- Email: [email protected]
Successful treatment of recalcitrant eczematous dermatitis with leflunomide
e148 Letters
Flutamide is a nonsteroidal antiandrogen that competes with androgens for binding to androgen receptors. Topical flutamide is absorbed into the skin and systemic absorption has been reported.5 A search of PubMed and Google Scholar using the terms ‘‘flutamide’’ and ‘‘Becker’s,’’ ‘‘Becker nevus,’’ or ‘‘Becker melanosis’’ showed no previous reports of flutamide used for treatment of Becker nevus. Our finding supports the theory of androgendependent nature of Becker nevus and introduces a potential treatment modality for this hyperpigmented anomaly. Although our patient showed a satisfactory response to topical flutamide, more studies are needed to support this finding and evaluate the safety of this treatment. Further studies should evaluate the ideal length of treatment and follow up patients after treatment to determine whether repigmentation occurs after cessation of therapy. In addition, because systemic absorption of topical flutamide occurs, this treatment should not be used in pregnant women to avoid feminization of male fetuses and male patients should be informed of potential for side effects such as gynecomastia. Arash Taheri, MD,a Parisa Mansoori, MD,b Laura F. Sandoval, DO,a and Steven R. Feldman, MD, PhDa,b,c Center for Dermatology Research, Departments of Dermatology,a Pathology,b and Public Health Sciences,c Wake Forest University School of Medicine, Winston-Salem, North Carolina The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories LP. Disclosure: Dr Feldman is a consultant and speaker for Galderma, Connetics, Abbott Labs, Warner Chilcott, Centocor, Amgen, Photomedex, Genentech, BiogenIdec, Taro, and Bristol Myers Squibb. Dr Feldman has received grants from Galderma, Connetics, Astellas, Abbott Labs, Warner Chilcott, Centocor, Amgen, Photomedex, Genentech, BiogenIdec, Coria, Pharmaderm, Ortho Pharmaceuticals, Aventis Pharmaceuticals, Roche Dermatology, 3M, Bristol Myers Squibb, Stiefel, GlaxoSmithKline, and Novartis and has received stock options from Photomedex. Drs Taheri, Mansoori, and Sandoval have no conflicts of interest to declare. Correspondence to: Arash Taheri, MD, Department of Dermatology, Wake Forest University School of Medicine, 4618 Country Club Rd, WinstonSalem, NC 27104 E-mail: [email protected]
J AM ACAD DERMATOL
SEPTEMBER 2013
REFERENCES 1. Bhawan J, Chang WH. Becker’s melanosis: an ultrastructural study. Dermatologica 1979;159:221-30. 2. Person JR, Longcope C. Becker’s nevus: an androgen-mediated hyperplasia with increased androgen receptors. J Am Acad Dermatol 1984;10:235-8. 3. Formig on M, Alsina MM, Mascar o JM, Rivera F. Becker’s nevus and ipsilateral breast hypoplasia: androgen-receptor study in two patients. Arch Dermatol 1992;128:992-3. 4. Nirde P, Dereure O, Belon C, Lumbroso S, Guilhou JJ, Sultan C. The association of Becker nevus with hypersensitivity to androgens. Arch Dermatol 1999;135:212-4. 5. Katchen B, Dancik S, Millington G. Percutaneous penetration and metabolism of topical (14C) flutamide in men. J Invest Dermatol 1976;66:379-82. http://dx.doi.org/10.1016/j.jaad.2013.03.026
Successful treatment of recalcitrant eczematous dermatitis with leflunomide To the Editor: Not all patients with eczematous dermatitis respond to conservative treatment, which means that systemic therapies or light therapy must be considered. Leflunomide may be of benefit in these patients. A 49-year-old healthy white woman presented with a 14-year history of eczematous dermatitis primarily affecting her hands and feet. Her condition fluctuated, with vesicles and bullae developing on the sides of her fingers and soles. Her plantar disease was variably incapacitating, with thickened, cracked, and painful skin (Fig 1), making walking difficult, leading to significant weight gain. She had been treated with high potency topical steroids, topical picrolimus, lactic acid and urea-containing creams, oral antibiotics, oral ketoconazole, and oral corticosteroids. None elicited more than temporary relief. A biopsy specimen of her left sole was obtained, and the histopathologic results were consistent with eczematous or atopic dermatitis. An intramuscular injection of triamcinolone 40 mg was unhelpful, as were topical coal tar and ichthammol. A patch test revealed allergies to fragrance mix, nickel sulfate, balsam of Peru, cobalt chloride, and cinnamaldehyde. Avoidance of these chemicals failed to result in improvement. The patient was prescribed mycophenolate mofetil 500 mg twice daily with only mild improvement. Because no relief had ensued after 4 months and the patient was anxious to pursue other options, the mycophenolate mofetil was discontinued and the patient was prescribed azathioprine 25 mg daily. Significant gastrointestinal upset ensued almost immediately, and she stopped taking azathioprine after 1 week. Because light therapy was impractical, leflunomide 20 mg daily was prescribed. After 1 month, her hands were largely disease-free and her feet had improved. After
J AM ACAD DERMATOL
Letters e149
VOLUME 69, NUMBER 3
Fig 1. Chronic eczematous dermatitis at presentation. Note the erosions and fissures.
