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Persistent actinic epidermolytic hyperkeratosis
Persistent actinic epidermolytic
hyperkeratosis
Hiroyuki Suzuki, MDT Hukiko Takahashi, MD,a Mitsuo Miyashita, Tsukasa Takemura, MDb Tokyo and Yono, Japan
MD,a and
Background: Epidermolytic hyperkeratosis is a distinctive histologic change noted in a vari-
ety of acquired and congenital dermatoses. Its pathogenesis is unknown. We have observed acquired epidermolytic hyperkeratosis in four Japanese men. Objective: Our purpose was to report four casesof acquired epidermolytic hyperkeratosis induced by sun exposure. Methods: Four cases were studied clinically, histopathologically, electron microscopically, and by tissue culture. Results: Flat, keratotic, slightly elevated, depigmented papules were located on the upper back, shoulders, and anterior aspect of the thighs. They appeared after excessivesun exposure. Depigmented macules coexisted with the pigmented macules. Histologic and ultrastructural examination revealed epidermolytic hyperkeratosis. Thick bundles of tonofilaments, which were also present in the cutaneous lesions, were seen in newly proliferated keratinocytes in cultures taken from depigmented papules. Conclusion: These resuits suggest that acquired epidermolytic hyperkeratosis may be induced by excessivesun exposure. We propose the term persistent actinic epidermolytic hyperkeratosis for these lesions. (J AM ACAD DERMATOL 1995;32:63-6.)
Epidermolytic hyperkeratosis is a distinctive histologic disorder of the epidermis that has been noted in a variety of acquired and congenital dermatoses. l-4 We observed acquired epidermolytic hyperkeratosis in four Japanese men. In each of these patients numerous flat, keratotic, depigmented papules with the histologic features of epidermolytic hyperkeratosis appeared on the upper back and shoulders after excessive sun exposure. The lesions had persisted for more than 2 years. CASE REPORTS Case 1. A 47-year-old Japanese man reported skin lesionson the shoulders and upper back of 3 years’ duration. He had spent 4 or 5 days at the beach during his summer vacations for the past 8 years. Examination revealed
From the Departments of Dermatology, Hospital, Tokyoa; and Ohmiya Japan Accepted
for publication
Surugadai Nihon Umversity Red Cross Hospital, Yono.b
July 26, 1994.
Reprint requests: Hiroyuki Suzuki, MD, Department of Dermatology, Surugadai Nihon University Hospital, l-8-13, Kanda-Surugadai, Chiyoda-lot, IO1 Tokyo, Japan. Copyright 0190-9622/95
@ 1995 by the American $3.00 + 0
16/l/59465
Academy
of Dermatology,
Inc.
about 20 irregularly shaped, flat, keratotic, depigmented papules and numerous small pigmented macules scattered on the upper back (Fig. 1, A). Case 2. A 3 1-year-old Japanese man had depigmented papules and pigmented macules on his shoulders and upper back. He had exposed the area to intense sunlight on Guam for 5 days in the summer 5 years earlier. The lesions appeared during the next 2 months. Examination revealed approximately 30 discrete, slightly elevated, flat keratotic, depigmented papules and numerous irregularly shaped, small, pigmented macules on the shoulders and upper back. Case 3. A 44-year-old Japanese man first noticed skin lesions on his shoulders and upper back 2 years earlier. He had spent 7 days at the beach in the summer every year for the preceding 10 years. Severe erythema and bullae had developed after prolonged exposure to the sun. Examination revealed approximately 15 irregularly shaped, slightly elevated, flat keratotic, depigmented papules and numerous pigmented macules on his shoulders and upper back. Case 4. A 52-year-old Japanese man reported skin lesions on his shoulders and upper back that he had first noticed approximately 20 years earlier. Examination revealed slightly elevated, keratotic, depigmented papules and numerous, small, irregularly shaped macules on his upper back and shoulders (Fig. 1, B). Similar pap&s were also present on the anterior thighs. 63
64
Suzuki et al.
