Dermatology Online Journal

Langerhans' Cell Histiocytosis
Hessein Mortazavi, Amirhoushang Ehsani, Mohammad Reza Namazi, and Mahbobeh Hosseini
Dermatology Online Journal 8(2): 18

From the Dermatology Department, Tehran University of Medical Sciences, Iran

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Abstract

Adult onset Langerhans cell histiocytosis is uncommon. A 29 year old man is presented who developed classic cutaneous disease with severe systemic involvement. He responded completely to a two month course of thalidomide.

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A 29- year-old male presented with a 4 year history of a rash involving the scalp, retroauricular area, and trunk. The patient developed slightly pruritic, tiny, yellow-orange papules over the scalp, retroauricular area, trunk, and inguinal as well as axillary folds from the age of 25. Also, he had developed poikiloderma-like plaques over the trunk. The patient was also suffering from dry cough, exertional dyspnea, polyuria and polydipsia. He was a cigarette smoker and addicted to opioids. He was not complaining of any mucosal lesions but had progressive dental loss for the past few years.

Physical Examination

Tiny, yellow-orange papules were present over the scalp, retroauricular area, trunk and inguinal as well as axillary folds (Figure 1). In contiguity with these lesions were poikiloderma-like erythematous plaques over the trunk.

Cardiac physical examination was within normal limits, but bilateral basilar pulmonary rales were present on pulmonary ausculation. Neither lymphadenopathy nor hepatosplenomegaly were present. The patient was kyphotic and of slightly short stature but otherwise was normally developed.

Figure 1	Figure 2
Fig 1: Erythematous plaques along with scaly, tiny, yellow-orange papules over the trunk.
Fig 2: Skull X-ray showing multiple sharply dermarcated lytic lesions in temporal and frontal bones.

Laboratory Data

Figure 3
Fig 3: Two representative skin biopsies revealed intense granuloma-like histiocytic infiltration along with the presence of numerous lymphocytes and eosinophils.

The patient's chest X-ray and chest-CT scans were consistent with interstitial lung disease. Skull X-ray revealed multiple sharply demarcated lytic lesions in temporal and frontal bones (Figure 2).

Abdominal sonography and CT-scan, biochemical laboratory studies and bone marrow aspiration and biopsy were normal.

The patient's 24-hour urinary volume was 4000 cc and his urine specific gravity was 1002.

Immunohistochemistry was positive for S100. Electron microscopic study showed Birbeck granules in the cytoplasma of the lesional cells.

Diagnosis

Langerhans cell histiocytosis

Comment

Langerhans cell histiocytosis (LCH), or histiocytosis X, is a group of diseases characterized by proliferation of the Langerhans cell. These disorders can involve many organ systems but primarily affect the bone, skin, lymph nodes, lungs, liver and spleen, endocrine glands, and nervous system. The separation of these conditions into separate entities, Letterer-Siwe disease, Hand-Schuller-Christian disease, and eosinophilic granuloma is of historical interest [1]. The disease affects young children from 1 to 4 years but can present from birth to the ninth decade. It is uncommon, with an incidence of 2 to 5 per million per year [1].

The pathogenesis of LCH is unknown. There remains debate as to whether the infiltrating cells are truly neoplastic or simply reactive [1].

In a large series of 124 patients, bone, lymph node and skin lesions were the most frequently seen, but 50% of patients showed liver disease and 23% lung disease with frequent hematological disease [3].

The most characteristic dermatological presentation is with scalp involvement. The scalp is erythematous with greasy scales, looking very much like seborrheic dermatitis. On the trunk, the lesions are discrete, yellow-brown, scaly papules, often showing areas of purpura. Lesions may become nodular and crusted or eroded Ulceration in the flexures and in the groin or perianal area is a common presentation in adult patients [2].

The most common oral presentation is with periodontal involvement, affecting particularly the lower molar areas [2,3]. There may be destruction of the alveolar ridge with infiltration of the gums with LCH cells, resulting in the teeth floating from their sockets [2].

Bone marrow involvement may be occult, or there may be pancytopenia [2]. This may present as skin purpura [1]. Lymph nodes are characteristically involved, especially the cervical nodes [1].

