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Hydroa vacciniforme: An unusual clinical manifestation
Hydroa vaccinifonne: An unusual clinical manifestation Vichit Leenutaphong, MD Bangkok, Thailand Hydroa vacciniforme is a rare, chronic photodermatosis with onset in childhood that is characterized by recurrent vesiculation, necrosis, and vacciniform scarring limited to sun-exposed skin. We report a case of nonvesicular hydroa vacciniforme in which only extensive crusting associated with hypertrophic scarring on sun-exposed skin was present. Multiple exposures to UVA, however, reproduced lesions with the typical clinical and histologic features of hydroa vacciniforme. Results of blood, urine, and fecal porphyrin studies were normal. (J AM ACAD DERMATOL
1991;25:892-5.)
Hydroa vacciniforme (HV) is a rare, chronic photodermatosis of unknown origin, characterized by recurrent vesiculation, necrotic lesions, and vacciniform scarring on sun-exposed areas.! Histopathologic features are intraepidermal reticular degeneration and cellular necrosis. 2,3 The course of the disease is usually marked by chronic, recurrent flares after sun exposure and in most cases the disorder involutes spontaneously by the late teenage years. 1, 4 Many researchers 2, 3, 5-7 have succeeded in reproducing the eruption by multiple exposures to UVA. We describe a patient with HV in whom only crusting associated with hypertrophic scarring on sun-exposed skin was present. Phototesting with repetitive exposures to artificial UVA reproduced lesions with the specific clinical and histologic features ofHV. CASE REPORT
A 20-year-old Thai woman had a photosensitive skin disorder for 15 years. At 5 years of age, blistering of the face, scalp, dorsa of the hands, and extensor aspects of forearms had developed after exposure to sunlight. The lesions developed several hours after sun exposure and healed, with scarring, within a few days. During the initiallO years of the patient's disease, vesicles occurred periodically. For the last 5 years only, crusting appeared on areas of previous scarring whenever her skin was exposed to sunlight. She also complained of photophobia and lac-
From the Department of Medicine, Division of Dermatology, Siriraj Hospital, Mahidol University. Reprint requests: V. Leenutaphong, MD, Division of Dermatology, Siriraj Hospital, Bangkok 10700, Thailand.
16/4/27451
892
rimation after sun exposure. There was no known exposure to photosensitizers, and the family history revealed no photosensitivity diseases. The patient had been treated with a topical sunscreen without significant effect. Physical examination revealed extensive crusting associated with hypertrophic scarring on the patient's lower lip, malar area, bridge of nose (Fig. l), vertex of the scalp, dorsa of the hands, and extensor surfaces of the forearms. No vesicles were observed. The index fingers of both hands were contracted (Fig. 2). The lower part of the cornea of both eyes was cloudy (Fig. 3). The remainder of the physical examination was unremarkable. The results of laboratory studies were within normal limits. Biopsy specimens from the crusted lesion showed only nonspecific inflammation with fibrosis. PHOTOTESTING Radiation sources Sunlamp. The source of polychromatic UVB was a bank of 10 fluorescent bulbs (Philips TL 20 W j 12) (UV 800, Waldmann, Villingen-Schwenningen, F.R.G.). The emission spectrum extended from 285 to 350 nm with a maximum between 310 and 315 nn. The UVB irradiance was 2.5 mWjcm2 at a target distance of 30 em. High-intensity UV A. The source of polychromatic UVA was a high-pressure metal halide lamp (UVASUN 3000, Mutzhas, Munich, F.R.G.) that emitted wavelengths between 330 and 460 nm without any measurable UVB. 8 The UVA irradiance was 66 mW jcm 2 at a target distance of 30 cm. Dosimetry. A UV meter with separate detectors for UVA and UVB (IL SOOA radiometer, International Light, Newburyport, Mass.) served to determine the UV irradiance of the UVASUN and the UV SOO.
