Thrombocytopenia in lupus: baseline C3 as an independent risk factor for relapse.
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Complement C3↗
Biomedical subjects
M Voulgarelis
Publications and source records attributed to M Voulgarelis.
Thrombocytopaenia in lupus as a marker of adverse outcome--seeking Ariadne's thread.
OBJECTIVE: To assess the role of thrombocytopaenia as an independent predictor of outcome in patients with systemic lupus erythematosus (SLE). METHODS: This was a single-centre, retrospective, matched case-control study (1:2). Fifty consecutive Greek SLE patients were selected at random who had developed thrombocytopaenia during the disease course (cases) were compared with 100 SLE patients with no history of thrombocytopaenia, and matched for age, sex and disease duration (controls). Overall damage was assessed at the end of follow-up, using Systemic Lupus International Collaborating Clinics index. Total number of irreversible organ-damage events for both groups were recorded. Rates for specific outcomes and incidence-rate ratios (IRRs) for damage were estimated. Multivariate analysis estimating influential clinical and immunological factors for outcome, including thrombocytopaenia, was performed. RESULTS: After 583 person-years of follow-up for cases and 1155 for controls, we found that thrombocytopaenic individuals have a higher risk for damage (IRR 1.96, 1.52-2.53) compared with their matched controls and this effect persists throughout the course of their disease. They also have a predilection to certain types of damage involving heart and kidneys. Among other significant factors associated with damage in multivariate analysis (disease activity, serositis, anti-cardiolipin antibodies, central nervous system involvement), thrombocytopaenia appears as the most influential. CONCLUSION: Thrombocytopaenia is a quantitive and qualitative marker of impending damage in SLE patients.
Adolescent↗
Bone marrow histological findings in systemic lupus erythematosus with hematologic abnormalities: a clinicopathological study.
BACKGROUND: The histopathologic features characterizing the involvement of the bone marrow (BM) in systemic lupus erythematosus (SLE) have not been systematically analyzed to date. OBJECTIVES: The aim of this study was to assess morphologic and immunohistochemical characteristics of BM involvement in SLE. PATIENTS AND METHODS: Clinical and serological data of 40 SLE patients with unexplained cytopenias were studied. Ten patients with myelodysplasia of refractory anemia (RA) were used as controls. BM aspiration, BM biopsy (BMB), and immunohistochemistry were carried out in patients and controls. BM fibrosis, BM necrosis, stromal edema, and abnormal localization of immature precursors (ALIP) were assessed according to standard criteria. RESULTS: Dyserythropoiesis and megakaryocytic atypias were uniform findings in SLE patients. The disruption of the normal BM architecture was a predominant SLE BM feature affecting cells of all three hemopoietic lineages, with both erythroid and megakaryocytic precursors tending to assume paratrabecular locations and ALIP aggregates being present in 27 cases. In addition, BM was hypocellular in 23 cases. BM necrotic alterations were evident in 90% of the cases. The density of reticulin content was generally increased. Vascular changes including dilatation of sinuses were manifest and were associated with the presence of necrotic alterations (P = 0.008). Hemoglobin levels correlated inversely with the presence of ALIP (P = 0.016). Upon comparing BMB features between SLE and RA controls there were striking similarities. CONCLUSIONS: BMB in patients with SLE and unexplained cytopenias presents a variety of histopathologic findings including BM necrosis, stromal alterations, hypocellularity, dyspoiesis, and distortion of normal BM architecture, characterized primarily by the presence of ALIP aggregates.
Adolescent↗
Suspects in the tale of lupus-associated thrombocytopenia.
Immunologically mediated thrombocytopenia is a frequent clinical manifestation in patients with systemic lupus erythematosus (SLE). Autoantibodies targeting platelet membrane glucoproteins have a central role in peripheral platelet destruction. Autoantibodies against thrombopoietin are also present in about one-third of patients, but their pathogenetic role is obscure. Thirty-eight serum samples from SLE patients were tested for anti-platelet antibodies, anti-thrombopoietin antibodies and levels of circulating thrombopoietin. Bone marrow histology was also assessed. Thirty-nine per cent of sera displayed anti-thrombopoietin antibodies and 29% had circulating anti-platelet antibodies. Anti-thrombopoietin antibodies were associated with lower thrombopoietin concentrations, and lower mean platelet values in long-term follow-up. Anti-platelet antibodies were present in about 40% of thrombocytopenic and non-thrombocytopenic individuals but were absent in patients who had recovered from thrombocytopenia, supporting their pathogenetic role. Both autoantibodies were absent in control sera from patients with rheumatoid arthritis and primary Sjögren's syndrome. Decreased bone marrow cellularity, normal or low number of hypolobulated, pyknotic megakaryocytes and stromal alterations were prominent findings in thrombocytopenic SLE patients, suggesting a defect in megakaryopoiesis. These findings were not evident in specimens from patients with idiopathic thrombocytopenic purpura who had increased megakaryocytes, normal cellularity and absence of stromal alterations. In conclusion, peripheral destruction due to platelet autoantibodies, anti-thrombopoetin antibodies, lower effective circulating thrombopoetin and impaired compensatory response due to bone marrow damage interact in SLE and thrombocytopenia ensues.
