- Email: [email protected]
Successful treatment of musk ketone-induced chronic actinic dermatitis with cyclosporine and PUVA
838
Journal of the American Academy of Dermatology
Halasz et al.
5. Anderson L J, Tsou C, Parker RA, et al. Detection of antibodies and antigens of human parvovirus B 19 by enzymelinked immunosorbent assay. J Clin Microbiol 1986;24: 522-6. 6. Bell LM, Naides S J, Stoffman P, et al. Human parvovirus B 19 infection among hospital staff members after contact with infected patients. N Engi J Med 1989;321:485-9l. 7. Anderson M J, Higgins PG, Davis LR, et al. Experimental parvoviral infection in humans. J Infect Dis 1985;152:25765. 8. Anderson M J, Lewis E, Kiss IM, et al. An outbreak of erythema infectiosum associated with human parvovirus infection. J Hyg (Camb) 1984;93:85-93. 9. Anderson MJ. Role of parvovirus B19 in haman disease. Pediatr Infect Dis J 1987;6:711-8. 10. Naides SJ, Piette W~ Veach L, et al. Human parvovirus B19-induced vesiculopustular skin eruption. Am J Med 1988;84:968-72.
11. Naides SJ. Transient liver enzyme abnormalities in acute human parvovirus (HPV) infection [Abstract]. Clin Res 1987;35:859A. 12. Kurtzman GJ, Gascon P, Caras M, et al. B19 parvovirus replicates in circulating cells of acutely infected patients. Blood 1988;71:1448-54. 13. Dinerman JL Corman LC. Human parvovirus B19 arthropathy associated with desquamation. Am J Med 1990; 89:826-8. 14. Anderson M J, Jones SE, Fisher-Hoch SP, et al. Human parvovirus, the cause of erythema infectiosum (fifth disease) [Letter]. Lancet 1983;1:1378. 15. Plummer FA, Hammond GW, Forward K, et al. An erythema infectiosum-like illness caused by human parvovirus infection. N Engl J Med 1985;313:74-9. 16. Zisman AS. Human parvovirus infection [Letter]. N Engl J Med 1986;314:645-7.
Successful treatment of musk ketone-induced chronic actinic dermatitis with cyclosporine and PUVA Jesfis Gardeazfibal, M D , M a r i a A. Arregui, M D , Natalia Gil, M D , N e r e a Landa, M D , Juan A. R a t 6 n , M D , and Jos6 L. Di/tz-Prrez, M D , P h D Bilbao, Spain We describe a patient with chronic actinic dermatitis whose photopatch tests revealed reactions to musk ketone and musk ambrette, both of which were found in his aftershave lotion. Minimal erythema doses of U V A and UVB were decreased. After initial unsuccessful treatment with P U V A therapy the patient was successfully treated with a combination of cyclosporine and PUVA. (J AM AcAo DERMATOL 1992;27:838-42.) Chronic actinic dermatitis ( C A D ) describes different, persistent, p h o t o i n d u c e d eruptions that are considered variants of the same clinicopathologic entity, l, 2 C A D has been described in patients after they have had topical exposure to halogetaated sap icylanilides, m u s k ambrette, a n d other sensitizers. 3, 4 S o m e t i m e s no cause c a n b e found, s T h e different synthetic nitromusks are used extensively as fragrances and fixatives in p e r f u m e s and m a n y toiletries. T r e a t m e n t o f C A D with P U V A , UVB, and azathioprine has h a d variable results. 69 G o o d reFromthe Departmentof Dermatotogy,Hospitalde Cruces,University of the BasqueCountry. Reprint requests: Jestls Gardeaz~ibal,MD, Servieiode Dermatologla, Hospital de Cruces,Plaza de Cruces s/n, Bilbao,Vizcaya,Spain. 16/4/34843
sponses to cyclosporine have recently been obtained, but all of the patients had relapses after discontinuation of the d r u g ] , 2o, 11 W e report a case of C A D that was induced by musk ketone and was successfully treated wkh cyclosporine and P U V A , with no relapse after discontinuation of cyclosporine. CASE R E P O R T A 53-year-old man with a cutaneous eruption that was limited to sun-exposed areas was examined in April 1990. Past history included hypertension, which was treated with hydrochlorothiazide from April 1988 until March 1990 and hand eczema, which had patch test reactions to nickel and chrome. The photodermatitis began 2~/~years before examination as a recurrent eruption that appeared on his face in the spring and summer and cleared during
Volume 27 Number 5, Part 2 November 1992
Chronic actinic dermatitis
839
Fig. 1. Diffuse infiltrated and scaling dermatitis localized to sun-exposed skin.