Volume 25 Number 5, Part 2 November 1991
Hydroa vacciniforme 893
Fig. 1. Extensive crusting associated with hypertrophic scarring on malar area and bridge of nose. Fig. 2. Contracture of both index fingers associated with hypertrophic scarring and crusting. Fig. 3. Cloudiness of lower part of cornea in both eyes.
Determination of minimal erythema doses of UVB and UVA UVB was applied to small skin fields (2 X 2 em) on the patient's back in doses ranging from 0.05 to 0.3 joulejcm2 , in increments of 0.05 joulejcm. 2 UVA was applied in doses of 10, 20, 40, 60, 80, and 100 joulejcm. 2 Test reactions were evaluated immediately after exposure and 24 hours later. Minimal erythema doses (MEDs) of UVB and UVA were determined to be 100 millijoulesjcm2 and 100 joulesjcm2, respectively, which were within normal limits for the patient's skin type. There was no induction of skin lesions in the MED test sites.
Provocative phototesting A large test site (5 X 8 em) on the patient's back was repeatedly irradiated with daily doses of 100 joulesjcm2 UVA on three consecutive days. Another test area was irradiated with daily doses of
150 millijoules j cm2 DVB on three consecutive days. Six hours after the last irradiation, stinging resulted and was followed within 2 hours by intensely edematous, 2 to 4 mm, firm, pale to erythematous papules at the UVA test site. These evolved into vesicles and then crusted, leaving hypopigmented scars after healing (Fig. 4). Repeated daily applications of 1.5 MEDs of VVB induced neither stinging nor blistering. The tissue specimens from UVA-induced lesions showed spongiosis and diffuse epidermal necrosis (Fig. 5). Within the papillary and reticular dermis, light and electron microscopy revealed a dense lymphohistiocyticinfiltrate with hemorrhage and thrombosis of the small vessels. Direct immunofluorescence studies of the perilesional and lesional skin were negative for IgM, IgG, IgA, and C3 deposition. A serum sample for indirect immunofluorescence studies was also negative. A single large dose
Journal of the American Academy of Dermatology
894 Leenutaphong
Fig. 4. UVA phototesting (3 X 100 joules/cm2) shows umbilicated vesicles. Fig. 5. Photoinduced vesicle shows epidermal necrosis and spongiosis, accompanied by a dense mononuclear infiltrate of the papillary and reticular dermis. This is consistent with the histologic pattern expected in vesicular lesions of hydroa vacciniforme. (Hematoxylin-eosin stain; X 100.)
ofUVA up to 200joules/ cm2 failed to reproduce the typical skin lesions of HV.
Determination of threshold doses of UVA required for reproduction of lesions on normal skin and hypertrophic scars UVA was applied to small skin fields (1 X 1 em) in daily doses of 10, 20, 40, 60, 80, and 100 joules/ cm2 on three consecutive days at scarred and normal skin sites on the extensor aspects of the patient's forearms. Test reactions were evaluated 24 hours after the last irradiation. The threshold doses of UVA required for reproduction of vesicles on normal skin and hypertrophic scars were 3 X 60 and 3 X 20 joules/cm2, respectively.
