ALERT! These are the!

A rare and alarming drug reaction recently drew urgent attention after a 55-year-old woman developed sudden, painful skin symptoms following a change in her respiratory medication. What initially appeared to be a routine adjustment in treatment quickly escalated into a serious dermatological emergency, underscoring the importance of vigilance when new medications are introduced—even those commonly prescribed.

The woman had a medical history that included hypertension and chronic obstructive pulmonary disease (COPD). For years, her conditions had been managed without major complications using enalapril for blood pressure control and formoterol as part of her inhalation therapy. Her health status was stable, and there had been no recent hospitalizations, infections, or notable changes in her daily routine.

That stability changed shortly after her inhaler regimen was modified. Her formoterol-based treatment was replaced with a combination inhaler containing indacaterol and glycopyrronium, a long-acting bronchodilator therapy frequently prescribed for COPD management. Within a short period, she began to experience alarming symptoms that were impossible to ignore.

She presented to medical services with intensely painful, red lesions affecting her face and neck. The skin changes were accompanied by a low-grade fever and a general sense of physical distress. The lesions were sharply defined, inflamed, and tender to the touch, causing both discomfort and concern. Importantly, she reported no recent exposure to new cosmetics, skincare products, or household chemicals. She denied dietary changes, recent travel, insect bites, or symptoms suggestive of infection. There was no personal or family history of autoimmune disease or dermatological conditions that might explain the sudden reaction.

Given the rapid onset and severity of symptoms, she was referred for urgent dermatological assessment. Clinicians immediately considered a possible drug-related reaction, particularly given the recent change in her inhalation therapy. The indacaterol/glycopyrronium medication was promptly discontinued as a precautionary measure. She was started on oral corticosteroids to control inflammation and prevent further progression of symptoms.

Blood tests revealed leukocytosis with marked neutrophilia, findings consistent with an acute inflammatory response. However, extensive serological testing failed to identify an infectious cause. Autoimmune markers were negative, and there were no laboratory signs pointing toward an underlying systemic illness. Despite the dramatic appearance of the skin lesions, her vital signs remained stable, and no organ involvement was detected.

Within 48 hours of stopping the new medication and initiating corticosteroid therapy, her symptoms began to improve significantly. The fever resolved, the pain diminished, and the erythematous plaques started to fade. This rapid response reinforced the suspicion of a drug-induced inflammatory condition.

To confirm the diagnosis, a skin biopsy was performed. Histological examination revealed dense neutrophilic infiltration in the dermis without evidence of vasculitis. These findings confirmed a diagnosis of Sweet syndrome, also known as acute febrile neutrophilic dermatosis.

Sweet syndrome is a rare inflammatory condition characterized by the sudden appearance of painful, red or purple plaques, often accompanied by fever and elevated white blood cell counts. While its exact mechanism is not fully understood, it is believed to involve immune system dysregulation leading to abnormal neutrophil activation and migration into the skin.

The condition is known to be associated with several triggers. These include infections, particularly of the upper respiratory or gastrointestinal tract; malignancies, most commonly hematologic cancers; autoimmune disorders; pregnancy; and medications. Drug-induced Sweet syndrome has been documented with agents such as granulocyte colony-stimulating factors, antibiotics, and certain chemotherapy drugs.

What made this case particularly notable was the absence of any previously reported association between Sweet syndrome and inhaled bronchodilators like indacaterol or glycopyrronium. Although drug-induced forms of the condition are more frequently observed in women, this specific class of medication had not been implicated before, making the case clinically significant.

The diagnostic process required careful exclusion of other conditions that can present with similar symptoms. Differential diagnoses included urticaria, allergic contact dermatitis, toxic drug eruptions, lupus erythematosus, and other inflammatory or autoimmune dermatoses. Each was systematically ruled out based on clinical presentation, laboratory findings, histological evidence, and the patient’s rapid improvement following withdrawal of the suspected medication.

This case highlights an important lesson for clinicians, particularly those in primary care and pulmonology: even medications with well-established safety profiles can, in rare cases, trigger unexpected and severe reactions. When new symptoms arise shortly after a change in therapy, especially when they involve systemic signs like fever and significant inflammation, drug reactions must remain high on the list of possibilities.

Prompt recognition of Sweet syndrome is critical. Beyond managing the acute skin manifestations, the diagnosis often prompts a broader systemic evaluation. Because the condition can be associated with malignancies or autoimmune diseases, patients typically undergo further screening to rule out underlying causes. In this case, no such associations were found, reinforcing the conclusion that the reaction was medication-induced.

Equally important is the speed with which appropriate action was taken. Discontinuation of the offending drug and initiation of corticosteroid therapy led to rapid improvement, preventing potential complications and prolonged suffering. Delayed recognition could have resulted in worsening symptoms, unnecessary treatments, or extensive investigations before the true cause was identified.

As the patient continued to recover, her COPD management was reassessed, and alternative treatment options were considered with caution. She was closely monitored for any recurrence of symptoms, and no further dermatological issues were reported following the resolution of the episode.

This case serves as a reminder that rare adverse drug reactions, while uncommon, are a real and meaningful part of clinical practice. Awareness, thorough history-taking, and attention to timing can make the difference between swift resolution and prolonged diagnostic uncertainty. For healthcare providers, maintaining a broad differential and recognizing when something does not fit the usual pattern is essential—not only for accurate diagnosis, but for patient safety and trust.