Clinical and Experimental Dermatology 1991; 16: 212-215.
Skin ulceration as sole manifestation of Langerhans-cell histiocytosis D.MODI AND E.J.SCHULZ Division of Dermatology, Department of Medicine, Baragmanath Hospital and University ofthe Witwatersrand, Johannesburg, South Africa Accepted for publication 2 October 1990
Summary A 65-year-old black woman presented with skin ulceration of 5 years' duration which affected the left axilla, left groin, intergluteal folds and ano-perineal region. The diagnosis of Langerhans-cell histiocytosis (LCH) was confirmed by light and electron-microscopic findings and a positive S-100 stain. Extensive investigations failed to reveal any evidence of systemic involvement. A review of the literature suggests that this clinical picture as the sole manifestation of the disease is rare. Case report A 65-year-old black woman was referred to the Dermatology Outpatient Clinic at the Baragwanath Hospital for management of chronic skin ulceration which had started 5 years previously. Ulcers had developed simultaneously in the left axilla, left groin, anogenital area and in the intergluteal fold. The lesions had failed to respond to prolonged courses of numerous topical and systemic antibiotics given at other hospitals. A year previously ulcers in the perianal and intergluteal areas had been surgically excised. The patient had no other complaints and there was no history of tuberculosis, diabetes or any other systemic illness. Physical examination revealed a woman in good general condition. There was a large ulcer approximately 1-5 cm in diameter in the left axilla (Fig. 1). A similar ulcer was present in the left groin just lateral to the labium major (Fig. 2). A wide atrophic hypopigmented scar due to previous excision extended from below this uleer around the anus and into the intergluteal fold. There were small ulcers in and at the edge ofthe scar in the anogenital area and an additional ulcer was present at the posterior pole ofthe scar in the intergluteal fold. All the ulcers had raised rolled edges and clean bases consisting of pink to red granulation tissue.
Figure 1. Ulcer left axilla.
Figure 2. Ulcer lateral to left labium majus.
Shotty lymph glands were palpable in the left axilla and both groins. No other abnormal physical findings were noted. Special investigations
Correspondence: Dr D.Modi, Division of Dermatology, Area 553, Johannesburg Hospital and University ofthe Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa.
212
The PPD test was weakly positive. Proctosigmoidoseopy and colonoscopy revealed no abnormalities. Gynaecologi-
SKIN ULCERATION AND LANGERHANS-CELL HISTIOCYTOSIS cal examination including cervical smears for cytology was normal. X-ray examination ofthe ehest and skull and a skeletal survey and a total body bone scan were normal. Laboratory investigations including a full blood count, erythrocyte sedimentation rate, serum urea and electrolytes, serum immunoglobulins, serum protein electrophoresis, liver-function tests, amoebic complement fixation test, stool examination and urine analysis were all within normal limits. Serological tests for syphilis and HIV antibodies were negative. Urine and serum osmolarity was normal. Microbiological examination of smears taken from ulcers in the left groin and perineum were negative for Donovan bodies. Skin biopsies
213
tissue and a dense infiltrate of eosinophils, histiocytes and lymphocytes in the upper and mid dermis (Fig. 3). Large histiocytes with irregularly shaped nuclei were seen scattered amongst the cellular infiltrate (Fig. 4). Numerous histiocytes within the infiltrate stained positively with the SI00 stain. Electron microscopy. Numerous dermal histiocytes showed features of epidermal Langerhans cells, containing a lobulated nucleus, vacuoles and numerous Langerhans (Birbeck) granules in their cytoplasm. The Birbeek granules showed the characteristic 'zipper' and 'tennis racket' appearances. Treatment and course
The patient was treated with fractionated doses of Light microscopy. Punch biopsies of ulcers in the axilla orthovoltage radiation given over a period of 6 weeks and groin showed a normal epidermis with granulation which induced complete resolution ofthe ulcers without scarring. There has been no recurrence of skin ulcers and no symptoms or signs of systemic disease in the following 12 months.