Arterial occlusion test The arterial supply to the forearm was occluded with a sphygmomanometer cuff, and 1 minute later an area of skin distal to the cuff was irradiated with daily doses of 3 joules/cm2 UVA, on 2 consecutive days. Approximately 45 seconds after each irradiation, when the dose of UVA had reached 3 joules/ cm2, the phototest was terminated because of severe burning sensation at the irradiated site. Immediately after each irradiation, the erythema that developed
at the test site became faint within 2 hours. Twentyfour hours after the second exposure, small papules appeared, which became vesicular and then hemorrhagic within 48 hours. This examination was repeated twice and comparable results were obtained. The same experiment was also done in a normal control subject. Neither immediate erythema nor vesicle formation was detected at the test site. TREATMENT
The patient was treated with oral chloroquine diphosphate, 500 mg/day, without the concomitant application of topical sunscreens. Two weeks after treatment, no clinical improvement was apparent, and the threshold doses of UVA (3 X 60 joules/ cm2 ) required for reproduction of skin lesions had not increased. She was then treated with topical application of an opaque sunscreen, every 2 hours while outdoors, and experienced considerable relief of symptoms. To prevent additional eye damage, the patient was advised to wear UV-protecting sunglasses. COMMENT
Hydroa vacciniforme has several distinctive features: (1) development of vesicles and crusts several
Volume 25 Number 5, Part 2 November 1991
hours to 1 to 2 days after sun exposure, (2) healing with varioliform scarring, (3) absence oflaboratory abnormalities, ( 4) characteristichistopathology, and (5) evocation by exposure to light. Most cases appear to occur sporadically, although there is a report of three affected siblings. 9 Although UVA was not implicated in early studies as being responsible for reproducing HV lesions,4,10 several subsequent reports have specifically implicated UVA light. The exact clinical and histopathologic findings of naturally occurring HV have been reproduced with artificially administered UVA light. 2, 3, 5-7 A single high dose of UVA irradiation did not reproduce the lesions. However, repetitive phototesting at the same site, even with lower doses of UVA light, induced erythema and subsequent vesiculation. Recently, Sunohara et al. ll demonstrated that the definite action spectrum for reproduction of HV was in the 330 to 360 nm range. The course of HV is usually that of chronic recurrent flares after sun exposure. In most instances the disorder involutes spontaneously by the late teenage years. 4 Such improvement also occurred in our patient. Her vesicular lesions during childhood did not occur after the age of 15 years. However, we showed that the scarred areas in our patient were more sensitive than normal skin to UVA. This may explain the crusting that developed only in scarred area but not on normal skin after sun exposure. To see whether the increased UVA sensitivity in the scarred areas was due to a diminished blood supply, we administered the arterial occlusion test. It showed that arterial occlusion increased the sensitivityofthe patient's skin to UVA by 20 times. We do not know whether this finding is specific to our patient or whether it applies to other cases of HV.
Hydroa vacciniforme 895 Eye involvement has been reported in a minority of cases. I, 12 Conjunctivitis with photophobia is most common. Corneal ulcerations and opacities, as in our patient, have been described in a few cases and often occur on the exposed area of the cornea.!' 12, 13 Protective sunglasses prevented further damage in our patient as in other reported cases. 13 REFERENCES 1. McGrae JD, Perry HO. Hydroa vacciniforme. Arch Der-
mato11963;87:124-31. 2. Goldgeier MH, Nordlund JJ, Lucky AW, et al Hydroa vacciniforme: diagnosis and therapy. Arch Dermatol 1982;118:588-91. 3. Halasz CLG, Leach EE, Walther RR, et a1. Hydroa vacciniforme: induction of lesions with ultraviolet A. J AM ACAD DERMATOL 1983;8:171-6. 4. Bickers DR, Demar LK, DeLeo V, et aI. Hydroa vacciniforme. Arch Dermato11978;114:1193-6. 5. Jaschke E, Honigsman H. Hydroa vacciniforme-Aktionspektrum. UV-Toleranz nach Photochemotberapie. Rautarzt 1981;32:350-3. 6. Galosi A, P1ewig G, Ring J, et al. Experimentelle Aus10sung von Hauterscheinungen bei Hydroa vacciniformia. Hautarzt 1985;36:566-72. 7. Eramo JR, Garden JM, Esterly NB. Hydroa vacciniforme: diagnosis by repetitive ultraviolet-A phototesting. Arch Dermatol 1986;122:1310-3. 8. Mutzhas MF, H51z1e E, Hofmann C, et al. A new apparatus with high radiation energy between 320-460 nm: physical description and dermatological applications. J Invest Dermatol 1981;76:42-7. 9. Annamalai R. Hydroa vacciniforme in three alternate siblings. Arch Dermatol 1971;103:224-5. 10. Schiff M, Jillson OF. Photoslcin tests in hydroa vacciniforme. Arch DermatoI1960;82:812-6. 11. Sunohara A, Mizuno N, Sakai M, et a1. Action spectrum for UV erythema and reproduction of the skin lesions in hydroa vacciniforme. Photodermatology 1988;5:139-45. 12. Stokes WHo Ocular manifestations in hydroa vacciniforme. Arch OpthamoI1940;23:1131-45. 13. Bennion SD, Major MC, Johnson C, et al. Hydroa vacciniform·e with inflammatory keratitis and secondary anterior uveitis. Pediatr Dermatol 1987;4:320-4.
