A pediatric case report of fixed drug eruption related to carmoisine colorant present in paracetamol syrup.

Various adverse drug reactions, including hypersensitivity skin reaction after the exposure to carmoisine colorant, have already been reported in the literature. This case report gives the details of a 5-year-old male child with a recurrent fixed drug eruption (FDE) over the neck and trunk after the use of paracetamol syrup containing carmoisine as a colorant. Patch test to the carmoisine colorant in the paracetamol syrup was positive. This case report adds an increased awareness of the probability of allergic skin reaction to carmoisine in a previously sensitized person. The report also emphasizes the necessity to consider artificial dyes in pharmaceutical products as a potential cause for FDE. Copyright:

Introduction

Fixed drug eruption (FDE) is an allergic or hypersensitivity skin reaction to a drug that generally reappears at the same anatomic regions and the number of sites may increase consequent to repeated administration of the causative drug.[1] The most frequent cutaneous adverse drug reaction (ADR) attributed to a drug in Indian patients was FDE.[1] FDE is observed generally in children and adolescent age groups.[2] Carmoisine is a Food and Drug Administration (FDA) approved synthetic azo dye used as a colorant in many drugs and has been reported in the literature for causing rare allergic skin reactions in vulnerable individuals, even at acceptable doses.[3] Children are getting attracted by the increased esthetic appearance of pharmaceutical products as a result of the use of dyes to increase their medication adherence.[3] However, this carmoisine is an organic substance that may have the potential to interact with the human body and can rarely cause adverse effects such as skin reactions, respiratory reactions, and hyperactivity in children.[3] This case report adds an increased awareness of the probability of allergic skin reaction to carmoisine in a previously sensitized person. This case report emphasizes the necessity to consider artificial dyes in pharmaceutical products as a potential cause in FDE. We present a case report of FDE to carmoisine colorant in a child.

Case Report

A 5-year-old male child presented to the pediatric outpatient department of the hospital with a history of skin rashes over the neck and trunk for a day. The skin rashes were associated with itching. Medication history revealed the intake of paracetamol syrup for his fever and cold before the development of itching and skin rashes. There was a previous history of similar skin reactions due to paracetamol syrup. The child was conscious and alert, and his pulse rate was 80 beats per minute, blood pressure of 100/60 mmHg, the temperature of 100° F, and respiratory rate of 27 breaths per minute. Laboratory investigations of complete blood count and biochemical investigations were performed and were found to be normal. On cutaneous examination, multiple hyperpigmented patches with surrounding erythema present over the neck and trunk and also few erythematous papules were seen over the trunk [Figures 1 and 2]. The excipients present in the paracetamol syrup such as the colorant (carmoisine, E122) and the preservatives (methyl parahydroxybenzoate E218, ethyl parahydroxybenzoate E214, and propyl parahydroxybenzoate E216) had reports in the literature for causing allergic skin reactions. The active ingredient paracetamol is also known to cause FDE. However, the medication history clearly revealed that the child had not experienced skin reactions after the administration of other dosage forms of paracetamol such as tablet and injection. The patient never developed allergic skin reactions with the multivitamin syrup, which has the same preservatives as that present in paracetamol syrup and is free of the colorant additives. Patch test to the carmoisine colorant in the paracetamol syrup was positive. Based on the patient medication history and the positivity of the patch test, the final diagnosis was made as FDE due to carmoisine colorant and the paracetamol syrup containing carmoisine colorant was stopped. The patient was prescribed with hydrocortisone cream and syrup cetirizine (free of colorant additives) as the treatment for FDE. Furthermore, advised using tablet paracetamol instead of taking syrup paracetamol as the paracetamol syrup without colorants are not available in our hospital. On follow-up evaluation, the child was recovered completely in a week time.

Figure 1

Multiple hyperpigmented patches with surrounding erythema over the face and neck

Figure 2

Hyperpigmented patch with surrounding erythema over the trunk

Discussion

FDE is first described by Bourn in 1889 and is defined as the drug-induced hypersensitivity skin reaction with a distinctive feature of re-occurrence at the similar sites of the skin after repeated administration of the causative agent. There is a latency period of 30 min to 1 day between the drug exposure and the beginning of symptoms. It mainly presents as sharply marginated, round or oval itchy plaques of erythema, and edema having a dusky violaceous/brown color. The most common locations are the extremities in females and the genitalia in males. In addition to this, perianal, periorbital, and trunk lesions can also be seen.[1]

Carmoisine is a red, water-soluble anionic mono-azo dye used as one of the additives in several drugs for commercial, psychological, and practical purposes. Recent studies available in the literature reports that carmoisine exposure may cause rare skin and respiratory reactions in susceptible individuals even at the FDA-approved dose.[4] The exact mechanism behind carmoisine induced FDE is not clear.[5] There may be an involvement of the immune-mediated reaction in this case.[5] In the case of children, ingestion of carmoisine-containing syrup is the main route for pharmaceutical products exposure.[5] The most effective management of carmoisine induced FDE is the withdrawal of the drug-containing carmoisine colorant followed by the application of topical steroids, emollients, and the administration of oral antihistamines.[1]

A number of factors favor carmoisine colorant as the causative agent in our case:First, the patch test to the carmoisine colorant in the paracetamol syrup was positive. Second, the time temporal relationship between carmoisine exposure and the development of FDE in the child was 2 hours. Third, paracetamol is known to cause FDE; however, in our case, the child had a safe medication history with the injection and the tablet forms of the paracetamol. Fourth, the patient had experienced a similar skin reaction to the carmoisine-containing paracetamol syrup in previous exposure. Fifth, the previous studies of the carmoisine reveal that it may cause rare allergic skin reactions. Sixth, the preservatives are identified to cause hypersensitivity skin reactions; however, in our case, the patient had no allergic skin reaction with the preservatives used in the multivitamin syrup and cetirizine syrup as these syrups were free of the colorant additives and also contained the same preservatives as that is present in the paracetamol syrup. Based on the patient medication history and the positivity of the patch test, the FDE can be attributed to the carmoisine colorant alone.

Causality assessment scales concerning causative agent reaction have been evaluated with Naranjo ADR Probability Scale and the World Health Organization (WHO) Uppsala Monitoring Centre causality assessment system. In this case, the causality assessment total score according to Naranjo's algorithm was 7 (5–8 being probable), and as per the WHO Assessment Scale also, it was “probable.” This adverse event was classified as moderate ADR (ADR-Level 3) according to the Hartwig ADR Severity Assessment Scale. This ADR was submitted to Pharmacovigilance Program of India (PvPI) as Department of Clinical Pharmacy, JSS Medical College and Hospital, Mysuru is an ADR monitoring centre (AMC) and southern regional training centre under PvPI.

Above case signifies the necessity to consider artificial dyes in pharmaceutical products as a potential cause in FDE.

Learning points

Rare side effects such as FDE with the use of artificial dyes in pharmaceutical products must be borne in mind while managing any allergic skin reaction in any children.

During the differential diagnosis of an ADR, the healthcare providers should be alert to the point that other than the active constituents, the additives used in the medication dosage form can also cause adverse events.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient's father has given his consent for images and other clinical information to be reported in the journal. The patient's father understands that the child's names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.