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Treatment of keratoderma blennorrhagicum with tazarotene gel 0.1%
Treatment of keratoderma blennorrhagicum with tazarotene gel 0.1% Alan Lewis, MD, Marjory Nigro, MD, and Theodore Rosen, MD Houston, Texas We report near clearing of keratoderma blennorrhagicum following topical application of tazarotene gel 0.1%. This is the first report detailing the use of tazarotene gel for this purpose. (J Am Acad Dermatol 2000;43:400-2.)
T
he hereditary or acquired palmo-plantar keratodermas are a heterogeneous group of diseases characterized by hyperkeratosis of the palms and/or soles. The majority of current treatments demonstrate inconsistent and transient results. This situation is particularly difficult in disorders in which the keratoderma is of less overall concern than other disease manifestations. Reiter’s syndrome (RS) is one such instance, as therapy is traditionally determined by and directed toward arthropathy. As a consequence, there remains a paucity of reported efforts to determine efficient and effective treatments primarily designed for relief of cutaneous symptoms. We report a case of RS, wherein the major cutaneous manifestation, keratoderma blennorrhagicum, nearly completely cleared after topical application of tazarotene gel 0.1%. We believe that this is the first publication detailing this use for tazarotene gel.
CASE REPORT A 64-year-old man with a 15-year history of Reiter’s syndrome with joint manifestations, penile lesions, and keratoderma blennorrhagicum presented for evaluation. His arthritis/arthralgia and penile lesions had adequately responded to nonsteroidal anti-inflammatory drugs (NSAIDs) and topical triamcinolone cream, respectively. His keratoderma had been consistently refractory to treatment with keratolytics (salicylic acid and urea), as well as to topical corticosteroids. On physical examination, the patient’s pedal surfaces This supplement is made possible through an educational grant from Ortho Dermatological to the American Academy of Dermatology. From the Department of Dermatology, Baylor College of Medicine, Veteran’s Affairs Medical Center. Reprint requests: Theodore Rosen, MD, Dermatology Department (F840), One Baylor Plaza, Houston, Texas 77030-3498. 16/4/101932 doi:10.1067/mjd.2000.101932
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were thick, and erythematous with painful superficial erosions (Fig 1). Toenails were dystrophic bilaterally, and both potassium hydroxide (KOH) examination and culture were negative for fungus. The patient was started on a once-daily application of tazarotene gel 0.1% to the soles. By week 4, the keratoderma had almost completely resolved (Fig 2), with markedly decreased pain and substantial resolution of hyperkeratosis. By week 8, the keratoderma completely resolved without any subjective and only minimal objective residual of disease. The patient discontinued application of the tarazotene gel and, at a 12-week follow-up clinic evaluation, the patient remained free of disease. The patient experienced a mild increase in plantar desquamation early in the treatment course, but otherwise experienced no other adverse side effects, no systemic side effects, or toxicities.
DISCUSSION Despite their great heterogeneity, the cutaneous keratodermas share the common denominator of hyperkeratosis. Regardless of cause, these disorders are often refractory to currently available therapies. Reiter’s syndrome is defined by the association of arthritis, urethritis, and conjunctivitis,1 although only about one third of patients fully demonstrate the classic triad. Our patient demonstrated arthritis and the classic cutaneous lesions located on the feet and glans penis. In North America and Great Britain, the most common predisposing cause of RS is nongonococcal urethritis, whereas bacterial (mainly Salmonella)2 and amebic dysenteries are the more common causes in other parts of the world. Disease expression may require both exposure to an antecedent factor (such as infection) and a genetic predisposition. We agree with Belz et al1 that Reiter’s syndrome and psoriasis/psoriatic arthropathy have many features in common. These include radiologic, cutaneous, and histologic findings; nail abnormalities;
J AM ACAD DERMATOL VOLUME 43, NUMBER 2, PART 2
Lewis, Nigro, and Rosen 401
Fig 1. Keratoderma blennorrhagicum pretreatment.
Fig 2. Keratoderma blennorrhagicum after 4 weeks of once-daily tazarotene.
sausage-shaped digits; oligoarthropathy; sacroiliitis; and heel pain. Both diseases are rheumatoid factor and antinuclear antibody (ANA) sero-negative, and both also have an increased incidence of HLA-B27 positivity. The 2 diseases may, in fact, represent a continuum of expression of a single entity. Keratoderma blennorrhagicum (KB) and the skin lesions of psoriasis are both hyperproliferative diseases. The similarity between the 2 diseases has prompted a search for KB treatment using those agents that have proven to be effective for psoriasis. Literature review disclosed a few instances of response associated with oral etretinate,1,3,4 methotrexate,5,6 azathioprine,7 bromocriptine,2 mesalamine,8 and ketoconazole.9 There have also been limited reports of calcipotriene,10 PUVA therapy,11 and occlusive fluorinated topical steroids12 being beneficial. Retinoids have proven to be effective in the treatment of plaque and pustular psoriasis. The clinical and histopathologic features of KB associated with Reiter’s syndrome are almost identical to those of pustular psoriasis.13 These similarities prompted our use of topical tararotene in this refractory case of KB.