1991;25:892-5.)
Hydroa vacciniforme (HV) is a rare, chronic photodermatosis of unknown origin, characterized by recurrent vesiculation, necrotic lesions, and vacciniform scarring on sun-exposed areas.! Histopathologic features are intraepidermal reticular degeneration and cellular necrosis. 2,3 The course of the disease is usually marked by chronic, recurrent flares after sun exposure and in most cases the disorder involutes spontaneously by the late teenage years. 1, 4 Many researchers 2, 3, 5-7 have succeeded in reproducing the eruption by multiple exposures to UVA. We describe a patient with HV in whom only crusting associated with hypertrophic scarring on sun-exposed skin was present. Phototesting with repetitive exposures to artificial UVA reproduced lesions with the specific clinical and histologic features ofHV. CASE REPORT
A 20-year-old Thai woman had a photosensitive skin disorder for 15 years. At 5 years of age, blistering of the face, scalp, dorsa of the hands, and extensor aspects of forearms had developed after exposure to sunlight. The lesions developed several hours after sun exposure and healed, with scarring, within a few days. During the initiallO years of the patient's disease, vesicles occurred periodically. For the last 5 years only, crusting appeared on areas of previous scarring whenever her skin was exposed to sunlight. She also complained of photophobia and lac-
From the Department of Medicine, Division of Dermatology, Siriraj Hospital, Mahidol University. Reprint requests: V. Leenutaphong, MD, Division of Dermatology, Siriraj Hospital, Bangkok 10700, Thailand.
16/4/27451
892
rimation after sun exposure. There was no known exposure to photosensitizers, and the family history revealed no photosensitivity diseases. The patient had been treated with a topical sunscreen without significant effect. Physical examination revealed extensive crusting associated with hypertrophic scarring on the patient's lower lip, malar area, bridge of nose (Fig. l), vertex of the scalp, dorsa of the hands, and extensor surfaces of the forearms. No vesicles were observed. The index fingers of both hands were contracted (Fig. 2). The lower part of the cornea of both eyes was cloudy (Fig. 3). The remainder of the physical examination was unremarkable. The results of laboratory studies were within normal limits. Biopsy specimens from the crusted lesion showed only nonspecific inflammation with fibrosis. PHOTOTESTING Radiation sources Sunlamp. The source of polychromatic UVB was a bank of 10 fluorescent bulbs (Philips TL 20 W j 12) (UV 800, Waldmann, Villingen-Schwenningen, F.R.G.). The emission spectrum extended from 285 to 350 nm with a maximum between 310 and 315 nn. The UVB irradiance was 2.5 mWjcm2 at a target distance of 30 em. High-intensity UV A. The source of polychromatic UVA was a high-pressure metal halide lamp (UVASUN 3000, Mutzhas, Munich, F.R.G.) that emitted wavelengths between 330 and 460 nm without any measurable UVB. 8 The UVA irradiance was 66 mW jcm 2 at a target distance of 30 cm. Dosimetry. A UV meter with separate detectors for UVA and UVB (IL SOOA radiometer, International Light, Newburyport, Mass.) served to determine the UV irradiance of the UVASUN and the UV SOO.
Volume 25 Number 5, Part 2 November 1991
Hydroa vacciniforme 893
Fig. 1. Extensive crusting associated with hypertrophic scarring on malar area and bridge of nose. Fig. 2. Contracture of both index fingers associated with hypertrophic scarring and crusting. Fig. 3. Cloudiness of lower part of cornea in both eyes.