Adult↗
Long term remission of Sjögren's syndrome associated aggressive B cell non-Hodgkin's lymphomas following combined B cell depletion therapy and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).
BACKGROUND: Primary Sjögren's syndrome (SS) is associated with an increased frequency of non-Hodgkin's lymphomas (NHLs), mainly of low histological grade. However, aggressive diffuse large B cell lymphomas (DLBCL) characterised by poor treatment outcome can also be encountered in SS. It has recently been shown that rituxan has significant therapeutic activity in this type of lymphoma. OBJECTIVE: To evaluate the efficacy of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) in combination with rituxan in SS patients with DLBCL, and to determine the outcome in such patients. METHODS: In an open, single case trial, six SS patients with DLBCL were assigned to receive eight cycles of CHOP every three weeks plus rituxan given on day 1 of each cycle. In a retrospective study, conducted by the European Concerted Action for SS, nine cases were diagnosed as DLBCL, all of whom had been treated with CHOP alone. These patients were used as historical controls. RESULTS: The difference in the overall survival between the two treatment groups was significant. The group treated with rituxan plus CHOP had a 100% two year overall survival rate, while the historical controls had only a 37% survival rate. Extraglandular manifestations serving as predictors for lymphoma development such as palpable purpura and peripheral neuropathy disappeared. The remission of these signs was accompanied by a decrease in both circulating monoclonal cryoglobulins and rheumatoid factor activity and an increase in C4 levels. Clinically relevant toxicity was not detected. CONCLUSIONS: The addition of rituxan to standard CHOP chemotherapy results in improved treatment outcome in SS patients with aggressive DLBCL, without increasing toxicity.
Adult↗
Anaemia in systemic lupus erythematosus: from pathophysiology to clinical assessment.
Haematological abnormalities are common in systemic lupus erythematosus. Anaemia is found in about 50% of patients, with anaemia of chronic disease being the most common form. Impaired erythropoietin response and presence of antibodies against erythropoietin may contribute to the pathogenesis of this type of anaemia. Patients with autoimmune haemolytic anaemia usually belong to a distinct category, which is associated with anticardiolipin antibodies, thrombosis, thrombocytopenia, and renal disease, often in the context of secondary antiphospholipid syndrome. Autoantibodies, T lymphocytes, and deregulation of the cytokine network can affect bone marrow erythropoiesis, leading to anaemia.
Anemia, Hemolytic, Autoimmune↗
Simultaneous occurrence of pure red cell aplasia and papular-purpuric 'gloves and socks' syndrome in parvovirus B-19 infection.
Papular-purpuric 'gloves and socks' syndrome (PPGSS) has been associated with parvovirus B-19 infection. We report a case of an adult immunocompetent male who presented with PPGSS. Bone marrow examination revealed pure red cell aplasia. Parvovirus B-19 DNA was detected by polymerase chain reaction in the patient's serum, whole blood and in the cutaneous lesions. This report illustrates the variety of clinical manifestations caused by B-19 infection, presents for the first time the concurrent appearance of pure red cell aplasia and PPGSS in the same patient and, finally, suggests that PPGSS may be due to direct lytic effect of the virus.
Adult↗
Lupus thrombocytopenia: clinical implications and prognostic significance.