In vitro studies have revealed that retinoids form complexes with receptors that modulate transcription, thereby suppressing hyperkeratosis.14,15 It is our belief that this mechanism of action allowed for successful treatment of our patient’s condition. Tazarotenic acid, the active ingredient in tazarotene, has proven to be an effective treatment for mild-to-moderate plaque stage psoriasis.16-20 Tazarotene, unlike other topical retinoids, is receptor selective, exerting its effects by binding specifically to rapidly adapting receptors (RARs) alpha, beta, and gamma. This specificity allows for decreased side effects, compared with the other topical retinoids.16 In addition, the limited systemic absorption of tazarotene may make it a better alternative than oral retinoids and immunosuppressive drugs in the treatment of limited cutaneous disease. In our case, a patient with recalcitrant, recurrent KB and Reiter’s syndrome, experienced nearly complete resolution of keratoderma blennorrhagicum after the topical application of tazarotene gel. The only side effects experienced by our patient were mild-to-moderate erythema and mild exfoliation.
402 Lewis, Nigro, and Rosen
REFERENCES 1. Belz J, Breneman D, Nordland J, Solinger A. Successful treatment of a patient with Reiter’s syndrome and acquired immunodeficiency syndrome using etretinate. J Am Acad Dermatol 1989;20:898-903. 2. Bravo G, Zazueta B, Lavalle C. An acute remission of Reiter’s syndrome in male patients treated with bromocriptine. J Rheumatol 1992;19:747-50. 3. Benoldi D, Alinovi A, Bianchi G, Buticchi G. Reiter’s disease: successful treatment of the skin manifestations with oral etretinate. Acta Derm Venereol 1984;64:352-4. 4. Richman TB, Kerdel FA. Reiter’s syndrome. Arch Dermatol 1988;124:1007-9. 5. Lally EV, Ho G Jr. A review of methotrexate therapy in Reiter’s syndrome. Semin Arthritis Rheum 1985;15:139-45. 6. Owen ET, Cohen ML. Methotrexate in Reiter’s disease. Ann Rheum Dis 1979;38:48-50. 7. Calin A. A placebo-controlled, crossover study of azathioprine in Reiter’s syndrome. Ann Rheum Dis 1986;45:653-5. 8. Thomson GT, McKibbon C, Inman RD. Mesalamine therapy in Reiter’s syndrome. J Rheumatol 1994;21:570-2. 9. Lesher JL, Chalker DK. Response of the cutaneous lesions of Reiter’s Syndrome to ketoconazole. J Am Acad Dermatol 1985; 13:161-3. 10. Thiers BH.The use of topical calcipotriene/calcipotriol in conditions other than plaque-type psoriasis. J Am Acad Dermatol 1997;37:S69-71. 11. Brenner W, Hammerschmied W, Scherak O. Reiter’s disease: successful therapy of keratoderma blennorrhagicum with oral photochemotherapy. Hautarzt 1981;32:193-5.
J AM ACAD DERMATOL AUGUST 2000
12. Volden G. Successful treatment of chronic diseases with clobetasol propionate and a hydrocolloid occlusive dressing. Acta Derm Venereol 1992;72:69-71. 13. Magro CM, Crowson AN, Peeling R. Vasculitis as the basis of cutaneous lesions in Reiter’s disease. Hum Pathol 1995;26:6338. 14. Mangelsdorf DJ, Umeseno K, Evans RM. The retinoid receptors. In: Span MB, Roberts AB, Goodman DS, editors. The retinoids: biology, chemistry and medicine. 2nd ed. New York: Parthenon; 1993. p. 319-49. 15. De Luca LM. Retinoids and their receptors in differentiation, embryogenesis and neoplasia. FASEB J 1991;5:292433. 16. Chandraratna RA. Tazarotene: first of a new generation of receptor-selective retinoids. Br J Dermatol 1996;135(suppl 49):18-25. 17. Marks R. Early clinical development of tazarotene. Br J Dermatol 1996;135(suppl 49):26-31. 18. Weinstein GD, Krueger GG, Lowe NJ, Duvic M, Friedman DJ, Jegasothy BV, et al. Tazarotene gel, a new retinoid, for topical therapy of psoriasis: vehicle-controlled study of safety, efficacy, and duration of therapeutic effect. J Am Acad Dermatol 1997; 37:85-92. 19. Nagpal S, Patel S, Asano AT, Johnson AT, Duvic M, Chandraratna RA, et al. Tazarotene-induced gene 1 (TIG 1), a novel retinoic acid receptor-responsive gene in skin. J Invest Dermatol 1996;106:269-74. 20. Weinstein GD.Tazarotene gel: efficacy and safety in plaque psoriasis. J Am Acad Dermatol 1997;37:S33-8.
