Journal of Cutaneous Pathology 1979: 6: 414-417
Ultraviolet Light in Familial Benign Chronic Pemphigus RAIMO SUHONEN AND KIRSTI-MARIA NIEMI Department of Dermatology, University Central Hospital, Helsinki, Finland
Ultraviolet light (UV) tests with high irradiation doses from a dysprosium lamp were performed on the normal appearing skin of seven patients with benign familial ehronie pemphigus (FBCP). The skin of the patients showed a more severe vulnerability when eompared with the reactivity of the skin of four healthy control persons. In each case the damaged skin of the patients had, in addition to the destructive features, the diagnostie histologieal aeantholysis of FBCP. There was great variation in individual responses to the provocative irradiation and thus the test cannot be considered practical for aeeurate diagnostie purposes. (Received for publication Mareh 23, 1979)
In the active phase the symptoms of familial benign chronic pemphigus (FBCP) are moist bullous or denuded, often crusted skin lesions in axillae, groin, on genitals, on the sides of the neck or on the scalp. A hot environment with high humidity and friction of the skin are the most coinmonly recognized provocative factors. Experimentally the lesions of FBCP have been induced also by bacterial inoculation (Montes et al. 1970) or, by heating or freezing the skin (Loewenthal 1959, Chorzclski 1962). In their original article in 1939 Hailey & Hailey did not believe ultraviolet light (UV) irradiation to be a provocative factor in FBCP. In 1967, however, Cratn et al. reported successful UV provocation of the lesions of FBCP in the members of one family. Our patients with clinically and histologically verified FBCP never complained of the effect of direct sun light, but they volunteered for the study of the effect of UV irradiation as a provocative factor. We also attempted to evaluate the UV-test as a diagnostic aid. The results were verified clinically, as well as with histopathological and immunohistological methods.
Material and Methods
Seven patients with FBCP, verified chnically and by biopsy, were studied. The duration of their disease was more than 5 years. During the study all of the patients had skin lesions in axillae and/or groins, while the skin of the back was intact. The study was performed in late summer. The test subjects were without any medication with light sensitizing potency. None of them had a history of light hypersensitivity. The radiation tests were performed on the midback skin paravertebrally. The light source was a dysprosium lamp (HQI-TS 400 W, Osram GmbH, Germany) with a lampto-skin-distance of 50cm. The relative distribution of UV energy of the light source was: UVC0.2, UVB 1.0 and UVA 19.0 based on the measurement according to Fischer & Alsins (1976). Before UV challenge a 24 h minimal erythema dose (MED) was determined for each patient. A skin area of 1.5 X 5.0cm was irradiated with a dose of 5 MED and another with 15 MED. The respective exposures were also performed through a water-filled quarz cuvette to study the role of heat (the light path in water was 1 cm).
0303-6987/79/050414-04 $02.50/0 © 1979 Munksgaard, Copenhagen
415
UV LIGHT IN FBCP Biopsy specimens were taken from both the normal skin and from all the irradiated skin areas 8, 24 and 48 h after irradiation, using a 2mm0 punch biopsy technique. Separate samples were taken for histopathological and for immunohistochemical study. The samples for light microscopy were fixed in neutral formalin, mounted in paraffin and stained with Hematoxylin and Eosin. All biopsied specimens were sectioned throughout. The immunofluoreseent study was performed as described by Reunala et al. (1977). Skin from the backs of four healthy volunteers was irradiated with 5 and 15 MED and biopsied as described above. Results
The direct immunohistological study revealed neither immunoglobulins nor complement in any of the biopsies. In healthy volunteers the vacuolization of the keratinocytes was also seen in almost every specimen. Dyskeratotic keratinocytes were found in two specimens taken at 24 h and in all four specimens at 48 h. The epidermal vesicles were not found in any specimen of the controls. Discussion
The effect of UV-light on the skin of the EBCP patients differed markedly from that of the controls. There was no difference in the clinical test results, but the histological study revealed that the epidermis of the patients is highly vulnerable to the large doses of UV-irradiation used in this study. The damage to the keratinocytes was, however, also seen in the skin of normal controls, although to a lesser degree. The typical acantholytic lesion was never seen in their skin, but was found in the skin of EBCP patients on almost every occasion, at least with the high UV-doses and in the late biopsies. This shows that the effect of UV-light probably is not specific, which is in accordance with previous studies (Chorzelski 1962). The large doses needed for the provocation of EBCP lesions also explain the fact that the patients experienced no harmful effects from normal direct sunlight. The diagnostic value of this type of test remains questionable: firstly, because the test result is not manifest clinically but needs histological confirmation, and secondly, the histological confirmation may require several biopsies with serial sections at various intervals because of the variable individual response to the UV-exposure.
