Multicentric reticulohistiocytosis with hydrarthrosis in both knee joints: disease stabilization with synovectomy, and medication with a steroid and low-dose methotrexate

 Multicentric reticulohistiocytosis is a rare systemic disease characterized by the infiltration of histiocytes and multinucleated giant cells with cutaneous nodules, and severe destructive arthritis. It is commonly the peripheral joints which are affected, and therefore symptoms in large joints have not been fully investigated. We describe the case of a 44-year-old woman with multicentric reticulohistiocytosis, who was suffering from swelling in both knee joints and cutaneous nodules, in addition to arthritis in the elbow, hip, and peripheral joints. Magnetic resonance imaging of both knee joints showed hydrarthrosis associated with a tumor-like overgrowth of synovial tissue. These symptoms were reduced following a resection of the synovial tissue and subsequent medication with prednisone and low-dose methotrexate. It should be noted that swelling in the knee joints can be one of the symptoms caused by multicentric reticulohistiocytosis, in addition to cutaneous nodules and arthritis in the peripheral joints. Resection of synovial tissue, and medication with prednisone and low-dose methotrexate were effective in the present case. Received: May 23, 2001 / Accepted: November 19, 2001     

Multicentric reticulohistiocytosis. Report of a case, with atyphical features and electron microscopic study of skin lesions

A case of multicentric reticulohistiocytosis is presented, with typical clinical and roentgenologic features but without the characteristic histologic criteria. Recurrent carpal tunnel syndrome, Dupuytren's contractures and pleural effusions are hitherto undescribed findings in multicentric reticulohistiocytosis. The sparsity of giant cells in the skin lesions of varying distribution, morphology and age (despite an infiltrate of histiocytes with staining characteristics of the multinucleate giant cell) is an unusual histologic feature. Electron microscopic studies of skin lesions did not demonstrate the cytoplasmic rod-like tubular structures reported in the malignant histiocytoses of the Hand-Schüller-Christian, Letterer-Siwe and eosinophilic granuloma type [18].     

A case of spontaneous femoral neck fracture associated with multicentric reticulohistiocytosis. Oversecretion of interleukin-1β, interleukin-6, and tumor necrosis factor α by affected synovial cells

We describe a case of left femoral neck fracture associated with multicentric reticulohistiocytosis (MR). Biopsy specimens from a skin nodule and from synovial tissue showed histiocytic multinucleated giant cells (MR cells) that are characteristic of MR. A surgical specimen from the resected femoral head revealed that multinucleated giant cells and mononuclear cells invaded the marginal subchondral bone, without evident pannus. These cells also infiltrated into the fracture site, with bone resorption by activated osteoclasts. Immunohistochemical studies of synovium from the left hip joint showed positive staining for interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α, and abundant cytokine production by cultured synovial cells was demonstrated. These findings suggest that the subchondral invasion and intramedullary infiltration by MR cells caused articular destruction and/or fracture as a result of oversecretion of the cytokines.     

Multicentric reticulohistiocytosis associated with ovarian cancer

Multicentric reticulohistiocytosis (MR) is an uncommon disease characterized by joint and cutaneous manifestations. The diagnosis must be confirmed by histological evidence of typical histiocytes and multinucleated giant cells. Many conditions, including malignancy, have been described in association with MR. We herein report a female case of MR in whom partial improvement was obtained by steroid and low-dose methotrexate treatments. However, ovarian cancer was found and therefore a surgical resection and chemotherapy were performed. These treatments resulted in the complete resolution of the skin and joint symptoms. These findings support the close linkage between MR and malignancy and the efficacy of cytotoxic drugs for the treatment of MR.     

Severe progressive erosive arthritis in multicentric reticulohistiocytosis: possible involvement of cytokines in synovial proliferation.

A case of multicentric reticulohistiocytosis complicated by severe progressive erosive arthritis in a 40-year-old man is described. The diagnosis was confirmed by biopsies of the cutaneous nodule and the synovial tissue of the right knee joint. Destructive changes in the multiple joints rapidly progressed and resulted in severe progressive erosive arthritis. Immunohistochemical staining revealed that the histiocytes reacted positively to interleukin 1 beta and platelet derived growth factor B, leading to the speculation that these cytokines may play a role in the synovial proliferation seen in patients with multicentric reticulohistiocytosis.     