T
he hereditary or acquired palmo-plantar keratodermas are a heterogeneous group of diseases characterized by hyperkeratosis of the palms and/or soles. The majority of current treatments demonstrate inconsistent and transient results. This situation is particularly difficult in disorders in which the keratoderma is of less overall concern than other disease manifestations. Reiter’s syndrome (RS) is one such instance, as therapy is traditionally determined by and directed toward arthropathy. As a consequence, there remains a paucity of reported efforts to determine efficient and effective treatments primarily designed for relief of cutaneous symptoms. We report a case of RS, wherein the major cutaneous manifestation, keratoderma blennorrhagicum, nearly completely cleared after topical application of tazarotene gel 0.1%. We believe that this is the first publication detailing this use for tazarotene gel.
CASE REPORT A 64-year-old man with a 15-year history of Reiter’s syndrome with joint manifestations, penile lesions, and keratoderma blennorrhagicum presented for evaluation. His arthritis/arthralgia and penile lesions had adequately responded to nonsteroidal anti-inflammatory drugs (NSAIDs) and topical triamcinolone cream, respectively. His keratoderma had been consistently refractory to treatment with keratolytics (salicylic acid and urea), as well as to topical corticosteroids. On physical examination, the patient’s pedal surfaces This supplement is made possible through an educational grant from Ortho Dermatological to the American Academy of Dermatology. From the Department of Dermatology, Baylor College of Medicine, Veteran’s Affairs Medical Center. Reprint requests: Theodore Rosen, MD, Dermatology Department (F840), One Baylor Plaza, Houston, Texas 77030-3498. 16/4/101932 doi:10.1067/mjd.2000.101932
400
were thick, and erythematous with painful superficial erosions (Fig 1). Toenails were dystrophic bilaterally, and both potassium hydroxide (KOH) examination and culture were negative for fungus. The patient was started on a once-daily application of tazarotene gel 0.1% to the soles. By week 4, the keratoderma had almost completely resolved (Fig 2), with markedly decreased pain and substantial resolution of hyperkeratosis. By week 8, the keratoderma completely resolved without any subjective and only minimal objective residual of disease. The patient discontinued application of the tarazotene gel and, at a 12-week follow-up clinic evaluation, the patient remained free of disease. The patient experienced a mild increase in plantar desquamation early in the treatment course, but otherwise experienced no other adverse side effects, no systemic side effects, or toxicities.
DISCUSSION Despite their great heterogeneity, the cutaneous keratodermas share the common denominator of hyperkeratosis. Regardless of cause, these disorders are often refractory to currently available therapies. Reiter’s syndrome is defined by the association of arthritis, urethritis, and conjunctivitis,1 although only about one third of patients fully demonstrate the classic triad. Our patient demonstrated arthritis and the classic cutaneous lesions located on the feet and glans penis. In North America and Great Britain, the most common predisposing cause of RS is nongonococcal urethritis, whereas bacterial (mainly Salmonella)2 and amebic dysenteries are the more common causes in other parts of the world. Disease expression may require both exposure to an antecedent factor (such as infection) and a genetic predisposition. We agree with Belz et al1 that Reiter’s syndrome and psoriasis/psoriatic arthropathy have many features in common. These include radiologic, cutaneous, and histologic findings; nail abnormalities;
J AM ACAD DERMATOL VOLUME 43, NUMBER 2, PART 2
Lewis, Nigro, and Rosen 401
Fig 1. Keratoderma blennorrhagicum pretreatment.
Fig 2. Keratoderma blennorrhagicum after 4 weeks of once-daily tazarotene.
sausage-shaped digits; oligoarthropathy; sacroiliitis; and heel pain. Both diseases are rheumatoid factor and antinuclear antibody (ANA) sero-negative, and both also have an increased incidence of HLA-B27 positivity. The 2 diseases may, in fact, represent a continuum of expression of a single entity. Keratoderma blennorrhagicum (KB) and the skin lesions of psoriasis are both hyperproliferative diseases. The similarity between the 2 diseases has prompted a search for KB treatment using those agents that have proven to be effective for psoriasis. Literature review disclosed a few instances of response associated with oral etretinate,1,3,4 methotrexate,5,6 azathioprine,7 bromocriptine,2 mesalamine,8 and ketoconazole.9 There have also been limited reports of calcipotriene,10 PUVA therapy,11 and occlusive fluorinated topical steroids12 being beneficial. Retinoids have proven to be effective in the treatment of plaque and pustular psoriasis. The clinical and histopathologic features of KB associated with Reiter’s syndrome are almost identical to those of pustular psoriasis.13 These similarities prompted our use of topical tararotene in this refractory case of KB.