Clinically the test sites showed only erythema with edema that was more intense the longer the exposure. Histopathological study revealed irradiation damage to the keratinocytes which markedly increased in severity with time, although individual variation was conspicuous. The water filter had n o clearly detectable protective effect. The exposure of 15 MED caused more destructive changes than 5 MED. In the specimens taken from the EBCP patients the slightest and most common disturbance was the vacuolization of the keratinocytes. This was found in almost every specimen. Dyskeratotic keratinocytes and pyknotic nuclei were found in the specimens taken at 24 h after irradiation. The most severe damage comprised the epidermal vesicles found in every specimen at 48 h. In some cases these were also found in the earlier specimens. The vesicles were partly acantholytic disruptions immediately above the intact row of basal cells (Eig. 1) or intraepidermal bullae with remnants of pyknotic nuclei or necrotic keratinocytes (Fig. 2). The former type of bullae were considered typical of FBCP. The occurrence Acknowledgments of these lesions is shown in Table 1. They were also found in two specimens taken We are indebted to Drs. Osmo P. Salo and from the nonirradiated skin of EBCP patients. Tapio Rantanen for their assistance.
416
SUHONEN AND NIEMI
Fi;?. 7. Patient No 2. The aeantholytic bulla formation at 48 h after irradation with 15 MED. (H & E X 500).
/>fe. 2. Patient No 7. Small bullae without definite signs of aeantholysis at 48 h after irradation with 5 MED. ( H & E X 125).
UV LIGHT IN FBCP
417
Table 1 The acantholytic changes in biopsy specimens at 8, 24 and 48 h after UV-irradiation with 5 or 15 MED Pat. No.
5 MED 24 48
15 MED 8 24
1 2 3 4 5 6 7
8
48
5 MED(W) 24 48
8
15 MED (W) 24 48
U
N
W = with a water-filled cuvette to exclude infra-red radiation. N = necrosis. U = noniiradiated skin.
References
Chorzelski, T. (1962) Experimentally induced acantholysis in Hailey's henign pemphigus. Dermatologiea 124, 21-30. Cram, M. D. L., Muller, S. A. & Winkelmann, R. K. (1967) Ultraviolet-induced acantholysis in familial benign chronic pemphigus. Arehives of Dertnatology 96, 6 3 6 - 6 4 1 . Fischer, T. & Alsins, J. (1976) Treatment of psoriasis with trioxsalen baths and dysprosium lamp. A eta Dermato- Venereologtea (Stoekholm) 56, 383-390. Hailey, 11. & Hailey, H. (1939) Familial benign chionic pemphigus. Arehives of Dermatology 39, 679-685. Loewenthal, L. J. A. (1959) Familial benign
chronic pemphigus: the role of pyogenic bacteria./Ircfti'ves o/Dermafoto,gj' 80, 318-326. Montes, L. F., Narkates, A. J., Hunt, D., Pittillo, R. F., Noojin, R. O. & Sherer, R. J. (1970) Microbial flora in familial benign chronic pempYiigus. Archives of Dermatology 101, 140-144. Reunala, T., Karvonen, J., Tiilikainen, A. & Salo, 0 . P. (1977) Herpes gesUtionis. British Journat of Dermatology 96, 563-568. Address: Kirsti-Maria Niemi Department of Dertnatology University Central Hospital Snellmaninkatu 14 00170 Helsinki 17 Finland
Ultraviolet Light in Familial Benign Chronic Pemphigus RAIMO SUHONEN AND KIRSTI-MARIA NIEMI Department of Dermatology, University Central Hospital, Helsinki, Finland
Ultraviolet light (UV) tests with high irradiation doses from a dysprosium lamp were performed on the normal appearing skin of seven patients with benign familial ehronie pemphigus (FBCP). The skin of the patients showed a more severe vulnerability when eompared with the reactivity of the skin of four healthy control persons. In each case the damaged skin of the patients had, in addition to the destructive features, the diagnostie histologieal aeantholysis of FBCP. There was great variation in individual responses to the provocative irradiation and thus the test cannot be considered practical for aeeurate diagnostie purposes. (Received for publication Mareh 23, 1979)
