Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 50-year-old woman was referred to our hospital for shoulder joint stiffness. She had a history of polyclonal hypergammaglobulinemia and an elevated C-reactive protein level. Her laboratory data revealed an elevated serum immunoglobulin G4 (IgG4) level, hypergammaglobulinemia, and rheumatoid factor positivity in the absence of anticyclic citrullinated peptide antibody. [18F]-Fluorodeoxyglucose positron emission tomography showed significant [18F]-fluorodeoxyglucose uptake in multiple lymph nodes (axillary, hilar, para-aortic, and inguinal). Biopsy of the inguinal lymph node showed expansion of the interfollicular areas by heavily infiltrating plasma cells, consistent with multicentric Castleman disease (MCD). Immunohistochemical analysis revealed a 37.3% IgG4-positive:IgG-positive plasma cell ratio, indicating overlapping IgG4-related disease. However, serological cytokine analysis revealed elevated levels of interleukin-6 (9.3 pg/ml) and vascular endothelial growth factor (VEGF) (1210 pg/ml), which are compatible with MCD. Corticosteroid treatment resolved the serological and imaging abnormalities. IgG4-related disease can mimic MCD, and it is crucial to distinguish between these two diseases. Serum interleukin-6 and VEGF levels may help to discriminate MCD from IgG4-related disease.
 ...
PMID:Multicentric Castleman disease mimicking IgG4-related disease: A case report. 2552 59

Human herpesvirus-8 (HHV-8)-negative, idiopathic multicentric Castleman disease (iMCD) is a rare and life-threatening disorder involving systemic inflammatory symptoms, polyclonal lymphoproliferation, cytopenias, and multiple organ system dysfunction caused by a cytokine storm often including interleukin-6. iMCD accounts for one third to one half of all cases of MCD and can occur in individuals of any age. Accurate diagnosis is challenging, because no standard diagnostic criteria or diagnostic biomarkers currently exist, and there is significant overlap with malignant, autoimmune, and infectious disorders. An international working group comprising 34 pediatric and adult pathology and clinical experts in iMCD and related disorders from 8 countries, including 2 physicians that are also iMCD patients, was convened to establish iMCD diagnostic criteria. The working group reviewed data from 244 cases, met twice, and refined criteria over 15 months (June 2015 to September 2016). The proposed consensus criteria require both Major Criteria (characteristic lymph node histopathology and multicentric lymphadenopathy), at least 2 of 11 Minor Criteria with at least 1 laboratory abnormality, and exclusion of infectious, malignant, and autoimmune disorders that can mimic iMCD. Characteristic histopathologic features may include a constellation of regressed or hyperplastic germinal centers, follicular dendritic cell prominence, hypervascularization, and polytypic plasmacytosis. Laboratory and clinical Minor Criteria include elevated C-reactive protein or erythrocyte sedimentation rate, anemia, thrombocytopenia or thrombocytosis, hypoalbuminemia, renal dysfunction or proteinuria, polyclonal hypergammaglobulinemia, constitutional symptoms, hepatosplenomegaly, effusions or edema, eruptive cherry hemangiomatosis or violaceous papules, and lymphocytic interstitial pneumonitis. iMCD consensus diagnostic criteria will facilitate consistent diagnosis, appropriate treatment, and collaborative research.
 ...
PMID:International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. 2808 40

Multicentric Castleman disease (MCD) is a rare entity that, unlike unicentric Castleman disease, involves generalized polyclonal lymphoproliferation, systemic inflammation, and multiple-organ system failure resulting from proinflammatory hypercytokinemia, including, in particular, interleukin-6. A subset of MCD is caused by human herpesvirus-8 (HHV-8), although the etiology for HHV-8-negative, idiopathic MCD (iMCD) cases is unknown at present. Recently, a consensus was reached on the diagnostic criteria for iMCD to aid in diagnosis, recognize mimics, and initiate prompt treatment. Pediatric iMCD remains particularly rare, and differentiation from MCD mimics in children presenting with systemic inflammation and lymphoproliferation is a challenge. We report on a young boy who presented with a HHV-8-negative, iMCD-like phenotype and was found to suffer from the monogenic disorder deficiency of adenosine deaminase 2 (DADA2), which is caused by loss-of-function mutations in CECR1 DADA2 prototypic features include early-onset ischemic and hemorrhagic strokes, livedoid rash, systemic inflammation, and polyarteritis nodosa vasculopathy, but marked clinical heterogeneity has been observed. Our patient's presentation remains unique, with predominant systemic inflammation, lymphoproliferation, and polyclonal hypergammaglobulinemia but without apparent immunodeficiency. On the basis of the iMCD-like phenotype with elevated interleukin-6 expression, treatment with tocilizumab was initiated, resulting in immediate normalization of clinical and biochemical parameters. In conclusion, iMCD and DADA2 should be considered in the differential diagnosis of children presenting with systemic inflammation and lymphoproliferation. We describe the first case of DADA2 that mimics the clinicopathologic features of iMCD, and our report extends the clinical spectrum of DADA2 to include predominant immune activation and lymphoproliferation.
 ...
PMID:ADA2 Deficiency Mimicking Idiopathic Multicentric Castleman Disease. 3013 8

A 26-year-old man presented with fever, multiple lymphadenopathies, polyclonal hypergammaglobulinemia, and an elevated serum interleukin-6 (IL-6) level. Multicentric Castleman disease (MCD) was diagnosed by lymph node biopsy. Treatment with prednisolone (PSL) was initiated; however, its efficacy was limited. During PSL tapering, rapidly progressive anemia and thrombocytopenia developed concurrently with increased reticulocyte level, elevated serum LDH level, decreased haptoglobin level, and positive direct Coombs test. Based on these findings, Evans syndrome, which is a concurrent development of autoimmune hemolytic anemia and immune thrombocytopenia, was confirmed. The PSL dose was increased but was ineffective. Therefore, treatment with tocilizumab was initiated, and the clinical findings of both MCD and Evans syndrome improved. The clinical course of this case suggests that tocilizumab could be a treatment option for Evans syndrome complicated with MCD. Three other cases of Evans syndrome complicated with MCD have also been reported; however, this is the first case that shows the efficacy of tocilizumab as treatment for both MCD and Evans syndrome.
 ...
PMID:[Evans syndrome complicated with multicentric Castleman disease successfully treated with tocilizumab]. 3018 17


<< Previous 1 2