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Psoralens and ultraviolet A therapy of pityriasis lichenoides
Volume 10 Number 1 January, 1984
remember where it had been applied; they were sure that they did a more thorough job with the greasier vehicles. (This may be another reason why less alcoholic lotion than cream from a jar was used.) The skip areas could become painfully sunbttmed when the alcoholic lotion is used as a sunscreen. It is important to stress that several layers of a sunscreen should be applied, especially to the back, ears, extremities, and areas immediately adjacent to the bathing suit. In summary, the amount of a topical medication used is influenced more by the size of the patient and the size of the container than by the physical characteristics of the vehicle. For one selfapplication to an entire human body, an average of 22 gm was used. The guideline of 30 gm per application, e.g., for treatment of scabies with lindane lotion, which was derived from clinical experience, has been experimentally vindicated.
Choosing and using a vehicle
Ping Lee at the Scientific Computer Center, SUNY Downstate Medical Center, Brooklyn, NY, performed the statistical review. Dorsey Laboratories, Lincoln, NE, and Westwood Pharmaceuticals Inc., Buffalo, NY, contributed medications. REFERENCES I. Sendroy J, Cecchini LP: Determination of human body surface area from height and weight. J Appl Physiol 7:112, 1954. 2. Harvey AM: Principles and practice of medicine, ed. 20. New York, 1980, Appleton-Century-Crofts, p. 1491. 3. Arndt KA: Manual of dermatologic therapeutics, ed. 2. Boston, 1978, Little, Brown & Co., p. 377. 4. Fitzpatrick TB: Dermatology in general medicine, ed. 2. New York, 1979, McGraw-Hill Book Co., p. 1757. 5. Schlagel CA, Sanborn EM: Weights of topical preparations requh-ed for total and partial body inunction. J Invest Dermatol 42:253-256, 1964.
Psoralens and ultraviolet A therapy of pityriasis lichenoides Frank C. Powell, M.B., M.R.C.P.I., and Sigfrid A. Muller, M.D. Rochester, MN Three patients with long-standing pityriasis lichenoides, which was resistant to other forms of therapy, were successfully treated with PUVA (psoralens and ultraviolet light of wavelength A). One patient had complete clearing of all lesions, and the other two had marked improvement. PUVA is being used to treat increasing numbers of patients with pityriasis lichenoides, and the results have been very good. (J A M ACADDERMATOL 10:59-64, 1984.)
Pityriasis lichenoides is an uncommon distinctive dermatosis of uncertain cause. It is characFrom the Departmentof Dermatology, Mayo Clinic and Mayo Foundation. Accepted for publication May 3, 1983. Reprint requests to: Dr. Frank C. Powell, c/o Section of Publications, Mayo Clinic, 200 First St., SW, Roohester, MN 55905.
terized clinically by discrete, erythematous, scaling papules that may develop hemorrhagic crusts or ulcerate. In most patients, the lesions heal spontaneously in a few months, but they can become chronic in some. The distinction between acute (Mucha-Habermann disease) and chronic (Juliusberg type) pityriasis lichenoides is n o t always clear, there being transitional forms that merge. 59
60
Powell and Muller
Journal of the American Academy of Dermatology
Fig. 1. Case 1. A and B, Before treatment. C and D, At completion of treatment. Lesions that do not heal spontaneously are frequently resistant to therapy, which usually includes antibiotics, sulfones, systemic steroids, and methotrexate. Sunlight m a y be beneficial in some patients. A few patients have responded favorably to PUVA therapy (psoralens and ultraviolet light of wavelength A). Herein we report our experience with PUVA in the management of three patients with pityriasis lichenoides that was resistant to other forms of treatment. PUVA also has been used successfully in the treatment of lymphomatoid papulosis, which has been considered to be a variant of pityriasis lichenoides, in which some of the inflammatory cells are atypical, simulating lymphoma. ~''-' MATERIALS AND METHODS All three patients were women, ages 27, 27, and 53 years old. All patients had persistently recurrent symptomatic papular lesions that were resistant to other
forms of therapy, but all were otherwise in good health. Patient 1 had generalized lesions ranging from vesiculopustules that became crusted or ulcerated to atrophic lesions characterized by postinflammatory pigmentation. Skin biopsy from the left hip showed changes consistent with Mucha-Habermann disease. Her skin disease had been present for 7 months before PUVA therapy was started and was resistant to tetracyclines and steroids systemically. Direct immunofluorescence of lesional skin was negative for IgA, IgM, IgG, C3, and fibrin. Patient 2 had a generalized eruption that had been present for 12 months, with po!ymorphic lesions consisting of guttate erythrosquamous papules (some of which were purpuric) and crusted, infarcted papulonodules with some healed atrophic macules. A skin biopsy specimen showed evidence of Mucha-Habermann disease. Direct immunofluorescence of a lesion showed a faint granular deposition of C3 at the basement membrane zone. The lesions were resistant to tetracyelines, systemic steroids, and methotrexate.
