warfarin and mizoribine

Palpable purpura tends to indicate involvement of small vessel vasculitis in the upper dermis. Livedo racemosa, nodular lesion and skin ulceration are indicative of involvement of small to medium-sized vessel vasculitis in the lower dermis to subcutaneous fat. We set out to establish a new algorithm (KAWAKAMI algorithm) for primary cutaneous vasculitis based on the Chapel Hill Consensus Conference classification and our research results, and apply to the diagnosis. The first step is to measure serum antineutrophil cytoplasmic antibodies (ANCA) levels. If myeloperoxidase-ANCA is positive, Churg-Strauss syndrome or microscopic polyangiitis can be suspected, and if the patient is positive for proteinase 3-ANCA, Wegener's granulomatosis is most likely. Next, if cryoglobulin is positive, cryoglobulinemic vasculitis should be suspected. Third, if direct immunofluorescence of the skin biopsy specimen reveals immunoglobulin A deposition within the affected vessels, Henoch-Schönlein purpura is indicated. Finally, the presence of anti-phosphatidylserine-prothrombin complex antibodies and/or lupus anticoagulant and histopathological necrotizing vasculitis in the upper to middle dermis (leukocytoclastic vasculitis) indicates cutaneous leukocytoclastic angiitis, whereas if necrotizing vasculitis exists in the lower dermis and/or is associated with the subcutaneous fat, cutaneous polyarteritis nodosa is indicated. The KAWAKAMI algorithm may allow us to refine our earlier diagnostic strategies and allow for efficacious treatment of primary cutaneous vasculitis. In cutaneous polyarteritis nodosa, warfarin or clopidogrel therapies should be administrated, and in cases that have associated active inflammatory lesions, corticosteroids or mizoribine (mycophenolate mofetil) therapy should be added. We further propose prophylactic treatment of renal complications in patients with Henoch-Schönlein purpura.

Topics: Adrenal Cortex Hormones; Algorithms; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Clopidogrel; Cryoglobulinemia; Diagnosis, Differential; Humans; IgA Vasculitis; Immunoglobulin A; Myeloblastin; Peroxidase; Polyarteritis Nodosa; Ribonucleosides; Ticlopidine; Vasculitis, Leukocytoclastic, Cutaneous; Warfarin

Topics: Azathioprine; Child; Dipyridamole; Drug Therapy, Combination; Evidence-Based Medicine; Glomerulonephritis, IGA; Heparin; Humans; Practice Guidelines as Topic; Prednisolone; Prognosis; Randomized Controlled Trials as Topic; Ribonucleosides; Warfarin

Two previous randomized controlled trials showed that treatment of severe childhood immunoglobulin A (IgA) nephropathy using prednisolone with azathioprine, heparin-warfarin, or dipyridamole prevented the increase of sclerosed glomeruli. Prednisolone alone, however, did not prevent further increase. These studies indicated the importance of immunosuppressants in the treatment. An additional pilot study using mizoribine instead of azathioprine enabled us to complete 2 years of combined regimen. It showed non-numerical inferior effectiveness compared with the azathioprine regimen. Further examination of the additional efficacy of warfarin and dipyridamole was required.. A randomized control trial of prednisolone and mizoribine with (group 1) or without (group 2) warfarin and dipyridamole was administered for treatment of 71 children with severe IgA nephropathy to evaluate the efficacy of additional warfarin and dipyridamole.. Thirty of 34 patients (88.2%) in group 1, and 27 of 36 patients (75.0%) showed the disappearance of proteinuria as defined by early morning urinary protein to creatinine ratio of < 0.2 during the 2-year treatment period. The cumulative disappearance rate of proteinuria determined by the Kaplan-Meier method showed that the disappearance rate of proteinuria was significantly higher in group 1 than in group 2 (log-rank P = 0.04). There was no significant difference in pathological findings, but there was a tendency of increase of global sclerosis in group1 which might be related to warfarin. Most of the adverse effects were related to prednisolone, but fortunately transient.. The balance between minimal benefits of warfarin/dipyridamole and potential adverse effects may be in favor of avoiding them in children with IgA nephropathy.