Journal of the American Academy of Dermatology January 1995
prominent hyperkeratosis, (2) an acanthotic epidermis characterized by hypergranulosis with coarse keratohyalin granules, (3) eosinophilic bodies in the cytoplasm of keratinocytes and (4) ring-shaped eosinophilic material in the perinuclear region of the degenerated keratinocytes in the upper epidermis (Fig. 2). Small nests composed of three to five eosinophilic dyskeratotic keratinocytes yere present in the rete ridges. Solar elastosis was not present in any specimens, but a moderate infiltration of lymphocytes was seen around capillaries in the papillary dermis beneath the epidermal lesions. Electron
microscopy
The findings were characterized by ( 1) abnormal aggregates and thick bundles of tonofilaments, (2) large keratohyalin-tonofilament complexes corresponding to the coarse keratohyalin granules seen in light microscopy, and (3) thickened bundles of tonofilaments surrounding the nuclei in the vacuoIated cytoplasm of the degenerated keratinocytes (Fig. 3). In dyskeratotic keratinocytes in small nests in the central portion of the rete ridges in the epidermis, thick bundles of tonofilaments were observed around the nuclei (Fig. 4). Thick bundles of tonofilaments were present within the newly proliferated keratinocytes in the cultured skin tissues taken from the depigmented skin lesion, but they were not seen in the cells from normal skin tissues taken from normal control specimens. DISCUSSION Fig. 1. Slightly elevated, depigmented papules (arrows,J
coexisting with pigmented macules on the shoulder (A, case 1) and upper back (B, case 4).
METHODS Biopsy specimenswere taken from depigmented lesions on the upper back or shoulder from all patients and were examined by light microscopy. In cases 1, 2, and 3, elec-
tron microscopy was also used. In case 3 small pieces of skin taken from a depigmented lesion were cultured. On day 14, the cultured tissue was examined by electron microscopy. In case 3 normal skin was also cultured as a control. RESULTS
Light microscopy Similar observations were made in all four patients. The histologic features were as follows: (1)
The four patients were characterized clinically by numerous flat keratotic, depigmented papules limited to sun-exposed areas intermingled with numerous pigmented macules. All patients noticed that the lesions appeared after excessive sun exposure. In all cases epidermolytic hyperkeratosis was present. Epidermolytic hyperkeratosis is a distinct histologic expression of a pathologic epithelial process. It occurs in some congenital dermatoses such as bullous congenital ichthyosiform erythroderma, systematized keratotic nevus, and hereditary palmoplantar keratosis (Voerner type).‘-’ It is also observed in some acquired dermatoses such as isolated epidermolytic acanthoma and disseminated epidermolytic acanthoma. 6-8 Our patients correspond to those reported by Hirone and Fukushiro,6 Miyamoto et a1.,7 and Shimizu and Kimura,8 all of whom were Japanese. The disease was reported as disseminated epidermolytic acanthoma.
Journal of the American Academy of Dermatology Volume 32, Number 1
Suzuki et al. 65
Fig. 2. Case 1. Epidermolytic hyperkeratosis with acanthotic, edematous epidermis and marked hyperkeratosis. (Hematoxylin-eosin stain; X80.)
Fig. 3. Case 3. Electron microscopy in epidermolytic hyperkeratosis. Abnormal aggregates of tonofilaments with partial deposition of keratohyalin substanceswere present in vacuolated cytoplasm and around nuclei. (x5400.)
Epidermolytic hyperkeratosis may also be observed as an incidental finding in sebaceous cysts, pilar cysts, seborrheic keratosis, squamous cell carcinema, basal cell carcinoma, and solar keratosis. l-4 However, the factor that triggers development of epidermolytic hyperkeratosis is unknown. Ackerman and Reed9 reported two cases of solar keratosis
in which epidermolytic hyperkeratosis was present throughout the epithelium. They stated that epidermolytic hyperkeratosis may rarely be induced by long-term sun exposure because solar elastosis was present beneath the epidermolytic solar keratosis. However, in our patients, nuclear atypia and solar elastosis in the dermis were not recognized histolog-
Journal
66
Suzuki et al.
of the American
Academy
of Dermatology January 1995
4. Case 2. Electron microscopy of small nest of epidermolytic hyperkeratosis in epiderma1 rete ridge. Four dyskeratotic cells in which abnormal aggregates and thick bundles of tonofilaments were present in cytoplasm. Intercellular spaces were wide. (~5400.)