Discussion The clinical appearance and distribution of the skin ulcers in our patient suggested the possible diagnoses of granuloma inguinale, cutaneous tuberculosis or amoebiasis which are causes of chronic recalcitrant skin ulceration in southern Africa. These conditions were excluded on histological examination of skin biopsies in which the possibility of LCH was considered and confirmed by electron microscopy. Extensive investigations failed to reveal involvement of organs other than the skin in our patient. Figure 3. liense inflammatory with prominent eosinophils in the Disorders previously called histiocytosis X are now dermis. Biopsy taken from the edge of the ulcer shown in Fig. 2 (I i&E X 20). known by the term Langerhans-cell histiocytosis (LCH).' LCH consists of a clinical spectrum of disease, commonest in children,^ which includes the entities of eosinophiiic granuloma, Hand-SchuUer-Christian disease, Letterer-Siwe disease and malignant acute and chronic histiocytosis X.'"^ In adults LCH is often localized to bone, usually the skull, but may occur in other organs, particularly skin and lung.^ The skin manifestations in the various syndromes consist of a seborrhoeic dermatitis-like eruption, a generalized papular eruption, nodules, and ulcers particularly in the skin folds of the axilla, inguinal, retroaurieular and intergluteal regions.''•^ Involvement of the skin as the only manifestation of LCH is uncommon.** Only 16 cases of pure cutaneous LCH have been reported in the literature (see Table 1). None of these patients showed evidence of further Figure 4. Abnormal histiocytes with large irregular nuclei (H&E systemic disease at follow-up periods ranging from 1 to 5 years. As the disease progresses slowly it is of course x51, oil).
214
D.MODI AND E.J.SCHULZ Table I. Langerhans-cell bistiocytosis confined to the skin—reports in the literature
Patients Authors
Year
Sex
Age
Clinical presentation
Butler and Garretts^ Kierland et «/.'" Esterley and Swick" Johansen'^ Feuerman and Sandbanks'^ Benish et al.^* Wolfson et at.^^
1953 1957 1969 1973 1976 1977 1980
M F F M M M
Nethercott et al.^^ Rose et al}' Magana-Garcia'** Goldberg et at.^^ Hall et al.^*^ Caputo et al.^^ Lee et al.^^
1983 1984 1986 1986 1987 1987 1988
22 months 2 years 2 months 21 months 62 years 76 years 18 months 1 month 82 years 50 years 3 years 76 years 16 years 32 years 9 months 4 months
generalized papules-f-skin ulceration seborrhoeic dermatitis like seborrhoeic dermatitis like seborrhoeic dermatitis like generalized papulonodular rash + flexural ulcers generalized papular rash generalized maculopapular rash seborrhoeic dermatitis like papules trunk vulval ulcers generalized nodular eruption generalized nodular eruption papules limbs nodules trunk-f genital ulcers papules abdomen papules trunk
F
M F F M M M
M F F
possible that further follow-up of these cases may reveal References involvement of other organs. Ulceration of the skin as the only type of cutaneous 1. The Writing Group of the Histiocyte Society. Histiocytosis syndromes in children. Lancet 1987; v. 208-209. involvement of LCH has been described previously, mainly in adults with additional systemic involvement. 2. Berry DH, Beeton BL. Natural history of Histiocytosis X In: Osband ME, Pochedly C, eds. Histiocytosis X. HaematologyMahzoon and Wood^' described a 20-year-old man with Oncology Climes of North America. Philadelphia: WB Saunders, persistent skin ulceration in the axillae and groin who also 1987: 23-34. had diabetes insipidus and thyroid disease. Charabi et 3. Risdall AJ, Dehner LP, Duray P et al. Histiocytosis X (Langeral.^^ described perianal ulceration due to LCH in an hans cell histiocytosis). Prognostic role of histopathology. Archives of Pathology and Laboratory Medicine 1983; 107: 59. 