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Brief reports 309
Allergic contact dermatitis to topical minoxidil
solution: Etiology and treatment
Edward S. Friedman, BS, Paul M. Friedman, MD, David E. Cohen, MD MPH, and Ken Washenik, MD, PhD New York, New York After more than a decade of use, topical minoxidil solution has proven to be a safe and effective treatmentfor androgenetic alopecia. However, some patients present with complaints of pruritus and scaling of thescalp. The most common causes of these symptoms include irritant contact dermatitis, allergic contactdermatitis, or an exacerbation of seborrheic dermatitis. Patients suffering from allergic contact dermatitismay benefit from patch testing to determine the causative allergen. Among the patients we patch tested,propylene glycol was found to be the contactant in a majority of cases, not the minoxidil itself. Many ofthese patients may be candidates for treatment with alternative formulations using other solvents, such asbutylene glycol, polysorbate, or glycerol. Although predictive, patch testing results do not ensure that thecompounded preparations will be tolerated. Unfortunately, patients found to be allergic to minoxidil are nolonger candidates for topical treatment of their alopecia with any preparations of minoxidil. (J Am AcadDermatol 2002;46:309-12.) Topical minoxidil solution is a hypertrichotic mulation and in 1.9% of the patients using the 2% agent used to treat androgenetic alopecia formulation.4 These included pruritus, erythema, (AGA). AGA results from miniaturization of hair follicles in androgen-sensitive areas of the scalp in genetically predisposed persons.1 Arresting the include irritant contact dermatitis, allergic contact process of miniaturization remains the goal of med- dermatitis, or an exacerbation of seborrheic der- ical treatment. Currently topical minoxidil solution matitis. Differentiation of these conditions is neces- (minoxidil, alcohol, propylene glycol, and purified sary for appropriate intervention because successful water) and oral finasteride are the only therapies for treatment of the local adverse reaction is necessary this condition approved by the Food and Drug for the patient to continue using topical minoxidil in Administration.2 Topical minoxidil solution is the treatment of their alopecia. This report focuses approved for this indication in 2% and 5% formula- on a series of patients whose presentation was most tions. Although minoxidil functions as a vasodilator consistent with an allergic contact dermatitis. The when used systemically for hypertension, its mech- goal in these patients was to utilize patch testing to anism of action in hair loss involves a direct stimu- elucidate the specific causative allergen involved.
latory effect on dermal papillae or follicular hair Identifying the specific contactant may allow contin- uation of the patient’s therapy with an alternative Topical minoxidil solution has a favorable safety profile and is currently available over the counter.
The adverse effects of topical minoxidil solution are SELECTED CASE REPORTS
predominantly dermatologic and limited to the Case 1. A 67-year-old woman with a history of
scalp. The phase III clinical trial listed application site AGA treated with topical minoxidil solution present- reactions in 5.7% of the patients using the 5% for- ed with mild erythema and scaling of the scalp. Shewas patch tested to a series of allergens and demon-strated a positive reaction to propylene glycol. Noreaction to butylene glycol or minoxidil was noted.
From The Ronald O. Perelman Department of Dermatology, New These results indicated that a propylene glycol–free preparation might have utility. The compounded for- mulation substituted butylene glycol for propylene Reprints not available from authors.
glycol. At 10 months, the patient was satisfied with Copyright 2002 by the American Academy of Dermatology, Inc.
the efficacy and tolerability of the compounded for- 16/54/119104
310 Brief reports
Fig 1. Positive allergic contact reaction to 1% minoxidil in isopropanol demonstrated by patch
testing.
Case 2. A 52-year-old woman using topical
Patients with a diagnosis of either irritant contact minoxidil solution to treat her hair loss presented dermatitis or seborrheic dermatitis can be effective- with a complaint of increased scaling and scalp pru- ly treated with anti-inflammatory agents including tar ritus. Patch testing revealed an allergy to propylene shampoo or topical corticosteroids while continuing glycol, but no reaction to butylene glycol or minoxi- their use of topical minoxidil solution. The subset of dil. Despite these patch testing results, she was patients diagnosed as having suspected allergic con- unable to tolerate the compounded formulation tact dermatitis should be patch tested to determine because of continued scaling and pruritus at the whether the allergen is the active ingredient minoxi- dil or the solvent propylene glycol.
