Langerhans cell histiocytosis

Published on 18/03/2015 by admin

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Last modified 18/03/2015

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Langerhans cell histiocytosis

Thiviyani Maruthappu and Anthony C. Chu

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

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Langerhans cell histiocytosis (LCH) is a reactive condition defined by the accumulation/proliferation of a clonal population of epidermal Langerhans cells. Patients can have either single or multiple organ involvement. Children tend to have more aggressive disease than adults.

LCH encompasses the diseases previously known as histiocytosis X, eosinophilic granuloma, Hand–Schuller–Christian disease, Letter Siwe disease, congenital self-healing reticulohistiocytosis (Hashimoto–Pritzker), Langerhans cell granulomatosis, and non-lipid reticuloendotheliosis.

Management strategy

Prior to institution of therapy a full investigation must be completed. A definitive diagnosis can be made histologically by identification of Langerhans cells that express CD1a by immunohistochemistry and the finding of Birbeck granules by electron microscopy.

Treatment depends on the organ(s) involved and the severity of the disease and thus should be tailored to the individual patient. Most published data is based on case reports and small case series in children and this evidence may not always be directly applicable to adults. Patients are staged as single system disease (with bone involvement this is further stratified into mono-ostotic and poly-ostotic bone disease), multisystem disease, and multisystem disease with evidence of organ dysfunction. Although some patients with LCH may undergo spontaneous remission, the disease is unpredictable and many patients progress from single system disease to multisystem disease. Organs most commonly involved include the bone, skin, lymph nodes, pituitary, liver, lungs, central nervous system, gastrointestinal tract, spleen, bone marrow, and endocrine system.

Single system bone or skin disease has a good prognosis and may not require treatment. Curettage or intralesional steroid injections can also be used in single system bone disease. Single system skin disease may respond to local measures with topical steroids, topical nitrogen mustard, topical tacrolimus or phototherapy. Single system lung disease may respond to prednisolone at 2 mg/kg/day. In single system disease that does not respond to these measures, single system lymph node disease and multisystem disease without organ dysfunction, systemic treatment with azathioprine (2 mg/kg/day) with or without low dose, weekly methotrexate (5–10 mg/week) may lead to resolution.

In recalcitrant disease or in multisystem disease with evidence of organ dysfunction, treatment will depend on the age of the patient. Organ dysfunction of key organs – liver, lungs, spleen and bone marrow – carries the worst prognosis. Trials have demonstrated that, in pediatric patients, prednisolone with vinblastin is the treatment of choice. This combination is less effective in adults, who are also more sensitive to their side effects. In adult patients, first-line treatment is etoposide. In pediatric studies the use of maintenance therapy has been shown to reduce the overall morbidity of the disease. Adults often have a more chronic and relapsing course to their disease and maintenance therapy with azathioprine for 1 year should be considered in all patients with multisystem disease. In both children and adults with multisystem disease with organ dysfunction, there remains a small group who do not respond to conventional therapy. In these patients, 2-chlorodeoxyadenosine has proved useful and, in severe disease, bone marrow transplantation has been successful. A number of drugs have been used in various stages of the disease but most are anecdotal case reports. Long-term morbidity can be correlated to organ involvement or occur as a direct consequence of treatment, and includes skeletal deformities, risk of secondary malignancies (particularly with the use of alkylating agents and radiotherapy), endocrine dysfunction, and infertility.

Specific investigations

First-line therapies

Skin disease
imageTopical nitrogen mustard C
imagePhototherapy (PUVA, narrowband UVB) E
imageTopical tacrolimus E
Multisystem disease
imageVinblastine B
imageEtoposide (VP16) B

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