Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Castleman disease (CD) is rare lymphoproliferative disorder with local lesionsor with multiple lessions (multicentric CD [MCD]-usually with plasma cell or mix cell morphology). Patients with human herpesvirus (HHV) type 8-positive MCD were included in a separate group owing to its extremely aggressive course and the high risk of transformation into HHV8(+) plasmablastic lymphoma. At our hematologic center, from 1996 to the present, the clinical and morphologic features of 87 patients with CD were analyzed. Immunohistochemical examination revealed DNA HHV8(+) lymph node tissue in patients with plasma cell and mixed cell morphology. In 45 patients, plasma cell or mixed cell variant CD was diagnosed. In 21 patients (8%), the manifestation of CD was local and in 29 (9%), it was multicentric. HHV8 was identified in only 6 cases (23.1%) of MCD (5 men and 1 woman, with a median age of 48.2 years; range, 36-77 years). The median follow-up point was 39.2 months. In 4 patients, the mixed cell variant was diagnosed and in 2, the plasma cell variant was diagnosed. In all the patients, constitutional symptoms, generalized lymphadenopathy, and hepatosplenomegaly were detected. Various laboratory changes were observed, but the most significant were anemia, thrombocytopenia, hypergammaglobulinemia, M-component, increased erythrocyte sedimentation rate, and circulating immune complexes. In 2 cases of HHV8(+) CD, MCD was combined with autoimmune hemolytic anemia and in 2 cases with non-Hodgkin lymphoma. At the last follow-up point, 2 patients were still alive after CHOP (cyclophosphamide, prednisone, Adriamycin, vincristine) and R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate [Oncovin], prednisone) therapy with rituximab maintenance. HHV8(+) MCD results in aggressive multiorgan lesions and pronounced changes in laboratory test results. It is characterized by an unfavorable prognosis with a high risk of transformation to plasmablastic lymphoma and a lethal outcome. Timely chemotherapy for patients with HHV8(+) MCD can result in remission and prolong life.
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PMID:Human Herpesvirus Type 8-positive Multicentric Castleman Disease. 2713 59

TAFRO syndrome is a systemic inflammatory disorder manifesting as thrombocytopenia; anasarca including pleural effusion and ascites; fever; renal insufficiency; and organomegaly including hepatosplenomegaly and lymphadenopathy. Its onset may be acute or sub-acute, but its etiology remains unknown. Although several clinical and pathological characteristics of TAFRO syndrome resemble those of Castleman's disease, other specific features can differentiate between the two. Some patients have been successfully treated with glucocorticoids and/or immunosuppressants including cyclosporin A, tocilizumab and rituximab, whereas others are refractory to treatment, eventually succumbing to the disease. Early and reliable diagnoses and early treatments with appropriate agents are essential to enhancing patient survival. The 2015 updated diagnostic criteria, disease severity classification and treatment strategy for TAFRO syndrome, as formulated by Japanese research teams, are presented herein. Furthermore, clinicopathological data on 28 patients with this condition and similar symptoms (e.g., MCD with serositis and thrombocytopenia) were analyzed retrospectively.
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PMID:Proposed diagnostic criteria, disease severity classification, and treatment strategy for a novel disorder; TAFRO syndrome. 2779 11

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.
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PMID:International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. 2808 40

Castleman disease (CD), also known as angiofollicular hyperplasia, is a rare disorder characterized by nonmalignant mediastinal lymph node enlargement provoked by excess interleukin-6 (IL-6) secretion. It could be unicentric or multicentric (MCD). Here, we describe a 27-year-old man with a prior history of AIDS, Kaposi sarcoma (KS), and latent syphilis who presented to the ED for persistent fatigue, fever, chills, night sweats, and productive cough. Infectious workup was negative, and the patient continued to have a high fever despite empiric antibiotic therapy. Bone marrow biopsy was performed and was negative for malignancy. The patient eventually underwent a left clavicular lymph node biopsy, which showed a plasma cell variant CD with positive immunostaining for human herpesvirus 8 (HHV-8), and high HHV-8 viral load. We started the patient on rituximab and liposomal doxorubicin, but unfortunately, the patient had a severe anaphylactic reaction to the rituximab, so we could not proceed with this treatment. We, therefore, started tocilizumab treatment, which improved the patient's general condition, and he was eventually discharged from our hospital. Upon follow-up 11-months later, a repeat CT scan of the chest and abdomen showed a near-complete treatment response with decreased lymphadenopathy throughout and hepatosplenomegaly. IL-6 overproduction in patients with CD is linked to the production of inflammatory cytokines and has a role in tumor angiogenesis, which makes it potential for IL-6 targeted therapy. The diagnosis of CD, especially MCD, requires a high index of suspicion, and a lymph node biopsy is essential in the diagnosis. Tocilizumab, an IL-6 receptor antibody, could potentially be considered as a practical therapeutic approach in managing HHV-8 positive MCD patients who do not tolerate or respond to initial rituximab therapy.
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PMID:The Potential Clinical Benefit of Tocilizumab Therapy for Patients with HHV-8-infected AIDS-related Multicentric Castleman Disease: A Case Report and Literature Review. 3239 23