reported in 32% of rheumatoid arthritis patients.1 It causes transaminase elevation in 2% to 4% of patients, usually within the first 6 months of therapy. It is contraindicated in pregnant women or women of childbearing potential who are not using reliable contraception. Three patients with recalcitrant atopic or eczematous dermatitis treated with this drug have been reported.2,3 All improved, with 1 patient being able to discontinue leflunomide. Eotaxin-3 levels and atopic dermatitis severity have been linked.4 There is also evidence that eotaxin release by eosinophils is inhibited by leflunomide in vitro, leading to speculation that this represents the drug’s mechanism of action in atopic dermatitis.5 As with psoriasis, leflunomide should not be considered a first-line treatment option; however, it does appear to be effective in some patients with recalcitrant disease. Alan S. Boyd, MD Departments of Medicine (Dermatology) and Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, Tennessee Funding sources: None. Conflicts of interest: None declared. Correspondence to: Alan S. Boyd, MD, 719 Thompson Ln, Ste 26300, Nashville, TN 37204
Fig 2. The chronic eczematous dermatitis resolved after 2 months of leflunomide therapy (20 mg/day).
2 months, her soles were essentially clear (Fig 2). After 5 months of therapy, the medication was reduced to every other day. The patient’s blood work was unremarkable. After 1 year of treatment, she remains disease-free and the drug is being tapered. She has resumed walking and has lost 35 pounds. Leflunomide is classified as an oral diseasemodifying antirheumatic drug and is used in the treatment of both rheumatoid and psoriatic arthritis.1 It also has a favorable track record in treating cutaneous psoriasis, although it is not considered a first-line medication. The drug inhibits dihydroorotate dehydrogenase, decreasing the available intracellular pyrimidines and making activated lymphocytes unable to enter the S phase of the cell cycle. The most common side effect is diarrhea,
E-mail: [email protected] REFERENCES 1. Boyd AS. Leflunomide in dermatology. J Am Acad Dermatol 2012;66:673-9. 2. Schmitt J, Wozel G, Pfeiffer C. Leflunomide as a novel treatment option in severe atopic dermatitis. Br J Dermatol 2004;150:1182-5. 3. Wozel G, Vitez L, Pfeiffer C. Severe atopic dermatitis and leflunomide: first clinical experience and highlights of pertinent experimental data. Dermatol Online J 2008;12:6. 4. Kagami S, Kakinuma T, Saeki H, Tsunemi Y, Fujita H, Nakamura K, et al. Significant elevation of serum levels of eotaxin-3/CCL26, but not of eotaxin-2/CCL24, in patients with atopic dermatitis: serum eotaxin-3/CCL26 levels reflect the disease activity of atopic dermatitis. Clin Exp Immunol 2003;134:309-13. 5. Kehere T, Blumlein K, Wozel G. Eotaxin release is suppressed by the metabolite A 77 1726 of the novel immunomodulating agent leflunomide. Eur J Allergy Clin Immunol 2001;56(suppl 68):144. http://dx.doi.org/10.1016/j.jaad.2013.04.003
Flutamide is a nonsteroidal antiandrogen that competes with androgens for binding to androgen receptors. Topical flutamide is absorbed into the skin and systemic absorption has been reported.5 A search of PubMed and Google Scholar using the terms ‘‘flutamide’’ and ‘‘Becker’s,’’ ‘‘Becker nevus,’’ or ‘‘Becker melanosis’’ showed no previous reports of flutamide used for treatment of Becker nevus. Our finding supports the theory of androgendependent nature of Becker nevus and introduces a potential treatment modality for this hyperpigmented anomaly. Although our patient showed a satisfactory response to topical flutamide, more studies are needed to support this finding and evaluate the safety of this treatment. Further studies should evaluate the ideal length of treatment and follow up patients after treatment to determine whether repigmentation occurs after cessation of therapy. In addition, because systemic absorption of topical flutamide occurs, this treatment should not be used in pregnant women to avoid feminization of male fetuses and male