Case report K E y W OR D S Hand-Schuller -Christian disease; Langerhans cell, oral involvement, histiocytic disorders Oral involvement in Hand-Schuller-Christian disease Severe oral involvem ent in a case of Hafld-Schulkr-Christian disease F. Kokelj and C. Plozzer SUMMARY We report the case of a patient with diabetes insipidus who came to our observation because of severe lesions of the oral mucosa. He referred that he had last all his molars and three incisors over the past two years. The clinical cutaneous examination revealed the presence of small yellowish-brown papules on the forehead only. A biopsy performed from the gingival mucosa showed the presence of Langherans cells and a dense inflammatory infiltrate. The immunohistochemical examination showed CD1 antigenic determinant and S-100 protein positive. Considering the presence of diabetes insipidus, the clinical, histological, immunohistochemical picture, the diagnosis was of a Hand-Shuller-Christian disease. The patient underwent chemotherapy and radiotherapy. Three months after the end of the therapy a gingival biopsy confirmed the success of the treatment. Introduction Histiocytic disorders are a group of heterogeneous diseases resulting from the proliferation and dissemi- nation of pathologic histiocytic cells or Langherans-like cells producing focal, localised single form or dissemi- natecl multisystem manifestations. A correct classifica- tion mainly depends on the histological aspects. Case report B.G. came to our observation because of the wors- ening of clinical manifestations of oral mucosa. For about ten years the patient was suffering from idiopathic diabetes insipidus and had been treated with desmopressin nasal spray. He reported a history of recurrent gingivitis since 1991 with halitosis, teeth unsteacliness, jaw swelling, periodontal lesions, haemorrhages and necrotic lesions that seriously destroyed his gums. He "had !ost ali his molars and three incisors over the past two years. Dur- ing the oral examination, made difficult by the limited opening of the mouth, it was possible to observe that the tissue of both the upper and lower gums appeared swollen, intensely red in-colour ancl prone to bleecling. Acta Dermatoven APA Vol 10, 2001, No 3 - ------------ - --- - ---- ~ - -------- --107 Oral involvernent in Hand-Schuller-Christian disease It was also possible to observe serious unsteadiness of ali the other teeth (Fig. 1). We took a panoramic radio- graph of both dental arches, which showed a remark- able atrophy of the alveolar ridge and a severe paro- dontitis. The remaining teeth were abnormally sited in an extra alveolar position (Fig. 2). The vertebral X-rays showed arthopathic changes that have spread mainly at cervical leve!. Thoracic radiography, !iver and spleen ecography didn't show any changes. The clinical cuta- neous examination revealed the presence of small yel- lowish-brown papules on the forehead. The patient reported that the periodic appearance of these lesions were out of the blue and , in his opinion, unrelated to any other symptoms. The lymphonodal apparatus was normal. A biopsy performed from the gingival mucous showed the presence of Langherans cells in a dense inflammatory infiltrate. The immunohistochemical ex- amination showed CDl antigenic determinant and S- 100 protein positive (Fig . 3). Considering the presence of diabetes insipidus, the histological and immunohistochemical data, the chronic evolution of the clinical picture the diagnosis was of a Figure 1. Oral rnanifestations in the patient. Hand-Shuller-Christian disease. Later the scintigraphic examination of the skull was performed on the patient. There was no evidence of any other localised bone lesions. The patient underwent chemotherapy (a cycle of vinblastine -0.2 mg/ kg once a week- plus prednisone - 30 mg/ day) and radiotherapy (radiation doses ranged from 800-1500 rad - 8-15 Gy - with a mean dose of 1066 rad - 10.66Gy). Three months after the end of the therapy a gingival biopsy confirmed the success of the combined treat- ment. Five years after the diagnosis was made , the pa- tient is symptom-free. Discussion Histiocytic disorders are a group of heterogeneous diseases resulting from the proliferation and dissemi- nation of pathologic histiocytic cells or Langherans like cells producing focal , localised single form or dissemi- nated, multisystem manifestations (1). A correct classi- fication mainly depends on the histological examina- tion, ultrastructural and immunocytochemical data (2). As far as Langherans celi histiocytosis (LCH) is con- cerned (Hand Shuller Christian disease, Abt Letterer Siwe disease, Eosinophilic granuloma), the diagnosis is suspected on the clinical presentation. Distinct lesions are usually seen in soft tissue and bone; lungs