838 CLINICAL REPORT
ActaDV ActaDV Advances in dermatology and venereology Acta Dermato-Venereologica
Clinical Spectrum , Quality of Life , BRAF Mutation Status and Treatment of Skin Involvement in Adult Langerhans Cell Histiocytosis
Etienne CRICKX 1 # , Jean-David BOUAZIZ 1 , 2 # , Gwenaël LORILLON 3 , Mathilde DE MENTHON 4 , Florence CORDOLIANI 1 , Emmanuelle BUGNET 3 , Martine BAGOT 1 , 2 , Michel RYBOJAD 1 , Samia MOURAH 2 , 5 and Abdellatif TAZI 3 , 6 Assistance Publique-Hôpitaux de Paris , 1 Département de Dermatologie , 3 Centre National de Référence de l ’ Histiocytose Langerhansienne , Service de Pneumologie , 4 Service de Médecine Interne , 5 Département de Pharmacologie Biologique , Hôpital Saint-Louis , Université Paris- Diderot , Sorbonne Paris Cité ; 2 INSERM U976 , and 6 INSERM U1153 CRESS , Equipe de Recherche en Biostatistiques et Epidémiologie Clinique , Paris , France
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These authors contributed equally and should be considered as first authors .
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 . BRAF V600 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 .
Key words : Langerhans cell histiocytosis ; quality of life ; thalidomide ; nitrogen mustard ; BRAF mutation .
Accepted Apr 18 , 2017 ; Epub ahead of print Apr 19 , 2017 Acta Derm Venereol 2017 ; 97 : 838 – 842 .
Corr : Abdellatif Tazi , Service de Pneumologie , Hôpital Saint-Louis , 1 Avenue Claude Vellefaux , FR-75475 , Paris cedex 10 , France . E-mail : abdellatif . tazi @ aphp . fr
Langerhans cell histiocytosis ( LCH ) is a rare disorder of unknown aetiology characterized by the infiltration of involved tissues by CD1a / CD207-positive Langerhans-like cells . LCH may involve virtually any tissue / organ and is encountered in patients of all ages , from neonates to the elderly ( 1 – 3 ). LCH cutaneous involvement in children ranges from single self-healing lesions to extensive lesions in life-threatening multisystem disease ( 4 – 7 ). There are few published studies describing LCH cutaneous involvement in adults . Edelbroek et al . ( 8 ) described 18 Dutch patients with LCH that first presented in the skin : 5 patients developed a second haematological malignancy ( 2 acute myelomonocytic leukaemias , 2 lymphomas and 1 histiocytic sarcoma ). Another study reported 3 skin-limited
LCH adult patients and reviewed 27 other cases in the literature ( 9 ). In the large international registry of the Histiocyte Society , describing 274 LCH adult patients ( 10 ), skin involvement was present in 37 % of patients , almost all with multisystem disease . However , no further information was provided about skin lesions or response to treatment .
Therapeutic options used in adult cutaneous LCH include surgery , radiotherapy , phototherapy , topical or systemic steroids , imiquimod , topical nitrogen mustard , methotrexate , 6-mercaptopurine / azathioprine , vinblastine , thalidomide , and cladribine ( 11 – 14 ). Recent identification of the activating oncogenic BRAF V600 gene mutation in approximately 50 % of LCH samples , including the skin , has represented a breakthrough in understanding LCH pathogenesis and offers new therapeutic opportunities with molecules targeting the MAPK pathway ( 15 – 19 ).
This study describes the clinical characteristics , quality of life ( QoL ), BRAF mutation status and outcomes of LCH with cutaneous involvement in a large cohort of adult patients from a national reference centre .
PATIENTS AND METHODS Patients
A retrospective monocentric study was conducted in a national reference centre for LCH . All patients had been included in the French registry for histiocytosis until 2014 and had a diagnosis of LCH with skin involvement according to the Writing Group of the Histiocyte Society criteria ( 20 ). Haematoxylin-eosin staining , CD1a , langerin and PS100 immunostaining were performed on all biopsy samples . The study was approved by the Institutional Review Board ( CPP Ile de France IV , IRB number 00003835 ).
Response to therapy and outcomes
Disease state and the response of LCH skin involvement to therapy was clinically assessed for all patients using the International LCH Study Group criteria ( 21 ). Patients were categorized as having either non-active skin disease ( NAD ) ( defined as complete resolution ) or active skin disease ( AD ). The response of skin involvement to treatment was classified as better ( complete resolution or regression , i . e . incomplete resolution ), intermediate ( stable or mixed , i . e . new lesions in one site , regression in another site ) or worse ( progression ). doi : 10.2340 / 00015555-2674 Acta Derm Venereol 2017 ; 97 : 838 – 842
This is an open access article under the CC BY-NC license . www . medicaljournals . se / acta Journal Compilation © 2017 Acta Dermato-Venereologica .