patients should be informed of potential for side effects such as gynecomastia. Arash Taheri, MD,a Parisa Mansoori, MD,b Laura F. Sandoval, DO,a and Steven R. Feldman, MD, PhDa,b,c Center for Dermatology Research, Departments of Dermatology,a Pathology,b and Public Health Sciences,c Wake Forest University School of Medicine, Winston-Salem, North Carolina The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories LP. Disclosure: Dr Feldman is a consultant and speaker for Galderma, Connetics, Abbott Labs, Warner Chilcott, Centocor, Amgen, Photomedex, Genentech, BiogenIdec, Taro, and Bristol Myers Squibb. Dr Feldman has received grants from Galderma, Connetics, Astellas, Abbott Labs, Warner Chilcott, Centocor, Amgen, Photomedex, Genentech, BiogenIdec, Coria, Pharmaderm, Ortho Pharmaceuticals, Aventis Pharmaceuticals, Roche Dermatology, 3M, Bristol Myers Squibb, Stiefel, GlaxoSmithKline, and Novartis and has received stock options from Photomedex. Drs Taheri, Mansoori, and Sandoval have no conflicts of interest to declare. Correspondence to: Arash Taheri, MD, Department of Dermatology, Wake Forest University School of Medicine, 4618 Country Club Rd, WinstonSalem, NC 27104 E-mail: [email protected]
J AM ACAD DERMATOL
SEPTEMBER 2013
REFERENCES 1. Bhawan J, Chang WH. Becker’s melanosis: an ultrastructural study. Dermatologica 1979;159:221-30. 2. Person JR, Longcope C. Becker’s nevus: an androgen-mediated hyperplasia with increased androgen receptors. J Am Acad Dermatol 1984;10:235-8. 3. Formig on M, Alsina MM, Mascar o JM, Rivera F. Becker’s nevus and ipsilateral breast hypoplasia: androgen-receptor study in two patients. Arch Dermatol 1992;128:992-3. 4. Nirde P, Dereure O, Belon C, Lumbroso S, Guilhou JJ, Sultan C. The association of Becker nevus with hypersensitivity to androgens. Arch Dermatol 1999;135:212-4. 5. Katchen B, Dancik S, Millington G. Percutaneous penetration and metabolism of topical (14C) flutamide in men. J Invest Dermatol 1976;66:379-82. http://dx.doi.org/10.1016/j.jaad.2013.03.026
Successful treatment of recalcitrant eczematous dermatitis with leflunomide To the Editor: Not all patients with eczematous dermatitis respond to conservative treatment, which means that systemic therapies or light therapy must be considered. Leflunomide may be of benefit in these patients. A 49-year-old healthy white woman presented with a 14-year history of eczematous dermatitis primarily affecting her hands and feet. Her condition fluctuated, with vesicles and bullae developing on the sides of her fingers and soles. Her plantar disease was variably incapacitating, with thickened, cracked, and painful skin (Fig 1), making walking difficult, leading to significant weight gain. She had been treated with high potency topical steroids, topical picrolimus, lactic acid and urea-containing creams, oral antibiotics, oral ketoconazole, and oral corticosteroids. None elicited more than temporary relief. A biopsy specimen of her left sole was obtained, and the histopathologic results were consistent with eczematous or atopic dermatitis. An intramuscular injection of triamcinolone 40 mg was unhelpful, as were topical coal tar and ichthammol. A patch test revealed allergies to fragrance mix, nickel sulfate, balsam of Peru, cobalt chloride, and cinnamaldehyde. Avoidance of these chemicals failed to result in improvement. The patient was prescribed mycophenolate mofetil 500 mg twice daily with only mild improvement. Because no relief had ensued after 4 months and the patient was anxious to pursue other options, the mycophenolate mofetil was discontinued and the patient was prescribed azathioprine 25 mg daily. Significant gastrointestinal upset ensued almost immediately, and she stopped taking azathioprine after 1 week. Because light therapy was impractical, leflunomide 20 mg daily was prescribed. After 1 month, her hands were largely disease-free and her feet had improved. After
J AM ACAD DERMATOL
Letters e149
VOLUME 69, NUMBER 3
Fig 1. Chronic eczematous dermatitis at presentation. Note the erosions and fissures.
