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Treatment of classic pityriasis rubra pilaris
THERAPY
Treatment of classic pityriasis rubra pilaris Charles H. Dicken, MD Rochester, Minnesota Background: Treatment of classic pityriasis rubra pilaris, which almost always progresses to a generalized erythrodermawithmarked,oftendisabling keratoderma ofthe palms andsoles, remains problematic. Objective: Our purpose was to evaluate the results of treatment in a recent period during which the retinoid group of drugs has been available. Methods: The clinical courseof75 patientswithclassic pityriasis rubra pilaris seen from 1982 to 1992 was reviewed. Results: Of 15patients treated withisotretinoin, 10had complete and 2 had partialclearing. Of six treated withetretinate,fourhad clearing. All eightpatients treatedwithmethotrexate had a favorable response. Other forms of treatment, including Goeckerman regimen, corticosteroids, vitamin A, and cyclosporine, were ineffective. Conclusion: Earlydiagnosis and earlytreatmentwithretinoids appeartoofferthebestchance for clearingof pityriasis rubra pilaris. If retinoids failor cannotbe used, methotrexate should be considered. (J AM ACAD DERMATOL 1994;31:997-9.)
A review of 75 patients with pityriasis rubra pilarisseen from 1982to 1992wasdoneto evaluate treatment. This periodwaschosen because retinoids have been available since 1982. The cause of pityriasis rubra pilaris is unknown, but the disorder usuallyproduces an extensive eruption and significant disability as it progresses to a generalized erythroderma. Typicalspread is caudal, with characteristic follicular hyperkeratosis. With time and spread, lesions tend to coalesce; therefore characteristic individual papulesmaynotbepresent. Even in patients with generalized erythroderma, islands of sparing of about 1 em are characteristic. Keratodermaofthepalmsand soles isalmostalways present. The erythemais distinctively orangeor yellow. With extensive disease, ectropion is frequently present. The nails may show longitudinal ridging, subungualhyperkeratosis, and splinterhemorrhage. Griffiths I has proposed five typesof pityriasis rubra pilaris, but hisatypical adult type(II) and atypical juvenile type (V) may represent disorders of keratinization. Thecircumscribedjuvenile type(IV) consists of localized plaques, usually on the elbows and knees, that are sharplydemarcatedareasoffollicular hyperkeratosis and erythema. Thistypedoes
not progress into the widespread classic (I and III) forms and may be a different disease. The classic adult (I) and classic juvenile (III) forms appearto be clinically the same except for the patient's age. According to Griffiths, 1,2 theclassic adulttype(I) has the bestprognosis, with80% clearing in 3 years. Allofthecases inthisreview areofthistype, andthe potential for spontaneous clearing, not the therapy theyreceived, could account forthe improvement in some of these patients. Vitamin A therapywasused, usually in a dosage range of 150,000 to 300,000 units daily. This treatment was not noted to provide significant benefit in this group of patients. Themaintherapy from 1982 to 1992 inthisgroup of patients was with the retinoids-isotretinoin or etretinate-or methotrexate. Almost all patients werehospitalized for 3 to 7 days, a few formoreextendedperiods. In thehospital, theyreceived topical triamcinolone cream 0.05% and tap water wet dressings. This regimen relieved itching, burning, and exfoliation. Allpatients continued touse topical steroids and lubrication for several weeks. Oral antihistamines were usedfor relief of pruritus. ISOTRETINOIN
From the Departmentof Dermatology, MayoClinicand MayoFoundation. Reprint requests: C. H. Dicken, MD, Department of Dermatology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905. Copyrightw 1994by the American Academy of Dermatology, Inc. 0190-9622/94 $3.00 + 0 16/1/57815
Fifteen patients, 16 to 81 years of age, 11 males and 4 females, were treatedwith isotretinoin. Duration of disease before the start of treatment with isotretinoin was 2 to 72 weeks. All patients but one had been hospitalized. Twohadpriortreatment with
997
998
Journal of the American Academy of Dermatology December 1994
Dicken
vitamin A; one of the two received 1 million units a day for 10 days.' The initialdosage of isotretinoin was40 mg twice a day for 12 patients, 60 mg per day for 1, and 40 mg per day for 2. Ten patients experienced clearing after 16to 44 weeks oftreatment,the averagebeing 25 weeks. Two patientshad partial clearingafter 16 and 24 weeks of treatment. Three patients showed no response after treatment for 20 to 24 weeks. Sideeffects were thosetypical for isotretinoin, but no patients stopped treatment because of side effects. Isotretinoin was suggested for another nine patients, but no follow-up was available. ETRETINATE
