D2.403 - When a Topical Drug Goes Systemic: A Case of Dual Hypersensitivity to Diltiazem

Background: Rectal drug administration is widely used for both local and systemic therapy. The rectal mucosa allows for effective systemic absorption, which can result in immediate or delayed hypersensitivity reactions. Such reactions are most commonly associated with nonsteroidal anti-inflammatory drugs (NSAIDs), anticonvulsants, and antibiotics.

Case report: We present the case of a 17-year-old female treated with topical diltiazem for a chronic anal fissure for one month who additionally began using topical lidocaine, zinc oxide, and panthenol one week before presentation. She developed a pruritic erythematous rash in the intergluteal region, followed by a pruritic maculopapular eruption on the neck, chest, abdomen, and back. The patient denied any additional symptoms and reported no use of systemic medications during the previous month.

Laboratory investigations revealed elevated total IgE (906 IU/mL) and eosinophilia (700 cells/µL). All topical agents were discontinued, and treatment with topical methylprednisolone 0.1%, systemic methylprednisolone (0.5–1 mg/kg/day), and bilastine 20 mg twice daily was initiated. The maculopapular rash resolved completely within five days, while the intergluteal lesions healed with residual hyperpigmentation.

Patch testing performed one month later was positive for diltiazem. Repeat laboratory testing demonstrated a decrease in eosinophil count (260 cells/µL).

The differential diagnosis included viral exanthema, systemic contact dermatitis, and drug reaction with eosinophilia and systemic symptoms (DRESS). However, the clinical presentation, investigation results, and disease course supported a diagnosis of allergic contact dermatitis with a delayed systemic hypersensitivity reaction due to systemic absorption of rectally administered diltiazem. Oral challenge was not performed, and the patient was advised to avoid topical and systemic diltiazem.

Discussion: Topical diltiazem is widely used in the management of anal fissures. Although contact dermatitis is a known adverse effect, to our knowledge, systemic hypersensitivity reactions following rectal administration have not previously been reported.

Conclusion: This case underscores the importance of considering both locally and systemically administered medications when evaluating patients with suspected drug allergy. Clinicians should remain vigilant for potential systemic adverse reactions arising from topical therapies, particularly when systemic absorption is possible.

Written informed consent was obtained prior to publication.