Clinical Spectrum, Quality of Life, BRAF Mutation Status and Treatment of Skin Involvement in Adult Langerhans Cell Histiocytosis

Abstract

Langerhans cell histiocytosis is a rare histiocytic disorder for which skin involvement and management are poorly described in adults. The aim of this retrospective monocentric study in a national reference centre is to describe the clinical characteristics, quality of life, BRAF mutation status and outcomes of skin involvement in adult patients with Langerhans cell histiocytosis. Twenty-five patients (14 females, mean age 47 years) were included, with a median follow-up of 33 months (range 4-420 months). Patients experienced poor dermatological quality of life despite low body surface involvement. BRAFV600 mutations were detected in 8 of the 18 patients analysed (45%). Eight patients had an associated malignancy. Several treatment options were used and consisted of surgery, topical steroids and carmustine, thalidomide, methotrexate, vinblastine and steroids and cladribine. This study highlights the need to evaluate quality of life and to screen for associated malignancy in adult patients with Langerhans cell histiocytosis.

Multifocal Cutaneous Langerhans Cell Histiocytosis

“…Histiocytoses are rare diseases characterized by the accumulation of macrophages and dendritic or monocyte-derived cells in various tissues and organs in children and adults [2,3]. Langerhans cell histiocytosis (LCH) refers to a proliferative disorder of antigenpresenting dendritic cells, being the most common disorder of the mononuclear phagocytic system, with etiology, pathogenesis and therapy not yet clarified [3,5,8,9].…”

“…Langerhans cell histiocytosis (LCH) refers to a proliferative disorder of antigenpresenting dendritic cells, being the most common disorder of the mononuclear phagocytic system, with etiology, pathogenesis and therapy not yet clarified [3,5,8,9]. LCH is a very rare disease (3 to 8/1,000,000 children), more frequent in men (male to female ratio 2:1), affects all age groups, predominantly in children (64%) [1][2][3]8,9,[17][18][19][21][22][23]. The skin is the second organ most commonly involved in single-system LCH, with a prevalence ranging from 4.4% to 7.01% of the cases [24].…”

“…The clinical presentation of this disease varies according to the disease stage, location and degree of involvement of the organs and systems [2,9]. LCH can compromise only a single site (SS) system and may disappear spontaneously or with multiple sites (MS), and as in multisystemic disease (MM) are often treated with chemotherapy [1,[3][4][5]13,25,26].…”

“…Langerhans cell histiocytosis (LCH) is a rare disease of the unknown etiology that is characterized by the clonal proliferation of Langerhans cells (LCs) S-100, CD1a and Birbeck granules or CD207 positive, ie with morphological, immunophenotypic and ultrastructural similarities [1][2][3][4][5][6][7][8][9][10][11].…”

“…LCs represent a subtype of antigen-presenting dendritic cells of myeloid origin, with CD1a [7] antigen expressed on the surface and with Birbeck granules in the cytoplasm [3], located in the epidermis and mucosal epithelium of various tissues and organs, comprising a broad spectrum of diseases with differents clinical manifestations [1][2][3]5,6,[8][9][10][11][12][13].…”