Fig. 2. The same patient after 4-month treatment with cyetosporine and PUVA.
the winter. During the previous summer the eruption extended to the dorsa of his hands and the V-area of his neck and forearms, and did not clear in the winter. Despite discontinuation of thiazide therapy in March 1990, the lesions remained unchanged. Examination in April 1990 revealed an intense, erythematous, eczematous eruption of the scalp, face, V-area of the neck, nuchal region, dorsa of the hands, and extensor forearms (Fig. 1). The results of two skin biopsy specimens were consistent with a diagnosis of chronic eczema. Results of direct immunofluorescence testing were negative. Phototesting of the normal-appearing skin of the lower back was performed with a solar simulator (Solar Light Co., Philadelphia, Pa.). The minimal erythemal doses (MED) were as follows: MED UVB (WG 320 filter, Schott Glass Technologies Inc., Duryea, Pa.) was 3 inch (normal, 39 to 51 inch); MED UVA (WG-360 filter, Schott Glass Technologies Inc., Duryea, Pa.) was 4 feet (normal reaction, no erythema with 10 feet); and MED with PUVA 800 measured with the ultraviolet meter (Herbert Waldmann GMBH & Co., Schwenningen, FRG) was 3 J/cm 2 (normal, 70 to 100 J/cm2). Cutane-
ous lesions were reproduced on nonaffected areas when the skin underwent irradiation with doses of UVA and UVB higher than the MED. Photopatch testing revealed reactions to musk ketone, musk ambrette, and the patient's aftershave lotion (Table I). The manufacturer confirmed the presence of musk ambrette (0.0007%) and musk ketone (0.0017%) in the aftershave lotion. In the hospital the patient was put in a dark room, the use of all his toiletries was stopped, and treatment with prednisone (60 mg/day) and chloroquine (250 rag/day) was begun. The eruption cleared in 2 weeks, and he was discharged from the hospital; he continued the same treatment as an outpatient and was given instructions to use sunscreens and to avoid exposure to the sun. He was readmitted to the hospital 3 weeks later with an intense eczematous eruption on the previously affected areas. The eruption again cleared after he spent 10 days in a dark room and continued treatment with prednisone and chloroquine. PUVA therapy was begun, but his eruption worsened on the previously affected areas within 24 hours of his first PUVA treatment. PUVA therapy was diseon-
840
Journal of the American Academy of Dermatology
Gardeazhbal et aL
Table I. Results of patch tests and photopatch tests
Scandinavian standard photopatch testn~ Balsam of Peru 25% petrolatum Musk ambrette 1% petrolatum Hydrochlorothiazide 5% petrolatum Nitromusk Musk ketone 1% petrolatum Musk xylene 1% petrolatum Musk tibetine 1% petrolatum Musk moskene 1% petrolatum Aftershave lotion (Flo'/d genuine) Foam shave
Patch tests*
Photopatch testst
++
++
w
+++
++
Results: *Patch tests (96 hours) and tphotopatch tests (48 hours after irradiation with 0.5 J/crn2). :l:ChernoteehniqueDiagnostics AB, MaimS, Sweden.
tinued, and oral cyclosporine (5 mg/kg/day in two divided doses) was started. Complete clearing of the eruption occurred within 10 days. Chloroquine was discontinued, and oral corticosteroids were withdrawn within 1 month. No disease exacerbation was observed, although his MED for UVA and UVB remained decreased. Three weeks after the initiation of cyclosporine, PUVA therapy was resumed with initial doses of 2 J/cm. 2 Because no side effects were observed, each exposure was increased by 0.2 J/cm 2 (with five exposures per week for 2 weeks) and then increased by 1 J/era; (with three exposures per week). When a dosage of 15 J/cm 2 per exposure 3 times a week was reached, cyclosporine was gradually withdrawn and completely discontinued after a total treatment period of 4 months (Fig. 2). Results of laboratory tests including a full blood cell count, renal and hepatic function tests, urine, plasma, and red blood cell porphyrin levels were normal or negative. The patient's blood pressure was normal. Cyclosporine blood levels remained below 105 ng/ml as determined by radioimmunoassay with monoclonal antiserum. Six months after the cessation of cyclosporine the patient remains disease free on low-dose PUVA therapy (10 J/cm 2 once every 2 weeks). MED cannot be assessed because of the intense hyperpigrnentation from the PUVA therapy. DISCUSSION Uniform criteria to define CAD have recently been established 2 and are as follows: (1) a persistent eczematous eruption sometimes associated with papules and plaques and predominantly involving exposed skin, although sometimes extending to covered areas; (2) reduction in the MED to UVB and often to U V A irradiation of covered skin, with reproduction of the lesions at irradiated sites; and (3) histologic appearance consistent with chronic ec-
