhal symptoms were noted.
Given the acute onset, the appearance of systemic symptoms, and the lesion morphology, an urgent dermatology referral was made.
Initial Management and Investigation
The Dermatology team advised immediate cessation of the new inhaled medication. They initiated systemic corticosteroids and performed a punch biopsy of one of the lesions. Blood tests were ordered, including:
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Complete blood count
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Autoimmune profile (including ANA and lupus anticoagulant)
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Erythrocyte sedimentation rate (ESR)
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Infectious disease serologies
Within 24–48 hours of starting corticosteroids, the patient experienced a notable improvement. The lesions faded in intensity, and the associated pain and fever resolved. Laboratory results showed leukocytosis with marked neutrophilia; autoimmune and infectious markers were negative.
Definitive Diagnosis
Twenty days later, the skin biopsy confirmed the diagnosis of Sweet syndrome (acute febrile neutrophilic dermatosis). The histopathology revealed a dense dermal infiltration of neutrophils without signs of leukocytoclastic vasculitis—hallmarks of the condition.
Discussion
Sweet syndrome is classified under neutrophilic dermatoses, characterized histologically by dense neutrophilic infiltrates in the dermis and clinically by the sudden appearance of painful, erythematous plaques or nodules. It often presents with systemic symptoms such as fever, arthralgia, and leukocytosis with neutrophilia.
The diagnostic criteria for Sweet syndrome (Table 1) include both major and minor components:
| Major Criteria | Minor Criteria |
|---|---|
| Sudden onset of painful erythematous plaques or nodules | Preceding fever or infection |
| Dermal neutrophilic infiltrates without vasculitis | Leukocytosis |
| Associated systemic symptoms (e.g., arthralgia, conjunctivitis, fever) | |
| Rapid response to systemic corticosteroids | |
| Elevated ESR |
The condition is often idiopathic but can be triggered by infections, autoimmune disorders, malignancies, and various pharmacological agents, including:
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Granulocyte colony-stimulating factors (G-CSF)
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Antiepileptics
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Antibiotics
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Oral contraceptives
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Vaccines
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Antihypertensives
To date, no cases have been documented linking Sweet syndrome to inhaled indacaterol/glycopyrronium therapy, making this the first reported instance, and emphasizing the importance of broad diagnostic consideration in primary care.
Clinical Relevance to Primary Care
This case underscores the vital role of primary care physicians in recognizing early signs of rare conditions such as Sweet syndrome—especially when triggered by common therapeutic adjustments. In this patient, the clear temporal association between initiating a new inhaled bronchodilator and symptom onset helped raise clinical suspicion.
Primary care providers should be aware that:
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Drug-induced Sweet syndrome may develop even with non-systemic or inhaled medications.
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Prompt recognition and referral can prevent misdiagnosis (e.g., as contact dermatitis, lupus, or urticaria).
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Early corticosteroid therapy typically results in rapid symptom relief and resolution.
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It is crucial to screen for associated systemic diseases such as hematologic malignancies, infections, or connective tissue disorders once Sweet syndrome is diagnosed.
Although Sweet syndrome remains rare, its significance lies in its potential as a paraneoplastic indicator and its systemic implications if left untreated.
Conclusion
This clinical case highlights an unusual but educational presentation of Sweet syndrome secondary to inhaled therapy. It stresses the importance of maintaining a high index of suspicion for rare dermatoses when encountering sudden-onset skin lesions with systemic symptoms, especially in patients with recent changes in medication.
For general practitioners, being attuned to such atypical reactions can lead to faster diagnosis, appropriate referrals, and improved patient outcomes. Rare diseases, while uncommon, should always remain within the diagnostic landscape—particularly when new treatments or unexplained symptoms arise.
Ethical and Legal Considerations
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Human and Animal Protection: No experiments were conducted on humans or animals.
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Data Confidentiality: All institutional protocols regarding the handling of patient information were observed.
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Patient Consent: Informed consent was obtained for the publication of clinical information and images. Documentation is retained by the corresponding author.