Langerhans cell histiocytosis in adults

Summary

Langerhans cell histiocytosis in adults is a rare disease with potential involvement of all organs with or without organ dysfunction. In our single institution, 95 patients with histologically confirmed LCH were treated. At time of diagnosis, more than 1/ 3 of the patients had shown multi system disease. Reactivations of LCH occurred in about 1/ 4 of the patients within a median of 6 years, especially in other individual organs. For staging and determination of organ dysfunction extensive diagnostic is necessary. There are a lot of treatment options in relation to isolated organ involvement or systemic disease. It makes sense to approach the disease in a multidisciplinary way.

Key words:
Langerhans cell histiocytosis

Introduction

In adults, Langerhans cell histiocytosis (LCH) is a rare disease with a predominantly good prognosis. But consequences of the non malignant proliferations of Langerhans cells in organs can be dysfunctions up to organ failures. Manifestations of LCH can vary from single organ involvement, usually of lungs, bones or skin, to multiple organ involvement. So, LCH is divided into a single system disease and into a multi system disease. The symptoms are related to the organs affected. Risk organs in adults are not yet defined [1]. Only a few cases of malignant courses are described [2]. Langerhans cell sarcoma can occur as well de novo as from an antecedent LCH [3].

Exact incidence and prevalence of LCH in adults are not known. There is an estimation of one to two new manifestations per million population per year [4]. An immune defect is presumed as the likely cause of the disease. Additional influences of environment, for example smoking, were widely dis­cussed [5]. Women are more frequent affected than men. The preferred age of manifestation is in the third to fourth decade. Accumulations in families are described.

There seems to be an association between LCH and malignant tumours. In most cases, LCH occurs before or concurrently with the associated neoplasma. The histopathology of malignant neoplasms are especially malignant lymphomas or solid tumours [6].

Patients and course of disease

From October 2000 until May 2010 95 patients with histologically confirmed LCH were treated in our single institution. Characteristics of patients are shown in tab. 1. Isolated lung manifestation only occurred in patients smoking or having smoked. At time of diagnosis, more than 1/ 3 of the patients had been suffering from multi system disease.

The course of LCH is variable with spontaneous remissions up to 70% in cutaneous manifestations and up to 50% in pulmonary disease. Osseous manifestations are difficult to measure. In active disease there are the categories regression, stable disease and progression. In non active disease reactivations are possible.

In 2008, we evaluated our patients with regard to reactivations (tab. 2). Reactivations of LCH in adults occurred in about 1/ 4 of the patients within a median of six years of follow up, especially in other individual organs. Eight patients have shown two to four further reactivations in course.

Diagnostic evaluation

For staging and determination of organ dysfunction an extensive diagnostic is necessary. The evaluation should embrace history and physical examination, especially inspection of skin and mucous membranes. Moreover, technical investigations are necessary: ultrasound of neck with thyreoid gland, abdomen and pelvis, X-ray and if need be CT scans of thorax, CT scan or NMR of skeleton, NMR of head, blood measurements and status of urine. Further investigations can be scintigraphy of bones, PET-(CT) scan, bone marrow bio­psy and other investigations because of specials symptoms, for example measurements of hormones. An experimental approach is the measurements of cytokines to correlate with the activity of the disease. Typical manifestations of LCH are shown in fig. 1– 5.

Treatment options and discussion

An optimal therapy for LCH in adults has not been established. But there are a lot of treatment options in relation to isolated organ involvement or systemic disease with or without organ dysfunction (tab. 3). Up to now, no controlled therapeutic studies have been performed in adults. So, approaches of therapy are following the experiences in children or take experimental results into consideration. Factors with unfavorable prognosis are advanced age, extensive organ involvement, number of organs affected, organ dysfunction and poor response to therapy. In cases of organ dysfunctions, supportive therapy is crucial.

Further options of therapy seemed to be an immunomodulatoric therapy with cyclosporine or interferon, the use of monoclonal antibodies like CD1a-  or CD52- antibodies, and treatment with TNF-α-inhibitors like etanercept or infliximab. The results of these approaches were disappointing or of questionable success. In a few patients with chronic active course of LCH, an anti-inflammatoric and angiostatic therapy with rofecoxib, pioglitazone and trofosfamide resulted in long-lasting non-active disease [7]. Autologous or allogenic stem cell transplantation can lead to healing of the disease, but is fraught with high morbidity and mortality [8]. Advanced organ failure can only be treated with transplantation, for example of liver or lung, but LCH may reappear in the transplanted organ [9]. A new promising approach is the treatment with an aggressive chemotherapy resulting in long-lasting regressions [10].

Because of missing studies, the treatment of Langerhans cell sarcoma has to be individual. There are a lot of open questions. For answering these questions, further studies are warranted.

Prof. Dr. med. Claus Doberauer

www.evk-ge.de

e-mail: doberauer@evk-ge.de

Doručeno do redakce: 9. 9. 2010