zema, with or without lymphoma-like changes. Our patient fulfilled all of these criteria. The origin of CAD is controversial. Many photoallergens such as halogenated salicylanilides have been implicated. 3 In 1979 patients were described who had photocontact dermatitis induced by musk ambrette contained in aftershave lotions. 4 Since then numerous cases of musk ambrette-induced photocontact dermatitis have been reported, either as permanent or transient reactions. 12d7 Synthetic musk compounds are used extensively as fixatives and fragrances in a variety of aftershave products, and musk ambrette has been the most commonly used musk subtype in the cosmetic industry. We have not found any reports implicating musk ketone in cases of CAD. In Wojnarowska and Calnan's 14 series of patients with contact and photocontact allergy to musk ambrette, the photopatch test of only 1 of 21 patients revealed a reaction to musk ketone. This patient's clinical picture and the intensity of the patch reaction were not described. In another series of 13 patients who had a reaction to musk ambrette, only one had a reaction to a photopatch test for musk ketone. 17 The low rate of simultaneous reactions to both musk compounds suggests that crossreactions between musk ambrette and musk ketone are not frequent. Our patient had photopatch test reactions to musk ketone and musk ambrette, both of which were found in his aftershave lotion. The intensity of the patch reaction to musk ketone was greater than the patch reaction to musk ambrette. These results suggest that musk ketone was mainly responsible for the photodermatitis of our patient and that musk ambrette was a concomitant sensitizer. Although
Volume 27 Number 5, Part 2 November 1992
CAD cases related to thiazide ingestion have been reported, 18 we ruled out the possibility of a link between our patient's CAD and thiazide ingestion because his eruption started several months before this drug was prescribed. The treatment of patients with CAD usually begins with a complete avoidance of all known topical or systemic photoallergens; patients are also instructed to avoid sun exposure and to use high-protection sunscreens. Because this approach alone is often ineffective, diverse therapies have also been tested. Topical and systemic corticosteroids induce a mild reduction of the inflammation and pruritus, but in most cases they do not result in clinical remission. Oral immunosuppressive therapy with azathioprine at doses of 0.5 to 2 mg/kg/day has been used,8, 9 with complete remission of the cutaneous eruption in many cases. This treatment is not always effective, however, and relapses occur after discontinuation of the drug. In addition, gastrointestinal, hematologic, and hepatotoxic side effects limit its long-term use. PUVA and UVB therapy, often accompanied by topical or systemic corticosteroids, have been used successfully to treat patients with CAD. 6, 7 Although the mechanism is not known, they seem to induce a progressive tolerance of the skin to ultraviolet radiation by producing a protective hyperpigmentation. In addition, the number of epidermal Langerhans cells and their function are diminished, which results in a reduced irnmunoresponsiveness of the skin. t9 However, initial doses of PUVA treatment may trigger or aggravate photosensitive dermatitis. This happened to our patient after his first exposure to PUVA. Treatment of CAD with cyclosporine at doses of 2 to 5 mg/kg/day has recently been reported], lo, 11 Complete remission was achieved, but relapses occurred in all patients after discontinuation of the drug. Our patient was treated with a combination of cyclosporine and PUVA. After cyclosporine brought the CAD into remission, PUVA treatments were started again. The PUVA dose was progressively increased and the cyclosporine dosage was then decreased. Cyclosporine was discontinued after 4 months of treatment, and PUVA therapy was continued. The patient is now receiving low-dose PUVA treatments and remains free of disease 6 months after cyclosporine was discontinued. We believe that the patient has had a long remission because PUVA
Chronic actinic dermatitis
841
therapy was added to the regimen of treatment with cyclosporine. Apparently, cyclosporine and PUVA act synergically in their immunomodulatory effects. The addition of PUVA therapy allows the patient to take lower doses of cyclosporine, which minimizes undesirable side effects, including long-term neoplasia induction. The combination of PUVA and cyclosporine treatments also seems to prolong remission. Our patient benefited from this combined treatment without experiencing side effects. To the best of our knowledge, no other case of CAD that was treated with a combination of cyclosporine and PUVA has been reported. However, this therapy has been used in patients w i t h psoriasis.2O, 21 REFERENCES 1. Hawk JLM, Magnus IA. Chronic actinic dermatitis--an idiopathic photosensitivity syndrome including actinic reticuloid and photosensitive eczema. Br J Dermatol 1979;101:2gs. 2. Norris PG, Hawk JLM. Chronic actinic dermatitis. A unifying concept. Arch Dermatol 1990;126:376-8. 3. Wilkinson DS. Photodermatitis due to tetrachlorsalycilanilide. Br J Derrnatol 1961;73:213-9. 4. Raugi G J, Storrs F J, Larsen WG. Photoallergie contact dermatitis to men's perfume. Contact Dermatitis 1979; 5:251-60. 5. Ive FA, Magnus IA, Warin RP, et ak Actinic reticuloid: a chronic dermatosis associated with severe photosensitivity and the histological resemblance to lymphoma. Br J Dermatol 1969;81:469-85. 6. Hindson C, Spire J, Downey A. PUVA therapy of chronic actinic dermatitis. Br J Dermatol 1985;113:15%60. 