Rhabdomyolysis and acute renal failure in a polymyositis patient

Abstract

Multicentric reticulohistiocytosis (MR) is an uncommon disease characterized by joint and cutaneous manifestations. The diagnosis must be confirmed by histological evidence of typical histiocytes and multinucleated giant cells. Many conditions, including malignancy, have been described in association with MR. We herein report a female case of MR in whom partial improvement was obtained by steroid and low-dose methotrexate treatments. However, ovarian cancer was found and therefore a surgical resection and chemotherapy were performed. These treatments resulted in the complete resolution of the skin and joint symptoms. These findings support the close linkage between MR and malignancy and the efficacy of cytotoxic drugs for the treatment of MR.     

Multicentric reticulohistiocytosis. Fine structural analysis of the synovium and synovial fluid cells

A patient with progressive multicentric reticulohistiocytosis (MR) had foamy giant cells in the synovial fluid as well as in the synovial membrane and dermis. These cells did not stain for neutral fat, but stained faintly with Sudan Black B and periodic acid-Schiff. Electron microscopy of these unusual macrophages showed they were filled with vacuoles and inclusions that contained a flocculent material. These inclusions bore a close relationship to the Golgi apparatus and, in some cells, appeared to be developing from smooth endoplasmic reticulum. A 3-month trial on azathioprine did not improve the patient's arthritis nor reduce the size and number of skin nodules. This is the first patient described with this disorder in whom synovial fluid analysis revealed foamy appearing giant cells and in whom intracellular inclusions were related to the endoplasmic reticuium.     

Multicentric reticulohistiocytosis

Multicentric reticulohistiocytosis (MR) is an uncommon disease with joint and cutaneous manifestations most commonly affecting women in middle age. The diagnosis must be confirmed by the histological evidence of typical mononuclear histiocytes and multinucleated giant cells. Many conditions have been described in association with MR, and the clinician should be aware that in many cases the disease is associated with malignancy. This eventuality must be accurately ruled out. If the typical nodular manifestations are missing at the onset, the arthritic complaints-usually localized but not confined to the interphalangeal joints-may be confused with those of more common rheumatic disorders. At this stage, a careful clinical and radiological evaluation may offer the key to the correct diagnosis. The natural course of the disease may develop into a severe, destructive arthropathy and disfiguring cutaneous lesions. In these cases an aggressive treatment with immunosuppressive drugs is strongly recommended. On the basis of recent reports, anti-tumor necrosis factor alpha agents and alendronate may also be added to the list of the drugs used in the treatment of this disease.     

多中心网状组织细胞增生症三例并文献复习

目的 探讨多中心网状组织细胞增生症的临床特点、诊断及鉴别诊断。方法 分析3例多中心网状组织细胞增生症的临床、X线、组织病理和免疫组织化学特征,并复习有关文献。结果 3例患者均有多发性皮肤丘疹和结节,残毁性关节炎,肌肉症状,X线片关节有侵蚀性变化,部分指骨可有囊样骨缺损;肌酶谱均正常;病理均有细胞质呈毛玻璃样的多核巨细胞;1例伴有肺部结节;2例免疫组织化学染色示CD68阳性;AE1／AE3、S－100和HHF35均阴性。结论 多中心网状组织细胞增生症是一种系统性疾病,临床上常伴有肌肉症状,易误诊为皮肌炎,应注意两者的鉴别。     

Multicentric reticulohistiocytosis associated arthritis responding to anti-TNF and methotrexate

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.     

