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Histologic studies in psoriatic patients treated at the Dead Sea: Comparison with photochemotherapy
Brief c o m m u n i c a t i o n s I
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Histologic studies in psoriatic patients treated at the D e a d Sea: C o m p a r i s o n with photochemotherapy Miriam Schewach-Millet, MD," Abraham Feinstein, MD, a Henri Trau, MD," Elizabeth A. Abel, MD, b and Alvin J. Cox, M D b
Tel-Hashomer and Tel-Aviv, Israel, and Palo Alto, California It is well known that chronic ultraviolet exposure may cause aging changes and skin cancer. Apart from studies in psoralen plus ultraviolet A (PUVA)-treated patients, l-s there have been few reports of the histologic side effects of predominantly ultraviolet A (UVA) phototherapy for psoriasis. Accelerated actinic changes, epidermal dystrophy, and melanocytic atypia have been observed following the intensive clearing phase of PUVA. 2'6'7 We were interested in seeing if similar changes occur in patients treated at the Dead Sea.
Materials and methods. For more than 20 years, climatotherapy has been used at the Dead Sea in Israel. This therapy
From Chaim Sheba Medical Center, Tel-Hashomer,Sadder School of Medicine,Tel-AvivUniversity,"and StanfordUniversityMedical Center, Palo Alto) Reprint requests: Miriam Sehewaeh-Millet, MD, Department of Dermatology,Chaim Sheba MedicalCenter, Tel-Hashomer52621, Israel.
I I
cembines exposure to high-intensity UVA due to the naturally filtrated ultravielet spectrum below sea level with other natural factors, such as the high concentration ef salts in the Sea) According to Kushelevsky and Shifrin, 9 the UV content of the sunlight reaching the Dead Sea in the erythemal band (290-330 nm) is particularly lew. The average stay at the Dead Sea for patients is 1 month yearly. Patients of all ages and different forms of psoriasis (mostly extensive plaque-type) are treated at the Dead Sea. The treatment censists of sun exposure, starting with 5 to 15 minutes twice daily, followed by an increase in increments of 10 minutes each day up to a maximum of approximately 6 to 8 hours each day. The patients are told to bathe in the Dead Sea for 10 minutes twice daily. Topical medications include sulfur-salicylic acid ointment used for keratolytic purposes during the first days, followed by coal tar ointments and skin emollients. A group ef 19 patients treated at the Dead Sea once yearly for an average ef 3 years (between 2 and 8 years) were examined by two investigators. All patients were carefully examined for the presence of keratetic lesions and skin cancer prier to therapy. Distribution of skin types among the patients was as follows: skin type II, five patients, skin type III, nine patients, and skin type IV, five patients (Table I). In all of the patients, pretreatment biopsy specimens were taken. In 10, repeat biopsies were done after short-term (1 month) treatment. Some ef the patients had multiple biopsy specimens taken from both involved (psoriatic) and uninvelved skin, as well as from sun-exposed (forearm) and non-sun-exposed areas (buttock).
Results. In this preliminary evaluation, no epidermal dystrophy nor melanocytic atypia was observed when
Table I. Biopsy specimens t a k e n in 19 patients No. of previous treatments at Dead Sea 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 502
3 4 4 3 2 3 4 3 4 4 3 2 3 2 3 2 2 3 3
2 3 1 1 3 5 2 3 1 3 1 1 1 1 1 7 7 2 8
Pretreatment biopsies Uninvolved [ Involved B'nttoek + + + + + + + + + + + + + + + + + +
+ + + + + + + + + + + +
+ + + + + + + + + + + +
I
+ + + + + + + + +
Posttreatment biopsies Uninvolved ~ Involved Butto-~- [ Arm [ Buttock + + + + + + +
+ + + +
+
+ + + + + + +
+ +
+ + +
+ + +
+ + +
+
Volume 20 Number 3 March 1989 biopsy specimens from uninvolved and involved sunexposed and non-sun-exposed skin were compared before and after treatment, as described by Cox and Abel 3 in 1979. Keratotic lesions or skin cancer were not present in our group of patients. The only significant finding, in fact, was the increase in epidermal pigmentation in comparison with pretreatment biopsy specimens in some cases. Discussion. Clinical side effects of skin cancer, pigmentary changes, and actinic damage have not been observed in this group of 19 patients, most of whom were treated for 3 to 4 weeks annually. Histologic studies, as well, failed to detect microscopic changes such as focal epidermal dystrophy or melanoeytic atypia, although five of the patients were of fair skin type (type II). This is in contrast with findings in chronically PUVA-exposed skin in which evidence of aging of the skin, characterized by fine wrinkling and dryness of non--sun-exposed areas, is commonly found. ~ Pigmentary changes consisting of widespread lentigines of both covered and sun-exposed skin (PUVA lentigines) are common following long-term PUVA therapy, although their exact incidence is unknown. Lentigines were not found in our group of patients following treatment at the Dead Sea. At the microscopic level, focal epidermal dystrophy and melanocytic atypia are common findings following long-term therapy with PUVA.I, 2 The lack of epidermal dystrophy or melanocytic atypia in our patients might be attributed to short-term exposure to climatotherapy at the Dead Sea (1 month yearly compared to approximately 4 months for clearing from PUVA). Other risk factors, such as prior x-ray therapy and previous skin cancer, were not present in any of our patient poPulation. Alternatively, because this treatment does not involve a photosensitizing drug that binds to deoxyribonucleic acid (DNA), potential risks of epidermal dystrophy and actinic keratoses may be considerably lessened. These are, of course, preliminary results because of the small number of patients. examined with posttreatment biopsy specimens and the short-term evaluation. Treatment at the Dead Sea may be considered an effective modality in the management spectrum of psoriasis. Further investigations are necessary before considering climatotherapy at the Dead Sea as a "safe" approach to the treatment of moderate to severe psoriasis.
