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Class I: Langerhans cell histiocytosis (LCH)

Cellular destructive tissue infiltration with LC. These are well differentiated large cells (15-25|jm) with an indented nucleus and inconspicuous nucleolus; they are not phagocytic. Other reactive cells (granulocytes, eosinophils, macrophages) are often present. Diagnostic criteria of LC include the presence of Burbeck granules on electron microscopy and immunochemical positivity for CDlA. The aetiology of LCH remains unclear. Despite some evidence of clonality (not itself evidence of malignancy), no genetic mutations have been identified and the disorder is not regarded as a form of cancer.

Clinical features: LCH is primarily a disease of the very young with a peak incidence of 1-3 years. It can present in a variety of ways, from a small bone lesion heavily admixed with eosinophils (eosinophilic granuloma), through multiple lytic bone lesions, exophthalmos and diabetes insipidus (Hand-Schuller-Christian disease) to multiple tissue infiltration involving skin, liver, lung bone and bone marrow (Letterer-Siwe disease). The eponymous terms are no longer used for what is now regarded as a common pathology and the overarching term LCH is preferred. This is staged on the basis of the number of organ systems showing infiltration, and virtually any can be involved. The skin rash of LCH is characteristically in skin folds and scaly with red/brown papules. It may be mistaken for nappy rash. Systemic symptoms including fever and weight loss are common in advanced disease. It can be staged as follows:

Stage A Involvement of bones ± local nodes and adjacent soft tissue.

Stage B Skin ± mucous membranes involvement, ± related nodes.

Stage C Soft tissue involvement—not stage A, B or D.

Stage D Multisystem disease with combinations of A, B, C.

Diagnosis

Based on tissue biopsy. Skeletal survey to define extent of disease; also bone scan, MRI. Urine osmolality studies for diabetes insipidus. BM aspirate and biopsy if anaemic or other cytopenias present.

Treatment

Local curettage of any isolated lesion, with or without intra-lesional steroids. Stable and symptomless disease can be simply observed for spontaneous resolution. Options for widespread disease include steroids and chemotherapy—rarely radiotherapy. Indications for chemotherapy include organ dysfunction and/or disease progression/recurrence. Drugs commonly used include steroids, vinblastine or etoposide, singly or combined.

Outcome

Generally good, but widespread organ involvement with dysfunction and progression indicates a poor prognosis. Overall mortality 15-20%. Long term sequelae include pulmonary/liver fibrosis, diabetes insipidus, growth failure. Risk of malignant disease increased, chiefly leukaemias and lymphomas.

Class II: macrophage functional disorders—haemophagocytic syndromes

Primary (genetic)

Primary haemophagocytic lymphohistiocytosis (HLH) is an autosomal recessively inherited disease of infants and young children (>50% <1 year) also known as familial erythrophagocytic lymphohistiocytosis (FEL) due to the striking degree of marrow red cell phagocytosis. The gene defect is not known, and the pathology of the condition is unclear apart from cytokine dysregulation and high concentrations of IL-1 and 2, GM-CSF and TNF. CNS involvement common. Laboratory investigation shows peripheral blood cytopenias, hypertrigliceridaemia and hypofibrinogenaemia. Histopathology shows histiocyte/lymphocyte infiltration and haemo-phagocytosis in BM, nodes and spleen.

Treatment and outcome: Seldom effective, steroids, chemotherapy, ALG, cyclosporin A, BMT. Disease usually rapidly fatal.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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