Rituximab appears to be a safe and effective therapeutic option in symptomatic patients with HCV-associated MC glomerulonephritis and signs of systemic vasculitis.
Type II mixed cryoglobulinemia (MC) is a systemic vasculitis, associated in most cases with hepatitis C virus (HCV) infection, sustained by proliferation of oligoclonal cells. Systemic B cell depletion and clinical remission can be achieved in non-Hodgkin lymphoma by human/mouse chimeric monoclonal antibody that specifically reacts with the CD20 antigen (rituximab). Similar effects could be expected in type II MC. Twelve patients, mean age 61.9 years (range 37-76), 11 with HCV infection genotype 2a2c (4 cases) or 1b (6 cases) and 3 (1 case) and symptomatic type II MC with systemic manifestations, including renal involvement, marrow clonal restriction, large necrotizing ulcers, and polyneuropathy, were considered eligible for rituximab therapy because of resistance or intolerance to conventional therapy or important bone marrow infiltration. Rituximab was administered intravenously at a dose of 375 mg/m2 on days 1, 8, 15, and 22. Two more doses were administered 1 and 2 months later. No other immunosuppressive drugs were added. Response was evaluated by assessing the changes in clinical signs, symptoms, and laboratory parameters. Levels of proteinuria, hematuria, erythrocyte sedimentation rate, cryocrit, rheumatoid factor, and IgM decreased while C4 values increased and HCV viral load remained stable during short- and medium-term observation. Bone marrow abnormalities were found to reverse to normal. Constitutional symptoms disappeared or ameliorated. No acute or delayed side effects were seen. Based on this experience and a number of reports published in the last 5 years, Rituximab appears to be a safe and effective therapeutic option in symptomatic patients with HCV-associated MC with signs of systemic vasculitis.
Objectives
To identify the aggregation of patients with aPL into different subgroups sharing common features in terms of clinical and laboratory phenotypes.
Methods
We applied a hierarchical cluster analysis from the multiple correspondence analysis to determine subgroups of patients according to clinical and laboratory characteristics in a cohort of subjects with confirmed aPL positivity who presented to our outpatient clinics from 2006 to 2018.
Results
A total of 486 patients [403 women; age 41.7 years (26)] were included, resulting in five clusters. Cluster 1 (n= 150) presented with thrombotic events (65.3% with venous thrombosis), with triple aPL positivity found in 34.7% of them (the highest rate among the different clusters). All the patients from cluster 2 (n = 91) had a confirmed diagnosis of SLE and the highest rate of anti-dsDNA positivity (91.7%). Cluster 3 included 79 women with pregnancy morbidity. Triple positivity was present in 3.8%, significantly lower when compared with Cluster 1 (34.7% versus 3.8%, P <0.01). Cluster 4 included 67 patients, 28 (41.8%) of whom with APS. Thrombotic events were observed in 23.9% patients. Cluster 4 had the highest rate of cytopenia, with thrombocytopenia as high 41.8% with no anti-dsDNA antibodies. Cluster 5 included 94 asymptomatic aPL carriers.
Conclusion
While clusters 1, 2, 3 and 5 corresponded to well-known entities, cluster 4 might represent a bridging condition between pure primary APS and defined SLE, with lower thrombotic risk when compared with primary APS but higher general features such as ANA and cytopenia (mainly thrombocytopenia).
Background: IgA nephropathy (IgAN) is a microcosm of glomerular lesions. Some histologic lesions are irreversible and progress toward obliteration of glomerular capillaries. Others are acute inflammatory processes potentially susceptible to reversal by means of immunosuppressive therapies. Methods: The effects of a combined schedule of steroids and mycophenolate mofetil (MMF) was prospectively examined in a subset of IgAN patients with acute inflammatory histologic changes associated with proteinuria (mean 2,400 mg/day, range 1,130-5,250), hematuria (76 red cells per high-power microscopic field, range 30-100) and renal failure (serum creatinine 1.6 mg/dL, range 1.2-2.9). Patients had diffuse mesangial proliferation with at least 10% florid crescents, mild to moderate degrees of glomerular sclerosis and interstitial changes, and both mesangial and capillary deposition of immunoreactants at immunofluorescence. Treatment consisted of 3 pulses of methylprednisolone (15 mg/kg) followed by oral prednisone (0.8 mg/ kg body weight, tapered until discontinuation within 4 months) and MMF 2 g for 6 months. Results: Serum creatinine, proteinuria and microscopic hematuria significantly dropped at 6 months compared with baseline values (p=0.01) and remained lower at the end of follow-up 51 months (range 24-90) later (p<0.01, for proteinuria and hematuria; p=0.08, for serum creatinine). Conclusion: Therapy with steroids and MMF may be considered in a subset of IgAN patients with florid glomerular changes, functional impairment and major urinary abnormalities, to prevent subsequent progression toward renal failure.
Primary IgA nephropathy is generally considered a benign disease, but progression to renal failure is not uncommon and a rapidly progressive course is observed in some cases, especially when extensive epithelial crescents are present. Circulating IgA-containing immune complexes (IgAIC) seem to play the most important pathogenetical role, hence the authors adopted plasmapheretic treatment in association with immunosuppressive drugs for 1 patient affected by primary IgA nephritis, with florid crescents and progressive renal failure. IgAIC decreased significantly after each plasma exchange and finally returned to normal values; over the same period urinary protein loss and heavy microscopic hematuria gradually disappeared and renal function was completely recovered.
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