Six patients,51 to 81 yearsof age, three men and three women, were treatedwithetretinate.Duration of disease before the start of treatment was 4 to 36 weeks. All patientshad been hospitalized. One had had prior vitamin A treatment, without significant improvement. The dosage of etretinate initiallywas 25 mg twice daily, except for one patient who was given 75 mg a day. Four patientsexperienced clearing after 3 to 15 months of treatment; the average was 8 months. Onepatientimproved, but the lesions had not cleared at 3 months; another had not improved at 3 months and decided to stop treatment. Side effects were typical of etretinate, but no patients stopped therapy because of side effects. Etretinate was suggested for another four patients, but no follow-up was available. METHOTREXATE
Eightpatients, 35to 74yearsof age,five men and three women, were treated with methotrexate. Duration of disease before the start of methotrexate therapy was 4 to 36 weeks. All patients had been hospitalized. Three had had prior vitamin A treatment andthree hadhad priorisotretinoin treatment, without significant improvement. The dosage of methotrexaterangedfrom1 to 25mgweekly either as a singledoseor as three doses divided at 12-hour intervals. All eight patients had a favorable response, with clearing in several months. Duration of treatment was 2 to 12 months; the average was 6 months. Treatment was well tolerated, and there were no significant side effects or laboratory abnormalities. Methotrexate was suggested for another five patients, but no follow-up was available.
°
OTHER TREATMENTS
Goeckerman treatment was used for 17 patients, and none had significant improvement. Several patients had previously been given varying courses of systemic corticosteroids; in no patient did these drugs cause remission or clearing. Several patients had vitamin A therapy in varying dosages but had no remissions or clearing. Several patients received onlytopicalcare, but follow-up was not availableto allow any meaningful comparison with other treatments.One patient wastreated withcyclosporine for 16 weeks and did not improve. One patient was treated with vitamin D3, but treatment had to be discontinued after 2 months because of elevated calcium levels. DISCUSSION
Pityriasis rubra pilaris in its classic form almost always progresses to a generalized erythroderma with marked keratoderma of the palms and soles. Oral vitaminA, 150,000 to 300,000IV daily,has beengiven for pityriasis rubra pilaris,but onlyabout onein three patientsshows improvement. In contrast to isotretinoin and etretinate, vitamin A is stored in the liver. Like isotretinoin and etretinate, it also has the potential side effects of teratogenicity and elevated triglycerides. The retinoids, isotretinoin and etretinate, appear to be more effective than vitamin A,4-7 and in this review 10 of 15 patients who were treated with isotretinoin had clearing oftheir lesions after an average of 25 weeks, and 2 others had partial clearing. Thus 12(80%)had significant benefit. It is unclear why three patients failed to respond. Similar results were observed with the six patients treated with etretinate. Success has been reported with methotrexate,but Griffiths! found that only 17of 44 patients had any response. Our experience with methotrexate in the eight patients so treated was more favorable; all eight showed significant clearingin several months. The average duration of treatment was 6 months. The reason for the high response rate as compared with that previously reported is not clear. Almostall patientstreated withisotretinoin, etretinate, or methotrexatewerehospitalized. Almostall were treated. with triamcinolone cream 0.05% and tap water wet dressings. These ancillary measures made the patients more comfortable but probably did not have any long-term therapeutic effect becausethe mostsignificant improvement usuallydoes not occur before manyweeks and may not occur before 4 to 6 months. Symptomatic improvement in
Journal of the American Academy of Dermatology Volume 31, Number 6
erythema, pruritus, scaling, ectropion, and keratoderma may occurby 4 weeks, but patients should be advised that significant improvement or clearing may take 16 to 24weeks or,in a few patients, longer. Experience indicates that dosages lower than the 2.13 mg/kg per day average reported in the multicenter study in 1982 are effective and cause fewer sideeffects." Dosages of0.5to 1mg/kg perday seem to be adequate for treatment-O.S rug/kg per day for etretinateand 1rug/kg perdayforisotretinoinbut the response may vary. It is my impression that early diagnosis and early treatment with retinoids lead to the best chance for clearing. If there is a lack of response to retinoids or a contraindication to their use, methotrexate should be considered. Dosages of 10 to 25 mg a week caused significant clearing in several months (average 6 months) and were well tolerated. UV light therapy is not helpful, as confirmed by the lack of response of any of 17 patients to the Goeckerman treatment.
