Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Castleman's disease, an atypical lymphoproliferative disorder, can be classified into 2 types: hyaline-vascular and plasma cell types according to the histologic features of the affected lymph nodes. The plasma cell type is frequently associated with systemic manifestations and is often refractory to systemic therapy including corticosteroids and chemotherapy, particularly in multicentric form. Dysregulated overproduction of interleukin-6 (IL-6) from affected lymph nodes is thought to be responsible for the systemic manifestations of this disease. Therefore, interference with IL-6 signal transduction may constitute a new therapeutic strategy for this disease. We used humanized anti-IL-6 receptor antibody (rhPM-1) to treat 7 patients with multicentric plasma cell or mixed type Castleman's disease. All patients had systemic manifestations including secondary amyloidosis in 3. With the approval of our institution's ethics committee and the consent of the patients, they were treated with 50 to 100 mg rhPM-1 either once or twice weekly. Immediately after administration of rhPM-1, fever and fatigue disappeared, and anemia as well as serum levels of C-reactive protein (CRP), fibrinogen, and albumin started to improve. After 3 months of treatment, hypergammaglobulinemia and lymphadenopathy were remarkably alleviated, as were renal function abnormalities in patients with amyloidosis. Treatment was well tolerated with only transient leukopenia. Histopathologic examination revealed reduced follicular hyperplasia and vascularity after rhPM-1 treatment. The pathophysiologic significance of IL-6 in Castleman's disease was thus confirmed, and blockade of the IL-6 signal by rhPM-1 is thought to have potential as a new therapy based on the pathophysiologic mechanism of multicentric Castleman's disease. (Blood. 2000;95:56-61)
 ...
PMID:Improvement in Castleman's disease by humanized anti-interleukin-6 receptor antibody therapy. 1060 84

A 52-year-old Japanese man presented with fever spikes, generalized fatigue, anorexia, and anasarca. The patient was referred for the evaluation of fever of unknown origin in association with swelling of cervical, axillary, and inguinal lymph nodes. He also manifested nephrotic syndrome, acute renal failure, hepatosplenomegaly, massive pleural effusion, ascites, disseminated intravascular coagulation, and hypergammaglobulinemia. C-reactive protein was positive and plasma vascular endothelial cell-derived growth factor (VEGF) and serum interleukin-6 levels were markedly elevated. Lymph node biopsy results showed that findings were compatible with Castleman's disease of hyaline vascular type associated with interfollicular plasmacytosis. In conjunction with the clinical findings, a diagnosis of multicentric Castleman's disease was made. The patient underwent renal biopsy because of nephrotic syndrome, and the results showed proliferation of mesangial cells, lobulation of glomeruli, and tram track pattern of the capillary wall without immune complex deposition. Electron microscopy showed widening of the subendothelial space. No electron-dense deposits were present in both mesangial and subendothelial regions. Pathologic features were compatible with glomerular microangiopathy and membranoproliferative glomerulonephritis-like lesions. With corticosteroid therapy, systemic symptoms disappeared; both VEGF and interleukin-6 levels were normalized, and he went into complete remission of nephrotic syndrome. In this article, the role VEGF plays in the pathogenesis of nephrotic syndrome and glomerular microangiopathy is discussed.
 ...
PMID:Multicentric Castleman's disease associated with glomerular microangiopathy and MPGN-like lesion: does vascular endothelial cell-derived growth factor play causative or protective roles in renal injury? 1471 66

A 52-year-old woman presented with low grade fever and fatigue. She had diffuse micronodules in both lung fields on chest X-ray. Chest CT showed diffuse multiple small nodules. Laboratory examination revealed high values for C-reactive protein, together with anemia and polyclonal hyper-immunoglobulinemia and an elevated interleukin-6 level. Although we suspected multicentric Castleman's disease, thoracoscopic lung biopsy revealed primary pulmonary MALT lymphoma by immunohistochemical analysis of tissue specimens. After COP and rituximab therapy, partial remission was obtained.
 ...
PMID:[A case of primary pulmonary MALT lymphoma with diffuse micronodules and anemia]. 1661 59

A 27-year-old man was admitted to our hospital with the complaint of general fatigue. He had cervical and mediastinal lymphadenopathy. Laboratory examination revealed anemia, hypergammaglobulinemia, and increased levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). A chest radiograph showed opacities in both lung fields. Pathological findings from thoracoscopic mediastinal lymph node and lung biopsies were compatible with multicentric Castleman's disease (MCD), plasma cell type with pulmonary involvement. Chemotherapy combined with radiation therapy resulted in no improvement of his lymphadenopathy and inflammatory symptoms. Eight mg/kg humanized anti-human IL-6 receptor antibody (tocilitumab) was thus administered biweekly. Soon after initiating the tocilitumab treatment, the patient's general fatigue disappeared, and anemia, CRP, ESR, hypergammaglobulinemia and lymphadenopathy all improved remarkably. Further treatment with tocilitumab for two years resulted in maintenance of this good response without any severe adverse events, but the pulmonary findings showed no obvious improvement. Tocilitumab therapy was effective in this MCD patient, however its influence on concurrent lung disease needs to be investigated further.
 ...
PMID:[Effectiveness of long term administration of humanized anti-interleukin-6 receptor antibody (tocilizumab) for multicentric Castleman's disease with pulmonary involvement]. 1698 13