Fig.
ically. The skin lesionswereon the facesof the two patientsof Ackerman and Reed,9but, in ours,they appearedon the upperback, shoulders,and thighs. Shimizu and Kimura* reporteda caseof disseminatedepidermolyticacanthomaand suggestedthat sunexposuremight havebeeninvolved.Nakagawa et al.tOreporteda caseof disseminatedepidermolytic acanthomaduring PUVA therapy(total 25 J/cm2) and statedthat most of the eruption had resolved within 5 months after the cessationof therapy. However, in our patients the lesionspersistedfor years.We proposethe term persistent actinic epidermolytic hyperkeratosis for this disorder. REFERENCES 1. Ackerman AB. Histopathologic concept of epidermolytic hyperkeratosis. Arch Dermatol 1970;102:253-9. 2. Sasaki T, Nakajima H. Incidental epidermolytic hyperkeratosis in progressive systemic sclerosis. J Dermatoll933; 20:178-g.
3. Mehregan AH. Epidermolytic hyperkeratosis: incidental findings in the epidermis and in the intraepidermal eccrine sweat duct units. J Cutan Path01 1978;5:76-80. 4. Barsky S, Doyle JH, Winkelmann RK. Nevus comedonicus with epidermolytic hyperkeratosis. Arch Dermatol 1981;117:86-8. 5. Wilgram GF, Caulfield JB. An electron microscopic study of epidermolytic hyperkeratosis: with a special note on the keratinosome as the “fourth” structural factor in the formation of the horny layer. Arch Dermatoll966;94:12743. 6. Hirone T, Fukushiro R. Disseminated epidermolytic acanthoma: nonsystematized multipleverrucoid lesions showing granular degeneration. Acta Derm Venereol (Stockh) 1973;53:393-420. 7. Miyamoto Y, Ueda K, Sato M, et al. Disseminated epidermolytic acanthoma. J Cutan Path01 1979;6:272-9. 8. Shimizu H, Kimura S. [Disseminated epidermolytic acanthoma]. Rinsho Hihuka 1981;35:1061-5. (In Japanese.) 9. Ackerman AB, Reed RJ. Epidermolytic variant of solar keratosis. Arch Dermatol 1973:107:104-6. 10. Nakagawa T, Nishimoto M, Takaiwa T. Disseminated epidermolytic acanthoma revealed by PUVA. Dermatologica 1986;173:150-3.
hyperkeratosis
Hiroyuki Suzuki, MDT Hukiko Takahashi, MD,a Mitsuo Miyashita, Tsukasa Takemura, MDb Tokyo and Yono, Japan
MD,a and
Background: Epidermolytic hyperkeratosis is a distinctive histologic change noted in a vari-
ety of acquired and congenital dermatoses. Its pathogenesis is unknown. We have observed acquired epidermolytic hyperkeratosis in four Japanese men. Objective: Our purpose was to report four casesof acquired epidermolytic hyperkeratosis induced by sun exposure. Methods: Four cases were studied clinically, histopathologically, electron microscopically, and by tissue culture. Results: Flat, keratotic, slightly elevated, depigmented papules were located on the upper back, shoulders, and anterior aspect of the thighs. They appeared after excessivesun exposure. Depigmented macules coexisted with the pigmented macules. Histologic and ultrastructural examination revealed epidermolytic hyperkeratosis. Thick bundles of tonofilaments, which were also present in the cutaneous lesions, were seen in newly proliferated keratinocytes in cultures taken from depigmented papules. Conclusion: These resuits suggest that acquired epidermolytic hyperkeratosis may be induced by excessivesun exposure. We propose the term persistent actinic epidermolytic hyperkeratosis for these lesions. (J AM ACAD DERMATOL 1995;32:63-6.)
Epidermolytic hyperkeratosis is a distinctive histologic disorder of the epidermis that has been noted in a variety of acquired and congenital dermatoses. l-4 We observed acquired epidermolytic hyperkeratosis in four Japanese men. In each of these patients numerous flat, keratotic, depigmented papules with the histologic features of epidermolytic hyperkeratosis appeared on the upper back and shoulders after excessive sun exposure. The lesions had persisted for more than 2 years. CASE REPORTS Case 1. A 47-year-old Japanese man reported skin lesionson the shoulders and upper back of 3 years’ duration. He had spent 4 or 5 days at the beach during his summer vacations for the past 8 years. Examination revealed
From the Departments of Dermatology, Hospital, Tokyoa; and Ohmiya Japan Accepted
for publication
Surugadai Nihon Umversity Red Cross Hospital, Yono.b
July 26, 1994.