Multicentric reticulohistiocytosis: a rare cause of erosive arthropathy of the distal interphalangeal finger joints

BACKGROUND: Multicentric reticulohistiocytosis (MRH) is a rare systemic disease, presenting with typical skin abnormalities and erosive polyarthritis, which is often associated with malignancy. CASE REPORT: A case of MRH arthropathy, in which the typical nodular skin manifestation of the disease was absent, is described in a patient with a past history of breast cancer and no evidence of recurrent or new malignancy. RESULTS: Careful clinical and roentgenological evaluation disclosed important clues to differentiate this condition from other more common distal interphalangeal arthritides--namely, osteoarthritis and its "erosive" variant, rheumatoid arthritis, psoriatic arthritis, tophaceous gout, dialysis related hand arthropathy, and from the rarer fibroblastic rheumatism, all of which can be mimicked by MRH. Histopathology showed the characteristic histiocytic and multinucleated giant cell infiltrate with ground glass cytoplasm, and immunohistochemical analysis showed markers evocative of a monocyte/macrophage origin of MRH.     

Multicentric reticulohistiocytosis with arthritis and cardiac infiltration: regression following treatment for underlying malignancy.

The case is reported of a 63 year old man presenting with a rapidly destructive symmetrical polyarthritis and widespread papular nodular skin lesions, confirmed by a biopsy to be due to multicentric reticulohistiocytosis. Biventricular cardiac failure developed secondary to extensive myocardial infiltration with multicentric reticulohistiocytosis, a complication of this disease which has not previously been reported. The joint, skin, and cardiac manifestations of multicentric reticulohistiocytosis substantially regressed following resection of an associated squamous cell carcinoma. This report adds to the small amount of published work which suggests that multicentric reticulohistiocytosis can be a paraneoplastic disease that may respond to treatment directed at the underlying tumour.     

Multicentric reticulohistiocytosis (lipoid dermatoarthritis). A multisystem disorder

Multicentric reticulohistiocytosis has been regarded as a rare disorder of the skin and synovium, simulating rheumatoid arthritis. Also known as lipoid dermatoarthritis, it has been classified among the lipid storage diseases. In the case reported, multicentric reticulohistiocytosis was documented in skin nodules, subcutaneous nodules, synovium of joint and tendon sheaths, perirenal fat and at the base of gastric ulcers. Lesions of the conjunctivas, retina and orbit were presumed to be on the same basis. Evidence is provided to permit classification of multicentric reticulohistiocytosis as a systemic disease. The clinical course was characterized from the beginning by dermatomyositis as well as polyarthritis.     

Multicentric reticulohistiocytosis, another lipid disorder with normolipidemic xanthomatosis?

This report describes a 72-year-old female patient with 2 types of severely disfiguring xanthomas, particularly on the facial area and the upper arms. Biopsy revealed xanthoma-type cells, histiocytes, and multiple giant cells. The soft yellowish facial xanthomata were rich in esterified cholesterol, whereas the cholesterol content of the colorless, firm, fibrous xanthoma of the arms was relatively low. The clinical course of insidiously starting polyarthritis, the formation of skin and tendon xanthomas (at the age of 63) and, finally, the histological findings verified the diagnosis of multicentric reticulohistiocytosis. The family history and findings were noncontributory. The patient had symptoms of moderate coronary heart disease and died from an acute myocardial infarction. Her total cholesterol and triglyceride levels were 182 and 89 mg/dl, and the HDL cholesterol value was 43 mg/dl. Plasma levels of apolipoprotein A-I, A-II and B were normal, and her apoprotein E pattern was E3/E3. The triglyceride/cholesterol ratio of VLDL, the concentration of apo-LDL (LDL protein) and the LDL-protein/cholesterol ratio were normal. The apo-LDL production, the total clearance rate of apo-LDL, and the receptor-mediated and receptor-independent catabolism of LDL were also normal. Fecal output of neutral sterols and bile acids and the total body cholesterol synthesis were normal, but cholesterol absorption tended to be increased. The response to cholestyramine treatment showed a 44% decrease in the serum cholesterol level and a normal 5-fold increase in cholesterol synthesis. The patient's xanthoma formation could not be associated with any of the causes known to promote the development of normolipidemic xanthomatosis. It is suggested that multicentric reticulohistiocytosis should be considered in the differential diagnosis of patients with normolipidemic xanthomatosis.     