83-year-old woman with lytic bone lesions. More recently 4. Mcl^elland J, Pritchard J, Chu AC. Current controversies. In: McLelland and Chu^^ reported tw o adults w ith multisysOsband ME, Pochedly C, eds. Htstiocytosis X. Haematologytem disease who had skin ulcers inflexuralareas. The first Oncology Clinics of North America. Philadelphia: WB Saunders, was a 17-year-old female with submammary skin ulcers 1987: 147-162. and the second a 59-year-old woman with an ulcerating 5. Greenberger JS, Crocker AC, Vawter G, Jaffe N, et al. Results of treatment of 127 patients with systemic histiocytosi.s (I-ettererpapular rash ofthe inguinal and submammary areas. Siwe syndrome, Schuller-Christian syndrome and multifocal There have been few case reports of LCH where ulcers eosinophiiic granuloma). Medicine 1981; 60: 311-338. were part of a disease process localized to the skin with no 6. Winkelmann RK. The skin in Histiocytosis X. Mayo Clinic evidence of systemic involvement. Butler and Garretts** Proceedings 1969; 44: 535-549. described a generalized papular rash with ulceration in a 7. Gianotti F, Caputo R. Histiocytic syndromes—a TQviQV/. Journal ofthe American Academy of Dermatology 1985; 13: 383-4(M. 1-month-old infant. Feuerman and Sandbanks'^ reported 8. Enriques P, Dahlin BC, Hayles AB. Histiocytosis X—a clinical a 62-year-old white man who had a generalized papulostudy. Mayo Clinic Proceedings 1967; 42: 88-99. nodular rash on the trunk and skin ulcers in the retro- 9. Butler NR, Garretts M. Eosinophiiic granuloma of the skin. auricular, inguinal and intergluteal skin folds. Caputo et Proceedings ofthe Royal Society of Medicine 1953; 46: 276-277. al.^^ described a 32-year-old man with nodules on his 10. Kierland RB, Epstein JG, Weber WE. Eosinophiiic granuloma of skin and mucous membranes: association with diabetes insipidus. trunk and lesions resembling multiple chancres on the Archives of Dermatology 1957; 75: 45-54. penile shaft. The case which resembled ours most closely NB, Swick HM. Cutaneous Letterer-Siwe disease. was a 50-year-old white woman with vulval ulcers as the 11. Esterly American Journal of Diseases of Children 1969; 117: 236-238. only manifestation of LCH reported by Rose et al^~ 12. JohansenAG. Case of Letterer-Siwe disease. Dfrffiaro/o^iVfl 1973; 146: 197-302. Because of the rarity of cutaneous ulceration as the presenting and only feature of LCH the diagnosis was 13. Feuerman EN, Sandbanks M. Histiocytosis X with skin lesions as the sole clinical expression. Acta Dermato-Venereologica (Stockoverlooked in our patient for many years and institution holm) 1976; 56: Id'i-Tll. of appropriate therapy delayed. In cases of chronic skin 14. Benisch B, Peison B, Carter M et al. Histiocytosis X of the skin of ulceration where the commoner causes have been an elderly man. American Journal of Clinical Pathology 1977; 67: 36-40. excluded, the possibility of LCH should be considered.
SKIN ULCERATION AND
LANGERHANS-CELL
15. Wolfson SL, Botero F, Hurwitz S et al. 'Pure' cutaneous histiocytosis X. Cancer 1981; 48: 2236-2238. 16. Nethercott JR, Murray AH, Medwidsky W. Histiocytosis X in two adults. Archives of Dermatology 1983; 119: 157-161. 17. Rose PG, Johnston GC, Toole RV. Pure cutaneous histiocytosis X ofthe vulva. Obstetrics Gynaecology 1984; 64: 587-591. 18. Magana-Garcia M. Pure cutaneous Histiocytosis X. International Journal of Dermatotogy 1986; 25: 106-108. 19. Goldberg NS, Bauer K, Rosen ST et al. Flow cytometric DNA content, immunohistocbemistry in diagnosis. Histopathotogy 1987; 11: 1181-1191. 20. Hall PA, O'Doherty CJ, Levison DA. Langerhans cell bistiocytosis—an unusual case illustrating tbe value of immunobisto-
HISTIOCYTOSIS
215
chemistry in diagnosis. Histopathology 1987; 11: 1181-1191. 21. Caputo R, Gianotti R, Monti M. Nodular 'pure' mucocutaneous histiocytosis X in an adult. Archives of Dermatology 1987; 123: 1274-1275. 22. Lee C, Park MH, Lee H. Recurrent cutaneous Langerbans cell histiocytosis in infancy. British Journal of Dermatology 1988; 119: 259-265. 23. Mahzoon S, Wood MG. Muttifocal eosinophiiic granuloma witb skin ulceration. Archives of Dermatology 1980; 116: 218-220. 24. Charabi S. Perianal histiocytosis X. Ugeskrift for Laeger 1985; 147:4113-4114. 25. McLelland J, Chu AC. Multisystem Langerhans-cell histiocytosis in adults. Clinical and Experimental Dermatology 1990; 15: 79-82.