Reprint requests: Hiroyuki Suzuki, MD, Department of Dermatology, Surugadai Nihon University Hospital, l-8-13, Kanda-Surugadai, Chiyoda-lot, IO1 Tokyo, Japan. Copyright 0190-9622/95
@ 1995 by the American $3.00 + 0
16/l/59465
Academy
of Dermatology,
Inc.
about 20 irregularly shaped, flat, keratotic, depigmented papules and numerous small pigmented macules scattered on the upper back (Fig. 1, A). Case 2. A 3 1-year-old Japanese man had depigmented papules and pigmented macules on his shoulders and upper back. He had exposed the area to intense sunlight on Guam for 5 days in the summer 5 years earlier. The lesions appeared during the next 2 months. Examination revealed approximately 30 discrete, slightly elevated, flat keratotic, depigmented papules and numerous irregularly shaped, small, pigmented macules on the shoulders and upper back. Case 3. A 44-year-old Japanese man first noticed skin lesions on his shoulders and upper back 2 years earlier. He had spent 7 days at the beach in the summer every year for the preceding 10 years. Severe erythema and bullae had developed after prolonged exposure to the sun. Examination revealed approximately 15 irregularly shaped, slightly elevated, flat keratotic, depigmented papules and numerous pigmented macules on his shoulders and upper back. Case 4. A 52-year-old Japanese man reported skin lesions on his shoulders and upper back that he had first noticed approximately 20 years earlier. Examination revealed slightly elevated, keratotic, depigmented papules and numerous, small, irregularly shaped macules on his upper back and shoulders (Fig. 1, B). Similar pap&s were also present on the anterior thighs. 63
64
Suzuki et al.
Journal of the American Academy of Dermatology January 1995
prominent hyperkeratosis, (2) an acanthotic epidermis characterized by hypergranulosis with coarse keratohyalin granules, (3) eosinophilic bodies in the cytoplasm of keratinocytes and (4) ring-shaped eosinophilic material in the perinuclear region of the degenerated keratinocytes in the upper epidermis (Fig. 2). Small nests composed of three to five eosinophilic dyskeratotic keratinocytes yere present in the rete ridges. Solar elastosis was not present in any specimens, but a moderate infiltration of lymphocytes was seen around capillaries in the papillary dermis beneath the epidermal lesions. Electron
microscopy
The findings were characterized by ( 1) abnormal aggregates and thick bundles of tonofilaments, (2) large keratohyalin-tonofilament complexes corresponding to the coarse keratohyalin granules seen in light microscopy, and (3) thickened bundles of tonofilaments surrounding the nuclei in the vacuoIated cytoplasm of the degenerated keratinocytes (Fig. 3). In dyskeratotic keratinocytes in small nests in the central portion of the rete ridges in the epidermis, thick bundles of tonofilaments were observed around the nuclei (Fig. 4). Thick bundles of tonofilaments were present within the newly proliferated keratinocytes in the cultured skin tissues taken from the depigmented skin lesion, but they were not seen in the cells from normal skin tissues taken from normal control specimens. DISCUSSION Fig. 1. Slightly elevated, depigmented papules (arrows,J
coexisting with pigmented macules on the shoulder (A, case 1) and upper back (B, case 4).
METHODS Biopsy specimenswere taken from depigmented lesions on the upper back or shoulder from all patients and were examined by light microscopy. In cases 1, 2, and 3, elec-
tron microscopy was also used. In case 3 small pieces of skin taken from a depigmented lesion were cultured. On day 14, the cultured tissue was examined by electron microscopy. In case 3 normal skin was also cultured as a control. RESULTS
Light microscopy Similar observations were made in all four patients. The histologic features were as follows: (1)
The four patients were characterized clinically by numerous flat keratotic, depigmented papules limited to sun-exposed areas intermingled with numerous pigmented macules. All patients noticed that the lesions appeared after excessive sun exposure. In all cases epidermolytic hyperkeratosis was present. Epidermolytic hyperkeratosis is a distinct histologic expression of a pathologic epithelial process. It occurs in some congenital dermatoses such as bullous congenital ichthyosiform erythroderma, systematized keratotic nevus, and hereditary palmoplantar keratosis (Voerner type).‘-’ It is also observed in some acquired dermatoses such as isolated epidermolytic acanthoma and disseminated epidermolytic acanthoma. 6-8 Our patients correspond to those reported by Hirone and Fukushiro,6 Miyamoto et a1.,7 and Shimizu and Kimura,8 all of whom were Japanese. The disease was reported as disseminated epidermolytic acanthoma.
