When the Skin Speaks First: A Rare Case of Drug-Induced Sweet’s Syndrome from Inhaled Therapy

It began with a soundless cry — not from the lungs, but from the skin. When a 55-year-old woman arrived at the clinic complaining of painful, red facial lesions, there was no immediate reason to suspect anything more than a mild skin reaction. Yet what unfolded would become a medical anomaly — a rare presentation of Sweet’s syndrome, not triggered by an antibiotic or antiepileptic, but by something few would imagine: an inhaled bronchodilator capsule.

Initial Presentation

The patient was a 55-year-old female with a longstanding history of hypertension and chronic obstructive pulmonary disease (COPD). She was a current smoker, averaging ten cigarettes per day, and had been on stable treatment with enalapril (for six years) and inhaled formoterol (for two years) without complications.

Due to a recent worsening of her COPD symptoms, her pulmonologist switched her therapy to a dual bronchodilator: a combination of indacaterol and glycopyrronium in capsule form, delivered via inhalation.

Two days after starting the new inhaler, she presented at the Primary Care clinic with:

• Painful, erythematous plaques on her cheeks and neck
• A low-grade fever
• General malaise

She denied using new skincare products, had made no dietary changes, and reported no recent infections. Sun exposure had been minimal, and she had used sunscreen consistently.

Escalation and Referral

Given the rapid onset and inflammatory appearance of the lesions, the Primary Care physician referred her urgently to Dermatology. There, the team suspected a systemic inflammatory condition and recommended:

• Immediate discontinuation of the new inhaler
• Initiation of systemic corticosteroids
• Laboratory testing, including a full blood count and autoimmune panel
• Skin biopsy from an active lesion

Over the next 48 hours, her symptoms began to subside. The erythematous plaques lightened in color, and her facial pain diminished.

Diagnostic Findings

Bloodwork revealed leukocytosis with marked neutrophilia.

Autoimmune panel: Negative for ANA, anti-dsDNA, lupus anticoagulant, and other connective tissue markers.

Skin biopsy: Showed dense neutrophilic infiltration of the dermis with no evidence of vasculitis.

Twenty days later, the biopsy confirmed the clinical suspicion: Sweet’s syndrome, also known as acute febrile neutrophilic dermatosis.

Understanding Sweet’s Syndrome

Sweet’s syndrome is a rare inflammatory condition that presents with:

• Sudden onset of painful, erythematous plaques or nodules
• Fever and systemic symptoms
• Elevated white blood cell counts
• Histopathology showing dermal neutrophilic infiltration without vasculitis

Triggers are often infections, malignancies, autoimmune disorders, or medications — typically systemic drugs like antibiotics, colony-stimulating factors, or immunosuppressants.

However, this case is exceptional: the presumed trigger was an inhaled medication. To date, no known reports have clearly linked indacaterol/glycopyrronium with Sweet’s syndrome, making this a likely first documented association.

Differential Diagnosis

Initial considerations included:

• Allergic contact dermatitis
• Phototoxic reaction
• Lupus erythematosus
• Drug-induced toxicoderma
• Rosacea flare with systemic symptoms

However, the pattern of painful, raised plaques accompanied by systemic signs and histological findings allowed these to be ruled out.

Treatment and Outcome

• Discontinuation of the suspected agent
• A short course of oral corticosteroids

This approach led to rapid clinical improvement, with complete resolution of the skin lesions within one week. No recurrence was noted on follow-up.

Clinical Implications

This case underscores several key lessons for clinicians:

Sweet’s syndrome should remain in the differential when new-onset, painful skin lesions with systemic symptoms follow medication changes.

Even inhaled therapies — typically considered low-risk for systemic side effects — can trigger rare immunologic reactions.

Prompt dermatological referral, skin biopsy, and early corticosteroid initiation can lead to full recovery.

A thorough medication history, including changes in delivery methods (e.g., from inhaler to capsule), is crucial.

Importantly, Sweet’s syndrome can also signal underlying malignancy or autoimmune disease, so broader systemic evaluation is warranted in every case.

Ethical Declarations

Human & Animal Protection: No experimental procedures were performed on humans or animals.

Confidentiality: Patient identity and personal data have been fully protected in accordance with clinical ethical standards.

Informed Consent: The patient provided written consent for the publication of this clinical case.

Conclusion

This case highlights a rare and possibly first-reported instance of Sweet’s syndrome triggered by an inhaled bronchodilator capsule. It challenges assumptions about the systemic safety of inhaled therapies and reinforces the need for vigilance when evaluating skin reactions after any medication change.

For Primary Care physicians, it’s a reminder that sometimes a red rash isn’t just a rash — it’s the immune system sounding an alarm. And in this case, the warning came not from the lungs, but through the skin.

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