Volume l0 Number 1 January, I984
Patient 3 had multiple erythematous crusted lesions, some of which had resolved with atrophic hyperpigmented scarring. A biopsy specimen of one lesion showed changes consistent with pityriasis lichenoides chronica. Direct immunofluorescence showed faint granular deposition of C3 at the basement membrane zone, which was considered nonspecific. The lesions, which had been present for 24 months, were resistant to tetracyclines, ultraviolet B light, and dapsone. PUVA therapy was administered in a standardized fashion with an upright Sylvania UVA cabinet as utilized by the Boston Cooperative Study Group for psoriasis a The intensity of the ultraviolet A light was measured daily with a caIibrated photometer, and treatment was commenced 2 to 3 hours after the ingestion of methoxsalen, three times a week (C-3 schedule). The duration of treatment ranged from 3 months in Patient 2 to 12 months in Patient 1. RESULTS
The lesions of all patients improved symptomatically, with accelerated healing of lesions during PUVA therapy. The initial response was a clearing of irritation, followed by a reduction in the number of lesions. This was noted after 2 weeks of PUVA therapy. All patients believed that the new lesions which appeared during treatment were less severe than previous ones, did not last as long, and resolved without scarring. No patient had an eruption exacerbated by PUVA. Patient 1 (Fig. 1) received fifty-seven treatments during a I2-month period on a C-3 schedule, for a total of 370.5 joules/cm 2. When therapy was discontinued, she was clear of all lesions and had had no significant recurrence after an 18-month followup. Patient 2, who was unable to complete therapy for personal reasons, received twenty-six treatments during a 3-month period on a C-3 schedule, for a total of 189 joules/cm 2. Eighty percent of her lesions had cleared when PUVA therapy was stopped, Lesions reappeared after cessation of therapy but were less severe than before. Patient 3 was still receiving therapy at the time of writing. She had had thirty-five treatments during a 5month period on a C-3 schedule, for a total of 284.5 joules/cm'-'; 95% of her lesions had cleared. DISCUSSION
Acute pityriasis lichenoides (Mucha-Habermann disease) is a polymorphous eruption of acute
PUVA therapy of pityriasis lichenoides
61
onset and unknown cause which is characterized by the appearance of crops of round or oval scaling papulovesicles in which foci of hemon'hage may occur, evolving into necrosis and ulcers. This type of eruption, which may clear in 3 months, can be associated with fever, malaise, and lymphadenopathy. 4 When lesions finally clear, there may be residual hyperpigmentation or varioliform scarring. Recurrent episodes of acute pityriasis lichenoides are not uncommon, and the disease may evolve into a more chronic type, which also can arise de novo. The chronic variant lacks the acute necrotic and varioliform lesions of MuchaHabermann disease, and systemic symptoms are rare. Individual lesions last 2 to 6 weeks on the average, "~ but the eruption may persist for years. The clinical and histologic features in our three patients resembled those of acute pityriasis lichenoides, but the course was prolonged, with the continuous development of new lesions. These cases are best classified as a persistent variant of acute pityriasis lichenoides. The exact nosologic classification of lymphomatoid papulosis remains to be determined, but some authors believe that at least some variants are related to Mucha-Habermann disease because of the similarity in clinical and histologic findings. G The histologic findings in pityriasis lichenoides are variable and may even vary in the same case. SzymanskF suggested that the basic histopathologic pattern in the acute fon'n is primarily one of lymphocytic vasculitis, although this has been disputed in the literature, s It is not always possible histologically to differentiate clearly between the acute and chronic forms, even though the epidermal features are believed to be more common in the former) Two of our patients had typical histologic changes of acute pityriasis lichenoides, with hemorrhage and necrosis of the epidermis, while one (Patient 3) had less acute lesions resembling an intermediate form similar to both acute and chronic forms. None of our patients had the large pleomorphic hyperchromatic cells that characterize the infiltrate of lymphomatoid papulosis. Treatment of pityriasis lichenoides is symptomatic and has little effect on the progress of the disease2 Suggested therapies have included gold
62
Journal of the American Academy of Dermatology
Powell and Mullet"
Table I. P U V A therapy o f pityriasis lichenoides (PL) and lymphomatoid papulosis No. of ] Totalenergy ] Follow-up Report patients ] Type of PL (joules/cm2) (mo) Acute (5 patients); lymphomatoid papulosis (I patient) Acute (3 patients); chronic (1 patient)
66.8 -+ 46.9 (M + SD)
1-8
34, 316, 56, and 344
20-36
2
Chronic (2 patients)
39 and 37
Thivolet et a125
2
Acute (2 patients)
244.5 and 69
Lange Wantzin and Thomsen zU
5
Lymphomatoid papulosis (5 patients)
57, 56, 92, 124, and 481
Present report
3