reported in 32% of rheumatoid arthritis patients.1 It causes transaminase elevation in 2% to 4% of patients, usually within the first 6 months of therapy. It is contraindicated in pregnant women or women of childbearing potential who are not using reliable contraception. Three patients with recalcitrant atopic or eczematous dermatitis treated with this drug have been reported.2,3 All improved, with 1 patient being able to discontinue leflunomide. Eotaxin-3 levels and atopic dermatitis severity have been linked.4 There is also evidence that eotaxin release by eosinophils is inhibited by leflunomide in vitro, leading to speculation that this represents the drug’s mechanism of action in atopic dermatitis.5 As with psoriasis, leflunomide should not be considered a first-line treatment option; however, it does appear to be effective in some patients with recalcitrant disease. Alan S. Boyd, MD Departments of Medicine (Dermatology) and Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, Tennessee Funding sources: None. Conflicts of interest: None declared. Correspondence to: Alan S. Boyd, MD, 719 Thompson Ln, Ste 26300, Nashville, TN 37204
Fig 2. The chronic eczematous dermatitis resolved after 2 months of leflunomide therapy (20 mg/day).
2 months, her soles were essentially clear (Fig 2). After 5 months of therapy, the medication was reduced to every other day. The patient’s blood work was unremarkable. After 1 year of treatment, she remains disease-free and the drug is being tapered. She has resumed walking and has lost 35 pounds. Leflunomide is classified as an oral diseasemodifying antirheumatic drug and is used in the treatment of both rheumatoid and psoriatic arthritis.1 It also has a favorable track record in treating cutaneous psoriasis, although it is not considered a first-line medication. The drug inhibits dihydroorotate dehydrogenase, decreasing the available intracellular pyrimidines and making activated lymphocytes unable to enter the S phase of the cell cycle. The most common side effect is diarrhea,
E-mail: [email protected] REFERENCES 1. Boyd AS. Leflunomide in dermatology. J Am Acad Dermatol 2012;66:673-9. 2. Schmitt J, Wozel G, Pfeiffer C. Leflunomide as a novel treatment option in severe atopic dermatitis. Br J Dermatol 2004;150:1182-5. 3. Wozel G, Vitez L, Pfeiffer C. Severe atopic dermatitis and leflunomide: first clinical experience and highlights of pertinent experimental data. Dermatol Online J 2008;12:6. 4. Kagami S, Kakinuma T, Saeki H, Tsunemi Y, Fujita H, Nakamura K, et al. Significant elevation of serum levels of eotaxin-3/CCL26, but not of eotaxin-2/CCL24, in patients with atopic dermatitis: serum eotaxin-3/CCL26 levels reflect the disease activity of atopic dermatitis. Clin Exp Immunol 2003;134:309-13. 5. Kehere T, Blumlein K, Wozel G. Eotaxin release is suppressed by the metabolite A 77 1726 of the novel immunomodulating agent leflunomide. Eur J Allergy Clin Immunol 2001;56(suppl 68):144. http://dx.doi.org/10.1016/j.jaad.2013.04.003