Medication Dyes as a Source of Drug Allergy

January 2013 | Volume 12 | Issue 1 | Original Article | 99 | Copyright © January 2013

Robert A. Swerlick MD aand Caren F. Campbell MD b

aDepartment of Dermatology, Emory University School of Medicine, Atlanta, GA bDepartment of Dermatology, Jefferson Medical College, Philadelphia, PA

table 1
above 10,000 IU. Skin biopsy demonstrated modest perivascular lymphohistiocytic infiltration with eosinophils, consistent with a hypersensitivity reaction. Direct immunofluorescence was negative for features of dermatitis herpetiformis or other blistering skin disease. Treatment with aggressive topical steroids resulted in marked clearance of the dermatitis. However, the pruritus persisted.
Over the subsequent 5 years, the patient was treated with systemic corticosteroids, azathioprine, mycophenolic acid, omalizumab, and rituximab, all in conjunction with aggressive anti-H1, anti-H2, and antileukotriene therapy. Pruritus was tolerable with systemic corticosteroid treatment, but response to the other agents was minimal, especially related to corticosteroid-sparing agents. Ultimately, systemic corticosteroid treatment was complicated by iatrogenic Addison’s disease and severe osteoporosis.
This patient used over-the-counter (OTC) diphenhydramine for acute severe itching. He routinely purchased the dye-free liquid, but at one point during his course, when he began to use a dye containing diphenhydramine product (D&C Red No. 27), he noted acute worsening of his pruritus within 1 hour of taking a dose. At that point, he also noted that the hard candy he bought in bulk to provide the calories required to maintain weight because of short bowel syndrome also triggered attacks of itching.
We subsequently reviewed all his medications and found dye-free substitutes for all except tamsulosin, which contained FD&C Blue No. 2. Upon substitution, his itching ceased except for transient itching when he took tamsulosin. Once a dye-free alternative was located, his itching ceased altogether, but when the dye- containing tamsulosin was reintroduced, his itching returned and resolved again when the dye-free form was substituted.
Case 4: A 61-year-old African American female was referred for evaluation of recurrent angioedema associated with bouts of generalized pruritus for 3 years. She was suspected to have an allergy to yellow dyes and an aspirin allergy, given the presence of nasal polyps and chronic urticaria. She had no history of asthma. However, avoidance of these triggers failed to alleviate her itching and angioedema. Control of hypertension was a major problem, with apparent flares of her skin problem with every regimen of oral agents tried. While oral clonidine induced angioedema and generalized pruritus, clonidine patches were tolerated and resulted in improved but not optimal blood pressure control. When evaluated in the dermatology department, her most recent oral regimen, consisting of metoprolol, hydrochlorothiazide, and amlodipine, was found to contain medication dyes, including FD&C Blue No. 1 and No. 2, FD&C Yellow No. 6 and No. 10, and FD&C Red No. 28 dyes. Based on the suspicion of excipients allergy, we recommended strict use of dye-free oral medications. In the intervening year, she has had only rare episodes of angioedema and itching, some of which were clearly attributable to inadvertent ingestion of offending dyes. In particular, she noted an episode of angioedema initiated by ingestion of OTC cetirizine that contained FD&C Blue No. 1.
Case 5: A 42-year-old white male with 9-month history of axillary, perianal, and waist itching with subtle urticarial eruption was initially unable to identify any specific triggers. The itch improved but did not completely resolve with oral H1 antihistamines. Paradoxically, he noted acute worsening with OTC cetirizine. His presentation suggested systematized allergic dermatitis, perhaps to FD&C Blue No. 1 in the cetirizine, but no additional source could be identified. Over the subsequent year, the symptoms waxed and waned without apparent triggers, with improvement but not resolution on treatment with fexofenadine and zafirlukast. In August 2011, he noted complete resolution of his itching when he traveled and forgot his usual personal care items. Of note, the only major change in products was substitution for Sensodyne Iso-Active Whitening Gel toothpaste (GlaxoSmithKline, Lewisburg, PA), which contains FD&C Blue No. 1.

Clinical Summary of Remainder of Patients

A total of 11 patients (5 men, 6 women) were identified where there was a high index of suspicion for a potential dye trigger. Their average age was 54.5 ± 19 years. The universal presenting symptom was pruritus with all but one patient presenting with generalized itching. Three patients presented with urticaria and/or angioedema. None of the patients reported wheezing or other respiratory symptoms. The duration of symptoms before initial presentation ranged from as short as 1 week to as long as 20 years. Seven of the 11 patients experienced continuous symptoms for more than 1 year before diagnosis.