Skin ulceration as sole manifestation of Langerhans-cell histiocytosis D.MODI AND E.J.SCHULZ Division of Dermatology, Department of Medicine, Baragmanath Hospital and University ofthe Witwatersrand, Johannesburg, South Africa Accepted for publication 2 October 1990
Summary A 65-year-old black woman presented with skin ulceration of 5 years' duration which affected the left axilla, left groin, intergluteal folds and ano-perineal region. The diagnosis of Langerhans-cell histiocytosis (LCH) was confirmed by light and electron-microscopic findings and a positive S-100 stain. Extensive investigations failed to reveal any evidence of systemic involvement. A review of the literature suggests that this clinical picture as the sole manifestation of the disease is rare. Case report A 65-year-old black woman was referred to the Dermatology Outpatient Clinic at the Baragwanath Hospital for management of chronic skin ulceration which had started 5 years previously. Ulcers had developed simultaneously in the left axilla, left groin, anogenital area and in the intergluteal fold. The lesions had failed to respond to prolonged courses of numerous topical and systemic antibiotics given at other hospitals. A year previously ulcers in the perianal and intergluteal areas had been surgically excised. The patient had no other complaints and there was no history of tuberculosis, diabetes or any other systemic illness. Physical examination revealed a woman in good general condition. There was a large ulcer approximately 1-5 cm in diameter in the left axilla (Fig. 1). A similar ulcer was present in the left groin just lateral to the labium major (Fig. 2). A wide atrophic hypopigmented scar due to previous excision extended from below this uleer around the anus and into the intergluteal fold. There were small ulcers in and at the edge ofthe scar in the anogenital area and an additional ulcer was present at the posterior pole ofthe scar in the intergluteal fold. All the ulcers had raised rolled edges and clean bases consisting of pink to red granulation tissue.
Figure 1. Ulcer left axilla.
Figure 2. Ulcer lateral to left labium majus.
Shotty lymph glands were palpable in the left axilla and both groins. No other abnormal physical findings were noted. Special investigations
Correspondence: Dr D.Modi, Division of Dermatology, Area 553, Johannesburg Hospital and University ofthe Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa.
212
The PPD test was weakly positive. Proctosigmoidoseopy and colonoscopy revealed no abnormalities. Gynaecologi-
SKIN ULCERATION AND LANGERHANS-CELL HISTIOCYTOSIS cal examination including cervical smears for cytology was normal. X-ray examination ofthe ehest and skull and a skeletal survey and a total body bone scan were normal. Laboratory investigations including a full blood count, erythrocyte sedimentation rate, serum urea and electrolytes, serum immunoglobulins, serum protein electrophoresis, liver-function tests, amoebic complement fixation test, stool examination and urine analysis were all within normal limits. Serological tests for syphilis and HIV antibodies were negative. Urine and serum osmolarity was normal. Microbiological examination of smears taken from ulcers in the left groin and perineum were negative for Donovan bodies. Skin biopsies
213
tissue and a dense infiltrate of eosinophils, histiocytes and lymphocytes in the upper and mid dermis (Fig. 3). Large histiocytes with irregularly shaped nuclei were seen scattered amongst the cellular infiltrate (Fig. 4). Numerous histiocytes within the infiltrate stained positively with the SI00 stain. Electron microscopy. Numerous dermal histiocytes showed features of epidermal Langerhans cells, containing a lobulated nucleus, vacuoles and numerous Langerhans (Birbeck) granules in their cytoplasm. The Birbeek granules showed the characteristic 'zipper' and 'tennis racket' appearances. Treatment and course
The patient was treated with fractionated doses of Light microscopy. Punch biopsies of ulcers in the axilla orthovoltage radiation given over a period of 6 weeks and groin showed a normal epidermis with granulation which induced complete resolution ofthe ulcers without scarring. There has been no recurrence of skin ulcers and no symptoms or signs of systemic disease in the following 12 months.