Acute persistent (3 patients)
370.5, 189, and 284
Brenner et al m
6
Boelen et al -.2,~-3
4
Hofmann et a124
injections and thorium X. 10 The more commonly used treatments are topical steroid creams and systemic antihistamines which, at best, relieve pruritus and have little influence on the course of the disease. Oxyphenbutazone was used by Kawada et a111 to suppress pityriasis lichenoides, although lesions tended to recur when treatment was stopped. Systemically administered steroids occasionally clear the lesions,12 but prolonged therapy may be required. Vitamin A, vitamin D~, and chinoline derivatives have all been reported to be effective in small groups o f patients, la,14 but these treatments are not recommended in current dermatologic texts. Antibiotics are sometimes useful in clearing the pityriasis lichenoides, and these include high-dose tetracyclines, 15 erythromycin, TM and penicillin, a7 Dapsone may be helpful in some cases. 18 Many cases are resistant to these forms of treatment, and all three o f our patients had no benefit from these agents. Methotrexate was shown to be suppressive in
Comment
Clearing in all 6 patients
Mild recurrences in 3 patients after 23, 23, and 25 mo Not specified Mild recurrences in both patients; lesions reappeared as acute PL in Patient 2 Not specified Cleared completely in 1 patient; lesions recurred after therapy was stopped in 1 patient 1-24 Complete remission in 1 patient; partial remission in 4 patients 18-24 Totally clear 2 yr after therapy in 1 patient; 80% of lesions cleared but recurred when PUVA was stopped in 1 patient; 95% of lesions cleared in 1 patient
most cases of pityriasis lichenoides, 19 but its potential side effects, together with the tendency for the disease to recur when treatment is stopped, make this sodality less attractive. Lesions of pityriasis lichenoides occur less frequently and in milder forms on sun-exposed surfaces, and sunlight has been reported to be beneficial. Takada et al '-'~ monitored fifteen patients with pityriasis lichenoides chronica who exposed themselves to sunlight at seaside resorts and noted some improvement in all and pronounced improvement in thirteen. One of our patients noted improvement with sunlight, which could not be maintained with the use of artificial ultraviolet light B. To date, only a few patients with pityriasis lichenoides have been treated with PUVA, but the overall response has been favorable (Table I). Brenner et a121 treated five patients with pityriasis lichenoides and obtained excellent results. In their series, PUVA therapy led to freedom from symptoms 2 to 6 weeks after commencement of the
Volume 10 Number 1 January, 1984
therapy, and the lesions faded, leaving only residual hyperpigmentation. In addition, these authors treated one patient who had lymphomatoid papulosis for 5 years. Within 31/2 months of therapy, all lesions had flattened and subsequently cleared, leaving only residual hyperpigmentation. Hofmann et al ~4 treated two patients who had pitytiasis lichenoides chronica; both had cleating of their lesions after fifteen to twenty-one PUVA treatments, but one patient subsequently had recurrence of lesions that resembled acute pityriasis lichenoides. Boelen et a122 successfully treated four patients who had pityriasis lichenoides chronica. The patients were free of recurrence from 2 to 18 months after PUVA therapy. Another patient did not respond to PUVA. Study by the same group showed that the patients remained free of lesions 20 to 36 months after treatment. 2"~Ttu'ee of the patients had reculTence of the disease after 25, 23, and 23 months, though the lesions were less extensive than before. Two patients with acute pityriasis lichenoides were treated by Thivolet et al. "~ One had clearance of all lesions after forty-one treatments (244.5 joules/cm=') and the other had clearance of more than 80% of his lesions after seventeen treatments. Recently, Lange Wantzin and Thomsen "6treated five patients with PUVA who had lymphomatoid papulosis for 13 years. One patient had complete remission, while four had partial remissions. All five patients had fewer lesions, and the life cycle of individual lesions was shortened to 1 week from 3 to 6 weeks. How PUVA works is not known, but one suggestion "~ was that PUVA could exert its beneficial effect by altering circulating or intradermal lymphocytes or by changes in superficial cutaneous vessels. It is recognized that PUVA can alter circulating blood cells and immunologic function, both in vivo and in vitro. ~ Our experience with the patients described herein and data from the previously reported thirteen cases of pityriasis lichenoides indicate that PUVA is a reasonable alternative treatment for patients with persistent pityriasis lichenoides, especially when simpler treatments (e.g., ultraviolet light B or antibiotics) have failed. PUVA probably should be considered before more toxic measures (systemic steroids or
PUVA therapy of pityriasis lichenoides
63
