Fixed Drug Eruption due to Chlorpheniramine: Case Report

Chlorphenamine or chlorpheniramine (chlorphenamine maleate) is an alkyl derivative first generation antihistamine, which competes with histamine for H1 receptors on effector cells in smooth muscle, the central nervous system, vascular endothelial cells and the heart. It is commonly used as a component of drugs to treat cold-related symptoms. We present a patient with a fixed drug eruption (FDE) after administration of chlorpheniramine, with a positive patch test to dexchlorpheniramine. A 53-year-old man with no atopy or allergological history of interest, was referred to the Allergology department because after the last time he received Frenadol Complex (paracetamol, chlorpheniramine, cafein, dextromethorphanascorbic, sucrose and polisorbate), he presented erythematous blistering lesions on the first left toe, first finger of the right hand and interdigital region between the 2nd and 3rd fingers of the left hand. He confirmed that he had previously received Frenadol Complex with similar skin lesions. Skin prick tests (SPT) were performed with dextromethorphan and chlorpheniramine with negative results. SPT and intradermal tests with paracetamol according to standard concentrations [1] gave negative results in immediate and late readings. Histamine was used as a positive control and normal saline as a negative control. The patient was tolerant to paracetamol, cafein and vitamin C and polysorbate as excipients of other drugs, so an oral challenge test (OCT) was carried out with Frenadol complex, increasing doses of ¼, ½ and 1 complete dose separated by 1 h, 1 h and 3 h, being immediately well tolerated. However, 24 h later, the patient presented with erythematous bullous lesions at the same sites as previously affected, compatible with FDE. For that reason, patient underwent epicutaneous patch tests on his back and on the first left toe of the FDE lesion with dexchlorpheniramine 1% pet (in-house preparation) [2]. The patch test were occluded for 2 days and readings (according to ESCD guidelines) on D2 and D4 showed a positive (3+) reaction on previously affected FDE skin (Figure 1), confirming a delayed hypersensitivity reaction to dexchlorpheniramine. The other test, on an unaffected site, remained negative. Subsequently, an OCT with dextromethorphan up to therapeutic doses were well tolerated, confirming the diagnosis of FDE due to chlorpheniramine and dexchlorpheniramine. The patient recognised previous tolerance to dexchlorpheniramine years ago, but didn't recall subsequent usage. AHs are widely used and well tolerated, however, they are not free from adverse events [3]. FDE due to AH were previously described [4, 5], but to our knowledge, a FDE due to the alkylamine group has only been published after pheniramine maleate intake [6]. Although infrequent, immediate [7] and delayed [8] hypersensitivity reactions have been described after chlorpheniramine intake, but a FDE is considered very rare [9, 10]. According to published recommendations [9], after a negative skin test with the main components of the cold drug, an OCT was performed. In the case of our patient, the OCT was positive, with similar lesions at the same sites as previously affected. A patch test was additionally performed but was only positive (Figure 1) on the previously affected skin area, in contrast to other FDA cases with AH [5], stressing the importance of the need to test the actual FDE site instead of just on the back. Given the structural similarity and because of a possibility of a cross-reaction [4], the alkylamine AH group were recommended to be avoided. In summary, we present the first reported case of FDE to chlorpheniramine with positive patch test to dexchlorpheniramine. Despite their known tolerability, AHs should be taken into account as a possible cause of adverse drug reactions. Vanesa García Paz: conceptualization, investigation, writing – original draft, project administration, data curation, supervision, methodology, validation, visualization, writing – review and editing. Laura Romero-Sánchez: writing – original draft, investigation, conceptualization, methodology, visualization, writing – review and editing, supervision, project administration, validation. Benigno Monteagudo-Sánchez: data curation, supervision, writing – review and editing, validation, investigation, project administration, methodology, visualization, conceptualization. Mónica Castro-Murga: writing – review and editing, visualization, methodology, validation, conceptualization, investigation, project administration, data curation, supervision. Pilar Iriarte-Sotés: conceptualization, investigation, validation, visualization, data curation, supervision, writing – review and editing, methodology, project administration. Informed consent was obtained from the patient for photographs to be taken. The authors declare no conflicts of interest.