Multicentric reticulohistiocytosis: a lesson in screening for malignancy

Rheumatology (Oxford, England) (Impact Factor: 4.48). 08/2008; 47(7):1102-3. DOI: 10.1093/rheumatology/ken131
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    • "The association was observed with several carcinoma, breast and ovarian being the most often identified, but including also stomach, cervix, lung, colon, pancreas as well as mesotelioma, malignant melanoma, sarcoma, malignant lymphoma and leukaemia or even metastasis from an unknown primary tumour [12,15,41–43]. MRH may occur also around the time of recurrence of metastasis of a previously diagnosed and treated cancer [44] [45]. That high association rate has led some authors to indicate MRH as a paraneoplastic syndrome, but this deserves some criticism because no specific malignancy has been consistently reported in Table 1 Autoimmune diseases associated with multicentric reticulohistiocytosis [37] [38] [39] [40]. "
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    ABSTRACT: Multicentric reticulohistiocytosis (MRH) and fibroblastic rheumatism (FR) are uncommon disorders with similar joint and skin manifestations. They are usually included among the non-Langerhans histiocytoses, but recent insights drive some criticism. The diagnosis is often challenging and must be confirmed by the histological typical features. If the skin manifestations are missing, the arthritic complaints may be confused with those of other rheumatic disorders. In these cases, only a careful clinical and radiological evaluation leads to the correct diagnosis. The natural course of the diseases may rapidly develop into disabling manifestations, making an aggressive treatment strongly recommendable. There is emerging evidence that anti-tumour necrosis factor-α agents and bisphosphonates are promising drugs for MRH, while a course of methotrexate and steroids seems to be the best option for FR. Finally, the clinician should be aware that in many cases MRH, but not FR, is associated with a large number of systemic manifestations and with malignancy. This eventuality must be accurately ruled out.
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    ABSTRACT: We present a patient with therapy resistant multicentric reticulohistiocytosis (MRH). MRH is a rare granulomatous, multisystem disease characterised most frequently by disfiguring papulonodular skin lesions and sometimes a destructive polyarthritis, though any organ can be involved. Abnormal histiocytic reactions to an undetermined stimulus (possibly an associated mycobacterial infection, auto immune process or neoplastic process) have been proposed as an underlying mechanism. The diagnosis is confirmed by histopathology of the cutaneous nodules and/or synovial membrane by the presence of CD68-positive histiocytes and multinucleated giant cells with an eosinophilic 'ground-glass' cytoplasm. Recent studies have identified TNFalpha and other inflammatory cytokines to be highly expressed in the synovium and synovial fluid of affected joints in patients with MRH. Based on these findings, we treated our patient with infliximab in combination with methotrexate with marked improvement of morning stiffness, tender and swollen joint count, visual analogue scale and health assessment questionnaire after his third infusion. However, the nodules did not markedly resolve. When treating patients with MRH with TNFa neutralizing drugs, one has to keep the possible association with malignancy in 15-30% of cases in mind and these products should be used with caution.
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