methotrexate) are used in an attempt to control the disease. REFERENCES 1. Black MM, Wilson Jones E: "Lymphomatoid" pityfiasis lichenoides. A variant with histological features simulating a lymphoma. A clinical and histopathoiogical study of 15 cases with details of long term follow up. Br J Dermatol 86:329-347, 1972. 2. Valentino LA, Helwig EB: Lymphomatoid papulosis. Arch Pathol 96:409-4161 1973. 3. Melski JW, Tanenbaum L, Parrish JA, et al: Oral methoxsalen photochemotherapy for the treatment of psoriasis. A cooperative clinical trial. J Invest DemaatoI 68:328-335, 1977. 4. Burke DP, Adams RM, Amndell FD: Febrile ulceronecrotic Mucha Habermann's disease. Arch Dermatol 100:200-206, 1969. 5. Rasmussen DM, Everett MA: Parapsoriasis, in Demis DJ, Dobson RL, McGuire J, editors: Clinical dermatology. Philadelphia, 1982, Harper & Row, Publishers Inc., unit 1-6, voL 1, pp. 1-14. 6. Black MM: Lymphomatoid papulosis and pityriasis lichenoides. Are they related.'? Br J Dermatol 106:717721, 1982. 7, Szymanski FJ: Pityriasis lichenoides et vadoliformis acuta. Histopathological evidence that it is an entity distinct from parapsoriasis. Arch Dermatol 79:7-15, 1959, 8. Marks R, Black M, Wilson Jones E: Pityriasis lichenoides: A reappraisal. Br J Derrnatol 86:215-225, 1972. 9. Editorial: Pityriasis lichenoides. Br Meal J 3:368-369, 1972. 10. Ingrain JT: Pityriasis liehenoides and parapsoriasis. Br J Dermatol 65:293-299, 1953. 11. Kawada T, Takada Y, lrisawa K: Treatment of parapsoriasis guttata with oxyphenebutazone. Jpn J Dermatol 75:462, 1965. 12. Winkelmann RK, Lorenc E: Treatment of acute parapsoriasis with corticotropin (.ACTH): Report of a case. Arch Dennatol 79:512-515, 1959. 13. Canizares O: Parapsoriasis: Its treatment with calciferol. Review of eighteen cases. Arch Dermatol Syph 65:675682, 1952. 14. Nagy E, Balogh EI~.:Clinical findings for the treatment of Mucha-Habemaann disease (parapsoriasis varioliformis) with acridine and chinoline derivatives. Dermatologica 118:391-396, 1959. 15. Shelley WB, Griffith RF: Pityriasis lichenoides et variolifomais acuta. A report of a case controlled by a high dosage of tetracycline. Arch Dermatol 100:596-597, 1969. 16. Shavin JS, Jones TM, Aton JK, et al: Mucha-Habermann's disease in children. Treatment with erythromycin. Arch Dermatol 114:1679-1680, 1978. 17. Verallo VM, Haserick JR: Mucha-Habermann's disease simulating lymphoma cuffs. Report of two cases. Arch Det'matol 94:295-299, 1966. 18. McMillan EM, Everett MA: Pityriasis lichenoides et variolifomfis acnta, in Maddin S, Carruthers A, editors: Current dermatologic therapy. Philadelphia, 1982, W. B. Saunders Co.. pp. 362-364.
Journal of the American Academy of Dermatology
Powell and Muller
19. Cornelison RL Jr, Knox JM, Everett MA: Methotrexate for the treatment of Mucha-Habermann disease. Arch Dermatol 106:50%508, 1972. 20. Takada Y, Irisawa K, Kawada A: Heliotherapy of pityriasis liehenoides chronica. Jpn J Dermatol 4.91-94, 1977. 21, Brenner W, Gschnait F, Hgnigsmann H, Fritsch P: Erprobung yon PUVA bei verschiedenen Dermatosen. Hautarzt 29:541-544, 1978. 22. Boelen RE, Lambers JCCA, Faber WR, Cormane RH: Photo(chemo)therapy in pityriasis lichenoides. Br J Dermatol 103:567, 1980, (Abst.) 23. Boelen RE, Faber WR, Lambers JCCA, Cormane RH: Long-term follow-up of photochemotherapy in pityriasis
24. 25. 26. 27.
lichenoides. Acta Derm Venereol (Stockh) 62:442-444, 1982. Hofmann C, Weissmann I, Plewig G: Pityriasis lichenoides chronica--eine neue Indikation zur PUVA-Therapie? Dermatologica 159:451-460, 1979. Thivolet J, Ortonne JP, Gianadda B, Gianadda E: Photochimoth6rapie orale du parapsoriasis en gouttes. Dermatologica 163:12-18,1981. Lange Wantzin G, Thomsen K: PUVA-treatment in lymphomatoid papulosis. Br J Dermatol 107:687-690, 1982. Abel EA, Farber EM: Photochemotherapy, in Rook A, Savin J, editors: Recent advances in dermatology, no. 5. New York, 1980, Churchill Livingstone Inc., pp. 259283.
Spectral power distributions of radiation sources used in phototherapy and photochernotherapy* Warwick L. Morison, M.D.,
and Richard A. Pike, B.S.
Frederick, MD Much attention is focused on the amount o f radiant energy emitted by treatment systems used in phototherapy and photochemotherapy; however, another important property of a radiation source, the spectral power distribution (SPD), has often been ignored. Measurement o f the SPDs of various radiation sources produced unexpected findings. The SPDs of fluorescent bulbs p r o m o t e d specifically for use in psoralen and ultraviolet A (PUVA) therapy was fairly uniform. However, of three blacklight bulbs that also m a y be used for P U V A therapy, each had a different SPD, and one of these bulbs emitted more than 90% of its energy in the ultraviolet (UV) wave band at wavelengths > 3 6 0 nm. The wavelengths emitted by sunlamp fluorescent bulbs and an A l p i n e U V lamp, both of which are used for p h o t o t h e r a p y , were predominantly < 3 2 0 nm. A fluorescent bulb recently introduced for phototherapy had an SPD that was different from that of a P U V A bulb and from that of a sunlamp bulb, with a high emission in the 300- to 3 4 0 - n m w a v e band. These findings indicate that consideration of both the S P D and the irradiance of a radiation source is necessary to determine its suitability for phototherapy or photochemotherapy. (J AM ACAD DERMATOL 10:64-68, 1984.)