REFERENCES 1. Abel EA, Cox A J, Farber EM. Epidermal dystrophy and actinic keratoses in psoriasis patients followingoral psoralen photochemotherapy (PUVA). J AM ACADDERMATOL 1982;7:333-40. 2. Abel EA, Reid H, Wood C, Hu C-H. PUVA induced melanocytic atypia: is it confined to PUVA lentigines? J AM ACADDERMATOL1985;13;761-8. 3. Cox AJ, Abel EA. Epidermal dystrophy: occurrence
Brief communications
4.
5. 6. 7. 8. 9.
503
after psoriasis with psoralen and long-wave ultraviolet light. Arch Dermatol 1979;115:567-70. Niemi KM, Niemi A, Kanerva L. Morphologic changes in epidermis of PUVA treated patients with psoriasis with or without a history of arsenic therapy. Arch Dermatol 1983;119:904-9. Gsehnait F. Long-term photochemotherapy: histopathological and immunofluorescence observations in 243 patients. Br J Dermatol 1980;103:11-2. Rhodes AR, Stern RS, Melski JW. The PUVA lentigo: an analysis of predisposing factors. J Invest Dermatol 1983;81:459-63. Stern SR, Parrish JA, Fitzpatrick TB, Bleich HL. Actinic degeneration in association with long-term use of PUVA. J Invest Dermatol 1985;84:135-8. Abels DJ, Katton-Byron J. Psoriasis treatment at the Dead Sea: a natural selective ultraviolet phototherapy. J AM ACADD~RMATOL1985;12:639-43. Kushelevsky AP, Shifrin MA. Ultraviolet measurements at the Dead Sea and at Beersheba. Isr J Meal Sei 1975;11:488-90.
Fixed drug eruption due to dimenhydrinate Daniel J. Hogan, MD, FRCP(C), a and Michael E. Rooney, BSP b Saskatoon, Saskatchewan, Canada
The fixed eruption is first seen as sharply demarcated erythema that always recurs in exactly the same place. The erythema darkens, becomes red or violaceous, and vesicles or bullae may occur. The lesion may vary in size. Usually there is only one lesion present. ~ The Guide to Drug Eruptions states that the fixed eruption is the only eruption for which drugs or food chemicals are implicated as the sole etiologic agent? Readministration of the drug is the most dependable test for identification of the responsible agent. Numerous drugs have been implicated as provoking fixed drug eruptions. 1 We report another drug as a cause of a recurrent fixed drug eruption, dimenhydrinate. Case report, A 30-year-old man complained of ten episodes of burning and vesiculation involving the same area of the penis. These episodesoccurred when he had flu associated with nausea. He would always take dimenhydrinate (Gravol) when he had nausea due to flu and never developed the skin eruption on the penis when he did not have a gastrointestinal type of flu and did not take dimenhydrinate. Examination of the penis revealed postinflammatory pigmentation on the distal shaft. The history suggested a fixed drug eruption due to dimenhydrinate, but this drug had not been listed as causing fixed drug eruptions, and the patient was advised to take a capsule of dimenhydrinate. Within a few
From Sectionof Dermatology,Department of Medicine, University Hospital," and College of Pharmacy,b University of Saskatchewan. Reprint requests: Daniel J, Hogan, MD, Section of Dermatology, UniversityHospital,Saskatoon,SK S7N 0X0, Canada.