Determination of minimal erythema doses of UVB and UVA UVB was applied to small skin fields (2 X 2 em) on the patient's back in doses ranging from 0.05 to 0.3 joulejcm2 , in increments of 0.05 joulejcm. 2 UVA was applied in doses of 10, 20, 40, 60, 80, and 100 joulejcm. 2 Test reactions were evaluated immediately after exposure and 24 hours later. Minimal erythema doses (MEDs) of UVB and UVA were determined to be 100 millijoulesjcm2 and 100 joulesjcm2, respectively, which were within normal limits for the patient's skin type. There was no induction of skin lesions in the MED test sites.
Provocative phototesting A large test site (5 X 8 em) on the patient's back was repeatedly irradiated with daily doses of 100 joulesjcm2 UVA on three consecutive days. Another test area was irradiated with daily doses of
150 millijoules j cm2 DVB on three consecutive days. Six hours after the last irradiation, stinging resulted and was followed within 2 hours by intensely edematous, 2 to 4 mm, firm, pale to erythematous papules at the UVA test site. These evolved into vesicles and then crusted, leaving hypopigmented scars after healing (Fig. 4). Repeated daily applications of 1.5 MEDs of VVB induced neither stinging nor blistering. The tissue specimens from UVA-induced lesions showed spongiosis and diffuse epidermal necrosis (Fig. 5). Within the papillary and reticular dermis, light and electron microscopy revealed a dense lymphohistiocyticinfiltrate with hemorrhage and thrombosis of the small vessels. Direct immunofluorescence studies of the perilesional and lesional skin were negative for IgM, IgG, IgA, and C3 deposition. A serum sample for indirect immunofluorescence studies was also negative. A single large dose
Journal of the American Academy of Dermatology
894 Leenutaphong
Fig. 4. UVA phototesting (3 X 100 joules/cm2) shows umbilicated vesicles. Fig. 5. Photoinduced vesicle shows epidermal necrosis and spongiosis, accompanied by a dense mononuclear infiltrate of the papillary and reticular dermis. This is consistent with the histologic pattern expected in vesicular lesions of hydroa vacciniforme. (Hematoxylin-eosin stain; X 100.)
ofUVA up to 200joules/ cm2 failed to reproduce the typical skin lesions of HV.
Determination of threshold doses of UVA required for reproduction of lesions on normal skin and hypertrophic scars UVA was applied to small skin fields (1 X 1 em) in daily doses of 10, 20, 40, 60, 80, and 100 joules/ cm2 on three consecutive days at scarred and normal skin sites on the extensor aspects of the patient's forearms. Test reactions were evaluated 24 hours after the last irradiation. The threshold doses of UVA required for reproduction of vesicles on normal skin and hypertrophic scars were 3 X 60 and 3 X 20 joules/cm2, respectively.
Arterial occlusion test The arterial supply to the forearm was occluded with a sphygmomanometer cuff, and 1 minute later an area of skin distal to the cuff was irradiated with daily doses of 3 joules/cm2 UVA, on 2 consecutive days. Approximately 45 seconds after each irradiation, when the dose of UVA had reached 3 joules/ cm2, the phototest was terminated because of severe burning sensation at the irradiated site. Immediately after each irradiation, the erythema that developed
at the test site became faint within 2 hours. Twentyfour hours after the second exposure, small papules appeared, which became vesicular and then hemorrhagic within 48 hours. This examination was repeated twice and comparable results were obtained. The same experiment was also done in a normal control subject. Neither immediate erythema nor vesicle formation was detected at the test site. TREATMENT
The patient was treated with oral chloroquine diphosphate, 500 mg/day, without the concomitant application of topical sunscreens. Two weeks after treatment, no clinical improvement was apparent, and the threshold doses of UVA (3 X 60 joules/ cm2 ) required for reproduction of skin lesions had not increased. She was then treated with topical application of an opaque sunscreen, every 2 hours while outdoors, and experienced considerable relief of symptoms. To prevent additional eye damage, the patient was advised to wear UV-protecting sunglasses. COMMENT