OBJECTIVES: To clarify clinical manifestations, association with disease activity, and prognostic impact of thrombocytopenia using simple and reliable indices. METHODS: 632 patients were reviewed retrospectively. Fifty patients with thrombocytopenia were included as cases and matched with 100 control patients. Clinical manifestations at first thrombocytopenic episode were recorded. Classification criteria at diagnosis, basic immunological profiles, disease activity (ECLAM), and end organ damage (SLICC) were recorded. RESULTS: 29/50 (58%) had thrombocytopenia at diagnosis of lupus. Haemorrhagic manifestations were associated with the degree of thrombocytopenia (p<0.001). Anticardiolipin antibodies were not related to the degree of thrombocytopenia or the severity of haemorrhagic manifestations. Megakaryocytes were normal or increased in 26/28 (93%) bone marrow specimens, indicating peripheral platelet destruction. Patients with high disease activity were more thrombocytopenic than controls (OR = 2.61, 95% CI 1.13 to 5.96, p = 0.009). Patients with low C3 or CH50 were more likely to be thrombocytopenic (OR = 2.36, 95% CI 1.05 to 5.26, p = 0.029). Median SLICC for lupus patients with thrombocytopenia was 2 (range 0-11) compared with 1 (range 0-12) for controls (p<0.001). No deaths occurred during thrombocytopenic episodes. CONCLUSIONS: Thrombocytopenia is not directly associated with end organ damage and mortality, but defines a subgroup of patients with higher morbidity and is thus a major complication of systemic lupus erythematosus, affecting overall prognosis.
Adult↗
Combined therapy with rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) for Sjögren's syndrome-associated B-cell aggressive non-Hodgkin's lymphomas.
OBJECTIVE: To determine the safety and therapeutic response of a regimen consisting of cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) plus rituximab in patients with Sjögren's syndrome (SS) and aggressive non-Hodgkin's lymphoma (NHL). METHODS: Four SS patients with aggressive marginal zone NHL were enrolled in this trial. All patients were classified according to the newly proposed revised European-American classification of lymphoid neoplasms. Three out of four patients also had mixed cryoglobulinaemia (MC) of type II. They were treated every 3 weeks for eight cycles of CHOP. Patients also received rituximab, at a dose of 375 mg per square metre, on day 1 of each of the eight cycles of CHOP. Four weeks after completion of the eighth course of CHOP plus rituximab and every 6 months thereafter, patients were re-evaluated for response. RESULTS: Complete remission of lymphoma was achieved in all four patients. The lymphoma patients remained in remission for a period of 23, 15, 12 and 10 months respectively, while certain signs and symptoms of MC type II (purpura, peripheral neuropathy and arthralgias) significantly improved with treatment. In addition, the titres of circulating cryoglobulins and RF decreased, while C4 levels returned to normal. CONCLUSION: CHOP plus rituximab was well tolerated and proved effective in SS patients with aggressive NHL. Our observations may warrant a larger controlled trial to assess the effectiveness of this regimen in such patients.
Adult↗
Autoimmune phenomena in myelodysplastic syndromes: a 4-yr prospective study.
OBJECTIVE: To determine the clinical aspects and evolution of autoimmune inflammatory manifestations (AIMs) in patients with myelodysplastic syndrome (MDS) and ascertain the prognostic implications of these manifestations in MDS. METHODS: Seventy patients diagnosed for MDS were enrolled in a prospective cohort study of 4-yr duration. Thirteen patients with AIMs were identified (group A). The remaining 57 MDS patients without AIMs constituted the control group (group B). Demographic, clinical features, laboratory data, treatment and outcome of all these cases were recorded. RESULTS: On comparing features between the two groups we were unable to identify any particular difference (P > or = 0.05) concerning bone marrow blast count [odds ratio (OR) = 0.68], international prognostic scoring system (IPSS) (OR = 1.36), favourable cytogenetic abnormalities (OR = 0.52), leukaemic transformation (OR = 1.30) and survival (P = 0.76). Furthermore there was a significant difference in survival between low vs non-low IPSS patients for both groups (P<0.01). CONCLUSION: In a 4-yr prospective study the prognosis of MDS patients with AIMs appeared to be closely related to the IPSS subcategory of the underlying haematological malignancy and not to the autoimmune process.
Adult↗
Oral manifestations of papular-purpuric 'gloves and socks' syndrome due to parvovirus B19 infection: the first case presented in Greece and review of the literature.
Papular-purpuric 'gloves and socks' syndrome (PPGSS) is a novel, rare, self-limited dermatosis initially described in 1990. It is characterized by painful, pruritic edema and erythema, rapidly evolving to papular-purpuric lesions on the distal extremities, in a gloves-and-socks distribution, accompanied by fever and oral lesions such as petechiae, vesiculopustules and small erosions. Parvovirus B19 has been implicated in most cases as the etiological factor. Herein we present the first case of PPGSS in a 42-year-old Greek man with von Willebrand disease. On admission the patient was febrile, and presented acral edema and erythema rapidly followed by purpuric lesions on the same sites, and palatal petechiae. Complete remission of the exanthem occurred 7 days after hospitalization. Clinical and laboratory evaluation including serologic tests and PCR, confirmed the presence of parvovirus B19. Review of the existing literature on this novel syndrome and its association with parvovirus B19 is also presented.