From the Immunobiology of Carcinogenesis Laboratory, LBI-Basic Research Program, NCI-Frederlck Cancer Research Facility. Research sponsored by the National Cancer Institute, Department of Health and Human Services, under Contract NO1-CO-23909 with Litton Bionetics, Inc. Accepted for publication May 18, 1983. 64
Reprint requests to: Dr. W. L. Morison, Immunobiology of Carcinogenesis Laboratory, NCI-Frederiek Cancer Research Facility, P.O. Box B, Frederick, MD 21701. *The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States government.
remember where it had been applied; they were sure that they did a more thorough job with the greasier vehicles. (This may be another reason why less alcoholic lotion than cream from a jar was used.) The skip areas could become painfully sunbttmed when the alcoholic lotion is used as a sunscreen. It is important to stress that several layers of a sunscreen should be applied, especially to the back, ears, extremities, and areas immediately adjacent to the bathing suit. In summary, the amount of a topical medication used is influenced more by the size of the patient and the size of the container than by the physical characteristics of the vehicle. For one selfapplication to an entire human body, an average of 22 gm was used. The guideline of 30 gm per application, e.g., for treatment of scabies with lindane lotion, which was derived from clinical experience, has been experimentally vindicated.
Choosing and using a vehicle
Ping Lee at the Scientific Computer Center, SUNY Downstate Medical Center, Brooklyn, NY, performed the statistical review. Dorsey Laboratories, Lincoln, NE, and Westwood Pharmaceuticals Inc., Buffalo, NY, contributed medications. REFERENCES I. Sendroy J, Cecchini LP: Determination of human body surface area from height and weight. J Appl Physiol 7:112, 1954. 2. Harvey AM: Principles and practice of medicine, ed. 20. New York, 1980, Appleton-Century-Crofts, p. 1491. 3. Arndt KA: Manual of dermatologic therapeutics, ed. 2. Boston, 1978, Little, Brown & Co., p. 377. 4. Fitzpatrick TB: Dermatology in general medicine, ed. 2. New York, 1979, McGraw-Hill Book Co., p. 1757. 5. Schlagel CA, Sanborn EM: Weights of topical preparations requh-ed for total and partial body inunction. J Invest Dermatol 42:253-256, 1964.
Psoralens and ultraviolet A therapy of pityriasis lichenoides Frank C. Powell, M.B., M.R.C.P.I., and Sigfrid A. Muller, M.D. Rochester, MN Three patients with long-standing pityriasis lichenoides, which was resistant to other forms of therapy, were successfully treated with PUVA (psoralens and ultraviolet light of wavelength A). One patient had complete clearing of all lesions, and the other two had marked improvement. PUVA is being used to treat increasing numbers of patients with pityriasis lichenoides, and the results have been very good. (J A M ACADDERMATOL 10:59-64, 1984.)
Pityriasis lichenoides is an uncommon distinctive dermatosis of uncertain cause. It is characFrom the Departmentof Dermatology, Mayo Clinic and Mayo Foundation. Accepted for publication May 3, 1983. Reprint requests to: Dr. Frank C. Powell, c/o Section of Publications, Mayo Clinic, 200 First St., SW, Roohester, MN 55905.
terized clinically by discrete, erythematous, scaling papules that may develop hemorrhagic crusts or ulcerate. In most patients, the lesions heal spontaneously in a few months, but they can become chronic in some. The distinction between acute (Mucha-Habermann disease) and chronic (Juliusberg type) pityriasis lichenoides is n o t always clear, there being transitional forms that merge. 59
60
Powell and Muller
Journal of the American Academy of Dermatology
Fig. 1. Case 1. A and B, Before treatment. C and D, At completion of treatment. Lesions that do not heal spontaneously are frequently resistant to therapy, which usually includes antibiotics, sulfones, systemic steroids, and methotrexate. Sunlight m a y be beneficial in some patients. A few patients have responded favorably to PUVA therapy (psoralens and ultraviolet light of wavelength A). Herein we report our experience with PUVA in the management of three patients with pityriasis lichenoides that was resistant to other forms of treatment. PUVA also has been used successfully in the treatment of lymphomatoid papulosis, which has been considered to be a variant of pityriasis lichenoides, in which some of the inflammatory cells are atypical, simulating lymphoma. ~''-' MATERIALS AND METHODS All three patients were women, ages 27, 27, and 53 years old. All patients had persistently recurrent symptomatic papular lesions that were resistant to other
forms of therapy, but all were otherwise in good health. Patient 1 had generalized lesions ranging from vesiculopustules that became crusted or ulcerated to atrophic lesions characterized by postinflammatory pigmentation. Skin biopsy from the left hip showed changes consistent with Mucha-Habermann disease. Her skin disease had been present for 7 months before PUVA therapy was started and was resistant to tetracyclines and steroids systemically. Direct immunofluorescence of lesional skin was negative for IgA, IgM, IgG, C3, and fibrin. Patient 2 had a generalized eruption that had been present for 12 months, with po!ymorphic lesions consisting of guttate erythrosquamous papules (some of which were purpuric) and crusted, infarcted papulonodules with some healed atrophic macules. A skin biopsy specimen showed evidence of Mucha-Habermann disease. Direct immunofluorescence of a lesion showed a faint granular deposition of C3 at the basement membrane zone. The lesions were resistant to tetracyelines, systemic steroids, and methotrexate.
