Fixed Drug Eruptions to Antihistamines with Challenge Test to Generate Safe List of Antihistamines

Dear Editor,

Fixed drug eruptions are commonly believed to occur due to antibiotics and nonsteroidal analgesics. Avoidance of the culprit drug is the mainstay of therapy. Antihistamines and topical steroids are used for the management of the disease. However, antihistamines may themselves lead to fixed drug eruptions, though such eruptions have not been widely reported in literature. A 35-year-old male presented with multiple hyperpigmented dark brown oval patches on the trunk for the last 2 years [Figure 1]. The patches repeatedly developed erythema and itching on exposure to over-the-counter medications taken for fever (paracetamol) and upper respiratory tract infections (antihistamines). His father, now deceased, was reported to have similar allergies to over-the-counter medications. Based on history and typical clinical appearance, a diagnosis of fixed drug eruptions to an unknown drug was made, and the patient was planned for rechallenge with 21 drugs to generate a safe drug list.^[1] The patient was advised not to take any drug for the last 5 days before commencing the challenge. On the day of the challenge, no erythema was seen on the lesions. The patient was challenged with Tab Levocetirizine 5 mg tablet under supervision (keeping a resuscitation tray ready) and kept under observation for the next 12 hours. The rationale for choosing levocetirizine is based on the fact that it is the most common available over-the-counter medication and also has a better safety profile compared to other antihistamines.

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Figure 1: The initial fixed drug eruption: Single oval patch with dusky red centre and erythematous halo.

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Within 15 minutes of ingestion, moderate to severe itching on the patches was seen. Within 1 hour, the patches had developed erythema at their borders. One new patch, which was erythematous, was seen on the trunk. A skin biopsy was taken from the erythematous patch, which showed dense lympho-histiocytic infiltrate with a band-like pattern at the dermo-epidermal junction. Necrotic keratinocytes were seen high up in the epidermis [Figures 2 and 3]. The patient was managed conservatively with clobetasol cream, with deferral of further challenge for 5 days. The lesions resolved completely with hyperpigmentation, thereby proving the rechallenge protocol. The patient reacted similarly to cetirizine, loratidine and desloartidine but not to bilastine and hydroxyzine.

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Figure 2: Development of newer patches on rechallenge.

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Figure 3: Histopathological image showing necrotic keratinocytes high up in the epidermis (black arrows) together with dense band-like lymphocytic infiltrate hugging the dermo-epidermal junction (a & b Haematoxylin and eosin (a) 10x (b) 40x).

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Fixed drug eruptions to antihistamines have been reported very rarely. It has been reported with Levocetrizine and other piperazine derivatives, identified by patch testing, which had cross-reacted to hydroxyzine but not to loratadine.^[2] However, the diagnosis was done by patch test, which sometimes does not faithfully reproduce clinical disease. Oral drug challenge is considered the gold standard for such diagnoses. Our case had cross-reacted to cetirizine, loratidine and desloratadine but not to hydroxyzine, despite hydroxyzine being chemically related to levocetrizine. Antihistamines are a little-known but definite culprit for fixed drug eruptions. Given their extremely large and widespread use throughout the world, this data becomes highly relevant when prescribing them. Bilastine and first-generation antihistamines are probably safer alternatives to conventional antihistamines.