D2.397 - Immediate and Delayed Hypersensitivity Reactions to Multiple Thyroid Hormone Preparations: A Challenging Case

Introduction: The coexistence of immediate- and delayed-type hypersensitivity reactions associated with different thyroid hormone preparations in the same patient is rarely reported. In this report, we present a patient in whom immediate- and delayed-type hypersensitivity reactions to different thyroid hormone preparations were observed and supported by in-vivo diagnostic testing.

Case Presentation: A 20-year-old female developed severe hypothyroidism following radioactive iodine ablation (10 mCi I-131) performed for uncontrolled Graves disease. Levothyroxine (Euthyrox®) was initiated at a dose of 75 µg, and within a few days the patient developed urticaria predominantly involving the knees, ankles, and wrists. Re-exposure at the same dose resulted in recurrent generalized urticaria, flushing accompanied by dyspnea, requiring emergency treatment.

Treatment was switched to Levothyroxine (Levotiron®). At a dose of 25 µg administered as part of a graded challenge protocol, the patient experienced intermittent, mild, non-specific pruritus without other objective cutaneous findings. However, dose escalation to 75 µg resulted in increased pruritus with occasional urticarial plaques, followed by the development of delayed-type cutaneous reactions characterized by pruritic erythematous and maculopapular eruptions. Skin biopsy obtained from the affected lesions revealed interface dermatitis with eosinophils, consistent with a delayed-type drug eruption.

Unlike most previously reported cases, both diagnostic testing and controlled clinical observation were feasible in this patient. Patch testing with Euthyrox®, Levotrion®, Tiromel®, and Tirosint® demonstrated +2 positive reactions at both 48 and 72 hours (Figure-1). Comprehensive evaluation failed to identify a consistent excipient trigger, and the patient tolerated multiple non-thyroid medications containing overlapping excipients without adverse reactions (Table-1).

An attempt was made to proceed with rapid desensitization; however, on the second day, a mixed-type hypersensitivity reaction was observed. Subsequently, a slow oral desensitization protocol over 28 days was initiated at our center. From day 11 onward, no significant adverse reactions were observed apart from a limited, treatment-responsive hyperemic maculopapular exanthem, and the desensitization process has been continued under close clinical monitoring.

ConclusionThis case demonstrates a rare coexistence of both immediate- and delayed-type hypersensitivity reactions associated with thyroid hormone preparations. The positivity patterns observed in the results of the multistep patch testing, the dose-dependent reaction pattern, systematic exclusion of excipient intolerance, and direct clinical observation suggest that the reactions may be related to the hormone itself. In such cases, slow oral desensitization may represent a feasible therapeutic option.