Case 3. A 63-year-old man treating his AGA with
Eight additional patients were patch tested in the 5% topical minoxidil solution complained of same manner as the patients described in the case increased pruritus and scaling of the scalp. His pres- reports. In total, there were 7 women and 4 men in entation was consistent with allergic contact der- the group, with an average age of 46.7 years. Nine of matitis, and patch testing was performed. The 11 patients (81.8%) showed a positive allergic reac- results demonstrated a positive reaction to minoxidil tion to propylene glycol by patch testing. Two of the (Fig 1). As a result, he was no longer a candidate for 9 were negative (ie, not sensitive) at a lower concen- using topical minoxidil solution to treat his hair loss.
tration and positive (ie, sensitive) at a higher con-centration of propylene glycol. One of 11 patients DISCUSSION
(9.1%) was reactive to butylene glycol, and 4 of 11 Topical minoxidil solution is an effective treat- patients (36.4%) reacted to the active ingredient ment for regrowth of hair in some patients and sta- bilizes hair loss and miniaturization in a majority of Among the patients we patch tested, propylene them.5 Long-term application is required for contin- glycol was found to be the agent most frequently ued benefit. As with long-term exposure to any responsible for allergic contact dermatitis to minoxi- medicament, over time some patients may develop dil solution. Two patients in our series demonstrated contact dermatitis to a specific ingredient in the a threshold sensitivity because they only reacted to a preparation. Although the safety profile of topical higher concentration of propylene glycol. This con- minoxidil solution is favorable, the most common cept is evident in previous patch test studies,6-9 in complaint among users is scalp pruritus and scaling.
which increasing concentrations of propylene glycol In addition to irritant and allergic contact dermatitis, are less well tolerated. Paradigms for elicitation these symptoms may be due to an exacerbation of thresholds for allergic and irritant contact dermatitis seborrheic dermatitis. While clinically similar, these have been described.8-11 Thus there is utility in using entities must be differentiated for optimal treatment the lowest possible solvent concentration in prepa- outcome and, more importantly, to allow the patient rations for patients with a history of allergic or irri- to continue treating his or her hair loss.
Brief reports 311
Table I. Patch test results for 11 patients suspected of having an allergic contact reaction to topical minoxidil
solution
Patient No.
Age (y)/Sex
Propylene glycol
Butylene glycol
Minoxidil
*Started on compounded preparation.
†Positive at 50%, negative at 20% concentration.
‡Positive at 50%, negative at 10% concentration.
Data from the phase III clinical trial for 2% and 5% lene glycol, glycerin and polysorbate are possible topical minoxidil solution support the concept of alternative solvents.20,21 Given the concept of threshold sensitivity. The 5% minoxidil formulation, threshold elicitation demonstrated in our series, as which contains more propylene glycol (50%) than well as in previous studies, there is utility in using the 2% minoxidil formulation (30%), was associated the lowest solvent concentration required to solubi- with a higher number of cases of itching, erythema, and dryness. This difference is not due to the minox- No clinical studies have been performed compar- idil concentration because the patients using the ing the efficacy of topical minoxidil prepared with vehicle with 50% propylene glycol reported a similar alternative solvents. However, these preparations incidence of adverse events to the patients using the provide a method for delivering minoxidil to the scalps of propylene glycol–sensitive patients. Previous reports have suggested that the active Because topical minoxidil solution is the only Food ingredient, minoxidil, was the more common aller- and Drug Administration–approved topical treatment gen.12-18 However, it should be noted that the series for AGA, the treatment options for hair loss in these of allergens utilized in these studies were not con- patients are very limited. Patients suspected of suffer- sistent and the patient numbers were small. Our ing from allergic contact dermatitis should be advised patch test study was specifically designed to deter- to undergo patch testing to determine the causative mine whether each individual patient was allergic to allergen. If the patients are found to be sensitive to propylene glycol, then they should be given the Patients found to be allergic to propylene glycol option of formulations compounded with alternative were candidates for compounded preparations of solvents. Unfortunately, patients found to be allergic topical minoxidil formulated without propylene gly- to minoxidil are no longer candidates for the topical col. For these patients, we chose butylene glycol treatment of their alopecia with minoxidil; our data when possible as a substitute. Chemical similarity suggest that this is not an infrequent scenario.
between butylene glycol and propylene glycol gives Systemic androgen modulators provide an alternate a high degree of confidence with regard to its poten- treatment option for some of these patients. tial for transcutaneous delivery of minoxidil. Despitethis chemical similarity, an immunologic distinction REFERENCES
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