Funk and M aibacn One patient failed to respond to cyclosporine. The lack of response to the Goeckerman regimen and to cyclosporine confirms that pityriasis rubra pilaris is different from psoriasis. REFERENCES 1. Griffiths WAD.Pityriasis rubra pilaris, ClinExp Dermatol 1980;5:105-12. 2. Griffiths WAD. Pityriasis rubra pilaris: the problemof its classification [Letter]. J AM ACAD DERMATOL 1992; 26:140-1. 3. Randle HW, Diaz-Perez JL, Winkelmann RK. Toxicdoses of vitamin A for pityriasis rubra pilaris. Arch Dermatol 1980;116:888-92. 4. Goldsmith LA, Weinrich AE, Shupack J. Pityriasis rubra pilaris response to 13-cis-retinoic acid (isotretinoin). J AM ACAD DERMATOL 1982;6:710-5. 5. Dicken CH. Isotretinoin treatmentofpityriasis rubra pilaris. JAM ACAD DERMATOL 1987;16:297-301. 6. CohenPR, Prystowsky JR. Pityriasis rubra pilaris: a review of diagnosis and treatment. J AM ACAD DERMATOL 1989;20:801·7. 7. Borok M, Lowe NJ. Pityriasis rubra pilaris. JAM ACAD DERMATOL 1990;22:792-5.
Horizons in pharmacologic intervention in allergic contact dermatitis Jens O. Funk, MD, * and Howard 1. Maibach, MD San Francisco, California The treatment ofallergic contactdermatitis remains a majorchallenge. Currentmanagement strategies consist ofelimination of the allergen when possible and therapy forsymptoms with topical or systemic corticosteroids. With increasing exposure of the human skin to environmental antigens and haptens, moreselective treatmentoptions are needed. Advances in the elucidation of the skin immunesystem and of thecellular and molecular events in immunologic processes may allow targeted methods ofcontrolling delayed hypersensitivity reactions. Thisreview focuses on mechanisms of established therapeutic agents andnewdevelopments, suchasFK 506(tacrolirnus), pentoxifyIIine, andvitamin D3 derivative, forsuppression ofany phaseof allergic contact dermatitis. (J AM ACAD DERMATOL 1994;31:999-1014.)
Allergic contact dermatitis (ACD) is a common and sometimes disabling inflammatory skin disease. The treatment of certain forms of ACD (e.g., from From theDepartment ofDermatology, School ofMedicine, University of California. Reprint requests: Howard I. Maibach, MD, Department ofDermatology, University ofCalifornia, Box 0989, Surge 110, SanFrancisco, CA 94143-0989. *Current address: Department ofDermatology, Ludwig-MaximillansUniversity, Munich, F. R. G. Copyright © 1994 bytheAmerican Academy of Dermatology, Inc. 0190-9622/94 $3.00 + 0
16/1/56475
chromate) remains a majorchallenge. Withincreasing exposure of human skin to environmental antigens and haptens, more efficacious and selective treatmentoptions areneeded. Presently treatment is predominantly prevention or alleviation of symptoms with broad immunosuppression. Advances in the elucidation of the skin immune system I, 2contribute greatly to the development of newstrategies in managing ACD. Thissystem is a complex interaction between immune cells and humoral factors. The afferent and efferent phases in the development ofACD3-6 areillustrated inFig. 1.