7. Toonstra J, Henquet CJM, Weelden H, et al. Actinic reticuloid: a clinical, photobiologic, histopathologic, and follow-up study of 16 patients. J AM ACAD DERMATOL 1989;21:205-14. 8. Leigh IM, Hawk JLM. Treatment of chronic actinic dermatitis with azathioprine. Br J Dermatol 1984;110:691-5. 9. Murphy GM, Mauriee PDL, Norris PG, et al. Azathioprine treatment in chronic actinic dermatitis: a double-blind controlled trial with monitoring of exposure to ultraviolet radiation. Br J Dermatol 1989;121:639-46. 10. Duschet P, Schwarz T, Oppolzer G, et al. Successful treatment of persistent light reaction with cyclosporin A: a case report. Acta Derm Venereol (Stockh) 1988;68:176-8. 11. Norris PG, Camp RDR, Hawk JLM. Actinic reticuloid: response to cyclosporine. J AM ACAD DERMATOL 1989; 21:307-9. 12. Lecha M, Romaguera C, Grimalt F, et al. Photosensitivity to musk ambrette. Photodermatol Photoimmunol Photomed 1984;1:313-5. 13. Serrano G, Aliaga A, de la Cuadra J, et al. Photodermatol Photoimmunol Photomed 1986;3:186-8. 14. Wojnarowska F, Calnan CD. Contact and photocontact allergy to musk ambrette, Br J Dermatol 1986; 114:667-75. 15. Sfinchez-Pedrefie P, Garcia-Bravo B, Rodfiguez-Pichardo
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A, et al. Differentclinicalpresentationsin photosensitivity to musk ambrette. Photodermatol Photoimmunol Photomed 1989;6:103-5. 16. Ramsay CA, Transient and persistentphotosensitivitydue to musk ambrette.Clinical and photobiologiealstudies. Br J Dermatol 1984;111:423-9. 17. Bruze M, Edman B, Niklasson B, et al. Thin layer chromatographyand high pressureliquidchromatography of musk ambretteand other nitromuskcompoundsincludingphotopatchstudies.PhotodermatolPhotoimmunolPhotomed 1985;2:295-302. 18. RobinsonHM, Morison WL, Hood AF. Thiazide diuretic therapy and chronic photosensitivity. Arch ,Dermatol 1985;121:522-4.
IIIII
III
19. Friedmann PSF. Disappearance of epidermal Langerhans cells during PUVA therapy. Br J Dermatol 1981;105:21924. 20. Korstanje M J, Hulsmans RFHJ. Combination therapy cyclosporine A-PUVA in psoriasis. Aeta Derm Venereol (Stockh) 1990;70:89-90. 21. Petzelbauer P, Honigsmann H, Langer K, et al. Cyclosporine Ain combinationwithphotochemotherapy (PUVA) in the treatment of psoriasis. Br J Dermatol 1990;123:641-7. 22. Jansen CT, Wennersten G, Rystedt I, et al. The Scandinavian standard photopatch test procedure. Contact Dermatitis 1982;8:155-8.
I
II
I
I
Long-term management of basal cell nevus syndrome with topical tretinoin and 5-fluorouracil PhiUip R. Strange, MD, and Pearon G. Lang, Jr., M D Albuquerque, New Mexico, and
Charleston, South Carolina The case of a child with basal cell nevus syndrome whose condition was successfully managed for I 0 years with a combination of topical 5-flurouracil and tretinoin is reported. The concurrent use of these two agents prevented the development of new tumors, inhibited the growth of existing tumors, and caused the regression of superficially invasive basal cell carcinomas. (J AM ACAD DERMATOL1992;27:842-5.) Basal cell nevus syndrome (BCNS) is an autosomal dominant multisystem disorder characterized by multiple basal cell carcinomas (BCCs) of the skin, pits of the palms or soles, odontogenic cysts, ectopic calcification, subnormal mentation, ocular hypertelorism, and skeletal abnormalities such as bifid ribs and spina bifida, t We describe a child with B C N S whose B C C s have been successfully treated for 10 years with topical tretinoin and 5-fluorouracil. CASE REPORT A 25-month-old white girl had a family history of BCNS; her father, paternal grandmother, great grandmother, and great uncle were affected. The patient had developed multiple skin lesions, and findings of a biopsy specimen of one of the lesions showed that it was a BCC.
FromtheDepartmentsof Dermatology,LovelaceMedicalCenterand the MedicalUniversityof South Carolina. Reprinksnot available. 16/'4/34733
On physical examination the patient had several red papules and numerous nevocellular nevilike and milialike lesions scattered on her body (Fig. 1). Findings of biopsy specimens of the red papules and several other lesions showed that all were BCCs. After all of the BCCs that were thought to be deeply invasive (Fig. 2) had been removed, groups of superficially invasive BCCs (Fig. 3) were treated during the next 3 months with one of three topical regimens: (I) 5% 5-fluorouracil cream occluded with tape for 8 hours twice a day; (2) tretinoin cream 0.1% applied twice daily; or (3) a combination of tretinoin cream 0,1% followed by 5% 5-fluorouracil cream, both of which were applied twice daily. Combination therapy most effectivelyinduced regression of the patient's BCCs, and during the next 4 years the patient was treated with total-body application of tretinoin cream 0.1% followed by 5-ftuorouracil cream twice a day. This regimen was discontinued only occasionally because of irritation. For lesions around the eyes 5-fluorouracil alone was carefully applied twice daily. During this time the child developed normally and showed no clinical or laboratory evidence of toxicity. After the combined topical regimen was initiated the hundreds of tumors the patient had on initial evaluation
Journal of the American Academy of Dermatology
Halasz et al.