and skin often show a more diffuse, patchy involvement; the le- sions are soft and yellow to brown with frequent areas of necrosis and haemorrhage. Histologically, LCH ex- hibits hyperplasia and proliferation of the reticuloen- dothelial system, infiltration with CDl positive histio- Figure 2. Panorarnic radiographs showing extensive alveolar bone destruction. Cas e report 108 -----------------------------------Acta Dermatoven APA Vol 10, 2001, No 3 Case report Oral involvement in Hand-Schuller-Christian disease onset and the extent of the disease (7,8). Treatment can be separated into management of solita1y symptomatic lesions and that of systemic disease (9). Among LCH, Hand-Shuller-Christian disease (15- 40% of cases) is the chronic form clinically characterised by a triad in which characteristic multifocal bone le- sions and extra-skeletal involvement of the reticulo- endotelial system are combined with exophtalmus in about 10% of cases and diabetes insipidus (6,10,11,12). The course is extremely variable: often chronic, seldom fatal (13). The histological diagnosis is based on the presence of a histiocytic infiltrate in the upper and middle dermis. In particular, the optical microscope ex- amination reveals in the papillary dermis an important oedema, large cells with a reniform or indented nucleus and a~Junclant eosinophilic cytoplasm. Histochemical colouring, showing positiveness for S-100 protein, the presence of CDl , CD4 and HLA-DR surface antigens confirm the diagnosis (12 ,14,15). Figure 3. Langerhans cells agglomerations mixed with inflammatory elements (hematoxylin - eosin, magnification x 40) Conclusion The therapy of the Hand-Schuller-Christian clisease varies according to the age of the patient, the severity and extent of the clinical picture. It includes an ortho- paeclic-surgical approach , racliotherapy, chemotherapy and/ or immunotherapeutic treatment (13). cytes disclosing intracytoplasmatic Birbek granules at the electron microscopic examination (3). Causes and pathogenesis of the disease remain un- clear. However, recent studies suggest a disorder of the immune system as an important factor in the aetiology ofLCH (4,5,6) . We report this case because of diagnostically im- portant lesions of the oral mucosa in a patient with dia- betes insipidus without exoftalmus and without eviclent cutaneous lesions. The prognosis depends on the patient's age at the REFEHENCES l. HistioMaria C. Velez-Yanguas and Raj P. Warrier. Langherans' celi Histiocytosis. Pediatr Orthop oncol. 1996; 27 (3): 615-23. 2. Nezelof C, Basset E Langerhans' celi Histiocytosis research. Past, present and future. Hematol Oncol Clin J\orth Am. 1998; 12 (2): 385-406. 3. Veyssier Belot C, Callot V. Histiocytosis. Rev Med Interne. 1996; 17 (11): 911-23. 4. Greenberger JS, Crocker AC, Vawter G, et al. Results of treatment of 127 patients with systemic histio- cytosis. Medicine (Baltimore) 1981; 60: 311-38. 5. Ladisch S, Jaffe ES. The Histiocytoses. In Pizzo PA, Poplack DG (eds): Principles and Practice of Pediatric Oncology, ed 2. Philadelphia, JB Lippincot, 1993; 617. 6. Stuli MA, Kransdorf MJ, Devaney KO. Langerhans' celi Histiocytosis of bone. Radiographics 1992; 12(4): 801-23. 7. Lahey ME. Prognostic factors in histiocytosis X. Am Pediatr Hematol Oncol 1981;ยท3: 57-60. 8. Nezelof C, Frileux-Herbert F, Cronier-Sachot J. Disseminated histiocytosis X: analysis of prognostic factors based ona retrospective study of 50 cases. Cancer 1979; 44: 1824-38. 9. Jones RO, Pillsbury HC. Histiocytosis X of the Head and Neck. Laryngoscope. 1984; 94:1031-5. 10. Hefti F, Jundt G. Langerhans' celi Histiocytosis. Orthopade. 1995 Feb; 24(1): 73-81. Acta Dermatoven APA Vol 10, 2001, No 3 --------- - --- --- - ----------------- 109 Oral involvement in Hand-Schuller-Christian disease AUTHORS' ADDRESSES 11. Sartoris DJ, Parker BR. Histiocytosis X: rate and pattern of resolution of osseous lesions. Radiology 1984; 152: 679-684. 12. Favara BE, McCarthy R, Mierau G. Histiocytosis X. Hum Pathol. 1983; 14: 663. 13. De Lacharriere O, Ougier E. Histiocytose langerhansienne de l'adulte a expression cutanee. Ann Dermatol Venereol. 1990; 117: 303-310. 14. Hashimoto K, Kagetsu N, Taniguchi Y et al. Immunohistochemistry and electron microscopy in Langer- hans cell histiocytosis confined to the skin. J Am Acad Dermatol. 1991; 25: 1044-1053. 15. Slater D, Rooney N, Harrington C, Tncker WFG et al. Generalized histiocytosis X in the elderly: a light and electron microscope and monoclonal antibody study. I-Iistopathology. 1984; 8: 927-936. Franco Kokelj, MD, Institute oj Dermatology, University of Trieste, Via Stocl-c 2, 34100 Trieste, Italy Carmela Plozzer, MD, same address Case report 110 - ------------------------------- --Acta Dermatoven APA Vol 10, 2001, No 3