Ill
I
I III II
I
Histologic studies in psoriatic patients treated at the D e a d Sea: C o m p a r i s o n with photochemotherapy Miriam Schewach-Millet, MD," Abraham Feinstein, MD, a Henri Trau, MD," Elizabeth A. Abel, MD, b and Alvin J. Cox, M D b
Tel-Hashomer and Tel-Aviv, Israel, and Palo Alto, California It is well known that chronic ultraviolet exposure may cause aging changes and skin cancer. Apart from studies in psoralen plus ultraviolet A (PUVA)-treated patients, l-s there have been few reports of the histologic side effects of predominantly ultraviolet A (UVA) phototherapy for psoriasis. Accelerated actinic changes, epidermal dystrophy, and melanocytic atypia have been observed following the intensive clearing phase of PUVA. 2'6'7 We were interested in seeing if similar changes occur in patients treated at the Dead Sea.
Materials and methods. For more than 20 years, climatotherapy has been used at the Dead Sea in Israel. This therapy
From Chaim Sheba Medical Center, Tel-Hashomer,Sadder School of Medicine,Tel-AvivUniversity,"and StanfordUniversityMedical Center, Palo Alto) Reprint requests: Miriam Sehewaeh-Millet, MD, Department of Dermatology,Chaim Sheba MedicalCenter, Tel-Hashomer52621, Israel.
I I
cembines exposure to high-intensity UVA due to the naturally filtrated ultravielet spectrum below sea level with other natural factors, such as the high concentration ef salts in the Sea) According to Kushelevsky and Shifrin, 9 the UV content of the sunlight reaching the Dead Sea in the erythemal band (290-330 nm) is particularly lew. The average stay at the Dead Sea for patients is 1 month yearly. Patients of all ages and different forms of psoriasis (mostly extensive plaque-type) are treated at the Dead Sea. The treatment censists of sun exposure, starting with 5 to 15 minutes twice daily, followed by an increase in increments of 10 minutes each day up to a maximum of approximately 6 to 8 hours each day. The patients are told to bathe in the Dead Sea for 10 minutes twice daily. Topical medications include sulfur-salicylic acid ointment used for keratolytic purposes during the first days, followed by coal tar ointments and skin emollients. A group ef 19 patients treated at the Dead Sea once yearly for an average ef 3 years (between 2 and 8 years) were examined by two investigators. All patients were carefully examined for the presence of keratetic lesions and skin cancer prier to therapy. Distribution of skin types among the patients was as follows: skin type II, five patients, skin type III, nine patients, and skin type IV, five patients (Table I). In all of the patients, pretreatment biopsy specimens were taken. In 10, repeat biopsies were done after short-term (1 month) treatment. Some ef the patients had multiple biopsy specimens taken from both involved (psoriatic) and uninvelved skin, as well as from sun-exposed (forearm) and non-sun-exposed areas (buttock).
Results. In this preliminary evaluation, no epidermal dystrophy nor melanocytic atypia was observed when
Table I. Biopsy specimens t a k e n in 19 patients No. of previous treatments at Dead Sea 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 502
3 4 4 3 2 3 4 3 4 4 3 2 3 2 3 2 2 3 3
2 3 1 1 3 5 2 3 1 3 1 1 1 1 1 7 7 2 8
Pretreatment biopsies Uninvolved [ Involved B'nttoek + + + + + + + + + + + + + + + + + +
+ + + + + + + + + + + +
+ + + + + + + + + + + +
I
+ + + + + + + + +
Posttreatment biopsies Uninvolved ~ Involved Butto-~- [ Arm [ Buttock + + + + + + +
+ + + +
+
+ + + + + + +
+ +
+ + +
+ + +
+ + +
+
Volume 20 Number 3 March 1989 biopsy specimens from uninvolved and involved sunexposed and non-sun-exposed skin were compared before and after treatment, as described by Cox and Abel 3 in 1979. Keratotic lesions or skin cancer were not present in our group of patients. The only significant finding, in fact, was the increase in epidermal pigmentation in comparison with pretreatment biopsy specimens in some cases. Discussion. Clinical side effects of skin cancer, pigmentary changes, and actinic damage have not been observed in this group of 19 patients, most of whom were treated for 3 to 4 weeks annually. Histologic studies, as well, failed to detect microscopic changes such as focal epidermal dystrophy or melanoeytic atypia, although five of the patients were of fair skin type (type II). This is in contrast with findings in chronically PUVA-exposed skin in which evidence of aging of the skin, characterized by fine wrinkling and dryness of non--sun-exposed areas, is commonly found. ~ Pigmentary changes consisting of widespread lentigines of both covered and sun-exposed skin (PUVA lentigines) are common following long-term PUVA therapy, although their exact incidence is unknown. Lentigines were not found in our group of patients following treatment at the Dead Sea. At the microscopic level, focal epidermal dystrophy and melanocytic atypia are common findings following long-term therapy with PUVA.I, 2 The lack of epidermal dystrophy or melanocytic atypia in our patients might be attributed to short-term exposure to climatotherapy at the Dead Sea (1 month yearly compared to approximately 4 months for clearing from PUVA). Other risk factors, such as prior x-ray therapy and previous skin cancer, were not present in any of our patient poPulation. Alternatively, because this treatment does not involve a photosensitizing drug that binds to deoxyribonucleic acid (DNA), potential risks of epidermal dystrophy and actinic keratoses may be considerably lessened. These are, of course, preliminary results because of the small number of patients. examined with posttreatment biopsy specimens and the short-term evaluation. Treatment at the Dead Sea may be considered an effective modality in the management spectrum of psoriasis. Further investigations are necessary before considering climatotherapy at the Dead Sea as a "safe" approach to the treatment of moderate to severe psoriasis.
