INTRODUCTION
Excipients are defined as inert substances added to a drug or food to confer a suitable consistency, appearance, or form. They may be added for bulk, to change dissolution or the kinetics of absorption, to improve stability, to influence palatability, or to create a distinctive appearance. The last function
may depend heavily on the use of coloring agents, especially
when there are multiple dosages (such as with warfarin or L-thyroxine), and dose confusion may result in profound complications.
More often than not, excipients account for the majority of the weight or volume of a medication. While described as inert,
excipients have been associated with triggering various skin reactions. This is rarely and inconsistently considered in common
practice when patients have reactions to medications, even when they appear to react to many different and distinct drugs. We have found a cohort of 11 patients over the past 5 years with chronic, unexplained pruritic skin disorders that have responded to medication changes centered around avoidance of coloring agents. We believe that reactions to agents that color medications
and foods may be more common than previously appreciated,
and recognition of this phenomenon may provide therapeutic
alternatives to patients with intractable pruritic disorders.
Cases
Case 1: The index case was a 61-year-old white male with a multiyear
history of chronic, low-grade hand dermatitis. The patient noticed an explosive flare in hand dermatitis after changing the manufacturer of glyburide/metformin (5 mg/500 mg) mix (Figure 1). He was aware of the change because he noted the appearance of the new tablet was markedly different from what he had previous received, going from a “light-colored†tablet to one he described as being almost black in color. When therapy was switched back to the lighter-colored tablets, the dermatitis promptly resolved. Review of the ingredients of the 2 forms demonstrated that the only difference was that the dark tablets contained FD&C Blue No. 2. He did not report any previous sulfonamide
allergy but did report a similar eruption when placed on hydrochlorothiazide at some point in the past.
Case 2: A 16-year-old white female presented with a severe flare of long-standing atopic eczema whose worsening skin symptoms could only be controlled by the concurrent administration of prednisone
30 mg/day, azathioprine 225 mg/day, cyclosporine 300 mg/day, cetirizine 10 mg twice a day, zafirlukast 20 mg twice a day, and doxepin 50 mg every night at bedtime. All attempts to taper the prednisone dose below 30 mg/day were accompanied by generalized
itching and dermatitis. At one point during the course of her disease, the patient became aware of repeated and acute worsening
of itching within an hour after taking her nighttime doses of doxepin. Further investigation into the inactive ingredients in doxepin led to the discovery that her medication was colored with multiple coloring agents, including FD&C Blue No. 1, FD&C Blue No. 2, D&C Yellow No. 10, D&C Yellow No. 6, and FD&C Red No. 40. The patient was switched from the dye-containing pills to a dye-free liquid form of doxepin. In addition, she also noted that particular prepared foods (eg, candy, breakfast cereals, breakfast bars, yogurt) she consumed also contained these same dyes. We eliminated medications with possible offending dyes and prepared
foods containing food coloring, particularly FD&C Blue No. 2, from her diet. Her long-standing eczema persisted, but within 1 month, the prednisone and cyclosporine were discontinued, and the azathioprine dose was ultimately decreased to 100 mg/day. Her eczema has been stable over the intervening 5 years.
Case 3: A 73-year-old white male with a complex medical history presented with generalized dermatitis and pruritus. He had a history of inflammatory bowel disease treated with small bowel resection, which left him with short bowel syndrome. He had documented gluten sensitivity and markedly elevated immunoglobulin E levels