999
Treatment of classic pityriasis rubra pilaris Charles H. Dicken, MD Rochester, Minnesota Background: Treatment of classic pityriasis rubra pilaris, which almost always progresses to a generalized erythrodermawithmarked,oftendisabling keratoderma ofthe palms andsoles, remains problematic. Objective: Our purpose was to evaluate the results of treatment in a recent period during which the retinoid group of drugs has been available. Methods: The clinical courseof75 patientswithclassic pityriasis rubra pilaris seen from 1982 to 1992 was reviewed. Results: Of 15patients treated withisotretinoin, 10had complete and 2 had partialclearing. Of six treated withetretinate,fourhad clearing. All eightpatients treatedwithmethotrexate had a favorable response. Other forms of treatment, including Goeckerman regimen, corticosteroids, vitamin A, and cyclosporine, were ineffective. Conclusion: Earlydiagnosis and earlytreatmentwithretinoids appeartoofferthebestchance for clearingof pityriasis rubra pilaris. If retinoids failor cannotbe used, methotrexate should be considered. (J AM ACAD DERMATOL 1994;31:997-9.)
A review of 75 patients with pityriasis rubra pilarisseen from 1982to 1992wasdoneto evaluate treatment. This periodwaschosen because retinoids have been available since 1982. The cause of pityriasis rubra pilaris is unknown, but the disorder usuallyproduces an extensive eruption and significant disability as it progresses to a generalized erythroderma. Typicalspread is caudal, with characteristic follicular hyperkeratosis. With time and spread, lesions tend to coalesce; therefore characteristic individual papulesmaynotbepresent. Even in patients with generalized erythroderma, islands of sparing of about 1 em are characteristic. Keratodermaofthepalmsand soles isalmostalways present. The erythemais distinctively orangeor yellow. With extensive disease, ectropion is frequently present. The nails may show longitudinal ridging, subungualhyperkeratosis, and splinterhemorrhage. Griffiths I has proposed five typesof pityriasis rubra pilaris, but hisatypical adult type(II) and atypical juvenile type (V) may represent disorders of keratinization. Thecircumscribedjuvenile type(IV) consists of localized plaques, usually on the elbows and knees, that are sharplydemarcatedareasoffollicular hyperkeratosis and erythema. Thistypedoes
not progress into the widespread classic (I and III) forms and may be a different disease. The classic adult (I) and classic juvenile (III) forms appearto be clinically the same except for the patient's age. According to Griffiths, 1,2 theclassic adulttype(I) has the bestprognosis, with80% clearing in 3 years. Allofthecases inthisreview areofthistype, andthe potential for spontaneous clearing, not the therapy theyreceived, could account forthe improvement in some of these patients. Vitamin A therapywasused, usually in a dosage range of 150,000 to 300,000 units daily. This treatment was not noted to provide significant benefit in this group of patients. Themaintherapy from 1982 to 1992 inthisgroup of patients was with the retinoids-isotretinoin or etretinate-or methotrexate. Almost all patients werehospitalized for 3 to 7 days, a few formoreextendedperiods. In thehospital, theyreceived topical triamcinolone cream 0.05% and tap water wet dressings. This regimen relieved itching, burning, and exfoliation. Allpatients continued touse topical steroids and lubrication for several weeks. Oral antihistamines were usedfor relief of pruritus. ISOTRETINOIN
From the Departmentof Dermatology, MayoClinicand MayoFoundation. Reprint requests: C. H. Dicken, MD, Department of Dermatology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905. Copyrightw 1994by the American Academy of Dermatology, Inc. 0190-9622/94 $3.00 + 0 16/1/57815
Fifteen patients, 16 to 81 years of age, 11 males and 4 females, were treatedwith isotretinoin. Duration of disease before the start of treatment with isotretinoin was 2 to 72 weeks. All patients but one had been hospitalized. Twohadpriortreatment with
997
998
Journal of the American Academy of Dermatology December 1994
Dicken
vitamin A; one of the two received 1 million units a day for 10 days.' The initialdosage of isotretinoin was40 mg twice a day for 12 patients, 60 mg per day for 1, and 40 mg per day for 2. Ten patients experienced clearing after 16to 44 weeks oftreatment,the averagebeing 25 weeks. Two patientshad partial clearingafter 16 and 24 weeks of treatment. Three patients showed no response after treatment for 20 to 24 weeks. Sideeffects were thosetypical for isotretinoin, but no patients stopped treatment because of side effects. Isotretinoin was suggested for another nine patients, but no follow-up was available. ETRETINATE