In the active phase the symptoms of familial benign chronic pemphigus (FBCP) are moist bullous or denuded, often crusted skin lesions in axillae, groin, on genitals, on the sides of the neck or on the scalp. A hot environment with high humidity and friction of the skin are the most coinmonly recognized provocative factors. Experimentally the lesions of FBCP have been induced also by bacterial inoculation (Montes et al. 1970) or, by heating or freezing the skin (Loewenthal 1959, Chorzclski 1962). In their original article in 1939 Hailey & Hailey did not believe ultraviolet light (UV) irradiation to be a provocative factor in FBCP. In 1967, however, Cratn et al. reported successful UV provocation of the lesions of FBCP in the members of one family. Our patients with clinically and histologically verified FBCP never complained of the effect of direct sun light, but they volunteered for the study of the effect of UV irradiation as a provocative factor. We also attempted to evaluate the UV-test as a diagnostic aid. The results were verified clinically, as well as with histopathological and immunohistological methods.
Material and Methods
Seven patients with FBCP, verified chnically and by biopsy, were studied. The duration of their disease was more than 5 years. During the study all of the patients had skin lesions in axillae and/or groins, while the skin of the back was intact. The study was performed in late summer. The test subjects were without any medication with light sensitizing potency. None of them had a history of light hypersensitivity. The radiation tests were performed on the midback skin paravertebrally. The light source was a dysprosium lamp (HQI-TS 400 W, Osram GmbH, Germany) with a lampto-skin-distance of 50cm. The relative distribution of UV energy of the light source was: UVC0.2, UVB 1.0 and UVA 19.0 based on the measurement according to Fischer & Alsins (1976). Before UV challenge a 24 h minimal erythema dose (MED) was determined for each patient. A skin area of 1.5 X 5.0cm was irradiated with a dose of 5 MED and another with 15 MED. The respective exposures were also performed through a water-filled quarz cuvette to study the role of heat (the light path in water was 1 cm).
0303-6987/79/050414-04 $02.50/0 © 1979 Munksgaard, Copenhagen
415
UV LIGHT IN FBCP Biopsy specimens were taken from both the normal skin and from all the irradiated skin areas 8, 24 and 48 h after irradiation, using a 2mm0 punch biopsy technique. Separate samples were taken for histopathological and for immunohistochemical study. The samples for light microscopy were fixed in neutral formalin, mounted in paraffin and stained with Hematoxylin and Eosin. All biopsied specimens were sectioned throughout. The immunofluoreseent study was performed as described by Reunala et al. (1977). Skin from the backs of four healthy volunteers was irradiated with 5 and 15 MED and biopsied as described above. Results
The direct immunohistological study revealed neither immunoglobulins nor complement in any of the biopsies. In healthy volunteers the vacuolization of the keratinocytes was also seen in almost every specimen. Dyskeratotic keratinocytes were found in two specimens taken at 24 h and in all four specimens at 48 h. The epidermal vesicles were not found in any specimen of the controls. Discussion
The effect of UV-light on the skin of the EBCP patients differed markedly from that of the controls. There was no difference in the clinical test results, but the histological study revealed that the epidermis of the patients is highly vulnerable to the large doses of UV-irradiation used in this study. The damage to the keratinocytes was, however, also seen in the skin of normal controls, although to a lesser degree. The typical acantholytic lesion was never seen in their skin, but was found in the skin of EBCP patients on almost every occasion, at least with the high UV-doses and in the late biopsies. This shows that the effect of UV-light probably is not specific, which is in accordance with previous studies (Chorzelski 1962). The large doses needed for the provocation of EBCP lesions also explain the fact that the patients experienced no harmful effects from normal direct sunlight. The diagnostic value of this type of test remains questionable: firstly, because the test result is not manifest clinically but needs histological confirmation, and secondly, the histological confirmation may require several biopsies with serial sections at various intervals because of the variable individual response to the UV-exposure.