5. Anderson L J, Tsou C, Parker RA, et al. Detection of antibodies and antigens of human parvovirus B 19 by enzymelinked immunosorbent assay. J Clin Microbiol 1986;24: 522-6. 6. Bell LM, Naides S J, Stoffman P, et al. Human parvovirus B 19 infection among hospital staff members after contact with infected patients. N Engi J Med 1989;321:485-9l. 7. Anderson M J, Higgins PG, Davis LR, et al. Experimental parvoviral infection in humans. J Infect Dis 1985;152:25765. 8. Anderson M J, Lewis E, Kiss IM, et al. An outbreak of erythema infectiosum associated with human parvovirus infection. J Hyg (Camb) 1984;93:85-93. 9. Anderson MJ. Role of parvovirus B19 in haman disease. Pediatr Infect Dis J 1987;6:711-8. 10. Naides SJ, Piette W~ Veach L, et al. Human parvovirus B19-induced vesiculopustular skin eruption. Am J Med 1988;84:968-72.
11. Naides SJ. Transient liver enzyme abnormalities in acute human parvovirus (HPV) infection [Abstract]. Clin Res 1987;35:859A. 12. Kurtzman GJ, Gascon P, Caras M, et al. B19 parvovirus replicates in circulating cells of acutely infected patients. Blood 1988;71:1448-54. 13. Dinerman JL Corman LC. Human parvovirus B19 arthropathy associated with desquamation. Am J Med 1990; 89:826-8. 14. Anderson M J, Jones SE, Fisher-Hoch SP, et al. Human parvovirus, the cause of erythema infectiosum (fifth disease) [Letter]. Lancet 1983;1:1378. 15. Plummer FA, Hammond GW, Forward K, et al. An erythema infectiosum-like illness caused by human parvovirus infection. N Engl J Med 1985;313:74-9. 16. Zisman AS. Human parvovirus infection [Letter]. N Engl J Med 1986;314:645-7.
Successful treatment of musk ketone-induced chronic actinic dermatitis with cyclosporine and PUVA Jesfis Gardeazfibal, M D , M a r i a A. Arregui, M D , Natalia Gil, M D , N e r e a Landa, M D , Juan A. R a t 6 n , M D , and Jos6 L. Di/tz-Prrez, M D , P h D Bilbao, Spain We describe a patient with chronic actinic dermatitis whose photopatch tests revealed reactions to musk ketone and musk ambrette, both of which were found in his aftershave lotion. Minimal erythema doses of U V A and UVB were decreased. After initial unsuccessful treatment with P U V A therapy the patient was successfully treated with a combination of cyclosporine and PUVA. (J AM AcAo DERMATOL 1992;27:838-42.) Chronic actinic dermatitis ( C A D ) describes different, persistent, p h o t o i n d u c e d eruptions that are considered variants of the same clinicopathologic entity, l, 2 C A D has been described in patients after they have had topical exposure to halogetaated sap icylanilides, m u s k ambrette, a n d other sensitizers. 3, 4 S o m e t i m e s no cause c a n b e found, s T h e different synthetic nitromusks are used extensively as fragrances and fixatives in p e r f u m e s and m a n y toiletries. T r e a t m e n t o f C A D with P U V A , UVB, and azathioprine has h a d variable results. 69 G o o d reFromthe Departmentof Dermatotogy,Hospitalde Cruces,University of the BasqueCountry. Reprint requests: Jestls Gardeaz~ibal,MD, Servieiode Dermatologla, Hospital de Cruces,Plaza de Cruces s/n, Bilbao,Vizcaya,Spain. 16/4/34843
sponses to cyclosporine have recently been obtained, but all of the patients had relapses after discontinuation of the d r u g ] , 2o, 11 W e report a case of C A D that was induced by musk ketone and was successfully treated wkh cyclosporine and P U V A , with no relapse after discontinuation of cyclosporine. CASE R E P O R T A 53-year-old man with a cutaneous eruption that was limited to sun-exposed areas was examined in April 1990. Past history included hypertension, which was treated with hydrochlorothiazide from April 1988 until March 1990 and hand eczema, which had patch test reactions to nickel and chrome. The photodermatitis began 2~/~years before examination as a recurrent eruption that appeared on his face in the spring and summer and cleared during
Volume 27 Number 5, Part 2 November 1992
Chronic actinic dermatitis
839
Fig. 1. Diffuse infiltrated and scaling dermatitis localized to sun-exposed skin.