Six patients,51 to 81 yearsof age, three men and three women, were treatedwithetretinate.Duration of disease before the start of treatment was 4 to 36 weeks. All patientshad been hospitalized. One had had prior vitamin A treatment, without significant improvement. The dosage of etretinate initiallywas 25 mg twice daily, except for one patient who was given 75 mg a day. Four patientsexperienced clearing after 3 to 15 months of treatment; the average was 8 months. Onepatientimproved, but the lesions had not cleared at 3 months; another had not improved at 3 months and decided to stop treatment. Side effects were typical of etretinate, but no patients stopped therapy because of side effects. Etretinate was suggested for another four patients, but no follow-up was available. METHOTREXATE
Eightpatients, 35to 74yearsof age,five men and three women, were treated with methotrexate. Duration of disease before the start of methotrexate therapy was 4 to 36 weeks. All patients had been hospitalized. Three had had prior vitamin A treatment andthree hadhad priorisotretinoin treatment, without significant improvement. The dosage of methotrexaterangedfrom1 to 25mgweekly either as a singledoseor as three doses divided at 12-hour intervals. All eight patients had a favorable response, with clearing in several months. Duration of treatment was 2 to 12 months; the average was 6 months. Treatment was well tolerated, and there were no significant side effects or laboratory abnormalities. Methotrexate was suggested for another five patients, but no follow-up was available.
°
OTHER TREATMENTS
Goeckerman treatment was used for 17 patients, and none had significant improvement. Several patients had previously been given varying courses of systemic corticosteroids; in no patient did these drugs cause remission or clearing. Several patients had vitamin A therapy in varying dosages but had no remissions or clearing. Several patients received onlytopicalcare, but follow-up was not availableto allow any meaningful comparison with other treatments.One patient wastreated withcyclosporine for 16 weeks and did not improve. One patient was treated with vitamin D3, but treatment had to be discontinued after 2 months because of elevated calcium levels. DISCUSSION
Pityriasis rubra pilaris in its classic form almost always progresses to a generalized erythroderma with marked keratoderma of the palms and soles. Oral vitaminA, 150,000 to 300,000IV daily,has beengiven for pityriasis rubra pilaris,but onlyabout onein three patientsshows improvement. In contrast to isotretinoin and etretinate, vitamin A is stored in the liver. Like isotretinoin and etretinate, it also has the potential side effects of teratogenicity and elevated triglycerides. The retinoids, isotretinoin and etretinate, appear to be more effective than vitamin A,4-7 and in this review 10 of 15 patients who were treated with isotretinoin had clearing oftheir lesions after an average of 25 weeks, and 2 others had partial clearing. Thus 12(80%)had significant benefit. It is unclear why three patients failed to respond. Similar results were observed with the six patients treated with etretinate. Success has been reported with methotrexate,but Griffiths! found that only 17of 44 patients had any response. Our experience with methotrexate in the eight patients so treated was more favorable; all eight showed significant clearingin several months. The average duration of treatment was 6 months. The reason for the high response rate as compared with that previously reported is not clear. Almostall patientstreated withisotretinoin, etretinate, or methotrexatewerehospitalized. Almostall were treated. with triamcinolone cream 0.05% and tap water wet dressings. These ancillary measures made the patients more comfortable but probably did not have any long-term therapeutic effect becausethe mostsignificant improvement usuallydoes not occur before manyweeks and may not occur before 4 to 6 months. Symptomatic improvement in
Journal of the American Academy of Dermatology Volume 31, Number 6
erythema, pruritus, scaling, ectropion, and keratoderma may occurby 4 weeks, but patients should be advised that significant improvement or clearing may take 16 to 24weeks or,in a few patients, longer. Experience indicates that dosages lower than the 2.13 mg/kg per day average reported in the multicenter study in 1982 are effective and cause fewer sideeffects." Dosages of0.5to 1mg/kg perday seem to be adequate for treatment-O.S rug/kg per day for etretinateand 1rug/kg perdayforisotretinoinbut the response may vary. It is my impression that early diagnosis and early treatment with retinoids lead to the best chance for clearing. If there is a lack of response to retinoids or a contraindication to their use, methotrexate should be considered. Dosages of 10 to 25 mg a week caused significant clearing in several months (average 6 months) and were well tolerated. UV light therapy is not helpful, as confirmed by the lack of response of any of 17 patients to the Goeckerman treatment.
