It started as a silent signal—one not from the lungs, but from the skin. When a 55-year-old woman arrived at her clinic with painful, red facial lesions, there was nothing at first glance to suggest anything more serious than a simple skin reaction. But what followed would unfold into a medical rarity: a case of Sweet’s syndrome likely triggered not by a systemic medication, but by something far less expected—an inhaled bronchodilator capsule. The progression, diagnosis, and outcome would challenge assumptions about what inhaled therapies can and cannot do, and would ultimately offer an important lesson for clinicians.
The patient, a 55-year-old woman, had a long history of hypertension and chronic obstructive pulmonary disease (COPD). She was still smoking around ten cigarettes a day and had been stable for years on enalapril for blood pressure control and formoterol as her maintenance inhaler. Neither medication had caused complications. However, a recent increase in shortness of breath led her pulmonologist to switch her to a dual bronchodilator inhaler containing indacaterol and glycopyrronium, delivered through a capsule-based device. It seemed like a routine adjustment—one common in COPD management and generally considered safe.
Within two days of starting the new inhaler, she returned to her Primary Care clinic with painful, warm, erythematous plaques scattered across her cheeks and neck. She also reported a low-grade fever and a general sense of fatigue she couldn’t shake. She insisted she had not introduced new skincare products, had made no dietary changes, and had not been exposed to significant sunlight. She denied recent infections and emphasized that the symptoms began abruptly after starting the new inhaler.
The Primary Care physician recognized that the swollen, painful plaques, combined with fever, were not typical of a simple skin irritation. Concerned by the inflammatory appearance and the rapid progression, the physician referred her urgently to Dermatology. There, specialists recommended immediate discontinuation of the inhaled medication, initiation of systemic corticosteroids, laboratory testing, and a skin biopsy from an active lesion. Over the following 48 hours—after stopping the bronchodilator capsule and beginning steroid therapy—her symptoms began to ease. The plaques softened, the redness faded, and the pain subsided significantly.
Her lab results revealed leukocytosis with marked neutrophilia, suggesting an inflammatory or immune-mediated process. The autoimmune panel returned negative for ANA, anti-dsDNA, lupus anticoagulant, and other connective tissue markers. The biopsy showed dense dermal neutrophilic infiltration without evidence of vasculitis. Twenty days later, final pathology confirmed the diagnosis that clinicians strongly suspected: Sweet’s syndrome, also known as acute febrile neutrophilic dermatosis.
Sweet’s syndrome is a rare inflammatory condition characterized by sudden painful plaques or nodules, fever, elevated white blood cell counts, and a skin biopsy showing neutrophilic infiltration without vasculitis. The condition often appears in connection with infections, hematologic diseases, autoimmune disorders, or with certain medications—most commonly antibiotics, colony-stimulating factors, or immunosuppressants. What makes this case extraordinary is the suspected trigger. No published medical literature has clearly linked the combination inhaler indacaterol/glycopyrronium with Sweet’s syndrome, making this likely one of the first documented instances in which such a reaction followed an inhaled bronchodilator capsule.
Initially, several possibilities were considered. Could this be allergic contact dermatitis? A phototoxic reaction? Lupus erythematosus? A drug-induced toxicoderma? Even a severe rosacea flare with systemic symptoms? But the combination of painful, raised plaques, fever, increased white blood cell counts, and the hallmark biopsy pattern ruled out these conditions. The diagnosis of Sweet’s syndrome stood firm.
Treatment focused on two essential steps: discontinuing the suspected medication and initiating a short course of systemic corticosteroids. This approach led to rapid improvement. Within one week, her symptoms resolved entirely. At follow-up visits, no recurrence was observed, even after her COPD management was adjusted using alternative inhaled therapies that did not contain the implicated ingredients.
Clinically, this case reinforces several valuable lessons. First, Sweet’s syndrome must remain on the differential diagnosis when painful skin lesions are accompanied by fever and appear shortly after a medication change. Second, even medications delivered through inhalation—typically assumed to have minimal systemic absorption and low risk of causing immune-mediated reactions—can occasionally provoke unexpected inflammatory responses. Third, the fast involvement of dermatology, combined with a skin biopsy and early steroid treatment, can dramatically improve patient outcomes. Fourth, clinicians must take a careful medication history that includes not only new drugs but also changes in delivery methods, such as switching from one inhaler type to another. Finally, because Sweet’s syndrome can sometimes be associated with malignancy or autoimmune diseases, a broader systemic evaluation is essential with every diagnosis.
The case also raises thoughtful questions about the pharmacological reach of inhaled medications. Although they are intended primarily for local lung action, small amounts can enter the bloodstream, potentially triggering rare systemic immune reactions in susceptible individuals. This does not imply these medications are unsafe, but rather that clinicians should remain aware that even low-risk treatments can have uncommon side effects.
Ethically, all proper steps were taken. No experimental procedures were performed, and the patient’s identity remained fully protected. She provided written consent for her case to be published in the interest of expanding clinical understanding.
In the end, this unusual presentation of Sweet’s syndrome challenges clinicians to look beyond the expected and to pay attention when the skin delivers an early warning. For Primary Care physicians especially, it serves as a reminder that a new rash may signal more than a surface reaction—it may be the body’s inflammatory alarm sounding before deeper harm sets in. In this rare case, the skin spoke first, and because clinicians listened, the patient fully recovered.
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