Journal of the American Academy of Dermatology Volume 32, Number 1
Suzuki et al. 65
Fig. 2. Case 1. Epidermolytic hyperkeratosis with acanthotic, edematous epidermis and marked hyperkeratosis. (Hematoxylin-eosin stain; X80.)
Fig. 3. Case 3. Electron microscopy in epidermolytic hyperkeratosis. Abnormal aggregates of tonofilaments with partial deposition of keratohyalin substanceswere present in vacuolated cytoplasm and around nuclei. (x5400.)
Epidermolytic hyperkeratosis may also be observed as an incidental finding in sebaceous cysts, pilar cysts, seborrheic keratosis, squamous cell carcinema, basal cell carcinoma, and solar keratosis. l-4 However, the factor that triggers development of epidermolytic hyperkeratosis is unknown. Ackerman and Reed9 reported two cases of solar keratosis
in which epidermolytic hyperkeratosis was present throughout the epithelium. They stated that epidermolytic hyperkeratosis may rarely be induced by long-term sun exposure because solar elastosis was present beneath the epidermolytic solar keratosis. However, in our patients, nuclear atypia and solar elastosis in the dermis were not recognized histolog-
Journal
66
Suzuki et al.
of the American
Academy
of Dermatology January 1995
4. Case 2. Electron microscopy of small nest of epidermolytic hyperkeratosis in epiderma1 rete ridge. Four dyskeratotic cells in which abnormal aggregates and thick bundles of tonofilaments were present in cytoplasm. Intercellular spaces were wide. (~5400.)
Fig.
ically. The skin lesionswereon the facesof the two patientsof Ackerman and Reed,9but, in ours,they appearedon the upperback, shoulders,and thighs. Shimizu and Kimura* reporteda caseof disseminatedepidermolyticacanthomaand suggestedthat sunexposuremight havebeeninvolved.Nakagawa et al.tOreporteda caseof disseminatedepidermolytic acanthomaduring PUVA therapy(total 25 J/cm2) and statedthat most of the eruption had resolved within 5 months after the cessationof therapy. However, in our patients the lesionspersistedfor years.We proposethe term persistent actinic epidermolytic hyperkeratosis for this disorder. REFERENCES 1. Ackerman AB. Histopathologic concept of epidermolytic hyperkeratosis. Arch Dermatol 1970;102:253-9. 2. Sasaki T, Nakajima H. Incidental epidermolytic hyperkeratosis in progressive systemic sclerosis. J Dermatoll933; 20:178-g.
3. Mehregan AH. Epidermolytic hyperkeratosis: incidental findings in the epidermis and in the intraepidermal eccrine sweat duct units. J Cutan Path01 1978;5:76-80. 4. Barsky S, Doyle JH, Winkelmann RK. Nevus comedonicus with epidermolytic hyperkeratosis. Arch Dermatol 1981;117:86-8. 5. Wilgram GF, Caulfield JB. An electron microscopic study of epidermolytic hyperkeratosis: with a special note on the keratinosome as the “fourth” structural factor in the formation of the horny layer. Arch Dermatoll966;94:12743. 6. Hirone T, Fukushiro R. Disseminated epidermolytic acanthoma: nonsystematized multipleverrucoid lesions showing granular degeneration. Acta Derm Venereol (Stockh) 1973;53:393-420. 7. Miyamoto Y, Ueda K, Sato M, et al. Disseminated epidermolytic acanthoma. J Cutan Path01 1979;6:272-9. 8. Shimizu H, Kimura S. [Disseminated epidermolytic acanthoma]. Rinsho Hihuka 1981;35:1061-5. (In Japanese.) 9. Ackerman AB, Reed RJ. Epidermolytic variant of solar keratosis. Arch Dermatol 1973:107:104-6. 10. Nakagawa T, Nishimoto M, Takaiwa T. Disseminated epidermolytic acanthoma revealed by PUVA. Dermatologica 1986;173:150-3.