Discussion The clinical appearance and distribution of the skin ulcers in our patient suggested the possible diagnoses of granuloma inguinale, cutaneous tuberculosis or amoebiasis which are causes of chronic recalcitrant skin ulceration in southern Africa. These conditions were excluded on histological examination of skin biopsies in which the possibility of LCH was considered and confirmed by electron microscopy. Extensive investigations failed to reveal involvement of organs other than the skin in our patient. Figure 3. liense inflammatory with prominent eosinophils in the Disorders previously called histiocytosis X are now dermis. Biopsy taken from the edge of the ulcer shown in Fig. 2 (I i&E X 20). known by the term Langerhans-cell histiocytosis (LCH).' LCH consists of a clinical spectrum of disease, commonest in children,^ which includes the entities of eosinophiiic granuloma, Hand-SchuUer-Christian disease, Letterer-Siwe disease and malignant acute and chronic histiocytosis X.'"^ In adults LCH is often localized to bone, usually the skull, but may occur in other organs, particularly skin and lung.^ The skin manifestations in the various syndromes consist of a seborrhoeic dermatitis-like eruption, a generalized papular eruption, nodules, and ulcers particularly in the skin folds of the axilla, inguinal, retroaurieular and intergluteal regions.''•^ Involvement of the skin as the only manifestation of LCH is uncommon.** Only 16 cases of pure cutaneous LCH have been reported in the literature (see Table 1). None of these patients showed evidence of further Figure 4. Abnormal histiocytes with large irregular nuclei (H&E systemic disease at follow-up periods ranging from 1 to 5 years. As the disease progresses slowly it is of course x51, oil).
214
D.MODI AND E.J.SCHULZ Table I. Langerhans-cell bistiocytosis confined to the skin—reports in the literature
Patients Authors
Year
Sex
Age
Clinical presentation
Butler and Garretts^ Kierland et «/.'" Esterley and Swick" Johansen'^ Feuerman and Sandbanks'^ Benish et al.^* Wolfson et at.^^
1953 1957 1969 1973 1976 1977 1980
M F F M M M
Nethercott et al.^^ Rose et al}' Magana-Garcia'** Goldberg et at.^^ Hall et al.^*^ Caputo et al.^^ Lee et al.^^
1983 1984 1986 1986 1987 1987 1988
22 months 2 years 2 months 21 months 62 years 76 years 18 months 1 month 82 years 50 years 3 years 76 years 16 years 32 years 9 months 4 months
generalized papules-f-skin ulceration seborrhoeic dermatitis like seborrhoeic dermatitis like seborrhoeic dermatitis like generalized papulonodular rash + flexural ulcers generalized papular rash generalized maculopapular rash seborrhoeic dermatitis like papules trunk vulval ulcers generalized nodular eruption generalized nodular eruption papules limbs nodules trunk-f genital ulcers papules abdomen papules trunk
F
M F F M M M
M F F
possible that further follow-up of these cases may reveal References involvement of other organs. Ulceration of the skin as the only type of cutaneous 1. The Writing Group of the Histiocyte Society. Histiocytosis syndromes in children. Lancet 1987; v. 208-209. involvement of LCH has been described previously, mainly in adults with additional systemic involvement. 2. Berry DH, Beeton BL. Natural history of Histiocytosis X In: Osband ME, Pochedly C, eds. Histiocytosis X. HaematologyMahzoon and Wood^' described a 20-year-old man with Oncology Climes of North America. Philadelphia: WB Saunders, persistent skin ulceration in the axillae and groin who also 1987: 23-34. had diabetes insipidus and thyroid disease. Charabi et 3. Risdall AJ, Dehner LP, Duray P et al. Histiocytosis X (Langeral.^^ described perianal ulceration due to LCH in an hans cell histiocytosis). Prognostic role of histopathology. Archives of Pathology and Laboratory Medicine 1983; 107: 59. 