REFERENCES 1. Abel EA, Cox A J, Farber EM. Epidermal dystrophy and actinic keratoses in psoriasis patients followingoral psoralen photochemotherapy (PUVA). J AM ACADDERMATOL 1982;7:333-40. 2. Abel EA, Reid H, Wood C, Hu C-H. PUVA induced melanocytic atypia: is it confined to PUVA lentigines? J AM ACADDERMATOL1985;13;761-8. 3. Cox AJ, Abel EA. Epidermal dystrophy: occurrence
Brief communications
4.
5. 6. 7. 8. 9.
503
after psoriasis with psoralen and long-wave ultraviolet light. Arch Dermatol 1979;115:567-70. Niemi KM, Niemi A, Kanerva L. Morphologic changes in epidermis of PUVA treated patients with psoriasis with or without a history of arsenic therapy. Arch Dermatol 1983;119:904-9. Gsehnait F. Long-term photochemotherapy: histopathological and immunofluorescence observations in 243 patients. Br J Dermatol 1980;103:11-2. Rhodes AR, Stern RS, Melski JW. The PUVA lentigo: an analysis of predisposing factors. J Invest Dermatol 1983;81:459-63. Stern SR, Parrish JA, Fitzpatrick TB, Bleich HL. Actinic degeneration in association with long-term use of PUVA. J Invest Dermatol 1985;84:135-8. Abels DJ, Katton-Byron J. Psoriasis treatment at the Dead Sea: a natural selective ultraviolet phototherapy. J AM ACADD~RMATOL1985;12:639-43. Kushelevsky AP, Shifrin MA. Ultraviolet measurements at the Dead Sea and at Beersheba. Isr J Meal Sei 1975;11:488-90.
Fixed drug eruption due to dimenhydrinate Daniel J. Hogan, MD, FRCP(C), a and Michael E. Rooney, BSP b Saskatoon, Saskatchewan, Canada
The fixed eruption is first seen as sharply demarcated erythema that always recurs in exactly the same place. The erythema darkens, becomes red or violaceous, and vesicles or bullae may occur. The lesion may vary in size. Usually there is only one lesion present. ~ The Guide to Drug Eruptions states that the fixed eruption is the only eruption for which drugs or food chemicals are implicated as the sole etiologic agent? Readministration of the drug is the most dependable test for identification of the responsible agent. Numerous drugs have been implicated as provoking fixed drug eruptions. 1 We report another drug as a cause of a recurrent fixed drug eruption, dimenhydrinate. Case report, A 30-year-old man complained of ten episodes of burning and vesiculation involving the same area of the penis. These episodesoccurred when he had flu associated with nausea. He would always take dimenhydrinate (Gravol) when he had nausea due to flu and never developed the skin eruption on the penis when he did not have a gastrointestinal type of flu and did not take dimenhydrinate. Examination of the penis revealed postinflammatory pigmentation on the distal shaft. The history suggested a fixed drug eruption due to dimenhydrinate, but this drug had not been listed as causing fixed drug eruptions, and the patient was advised to take a capsule of dimenhydrinate. Within a few
From Sectionof Dermatology,Department of Medicine, University Hospital," and College of Pharmacy,b University of Saskatchewan. Reprint requests: Daniel J, Hogan, MD, Section of Dermatology, UniversityHospital,Saskatoon,SK S7N 0X0, Canada.