Primary pulmonary LCH is rare and is usually seen in young or middle-aged adults. In adult patients, smoking is invariably associated with lung involvement [2,4]. A diffuse micronodular pattern on chest radiograph may progress to cyst formation (honeycomb lung), large bullae, and pneumothorax [1].

Solitary bone involvement with LCH is common but generally goes undiagnosed. The most common sites are the bones of the calvarium. Lesions may be asymptomatic or may present with swelling over the affected bone, pain or pathological fracture [2].

Diabetes insipidus is the most common endocrine problem and may be the presenting feature of LCH [2,5].

Involvement of the ears is common and presents as persistent aural discharge, polypoid involvement of the external auditory canal, or deafness [6].

Histologically, there is a dense dermal infiltrate of Langerhans cells. The Langerhans cells are recognized by their abundant, amphophilic cytoplasm and round or kidney bean-shaped nucleus. Exocytosis of the abnormal cells into the overlying epidermis is frequently observed. Dermal hemorrhage is characteristically present [7].

Immunohistochemistry is helpful in confirming the diagnosis of LCH. The infiltrating cells in LCH are S-100, CD1, CD4, and HLA-DR positive. Electron microscopy will detect the presence of Birbeck granules [1].

Treatment of LCH is controversial. Corticosteroids, vinblastine, other chemotherapeutic agents such as nitrogen mustard, cyclosporine, and radiation therapy have all been helpful [8,9,10].

In refractory cases, 2-chlorodeoxyadenosine has been successful [1]. There are some reports of the usefulness of PUVA, interferon alpha, isotretinoin, and thalidomide. Our patient showed dramatic improvement after receiving a 2 month course of thalidomide in the dosage of 100 mg/day. No side effects were noted during the treatment period and the patient was still in remission at the 6 month post treatment follow up visit. Thalidiomide probably works through inhibition of Tumor necrosis factor(TNF) production, which has an important role in the proliferation of Langerhans cells [7].

Acknowledgment The authors are thankful to Drs. Z. Naraghi and M. Asgari for the pathologic study of the specimens.

References

1. Odom RB, James WD, Berger TG, Andrews' Disease of the Skin. Philadelphia, W.B. Saunders company 2000: 913-917

2. Chu AC. Histiocytoses In: Champion RH, Burton JL, Bums DA, et al eds. Textbook of Dermatology. Oxford: Blackwell Science, 1998: 2315-2316.

3. Rivera-Luna R, Martinez-Guerra G, Altamirano-Awarez E, et al. Langerhans' cell histiocytosis: Clinical experience with 124 patients. Pediatr Dermatol 1988; 5: 145-150.

4. Artzi Z, Grosky M, Raviv M. Periodonal manifestations of adult onset histiocytosis. J Periodonal 1989; 60: 57-66.

5. Braunstein GD, Kohler PO. Endocrine manifestations of histiocytosis. Am J Pediatr Hematol Oncol 1981; 3:67-75.

6. Cunningham MJ, Curtin HD, Jaffe R, et al. Otologic manifestations of Langerhans' cell histiocytosis. Arch Otolaryngal Head Neck Surg 1989; 115: 807-13.

7. Dallafior S, Pugin P, Cerny T, et al. Successful treatment of a case of cutaneous Langerhans' cell histiocytosis with 2-chlorodeoxyadenosine and thalidomide. Hautarzt 1995; 46: 553-560.

8. Tsambaos D, Georglou S, Kapranos N, et al. Langerhans' cell histiocytosis: Complete remission after oral isotretinoin therapy. Acta Derm Venereol 1995; 75: 62-64.

9. Lair G, Marie I, Collieux N, et al. Langerhans' histiocytosis in adults: Cutaneous and mucous lesion regression after treatment with thalidomide. Rev Med Interne 1998; 19: 196-198.

10. Thomas L , Ducros B, Sechi T, et al. Successful treatment of adult Langerhons' cell histiocytosis with thalidomide. Arch Dermatol 1993; 129: 1261-1264.

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