83-year-old woman with lytic bone lesions. More recently 4. Mcl^elland J, Pritchard J, Chu AC. Current controversies. In: McLelland and Chu^^ reported tw o adults w ith multisysOsband ME, Pochedly C, eds. Htstiocytosis X. Haematologytem disease who had skin ulcers inflexuralareas. The first Oncology Clinics of North America. Philadelphia: WB Saunders, was a 17-year-old female with submammary skin ulcers 1987: 147-162. and the second a 59-year-old woman with an ulcerating 5. Greenberger JS, Crocker AC, Vawter G, Jaffe N, et al. Results of treatment of 127 patients with systemic histiocytosi.s (I-ettererpapular rash ofthe inguinal and submammary areas. Siwe syndrome, Schuller-Christian syndrome and multifocal There have been few case reports of LCH where ulcers eosinophiiic granuloma). Medicine 1981; 60: 311-338. were part of a disease process localized to the skin with no 6. Winkelmann RK. The skin in Histiocytosis X. Mayo Clinic evidence of systemic involvement. Butler and Garretts** Proceedings 1969; 44: 535-549. described a generalized papular rash with ulceration in a 7. Gianotti F, Caputo R. Histiocytic syndromes—a TQviQV/. Journal ofthe American Academy of Dermatology 1985; 13: 383-4(M. 1-month-old infant. Feuerman and Sandbanks'^ reported 8. Enriques P, Dahlin BC, Hayles AB. Histiocytosis X—a clinical a 62-year-old white man who had a generalized papulostudy. Mayo Clinic Proceedings 1967; 42: 88-99. nodular rash on the trunk and skin ulcers in the retro- 9. Butler NR, Garretts M. Eosinophiiic granuloma of the skin. auricular, inguinal and intergluteal skin folds. Caputo et Proceedings ofthe Royal Society of Medicine 1953; 46: 276-277. al.^^ described a 32-year-old man with nodules on his 10. Kierland RB, Epstein JG, Weber WE. Eosinophiiic granuloma of skin and mucous membranes: association with diabetes insipidus. trunk and lesions resembling multiple chancres on the Archives of Dermatology 1957; 75: 45-54. penile shaft. The case which resembled ours most closely NB, Swick HM. Cutaneous Letterer-Siwe disease. was a 50-year-old white woman with vulval ulcers as the 11. Esterly American Journal of Diseases of Children 1969; 117: 236-238. only manifestation of LCH reported by Rose et al^~ 12. JohansenAG. Case of Letterer-Siwe disease. Dfrffiaro/o^iVfl 1973; 146: 197-302. Because of the rarity of cutaneous ulceration as the presenting and only feature of LCH the diagnosis was 13. Feuerman EN, Sandbanks M. Histiocytosis X with skin lesions as the sole clinical expression. Acta Dermato-Venereologica (Stockoverlooked in our patient for many years and institution holm) 1976; 56: Id'i-Tll. of appropriate therapy delayed. In cases of chronic skin 14. Benisch B, Peison B, Carter M et al. Histiocytosis X of the skin of ulceration where the commoner causes have been an elderly man. American Journal of Clinical Pathology 1977; 67: 36-40. excluded, the possibility of LCH should be considered.
SKIN ULCERATION AND
LANGERHANS-CELL
15. Wolfson SL, Botero F, Hurwitz S et al. 'Pure' cutaneous histiocytosis X. Cancer 1981; 48: 2236-2238. 16. Nethercott JR, Murray AH, Medwidsky W. Histiocytosis X in two adults. Archives of Dermatology 1983; 119: 157-161. 17. Rose PG, Johnston GC, Toole RV. Pure cutaneous histiocytosis X ofthe vulva. Obstetrics Gynaecology 1984; 64: 587-591. 18. Magana-Garcia M. Pure cutaneous Histiocytosis X. International Journal of Dermatotogy 1986; 25: 106-108. 19. Goldberg NS, Bauer K, Rosen ST et al. Flow cytometric DNA content, immunohistocbemistry in diagnosis. Histopathotogy 1987; 11: 1181-1191. 20. Hall PA, O'Doherty CJ, Levison DA. Langerhans cell bistiocytosis—an unusual case illustrating tbe value of immunobisto-
HISTIOCYTOSIS
215
chemistry in diagnosis. Histopathology 1987; 11: 1181-1191. 21. Caputo R, Gianotti R, Monti M. Nodular 'pure' mucocutaneous histiocytosis X in an adult. Archives of Dermatology 1987; 123: 1274-1275. 22. Lee C, Park MH, Lee H. Recurrent cutaneous Langerbans cell histiocytosis in infancy. British Journal of Dermatology 1988; 119: 259-265. 23. Mahzoon S, Wood MG. Muttifocal eosinophiiic granuloma witb skin ulceration. Archives of Dermatology 1980; 116: 218-220. 24. Charabi S. Perianal histiocytosis X. Ugeskrift for Laeger 1985; 147:4113-4114. 25. McLelland J, Chu AC. Multisystem Langerhans-cell histiocytosis in adults. Clinical and Experimental Dermatology 1990; 15: 79-82.