Volume l0 Number 1 January, I984
Patient 3 had multiple erythematous crusted lesions, some of which had resolved with atrophic hyperpigmented scarring. A biopsy specimen of one lesion showed changes consistent with pityriasis lichenoides chronica. Direct immunofluorescence showed faint granular deposition of C3 at the basement membrane zone, which was considered nonspecific. The lesions, which had been present for 24 months, were resistant to tetracyclines, ultraviolet B light, and dapsone. PUVA therapy was administered in a standardized fashion with an upright Sylvania UVA cabinet as utilized by the Boston Cooperative Study Group for psoriasis a The intensity of the ultraviolet A light was measured daily with a caIibrated photometer, and treatment was commenced 2 to 3 hours after the ingestion of methoxsalen, three times a week (C-3 schedule). The duration of treatment ranged from 3 months in Patient 2 to 12 months in Patient 1. RESULTS
The lesions of all patients improved symptomatically, with accelerated healing of lesions during PUVA therapy. The initial response was a clearing of irritation, followed by a reduction in the number of lesions. This was noted after 2 weeks of PUVA therapy. All patients believed that the new lesions which appeared during treatment were less severe than previous ones, did not last as long, and resolved without scarring. No patient had an eruption exacerbated by PUVA. Patient 1 (Fig. 1) received fifty-seven treatments during a I2-month period on a C-3 schedule, for a total of 370.5 joules/cm 2. When therapy was discontinued, she was clear of all lesions and had had no significant recurrence after an 18-month followup. Patient 2, who was unable to complete therapy for personal reasons, received twenty-six treatments during a 3-month period on a C-3 schedule, for a total of 189 joules/cm 2. Eighty percent of her lesions had cleared when PUVA therapy was stopped, Lesions reappeared after cessation of therapy but were less severe than before. Patient 3 was still receiving therapy at the time of writing. She had had thirty-five treatments during a 5month period on a C-3 schedule, for a total of 284.5 joules/cm'-'; 95% of her lesions had cleared. DISCUSSION
Acute pityriasis lichenoides (Mucha-Habermann disease) is a polymorphous eruption of acute
PUVA therapy of pityriasis lichenoides
61
onset and unknown cause which is characterized by the appearance of crops of round or oval scaling papulovesicles in which foci of hemon'hage may occur, evolving into necrosis and ulcers. This type of eruption, which may clear in 3 months, can be associated with fever, malaise, and lymphadenopathy. 4 When lesions finally clear, there may be residual hyperpigmentation or varioliform scarring. Recurrent episodes of acute pityriasis lichenoides are not uncommon, and the disease may evolve into a more chronic type, which also can arise de novo. The chronic variant lacks the acute necrotic and varioliform lesions of MuchaHabermann disease, and systemic symptoms are rare. Individual lesions last 2 to 6 weeks on the average, "~ but the eruption may persist for years. The clinical and histologic features in our three patients resembled those of acute pityriasis lichenoides, but the course was prolonged, with the continuous development of new lesions. These cases are best classified as a persistent variant of acute pityriasis lichenoides. The exact nosologic classification of lymphomatoid papulosis remains to be determined, but some authors believe that at least some variants are related to Mucha-Habermann disease because of the similarity in clinical and histologic findings. G The histologic findings in pityriasis lichenoides are variable and may even vary in the same case. SzymanskF suggested that the basic histopathologic pattern in the acute fon'n is primarily one of lymphocytic vasculitis, although this has been disputed in the literature, s It is not always possible histologically to differentiate clearly between the acute and chronic forms, even though the epidermal features are believed to be more common in the former) Two of our patients had typical histologic changes of acute pityriasis lichenoides, with hemorrhage and necrosis of the epidermis, while one (Patient 3) had less acute lesions resembling an intermediate form similar to both acute and chronic forms. None of our patients had the large pleomorphic hyperchromatic cells that characterize the infiltrate of lymphomatoid papulosis. Treatment of pityriasis lichenoides is symptomatic and has little effect on the progress of the disease2 Suggested therapies have included gold
62
Journal of the American Academy of Dermatology
Powell and Mullet"
Table I. P U V A therapy o f pityriasis lichenoides (PL) and lymphomatoid papulosis No. of ] Totalenergy ] Follow-up Report patients ] Type of PL (joules/cm2) (mo) Acute (5 patients); lymphomatoid papulosis (I patient) Acute (3 patients); chronic (1 patient)
66.8 -+ 46.9 (M + SD)
1-8
34, 316, 56, and 344
20-36
2
Chronic (2 patients)
39 and 37
Thivolet et a125
2
Acute (2 patients)
244.5 and 69
Lange Wantzin and Thomsen zU
5
Lymphomatoid papulosis (5 patients)
57, 56, 92, 124, and 481
Present report
3
Acute persistent (3 patients)
370.5, 189, and 284
Brenner et al m
6
Boelen et al -.2,~-3
4
Hofmann et a124