Fig. 2. The same patient after 4-month treatment with cyetosporine and PUVA.
the winter. During the previous summer the eruption extended to the dorsa of his hands and the V-area of his neck and forearms, and did not clear in the winter. Despite discontinuation of thiazide therapy in March 1990, the lesions remained unchanged. Examination in April 1990 revealed an intense, erythematous, eczematous eruption of the scalp, face, V-area of the neck, nuchal region, dorsa of the hands, and extensor forearms (Fig. 1). The results of two skin biopsy specimens were consistent with a diagnosis of chronic eczema. Results of direct immunofluorescence testing were negative. Phototesting of the normal-appearing skin of the lower back was performed with a solar simulator (Solar Light Co., Philadelphia, Pa.). The minimal erythemal doses (MED) were as follows: MED UVB (WG 320 filter, Schott Glass Technologies Inc., Duryea, Pa.) was 3 inch (normal, 39 to 51 inch); MED UVA (WG-360 filter, Schott Glass Technologies Inc., Duryea, Pa.) was 4 feet (normal reaction, no erythema with 10 feet); and MED with PUVA 800 measured with the ultraviolet meter (Herbert Waldmann GMBH & Co., Schwenningen, FRG) was 3 J/cm 2 (normal, 70 to 100 J/cm2). Cutane-
ous lesions were reproduced on nonaffected areas when the skin underwent irradiation with doses of UVA and UVB higher than the MED. Photopatch testing revealed reactions to musk ketone, musk ambrette, and the patient's aftershave lotion (Table I). The manufacturer confirmed the presence of musk ambrette (0.0007%) and musk ketone (0.0017%) in the aftershave lotion. In the hospital the patient was put in a dark room, the use of all his toiletries was stopped, and treatment with prednisone (60 mg/day) and chloroquine (250 rag/day) was begun. The eruption cleared in 2 weeks, and he was discharged from the hospital; he continued the same treatment as an outpatient and was given instructions to use sunscreens and to avoid exposure to the sun. He was readmitted to the hospital 3 weeks later with an intense eczematous eruption on the previously affected areas. The eruption again cleared after he spent 10 days in a dark room and continued treatment with prednisone and chloroquine. PUVA therapy was begun, but his eruption worsened on the previously affected areas within 24 hours of his first PUVA treatment. PUVA therapy was diseon-
840
Journal of the American Academy of Dermatology
Gardeazhbal et aL
Table I. Results of patch tests and photopatch tests
Scandinavian standard photopatch testn~ Balsam of Peru 25% petrolatum Musk ambrette 1% petrolatum Hydrochlorothiazide 5% petrolatum Nitromusk Musk ketone 1% petrolatum Musk xylene 1% petrolatum Musk tibetine 1% petrolatum Musk moskene 1% petrolatum Aftershave lotion (Flo'/d genuine) Foam shave
Patch tests*
Photopatch testst
++
++
w
+++
++
Results: *Patch tests (96 hours) and tphotopatch tests (48 hours after irradiation with 0.5 J/crn2). :l:ChernoteehniqueDiagnostics AB, MaimS, Sweden.
tinued, and oral cyclosporine (5 mg/kg/day in two divided doses) was started. Complete clearing of the eruption occurred within 10 days. Chloroquine was discontinued, and oral corticosteroids were withdrawn within 1 month. No disease exacerbation was observed, although his MED for UVA and UVB remained decreased. Three weeks after the initiation of cyclosporine, PUVA therapy was resumed with initial doses of 2 J/cm. 2 Because no side effects were observed, each exposure was increased by 0.2 J/cm 2 (with five exposures per week for 2 weeks) and then increased by 1 J/era; (with three exposures per week). When a dosage of 15 J/cm 2 per exposure 3 times a week was reached, cyclosporine was gradually withdrawn and completely discontinued after a total treatment period of 4 months (Fig. 2). Results of laboratory tests including a full blood cell count, renal and hepatic function tests, urine, plasma, and red blood cell porphyrin levels were normal or negative. The patient's blood pressure was normal. Cyclosporine blood levels remained below 105 ng/ml as determined by radioimmunoassay with monoclonal antiserum. Six months after the cessation of cyclosporine the patient remains disease free on low-dose PUVA therapy (10 J/cm 2 once every 2 weeks). MED cannot be assessed because of the intense hyperpigrnentation from the PUVA therapy. DISCUSSION Uniform criteria to define CAD have recently been established 2 and are as follows: (1) a persistent eczematous eruption sometimes associated with papules and plaques and predominantly involving exposed skin, although sometimes extending to covered areas; (2) reduction in the MED to UVB and often to U V A irradiation of covered skin, with reproduction of the lesions at irradiated sites; and (3) histologic appearance consistent with chronic ec-