We report three cases of multicentric Castleman's disease (MCD) successfully treated with anti-interleukin-6 receptor antibody (tocilizumab). Tocilizumab was administered intravenously at a dose of 8 mg/kg every 2 weeks. In each case, tocilizumab alleviated symptoms, including generalized fatigue, pyrexia, and alleviated biochemical abnormalities, including anemia, hypoalbuminemia, hypergammaglobulinemia, and increased C-reactive protein (CRP). Side effects included hypercholesterolemia, acute pyelonephritis, mild inflammation of the parotid glands, and upper respiratory system inflammation. Other severe side effects were not observed. These results indicate that tocilizumab is effective for the treatment of MCD. This is the first report on tocilizumab efficacy for Castleman's disease after approval for use for Castleman's disease.
 ...
PMID:Anti-interleukin-6 receptor antibody (tocilizumab) treatment of multicentric Castleman's disease. 1754 Dec 33

A 42-year-old Japanese woman was referred to our university hospital due to progressive anemia and bilateral hilar lymphadenopathy with diffuse ground-glass attenuation on chest computed tomography in December 2009. She had suffered from exertional dyspnea and fatigue for several months. Laboratory findings on admission demonstrated leukocytosis (10,950/ul), elevation of C-reactive protein (4.7 mg/dl), IL-6 (19.9 pg/ml), IgG4 (567 mg/dl) and polyclonal hyper gamma-globulinemia. Chest computed tomography represented mediastinal and bilateral hilar lymphadenopathy with diffuse centrilobular fine nodules and intralobular septal thickening. Histopathological findings of the specimens obtained by thoracoscopic lung and mediastinal lymph node biopsies revealed massive infiltration of IgG4-positive plasma cells in lung tissue and lymph nodes. Pathological findings and high levels of C-reactive protein and interleukin-6 suggested a diagnosis of multicentric Castleman's disease (MCD). In addition, pathological findings of peribronchiolar infiltration of IgG4-positive plasma cells and lymphoid follicles with infiltration of IgG4-positive plasma cells with a high level of IgG4 were indicative of the complication of IgG4-related lung disease. Radiological and serological findings improved rapidly soon after the initiation of oral corticosteroid treatment. It was speculated that this case indicated the close relationship between MCD and IgG4-related lung disease.
 ...
PMID:[A case of multicentric Castleman disease with massive infiltration of plasmacytes presenting IgG4]. 2173 45

A 49-year-old man with superficial lymphadenopathy presented with symptoms of low-grade fever, general fatigue and weight loss. On examination, multiple superficial lymphadenopathies and brown macules were observed on the trunk. Laboratory studies revealed an elevation of serum C reactive protein and interleukin 6 (IL-6) in addition to polyclonal hyperimmunoglobulinaemia. High-resolution CT of the chest showed bilateral multiple nodules and patchy ground-glass opacities with interstitial thickening. Biopsy of the cervical lymph node and skin biopsy showed numerous perivascular plasma cells, which were characteristic of the plasma cell type of Castleman's disease. Surgical lung biopsy showed hyalinising granuloma, which are hyalinous nodular lesions surrounded by lymphoid cells. He was diagnosed with multicentric Castleman's disease complicated by pulmonary hyalinising granulomas; his symptoms improved by treatment with tocilizumab, which is a humanised antihuman IL-6 receptor monoclonal antibody and corticosteroid. This is the first report of a comorbid case successfully treated with tocilizumab and corticosteroid.
...
PMID:A comorbid case of multicentric Castleman's disease and pulmonary hyalinising granuloma successfully treated with tocilizumab and corticosteroid. 2407 26

Siltuximab is a chimeric monoclonal antibody targeting interleukin-6 (IL-6), which in the fall of 2014 became the first FDA-approved treatment of the rare disease idiopathic multicentric Castleman's disease (MCD). MCD is a non-clonal lymphoproliferative disorder in which common symptoms include fever, night sweats, weight loss, and fatigue. Symptoms are driven by an overall hypercytokinemia, predominantly IL-6. While under clinical development, siltuximab was studied in several other disease states including multiple myeloma, non-Hodgkin lymphomas, and several solid tumors in which it did not demonstrate significant benefit. The efficacy of siltuximab in MCD is mainly confined to systemic symptomatic response and quality of life benefits with minimal complete responses and approximately 30 % partial responses, by radiographic criteria. Siltuximab treatment therefore is important in the overall treatment of this rare disease state. This review focuses on the clinical development and pharmaceutical approval of siltuximab.
 ...
PMID:Clinical development of siltuximab. 2598 20