injections and thorium X. 10 The more commonly used treatments are topical steroid creams and systemic antihistamines which, at best, relieve pruritus and have little influence on the course of the disease. Oxyphenbutazone was used by Kawada et a111 to suppress pityriasis lichenoides, although lesions tended to recur when treatment was stopped. Systemically administered steroids occasionally clear the lesions,12 but prolonged therapy may be required. Vitamin A, vitamin D~, and chinoline derivatives have all been reported to be effective in small groups o f patients, la,14 but these treatments are not recommended in current dermatologic texts. Antibiotics are sometimes useful in clearing the pityriasis lichenoides, and these include high-dose tetracyclines, 15 erythromycin, TM and penicillin, a7 Dapsone may be helpful in some cases. 18 Many cases are resistant to these forms of treatment, and all three o f our patients had no benefit from these agents. Methotrexate was shown to be suppressive in
Comment
Clearing in all 6 patients
Mild recurrences in 3 patients after 23, 23, and 25 mo Not specified Mild recurrences in both patients; lesions reappeared as acute PL in Patient 2 Not specified Cleared completely in 1 patient; lesions recurred after therapy was stopped in 1 patient 1-24 Complete remission in 1 patient; partial remission in 4 patients 18-24 Totally clear 2 yr after therapy in 1 patient; 80% of lesions cleared but recurred when PUVA was stopped in 1 patient; 95% of lesions cleared in 1 patient
most cases of pityriasis lichenoides, 19 but its potential side effects, together with the tendency for the disease to recur when treatment is stopped, make this sodality less attractive. Lesions of pityriasis lichenoides occur less frequently and in milder forms on sun-exposed surfaces, and sunlight has been reported to be beneficial. Takada et al '-'~ monitored fifteen patients with pityriasis lichenoides chronica who exposed themselves to sunlight at seaside resorts and noted some improvement in all and pronounced improvement in thirteen. One of our patients noted improvement with sunlight, which could not be maintained with the use of artificial ultraviolet light B. To date, only a few patients with pityriasis lichenoides have been treated with PUVA, but the overall response has been favorable (Table I). Brenner et a121 treated five patients with pityriasis lichenoides and obtained excellent results. In their series, PUVA therapy led to freedom from symptoms 2 to 6 weeks after commencement of the
Volume 10 Number 1 January, 1984
therapy, and the lesions faded, leaving only residual hyperpigmentation. In addition, these authors treated one patient who had lymphomatoid papulosis for 5 years. Within 31/2 months of therapy, all lesions had flattened and subsequently cleared, leaving only residual hyperpigmentation. Hofmann et al ~4 treated two patients who had pitytiasis lichenoides chronica; both had cleating of their lesions after fifteen to twenty-one PUVA treatments, but one patient subsequently had recurrence of lesions that resembled acute pityriasis lichenoides. Boelen et a122 successfully treated four patients who had pityriasis lichenoides chronica. The patients were free of recurrence from 2 to 18 months after PUVA therapy. Another patient did not respond to PUVA. Study by the same group showed that the patients remained free of lesions 20 to 36 months after treatment. 2"~Ttu'ee of the patients had reculTence of the disease after 25, 23, and 23 months, though the lesions were less extensive than before. Two patients with acute pityriasis lichenoides were treated by Thivolet et al. "~ One had clearance of all lesions after forty-one treatments (244.5 joules/cm=') and the other had clearance of more than 80% of his lesions after seventeen treatments. Recently, Lange Wantzin and Thomsen "6treated five patients with PUVA who had lymphomatoid papulosis for 13 years. One patient had complete remission, while four had partial remissions. All five patients had fewer lesions, and the life cycle of individual lesions was shortened to 1 week from 3 to 6 weeks. How PUVA works is not known, but one suggestion "~ was that PUVA could exert its beneficial effect by altering circulating or intradermal lymphocytes or by changes in superficial cutaneous vessels. It is recognized that PUVA can alter circulating blood cells and immunologic function, both in vivo and in vitro. ~ Our experience with the patients described herein and data from the previously reported thirteen cases of pityriasis lichenoides indicate that PUVA is a reasonable alternative treatment for patients with persistent pityriasis lichenoides, especially when simpler treatments (e.g., ultraviolet light B or antibiotics) have failed. PUVA probably should be considered before more toxic measures (systemic steroids or
PUVA therapy of pityriasis lichenoides
63