Multinucleated histiocytes in esophageal squamous mucosa secondary to gastroesophageal reflux disease in a patient with esophageal stricture

We present a novel finding of multinucleated histiocytes associated with acute and chronic inflammation secondary to gastroesophageal reflux in a patient with a history of esophageal stricture, representing the first documented case after a review of the literature. Multinucleated squamous cells, while rare, are a more common finding in association with reactive and inflammatory conditions and have been reported in other areas of the body, such as the vulva, skin, and colon. Esophageal involvement with multinucleated epithelial giant cells appears to be a much less frequently encountered occurrence with only one previous report in the literature. We add to this series an interesting case of esophageal multinucleated giant cells that are histiocytes rather than epithelial cells, supported with positive CD68 immunohistochemical staining. Our patient had severe esophageal dysphagia with stricture with history of food impaction, requiring several dilation sessions to achieve an esophageal luminal diameter of 17 mm. There was marked clinical and endoscopic improvement with proton pump inhibitor and endoscopic therapy. The multinucleated mucosal histiocytes at the time of biopsy were likely due to reactive changes from chronic injury due to food stasis and reflux.     

Multicentric reticulohistiocytosis

Multicentric reticulohistiocytosis (MRH) is a rare disease characterized by erosive polyarthritis and nodular skin lesions which is associated with malignancy in some cases. We describe a 44‐year‐old woman with polyarthralgia, numerous skin nodules, mucosal lesions and elevated erythrocyte sedimentation rate who was admitted to hospital for further evaluation. Tissue biopsy of skin nodules showed large histiocytes with ground‐glass eosinophilic cytoplasm, typical of MRH. Clinical manifestation and radiological pattern of MRH may be misdiagnosed as other diseases like rheumatoid arthritis, psoriatic arthritis and nodal osteoarthritis, but histopathology the characteristic pattern can differentiate MRH from any other condition.     

Multicentric reticulohistiocytosis associated with subclinical Sjögren's syndrome

Summary A case of multicentric reticulohistiocytosis in a 60-year-old Japanese woman associated with subclinical Sjögren's syndrome is presented. The clinical features along with the light microscopic studies are commented. Partial improvement of the skin lesions and tendon sheath swelling was achieved after treatment with cyclophosphamide but the patient's general condition remained unchanged. Taking the rarity of multicentric reticulohistiocytosis into account, coexistence of these two conditions in the present and previously reported cases suggests that an autoimmune mechanism may play a part in the pathogenesis of multicentric reticulohistiocytosis.     

Close temporal and anatomic relationship between multicentric reticulohistiocytosis and carcinoma of the breast.

We describe a case of simultaneous development of a medullary carcinoma of the breast and multicentric reticulohistiocytosis (MRH) with identical characteristic histological lesions being found not only in the skin and synovium, but also in close proximity to the breast cancer as well as the connective tissue surrounding the tumor involved axillary lymph nodes. Successful treatment of the primary malignancy resulted in complete resolution of the MRH over 4 months. A close temporal relationship existed between the development and clinical remission of the malignancy and the course of the arthritis and skin lesions. Characteristics of this rare syndrome with particular reference to its association with malignancy are reviewed.     

A case of multicentric reticulohistiocytosis

Multicentric reticulohistiocytosis (MRH) is a rare non-Langerhans histiocytosis of unknown etiology with a predilection for joint and skin. The characteristic clinical features are papulonodular skin eruptions and inflammatory polyarthritis, sometimes progressive to arthritis mutilans, a severe destructive arthropathy. Although these manifestations can present at the same time, it is more common that one feature precedes the others. Notably, these features are similar to those found in some rheumatic diseases, such as rheumatoid arthritis or dermatomyositis, and this can lead to a misdiagnosis, especially during periods where only one feature is present. Herein, we report a female patient with polyarthralgia and subsequent skin eruptions, who was eventually diagnosed with MRH. Her symptoms seemed to resemble those of some rheumatic diseases, but several features such as affected joints and the characteristic shape of the skin lesions did not correspond to that. The histological result of infiltration of histiocytes and multinucleated giant cells in the skin ultimately facilitated the correct diagnosis.

In this paper, we review MRH briefly and highlight several differential points which enable us to increase the likelihood of correctly diagnosing MRH.