Topics: Adolescent; Biopsy; Child; Dipyridamole; Drug Therapy, Combination; Female; Glomerular Mesangium; Glomerulonephritis, IGA; Humans; Immunosuppressive Agents; Male; Prednisolone; Prospective Studies; Proteinuria; Ribonucleosides; Severity of Illness Index; Treatment Outcome; Warfarin

The aim of this study was to determine whether serum immunoglobulin A/complement factor 3 (IgA/C3) ratio and glomerular C3 staining predict outcome in IgA nephropathy.. We collected data for 44 IgA nephropathy children treated with multi-drug combination therapy. The children were retrospectively divided into four groups based on serum IgA/C3 ratio and glomerular C3 staining: group A, IgA/C3 ratio >2.68 (median) and glomerular C3 staining ≥2.0, n = 9; group B, IgA/C3 ratio >2.68 and glomerular C3 staining <2.0, n = 7; group C, IgA/C3 ratio <2.68 and glomerular C3 staining ≥2.0, n = 7; and group D, IgA/C3 ratio <2.68 and glomerular C3 staining <2.0, n = 21. Clinical features; pathology at the first and second renal biopsy and at the latest follow up; and prognosis were analyzed for the four groups.. At the most recent follow up, urinary protein excretion, incidence of hematuria, and serum creatinine in group A were all higher than in group D. At the second biopsy, crescent absence/presence ratio; mesangial hypercellularity, segmental glomerulosclerosis or adhesion, endocapillary hypercellularity, and tubular atrophy/interstitial fibrosis as well as crescents and global glomerulosclerosis (MESTCG) score; and clonicity index in group A were higher than in group D. All patients in group D had normal urine, and the prevalence of persistent nephropathy in group A was higher than in group D.. Serum IgA/C3 ratio and glomerular C3 staining can predict outcome in IgA nephropathy.

Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Biopsy; Child; Complement C3; Dilazep; Female; Glomerulonephritis, IGA; Glucocorticoids; Humans; Immunoglobulin A; Kidney Function Tests; Kidney Glomerulus; Male; Prednisolone; Prognosis; Retrospective Studies; Ribonucleosides; Vasodilator Agents; Warfarin

The prognosis of children with severe IgA nephropathy showing diffuse mesangial proliferation is poor. However, the prognosis can be improved by combination therapy (prednisolone + azathioprine or mizoribine + warfarin + dipyridamole) or prednisolone alone over a 2-year period, and disappearance of glomerular IgA deposits is often observed. Details of the incidence and clinicopathological significance of glomerular IgA disappearance remain unclear.. To investigate this phenomenon, we retrospectively screened and analysed 124 consecutive children (age ≤ 18 years at first biopsy) with newly diagnosed severe IgA nephropathy showing diffuse mesangial proliferation, who received combination therapy or prednisolone alone for 2 years and underwent repeat biopsies.. Among these patients, 90 received combination therapy, and 34 received prednisolone alone. After 2 years of treatment, 27 of the patients (21.8%) showed disappearance of glomerular IgA. Logistic analysis showed that IgA disappearance was associated with less severe urinary protein excretion at the end of treatment. Kaplan-Meier analysis of the long-term course revealed a significant difference in proteinuria-free survival after the 2-year treatment period between the patients with IgA disappearance and those without (P = 0.008; log-rank test). The Cox proportional hazards model showed that disappearance of glomerular IgA after the treatment was a factor significantly associated with proteinuria-free survival in both univariate and multivariate analyses.. The present results suggest that disappearance of IgA after 2 years of treatment indicates milder disease severity, even in patients with diffuse mesangial proliferation, and is a prognostic factor related to proteinuria-free survival.

Topics: Anti-Inflammatory Agents; Anticoagulants; Azathioprine; Child; Dipyridamole; Drug Therapy, Combination; Female; Glomerular Mesangium; Glomerulonephritis, IGA; Humans; Immunoglobulin A; Immunosuppressive Agents; Kidney Glomerulus; Male; Prednisolone; Retrospective Studies; Ribonucleosides; Survival Rate; Treatment Outcome; Vasodilator Agents; Warfarin