Adult↗
A case of reversible posterior leucoencephalopathy syndrome after rituximab infusion.
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Adult↗
Myelodysplasia-associated autoimmunity: clinical and pathophysiologic concepts.
Myelodysplastic syndrome (MDS), an acquired clonal disorder of haemopoietic progenitor cells, is characterized by haemopoietic insufficiency associated with cytopenias, leading to serious morbidity plus the additional risk of leukaemic transformation. In MDS an acquired insult to the haemopoietic stem cell leads to impaired differentiation and myelodysplasia. However, there is increasing evidence that the marrow failure of MDS is immune-mediated. A model of MDS pathophysiology suggests that transformation of normal stem cells induces an autoimmune T-cell response with the bone marrow as the target organ. This autoimmune attack results in chronic overproduction of pro-apoptotic cytokines, especially tumour necrosis factor alpha (TNFalpha). In addition, several reports have revealed that approximately 10% of MDS patients have clinical autoimmune disorders. This review illustrates the cellular/molecular mechanisms and the implication of the tumour suppressor gene interferon regulatory factor-1 (IRF-1) in the pathophysiology of MDS-associated autoimmune deregulation.
Apoptosis↗
Autoimmune manifestations in human myelodysplasia: a positive correlation with interferon regulatory factor-1 (IRF-1) expression.
BACKGROUND: Patients with myelodysplasia may have autoimmune manifestations (AIM). Interferon regulatory factor-1 (IRF-1) is a transcription factor involved in interferon signalling, leukaemogenesis, and the development of the immune system. OBJECTIVES: To determine whether IRF-1 is implicated in the pathophysiology of AIM in myelodysplasia. METHODS: 14 patients with myelodysplasia were studied, seven with AIM and seven without. Five patients with vasculitis and seven normal subjects served as controls. The expression of IRF-1 was studied in bone marrow mononuclear cells taken from patients and controls, using a relative quantitative reverse transcriptase polymerase chain reaction. RESULTS: A 10-fold reduction in full length IRF-1 mRNA was detected in the myelodysplasia patients without AIM compared with the normal controls. In contrast, the group with AIM had increased IRF-1 transcripts, to a level almost equal to that observed in patients with vasculitis and normal controls. CONCLUSIONS: Myelodysplasia patients without IRF-1 expression had a decreased incidence of AIM. Thus the absence of IRF-1 transcription factor appears to protect against the development of autoimmunity in myelodysplasia.
Aged↗
Risk of myelotoxicity with intravenous cyclophosphamide in patients with systemic lupus erythematosus.
OBJECTIVES: To determine the incidence of serious myelotoxicity from intravenous cyclophosphamide (IC) in systemic lupus erythematosus (SLE). METHODS: In a retrospective study, white blood cell (WBC) counts with differential and platelet counts were determined in 92 SLE patients (96 courses) given 1623 doses of IC. RESULTS: Only one patient developed a total leucocyte count <1000/mm3, one developed a neutrophil count <500/mm3, two had a lymphocyte count <100/mm3 and no patients had platelet counts <50000/mm3 during follow-up. The risk of a neutrophil count <500/mm3 was 0.06 per 100 visits [95% confidence interval (CI) 0.00-0.34]. Two patients discontinued IC due to neutropenia [rate of 0.12 per 100 doses (95% CI 0.01-0.44)]. No clinical consequences were recorded in conjunction with low blood cell counts. In multivariate models, both the cumulative number of IC doses and European Consensus Lupus Activity Measurement (ECLAM) score affected neutrophil and lymphocyte counts adversely. For neutrophils, lowering the ECLAM score by 1 point counteracted four additional doses of IC after adjusting for steroid dose. CONCLUSIONS: IC and SLE disease activity have independent effects in lowering white blood cell counts, but serious myelotoxicity of IC is uncommon.
Adult↗
Monoclonal expansion of B cells in Sjögren's syndrome: comment on the article by Martin et al.
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Antibodies, Monoclonal↗
Malignant lymphoma in primary Sjogren's syndrome.
Sjogren's syndrome is a chronic inflammatory process involving primarily the exocrine glands. Its association with lymphoma is well documented. A low grade marginal-zone lymphoma related to mucosa-associated lymphoid tissue is the commonest lymphoid neoplasia in Sjogren's syndrome. We review the literature and comment on the molecular, clinical, histopathologic and therapeutic aspects of these tumors in Sjogren's syndrome.
Humans↗