zema, with or without lymphoma-like changes. Our patient fulfilled all of these criteria. The origin of CAD is controversial. Many photoallergens such as halogenated salicylanilides have been implicated. 3 In 1979 patients were described who had photocontact dermatitis induced by musk ambrette contained in aftershave lotions. 4 Since then numerous cases of musk ambrette-induced photocontact dermatitis have been reported, either as permanent or transient reactions. 12d7 Synthetic musk compounds are used extensively as fixatives and fragrances in a variety of aftershave products, and musk ambrette has been the most commonly used musk subtype in the cosmetic industry. We have not found any reports implicating musk ketone in cases of CAD. In Wojnarowska and Calnan's 14 series of patients with contact and photocontact allergy to musk ambrette, the photopatch test of only 1 of 21 patients revealed a reaction to musk ketone. This patient's clinical picture and the intensity of the patch reaction were not described. In another series of 13 patients who had a reaction to musk ambrette, only one had a reaction to a photopatch test for musk ketone. 17 The low rate of simultaneous reactions to both musk compounds suggests that crossreactions between musk ambrette and musk ketone are not frequent. Our patient had photopatch test reactions to musk ketone and musk ambrette, both of which were found in his aftershave lotion. The intensity of the patch reaction to musk ketone was greater than the patch reaction to musk ambrette. These results suggest that musk ketone was mainly responsible for the photodermatitis of our patient and that musk ambrette was a concomitant sensitizer. Although
Volume 27 Number 5, Part 2 November 1992
CAD cases related to thiazide ingestion have been reported, 18 we ruled out the possibility of a link between our patient's CAD and thiazide ingestion because his eruption started several months before this drug was prescribed. The treatment of patients with CAD usually begins with a complete avoidance of all known topical or systemic photoallergens; patients are also instructed to avoid sun exposure and to use high-protection sunscreens. Because this approach alone is often ineffective, diverse therapies have also been tested. Topical and systemic corticosteroids induce a mild reduction of the inflammation and pruritus, but in most cases they do not result in clinical remission. Oral immunosuppressive therapy with azathioprine at doses of 0.5 to 2 mg/kg/day has been used,8, 9 with complete remission of the cutaneous eruption in many cases. This treatment is not always effective, however, and relapses occur after discontinuation of the drug. In addition, gastrointestinal, hematologic, and hepatotoxic side effects limit its long-term use. PUVA and UVB therapy, often accompanied by topical or systemic corticosteroids, have been used successfully to treat patients with CAD. 6, 7 Although the mechanism is not known, they seem to induce a progressive tolerance of the skin to ultraviolet radiation by producing a protective hyperpigmentation. In addition, the number of epidermal Langerhans cells and their function are diminished, which results in a reduced irnmunoresponsiveness of the skin. t9 However, initial doses of PUVA treatment may trigger or aggravate photosensitive dermatitis. This happened to our patient after his first exposure to PUVA. Treatment of CAD with cyclosporine at doses of 2 to 5 mg/kg/day has recently been reported], lo, 11 Complete remission was achieved, but relapses occurred in all patients after discontinuation of the drug. Our patient was treated with a combination of cyclosporine and PUVA. After cyclosporine brought the CAD into remission, PUVA treatments were started again. The PUVA dose was progressively increased and the cyclosporine dosage was then decreased. Cyclosporine was discontinued after 4 months of treatment, and PUVA therapy was continued. The patient is now receiving low-dose PUVA treatments and remains free of disease 6 months after cyclosporine was discontinued. We believe that the patient has had a long remission because PUVA
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therapy was added to the regimen of treatment with cyclosporine. Apparently, cyclosporine and PUVA act synergically in their immunomodulatory effects. The addition of PUVA therapy allows the patient to take lower doses of cyclosporine, which minimizes undesirable side effects, including long-term neoplasia induction. The combination of PUVA and cyclosporine treatments also seems to prolong remission. Our patient benefited from this combined treatment without experiencing side effects. To the best of our knowledge, no other case of CAD that was treated with a combination of cyclosporine and PUVA has been reported. However, this therapy has been used in patients w i t h psoriasis.2O, 21 REFERENCES 1. Hawk JLM, Magnus IA. Chronic actinic dermatitis--an idiopathic photosensitivity syndrome including actinic reticuloid and photosensitive eczema. Br J Dermatol 1979;101:2gs. 2. Norris PG, Hawk JLM. Chronic actinic dermatitis. A unifying concept. Arch Dermatol 1990;126:376-8. 3. Wilkinson DS. Photodermatitis due to tetrachlorsalycilanilide. Br J Derrnatol 1961;73:213-9. 4. Raugi G J, Storrs F J, Larsen WG. Photoallergie contact dermatitis to men's perfume. Contact Dermatitis 1979; 5:251-60. 5. Ive FA, Magnus IA, Warin RP, et ak Actinic reticuloid: a chronic dermatosis associated with severe photosensitivity and the histological resemblance to lymphoma. Br J Dermatol 1969;81:469-85. 6. Hindson C, Spire J, Downey A. PUVA therapy of chronic actinic dermatitis. Br J Dermatol 1985;113:15%60. 