In vitro studies have revealed that retinoids form complexes with receptors that modulate transcription, thereby suppressing hyperkeratosis.14,15 It is our belief that this mechanism of action allowed for successful treatment of our patient’s condition. Tazarotenic acid, the active ingredient in tazarotene, has proven to be an effective treatment for mild-to-moderate plaque stage psoriasis.16-20 Tazarotene, unlike other topical retinoids, is receptor selective, exerting its effects by binding specifically to rapidly adapting receptors (RARs) alpha, beta, and gamma. This specificity allows for decreased side effects, compared with the other topical retinoids.16 In addition, the limited systemic absorption of tazarotene may make it a better alternative than oral retinoids and immunosuppressive drugs in the treatment of limited cutaneous disease. In our case, a patient with recalcitrant, recurrent KB and Reiter’s syndrome, experienced nearly complete resolution of keratoderma blennorrhagicum after the topical application of tazarotene gel. The only side effects experienced by our patient were mild-to-moderate erythema and mild exfoliation.
402 Lewis, Nigro, and Rosen
REFERENCES 1. Belz J, Breneman D, Nordland J, Solinger A. Successful treatment of a patient with Reiter’s syndrome and acquired immunodeficiency syndrome using etretinate. J Am Acad Dermatol 1989;20:898-903. 2. Bravo G, Zazueta B, Lavalle C. An acute remission of Reiter’s syndrome in male patients treated with bromocriptine. J Rheumatol 1992;19:747-50. 3. Benoldi D, Alinovi A, Bianchi G, Buticchi G. Reiter’s disease: successful treatment of the skin manifestations with oral etretinate. Acta Derm Venereol 1984;64:352-4. 4. Richman TB, Kerdel FA. Reiter’s syndrome. Arch Dermatol 1988;124:1007-9. 5. Lally EV, Ho G Jr. A review of methotrexate therapy in Reiter’s syndrome. Semin Arthritis Rheum 1985;15:139-45. 6. Owen ET, Cohen ML. Methotrexate in Reiter’s disease. Ann Rheum Dis 1979;38:48-50. 7. Calin A. A placebo-controlled, crossover study of azathioprine in Reiter’s syndrome. Ann Rheum Dis 1986;45:653-5. 8. Thomson GT, McKibbon C, Inman RD. Mesalamine therapy in Reiter’s syndrome. J Rheumatol 1994;21:570-2. 9. Lesher JL, Chalker DK. Response of the cutaneous lesions of Reiter’s Syndrome to ketoconazole. J Am Acad Dermatol 1985; 13:161-3. 10. Thiers BH.The use of topical calcipotriene/calcipotriol in conditions other than plaque-type psoriasis. J Am Acad Dermatol 1997;37:S69-71. 11. Brenner W, Hammerschmied W, Scherak O. Reiter’s disease: successful therapy of keratoderma blennorrhagicum with oral photochemotherapy. Hautarzt 1981;32:193-5.
J AM ACAD DERMATOL AUGUST 2000
12. Volden G. Successful treatment of chronic diseases with clobetasol propionate and a hydrocolloid occlusive dressing. Acta Derm Venereol 1992;72:69-71. 13. Magro CM, Crowson AN, Peeling R. Vasculitis as the basis of cutaneous lesions in Reiter’s disease. Hum Pathol 1995;26:6338. 14. Mangelsdorf DJ, Umeseno K, Evans RM. The retinoid receptors. In: Span MB, Roberts AB, Goodman DS, editors. The retinoids: biology, chemistry and medicine. 2nd ed. New York: Parthenon; 1993. p. 319-49. 15. De Luca LM. Retinoids and their receptors in differentiation, embryogenesis and neoplasia. FASEB J 1991;5:292433. 16. Chandraratna RA. Tazarotene: first of a new generation of receptor-selective retinoids. Br J Dermatol 1996;135(suppl 49):18-25. 17. Marks R. Early clinical development of tazarotene. Br J Dermatol 1996;135(suppl 49):26-31. 18. Weinstein GD, Krueger GG, Lowe NJ, Duvic M, Friedman DJ, Jegasothy BV, et al. Tazarotene gel, a new retinoid, for topical therapy of psoriasis: vehicle-controlled study of safety, efficacy, and duration of therapeutic effect. J Am Acad Dermatol 1997; 37:85-92. 19. Nagpal S, Patel S, Asano AT, Johnson AT, Duvic M, Chandraratna RA, et al. Tazarotene-induced gene 1 (TIG 1), a novel retinoic acid receptor-responsive gene in skin. J Invest Dermatol 1996;106:269-74. 20. Weinstein GD.Tazarotene gel: efficacy and safety in plaque psoriasis. J Am Acad Dermatol 1997;37:S33-8.