methotrexate) are used in an attempt to control the disease. REFERENCES 1. Black MM, Wilson Jones E: "Lymphomatoid" pityfiasis lichenoides. A variant with histological features simulating a lymphoma. A clinical and histopathoiogical study of 15 cases with details of long term follow up. Br J Dermatol 86:329-347, 1972. 2. Valentino LA, Helwig EB: Lymphomatoid papulosis. Arch Pathol 96:409-4161 1973. 3. Melski JW, Tanenbaum L, Parrish JA, et al: Oral methoxsalen photochemotherapy for the treatment of psoriasis. A cooperative clinical trial. J Invest DemaatoI 68:328-335, 1977. 4. Burke DP, Adams RM, Amndell FD: Febrile ulceronecrotic Mucha Habermann's disease. Arch Dermatol 100:200-206, 1969. 5. Rasmussen DM, Everett MA: Parapsoriasis, in Demis DJ, Dobson RL, McGuire J, editors: Clinical dermatology. Philadelphia, 1982, Harper & Row, Publishers Inc., unit 1-6, voL 1, pp. 1-14. 6. Black MM: Lymphomatoid papulosis and pityriasis lichenoides. Are they related.'? Br J Dermatol 106:717721, 1982. 7, Szymanski FJ: Pityriasis lichenoides et vadoliformis acuta. Histopathological evidence that it is an entity distinct from parapsoriasis. Arch Dermatol 79:7-15, 1959, 8. Marks R, Black M, Wilson Jones E: Pityriasis lichenoides: A reappraisal. Br J Derrnatol 86:215-225, 1972. 9. Editorial: Pityriasis lichenoides. Br Meal J 3:368-369, 1972. 10. Ingrain JT: Pityriasis liehenoides and parapsoriasis. Br J Dermatol 65:293-299, 1953. 11. Kawada T, Takada Y, lrisawa K: Treatment of parapsoriasis guttata with oxyphenebutazone. Jpn J Dermatol 75:462, 1965. 12. Winkelmann RK, Lorenc E: Treatment of acute parapsoriasis with corticotropin (.ACTH): Report of a case. Arch Dennatol 79:512-515, 1959. 13. Canizares O: Parapsoriasis: Its treatment with calciferol. Review of eighteen cases. Arch Dermatol Syph 65:675682, 1952. 14. Nagy E, Balogh EI~.:Clinical findings for the treatment of Mucha-Habemaann disease (parapsoriasis varioliformis) with acridine and chinoline derivatives. Dermatologica 118:391-396, 1959. 15. Shelley WB, Griffith RF: Pityriasis lichenoides et variolifomais acuta. A report of a case controlled by a high dosage of tetracycline. Arch Dermatol 100:596-597, 1969. 16. Shavin JS, Jones TM, Aton JK, et al: Mucha-Habermann's disease in children. Treatment with erythromycin. Arch Dermatol 114:1679-1680, 1978. 17. Verallo VM, Haserick JR: Mucha-Habermann's disease simulating lymphoma cuffs. Report of two cases. Arch Det'matol 94:295-299, 1966. 18. McMillan EM, Everett MA: Pityriasis lichenoides et variolifomfis acnta, in Maddin S, Carruthers A, editors: Current dermatologic therapy. Philadelphia, 1982, W. B. Saunders Co.. pp. 362-364.
Journal of the American Academy of Dermatology
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19. Cornelison RL Jr, Knox JM, Everett MA: Methotrexate for the treatment of Mucha-Habermann disease. Arch Dermatol 106:50%508, 1972. 20. Takada Y, Irisawa K, Kawada A: Heliotherapy of pityriasis liehenoides chronica. Jpn J Dermatol 4.91-94, 1977. 21, Brenner W, Gschnait F, Hgnigsmann H, Fritsch P: Erprobung yon PUVA bei verschiedenen Dermatosen. Hautarzt 29:541-544, 1978. 22. Boelen RE, Lambers JCCA, Faber WR, Cormane RH: Photo(chemo)therapy in pityriasis lichenoides. Br J Dermatol 103:567, 1980, (Abst.) 23. Boelen RE, Faber WR, Lambers JCCA, Cormane RH: Long-term follow-up of photochemotherapy in pityriasis
24. 25. 26. 27.
lichenoides. Acta Derm Venereol (Stockh) 62:442-444, 1982. Hofmann C, Weissmann I, Plewig G: Pityriasis lichenoides chronica--eine neue Indikation zur PUVA-Therapie? Dermatologica 159:451-460, 1979. Thivolet J, Ortonne JP, Gianadda B, Gianadda E: Photochimoth6rapie orale du parapsoriasis en gouttes. Dermatologica 163:12-18,1981. Lange Wantzin G, Thomsen K: PUVA-treatment in lymphomatoid papulosis. Br J Dermatol 107:687-690, 1982. Abel EA, Farber EM: Photochemotherapy, in Rook A, Savin J, editors: Recent advances in dermatology, no. 5. New York, 1980, Churchill Livingstone Inc., pp. 259283.
Spectral power distributions of radiation sources used in phototherapy and photochernotherapy* Warwick L. Morison, M.D.,
and Richard A. Pike, B.S.
Frederick, MD Much attention is focused on the amount o f radiant energy emitted by treatment systems used in phototherapy and photochemotherapy; however, another important property of a radiation source, the spectral power distribution (SPD), has often been ignored. Measurement o f the SPDs of various radiation sources produced unexpected findings. The SPDs of fluorescent bulbs p r o m o t e d specifically for use in psoralen and ultraviolet A (PUVA) therapy was fairly uniform. However, of three blacklight bulbs that also m a y be used for P U V A therapy, each had a different SPD, and one of these bulbs emitted more than 90% of its energy in the ultraviolet (UV) wave band at wavelengths > 3 6 0 nm. The wavelengths emitted by sunlamp fluorescent bulbs and an A l p i n e U V lamp, both of which are used for p h o t o t h e r a p y , were predominantly < 3 2 0 nm. A fluorescent bulb recently introduced for phototherapy had an SPD that was different from that of a P U V A bulb and from that of a sunlamp bulb, with a high emission in the 300- to 3 4 0 - n m w a v e band. These findings indicate that consideration of both the S P D and the irradiance of a radiation source is necessary to determine its suitability for phototherapy or photochemotherapy. (J AM ACAD DERMATOL 10:64-68, 1984.)
From the Immunobiology of Carcinogenesis Laboratory, LBI-Basic Research Program, NCI-Frederlck Cancer Research Facility. Research sponsored by the National Cancer Institute, Department of Health and Human Services, under Contract NO1-CO-23909 with Litton Bionetics, Inc. Accepted for publication May 18, 1983. 64
Reprint requests to: Dr. W. L. Morison, Immunobiology of Carcinogenesis Laboratory, NCI-Frederiek Cancer Research Facility, P.O. Box B, Frederick, MD 21701. *The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States government.