7. Toonstra J, Henquet CJM, Weelden H, et al. Actinic reticuloid: a clinical, photobiologic, histopathologic, and follow-up study of 16 patients. J AM ACAD DERMATOL 1989;21:205-14. 8. Leigh IM, Hawk JLM. Treatment of chronic actinic dermatitis with azathioprine. Br J Dermatol 1984;110:691-5. 9. Murphy GM, Mauriee PDL, Norris PG, et al. Azathioprine treatment in chronic actinic dermatitis: a double-blind controlled trial with monitoring of exposure to ultraviolet radiation. Br J Dermatol 1989;121:639-46. 10. Duschet P, Schwarz T, Oppolzer G, et al. Successful treatment of persistent light reaction with cyclosporin A: a case report. Acta Derm Venereol (Stockh) 1988;68:176-8. 11. Norris PG, Camp RDR, Hawk JLM. Actinic reticuloid: response to cyclosporine. J AM ACAD DERMATOL 1989; 21:307-9. 12. Lecha M, Romaguera C, Grimalt F, et al. Photosensitivity to musk ambrette. Photodermatol Photoimmunol Photomed 1984;1:313-5. 13. Serrano G, Aliaga A, de la Cuadra J, et al. Photodermatol Photoimmunol Photomed 1986;3:186-8. 14. Wojnarowska F, Calnan CD. Contact and photocontact allergy to musk ambrette, Br J Dermatol 1986; 114:667-75. 15. Sfinchez-Pedrefie P, Garcia-Bravo B, Rodfiguez-Pichardo
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Gardeazhbalet aL
A, et al. Differentclinicalpresentationsin photosensitivity to musk ambrette. Photodermatol Photoimmunol Photomed 1989;6:103-5. 16. Ramsay CA, Transient and persistentphotosensitivitydue to musk ambrette.Clinical and photobiologiealstudies. Br J Dermatol 1984;111:423-9. 17. Bruze M, Edman B, Niklasson B, et al. Thin layer chromatographyand high pressureliquidchromatography of musk ambretteand other nitromuskcompoundsincludingphotopatchstudies.PhotodermatolPhotoimmunolPhotomed 1985;2:295-302. 18. RobinsonHM, Morison WL, Hood AF. Thiazide diuretic therapy and chronic photosensitivity. Arch ,Dermatol 1985;121:522-4.
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19. Friedmann PSF. Disappearance of epidermal Langerhans cells during PUVA therapy. Br J Dermatol 1981;105:21924. 20. Korstanje M J, Hulsmans RFHJ. Combination therapy cyclosporine A-PUVA in psoriasis. Aeta Derm Venereol (Stockh) 1990;70:89-90. 21. Petzelbauer P, Honigsmann H, Langer K, et al. Cyclosporine Ain combinationwithphotochemotherapy (PUVA) in the treatment of psoriasis. Br J Dermatol 1990;123:641-7. 22. Jansen CT, Wennersten G, Rystedt I, et al. The Scandinavian standard photopatch test procedure. Contact Dermatitis 1982;8:155-8.
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Long-term management of basal cell nevus syndrome with topical tretinoin and 5-fluorouracil PhiUip R. Strange, MD, and Pearon G. Lang, Jr., M D Albuquerque, New Mexico, and
Charleston, South Carolina The case of a child with basal cell nevus syndrome whose condition was successfully managed for I 0 years with a combination of topical 5-flurouracil and tretinoin is reported. The concurrent use of these two agents prevented the development of new tumors, inhibited the growth of existing tumors, and caused the regression of superficially invasive basal cell carcinomas. (J AM ACAD DERMATOL1992;27:842-5.) Basal cell nevus syndrome (BCNS) is an autosomal dominant multisystem disorder characterized by multiple basal cell carcinomas (BCCs) of the skin, pits of the palms or soles, odontogenic cysts, ectopic calcification, subnormal mentation, ocular hypertelorism, and skeletal abnormalities such as bifid ribs and spina bifida, t We describe a child with B C N S whose B C C s have been successfully treated for 10 years with topical tretinoin and 5-fluorouracil. CASE REPORT A 25-month-old white girl had a family history of BCNS; her father, paternal grandmother, great grandmother, and great uncle were affected. The patient had developed multiple skin lesions, and findings of a biopsy specimen of one of the lesions showed that it was a BCC.
FromtheDepartmentsof Dermatology,LovelaceMedicalCenterand the MedicalUniversityof South Carolina. Reprinksnot available. 16/'4/34733
On physical examination the patient had several red papules and numerous nevocellular nevilike and milialike lesions scattered on her body (Fig. 1). Findings of biopsy specimens of the red papules and several other lesions showed that all were BCCs. After all of the BCCs that were thought to be deeply invasive (Fig. 2) had been removed, groups of superficially invasive BCCs (Fig. 3) were treated during the next 3 months with one of three topical regimens: (I) 5% 5-fluorouracil cream occluded with tape for 8 hours twice a day; (2) tretinoin cream 0.1% applied twice daily; or (3) a combination of tretinoin cream 0,1% followed by 5% 5-fluorouracil cream, both of which were applied twice daily. Combination therapy most effectivelyinduced regression of the patient's BCCs, and during the next 4 years the patient was treated with total-body application of tretinoin cream 0.1% followed by 5-ftuorouracil cream twice a day. This regimen was discontinued only occasionally because of irritation. For lesions around the eyes 5-fluorouracil alone was carefully applied twice daily. During this time the child developed normally and showed no clinical or laboratory evidence of toxicity. After the combined topical regimen was initiated the hundreds of tumors the patient had on initial evaluation