Clinically the test sites showed only erythema with edema that was more intense the longer the exposure. Histopathological study revealed irradiation damage to the keratinocytes which markedly increased in severity with time, although individual variation was conspicuous. The water filter had n o clearly detectable protective effect. The exposure of 15 MED caused more destructive changes than 5 MED. In the specimens taken from the EBCP patients the slightest and most common disturbance was the vacuolization of the keratinocytes. This was found in almost every specimen. Dyskeratotic keratinocytes and pyknotic nuclei were found in the specimens taken at 24 h after irradiation. The most severe damage comprised the epidermal vesicles found in every specimen at 48 h. In some cases these were also found in the earlier specimens. The vesicles were partly acantholytic disruptions immediately above the intact row of basal cells (Eig. 1) or intraepidermal bullae with remnants of pyknotic nuclei or necrotic keratinocytes (Fig. 2). The former type of bullae were considered typical of FBCP. The occurrence Acknowledgments of these lesions is shown in Table 1. They were also found in two specimens taken We are indebted to Drs. Osmo P. Salo and from the nonirradiated skin of EBCP patients. Tapio Rantanen for their assistance.
416
SUHONEN AND NIEMI
Fi;?. 7. Patient No 2. The aeantholytic bulla formation at 48 h after irradation with 15 MED. (H & E X 500).
/>fe. 2. Patient No 7. Small bullae without definite signs of aeantholysis at 48 h after irradation with 5 MED. ( H & E X 125).
UV LIGHT IN FBCP
417
Table 1 The acantholytic changes in biopsy specimens at 8, 24 and 48 h after UV-irradiation with 5 or 15 MED Pat. No.
5 MED 24 48
15 MED 8 24
1 2 3 4 5 6 7
8
48
5 MED(W) 24 48
8
15 MED (W) 24 48
U
N
W = with a water-filled cuvette to exclude infra-red radiation. N = necrosis. U = noniiradiated skin.
References
Chorzelski, T. (1962) Experimentally induced acantholysis in Hailey's henign pemphigus. Dermatologiea 124, 21-30. Cram, M. D. L., Muller, S. A. & Winkelmann, R. K. (1967) Ultraviolet-induced acantholysis in familial benign chronic pemphigus. Arehives of Dertnatology 96, 6 3 6 - 6 4 1 . Fischer, T. & Alsins, J. (1976) Treatment of psoriasis with trioxsalen baths and dysprosium lamp. A eta Dermato- Venereologtea (Stoekholm) 56, 383-390. Hailey, 11. & Hailey, H. (1939) Familial benign chionic pemphigus. Arehives of Dermatology 39, 679-685. Loewenthal, L. J. A. (1959) Familial benign
chronic pemphigus: the role of pyogenic bacteria./Ircfti'ves o/Dermafoto,gj' 80, 318-326. Montes, L. F., Narkates, A. J., Hunt, D., Pittillo, R. F., Noojin, R. O. & Sherer, R. J. (1970) Microbial flora in familial benign chronic pempYiigus. Archives of Dermatology 101, 140-144. Reunala, T., Karvonen, J., Tiilikainen, A. & Salo, 0 . P. (1977) Herpes gesUtionis. British Journat of Dermatology 96, 563-568. Address: Kirsti-Maria Niemi Department of Dertnatology University Central Hospital Snellmaninkatu 14 00170 Helsinki 17 Finland