Funk and M aibacn One patient failed to respond to cyclosporine. The lack of response to the Goeckerman regimen and to cyclosporine confirms that pityriasis rubra pilaris is different from psoriasis. REFERENCES 1. Griffiths WAD.Pityriasis rubra pilaris, ClinExp Dermatol 1980;5:105-12. 2. Griffiths WAD. Pityriasis rubra pilaris: the problemof its classification [Letter]. J AM ACAD DERMATOL 1992; 26:140-1. 3. Randle HW, Diaz-Perez JL, Winkelmann RK. Toxicdoses of vitamin A for pityriasis rubra pilaris. Arch Dermatol 1980;116:888-92. 4. Goldsmith LA, Weinrich AE, Shupack J. Pityriasis rubra pilaris response to 13-cis-retinoic acid (isotretinoin). J AM ACAD DERMATOL 1982;6:710-5. 5. Dicken CH. Isotretinoin treatmentofpityriasis rubra pilaris. JAM ACAD DERMATOL 1987;16:297-301. 6. CohenPR, Prystowsky JR. Pityriasis rubra pilaris: a review of diagnosis and treatment. J AM ACAD DERMATOL 1989;20:801·7. 7. Borok M, Lowe NJ. Pityriasis rubra pilaris. JAM ACAD DERMATOL 1990;22:792-5.
Horizons in pharmacologic intervention in allergic contact dermatitis Jens O. Funk, MD, * and Howard 1. Maibach, MD San Francisco, California The treatment ofallergic contactdermatitis remains a majorchallenge. Currentmanagement strategies consist ofelimination of the allergen when possible and therapy forsymptoms with topical or systemic corticosteroids. With increasing exposure of the human skin to environmental antigens and haptens, moreselective treatmentoptions are needed. Advances in the elucidation of the skin immunesystem and of thecellular and molecular events in immunologic processes may allow targeted methods ofcontrolling delayed hypersensitivity reactions. Thisreview focuses on mechanisms of established therapeutic agents andnewdevelopments, suchasFK 506(tacrolirnus), pentoxifyIIine, andvitamin D3 derivative, forsuppression ofany phaseof allergic contact dermatitis. (J AM ACAD DERMATOL 1994;31:999-1014.)
Allergic contact dermatitis (ACD) is a common and sometimes disabling inflammatory skin disease. The treatment of certain forms of ACD (e.g., from From theDepartment ofDermatology, School ofMedicine, University of California. Reprint requests: Howard I. Maibach, MD, Department ofDermatology, University ofCalifornia, Box 0989, Surge 110, SanFrancisco, CA 94143-0989. *Current address: Department ofDermatology, Ludwig-MaximillansUniversity, Munich, F. R. G. Copyright © 1994 bytheAmerican Academy of Dermatology, Inc. 0190-9622/94 $3.00 + 0
16/1/56475
chromate) remains a majorchallenge. Withincreasing exposure of human skin to environmental antigens and haptens, more efficacious and selective treatmentoptions areneeded. Presently treatment is predominantly prevention or alleviation of symptoms with broad immunosuppression. Advances in the elucidation of the skin immune system I, 2contribute greatly to the development of newstrategies in managing ACD. Thissystem is a complex interaction between immune cells and humoral factors. The afferent and efferent phases in the development ofACD3-6 areillustrated inFig. 1.
999