Hydroa vacciniforme has several distinctive features: (1) development of vesicles and crusts several
Volume 25 Number 5, Part 2 November 1991
hours to 1 to 2 days after sun exposure, (2) healing with varioliform scarring, (3) absence oflaboratory abnormalities, ( 4) characteristichistopathology, and (5) evocation by exposure to light. Most cases appear to occur sporadically, although there is a report of three affected siblings. 9 Although UVA was not implicated in early studies as being responsible for reproducing HV lesions,4,10 several subsequent reports have specifically implicated UVA light. The exact clinical and histopathologic findings of naturally occurring HV have been reproduced with artificially administered UVA light. 2, 3, 5-7 A single high dose of UVA irradiation did not reproduce the lesions. However, repetitive phototesting at the same site, even with lower doses of UVA light, induced erythema and subsequent vesiculation. Recently, Sunohara et al. ll demonstrated that the definite action spectrum for reproduction of HV was in the 330 to 360 nm range. The course of HV is usually that of chronic recurrent flares after sun exposure. In most instances the disorder involutes spontaneously by the late teenage years. 4 Such improvement also occurred in our patient. Her vesicular lesions during childhood did not occur after the age of 15 years. However, we showed that the scarred areas in our patient were more sensitive than normal skin to UVA. This may explain the crusting that developed only in scarred area but not on normal skin after sun exposure. To see whether the increased UVA sensitivity in the scarred areas was due to a diminished blood supply, we administered the arterial occlusion test. It showed that arterial occlusion increased the sensitivityofthe patient's skin to UVA by 20 times. We do not know whether this finding is specific to our patient or whether it applies to other cases of HV.
Hydroa vacciniforme 895 Eye involvement has been reported in a minority of cases. I, 12 Conjunctivitis with photophobia is most common. Corneal ulcerations and opacities, as in our patient, have been described in a few cases and often occur on the exposed area of the cornea.!' 12, 13 Protective sunglasses prevented further damage in our patient as in other reported cases. 13 REFERENCES 1. McGrae JD, Perry HO. Hydroa vacciniforme. Arch Der-
mato11963;87:124-31. 2. Goldgeier MH, Nordlund JJ, Lucky AW, et al Hydroa vacciniforme: diagnosis and therapy. Arch Dermatol 1982;118:588-91. 3. Halasz CLG, Leach EE, Walther RR, et a1. Hydroa vacciniforme: induction of lesions with ultraviolet A. J AM ACAD DERMATOL 1983;8:171-6. 4. Bickers DR, Demar LK, DeLeo V, et aI. Hydroa vacciniforme. Arch Dermato11978;114:1193-6. 5. Jaschke E, Honigsman H. Hydroa vacciniforme-Aktionspektrum. UV-Toleranz nach Photochemotberapie. Rautarzt 1981;32:350-3. 6. Galosi A, P1ewig G, Ring J, et al. Experimentelle Aus10sung von Hauterscheinungen bei Hydroa vacciniformia. Hautarzt 1985;36:566-72. 7. Eramo JR, Garden JM, Esterly NB. Hydroa vacciniforme: diagnosis by repetitive ultraviolet-A phototesting. Arch Dermatol 1986;122:1310-3. 8. Mutzhas MF, H51z1e E, Hofmann C, et al. A new apparatus with high radiation energy between 320-460 nm: physical description and dermatological applications. J Invest Dermatol 1981;76:42-7. 9. Annamalai R. Hydroa vacciniforme in three alternate siblings. Arch Dermatol 1971;103:224-5. 10. Schiff M, Jillson OF. Photoslcin tests in hydroa vacciniforme. Arch DermatoI1960;82:812-6. 11. Sunohara A, Mizuno N, Sakai M, et a1. Action spectrum for UV erythema and reproduction of the skin lesions in hydroa vacciniforme. Photodermatology 1988;5:139-45. 12. Stokes WHo Ocular manifestations in hydroa vacciniforme. Arch OpthamoI1940;23:1131-45. 13. Bennion SD, Major MC, Johnson C, et al. Hydroa vacciniform·e with inflammatory keratitis and secondary anterior uveitis. Pediatr Dermatol 1987;4:320-4.