Presentation and Prognosis of Cardiac Involvement in Hepatitis C Virus-Related Vasculitis
2012; Elsevier BV; Volume: 111; Issue: 2 Linguagem: Inglês
10.1016/j.amjcard.2012.09.028
ISSN1879-1913
AutoresBenjamin Terrier, Alexandre Karras, Philippe Cluzel, Jean‐Philippe Collet, D. Sène, David Saadoun, P. Cacoub,
Tópico(s)Coagulation, Bradykinin, Polyphosphates, and Angioedema
ResumoCardiac manifestation in primary systemic vasculitides is associated with poor outcomes, leading to the use of immunosuppressive therapy. In contrast, the spectrum and the outcome of cardiac involvement in the setting of mixed cryoglobulinemia vasculitis (CryoVas) have never been evaluated. To describe the clinical presentation and to evaluate clinical outcomes of cardiac manifestations during hepatitis C virus (HCV)–related mixed CryoVas, the clinical records of 165 consecutive patients with HCV-related mixed CryoVas followed from January 1, 1993, to January 1, 2010, were reviewed. Of the 165 patients with HCV-related mixed CryoVas, 7 (4%) had cardiac manifestations. Thoracic pain and congestive heart failure manifestations were the main clinical manifestations (n = 4 [57%] each). Cardiac imaging showed dilated cardiomyopathy in 5 patients and hypertrophic cardiomyopathy in 1. In multivariate analysis, patients with cardiac manifestations had more frequent B-cell lymphoma (odds ratio 18.1, 95% confidence interval 2.8 to 116.7, p = 0.0023) and gastrointestinal involvement (odds ratio 14.6, 95% confidence interval 2.0 to 104.9, p = 0.0078). All cardiac manifestations were reversible early after the initiation of corticosteroids and aggressive immunosuppressive therapy. However, after a median follow-up period of 19 months, 3 patients (43%) had died. Respective 6-month, 1-year, and 2-year survival rates in patients with and without cardiac involvement were 86% and 99%, 71% and 96%, and 48% and 90% (hazard ratio 5.01, p = 0.003). In conclusion, cardiac damage is a rare manifestation of HCV-related mixed cryoglobulinemia vasculitis. Cardiac involvement is associated with B-cell lymphoma and life-threatening manifestations. Despite favorable early outcomes, patients with cardiac damage had poorer survival than those without. Cardiac manifestation in primary systemic vasculitides is associated with poor outcomes, leading to the use of immunosuppressive therapy. In contrast, the spectrum and the outcome of cardiac involvement in the setting of mixed cryoglobulinemia vasculitis (CryoVas) have never been evaluated. To describe the clinical presentation and to evaluate clinical outcomes of cardiac manifestations during hepatitis C virus (HCV)–related mixed CryoVas, the clinical records of 165 consecutive patients with HCV-related mixed CryoVas followed from January 1, 1993, to January 1, 2010, were reviewed. Of the 165 patients with HCV-related mixed CryoVas, 7 (4%) had cardiac manifestations. Thoracic pain and congestive heart failure manifestations were the main clinical manifestations (n = 4 [57%] each). Cardiac imaging showed dilated cardiomyopathy in 5 patients and hypertrophic cardiomyopathy in 1. In multivariate analysis, patients with cardiac manifestations had more frequent B-cell lymphoma (odds ratio 18.1, 95% confidence interval 2.8 to 116.7, p = 0.0023) and gastrointestinal involvement (odds ratio 14.6, 95% confidence interval 2.0 to 104.9, p = 0.0078). All cardiac manifestations were reversible early after the initiation of corticosteroids and aggressive immunosuppressive therapy. However, after a median follow-up period of 19 months, 3 patients (43%) had died. Respective 6-month, 1-year, and 2-year survival rates in patients with and without cardiac involvement were 86% and 99%, 71% and 96%, and 48% and 90% (hazard ratio 5.01, p = 0.003). In conclusion, cardiac damage is a rare manifestation of HCV-related mixed cryoglobulinemia vasculitis. Cardiac involvement is associated with B-cell lymphoma and life-threatening manifestations. Despite favorable early outcomes, patients with cardiac damage had poorer survival than those without. Systemic vasculitides are a group of disorders defined by inflammation of the blood vessel walls. Among the pathogenic mechanisms that have been implicated in the induction of vasculitis, circulating mixed cryoglobulinemia (MC) may be responsible for immune complex–mediated inflammation, leading to the occurrence of systemic manifestations.1Guillevin L. Dorner T. Vasculitis: mechanisms involved and clinical manifestations.Arthritis Res Ther. 2007; 9: S9Crossref PubMed Scopus (65) Google Scholar Shortly after the discovery of the hepatitis C virus (HCV) in 1989, there was evidence that >80% of MC cases were associated with HCV infection.2Ferri C. Greco F. Longombardo G. Palla P. Moretti A. Marzo E. Fosella P.V. Pasero G. Bombardieri S. Antibodies to hepatitis C virus in patients with mixed cryoglobulinemia.Arthritis Rheum. 1991; 34: 1606-1610Crossref PubMed Scopus (307) Google Scholar, 3Agnello V. Chung R.T. Kaplan L.M. A role for hepatitis C virus infection in type II cryoglobulinemia.N Engl J Med. 1992; 327: 1490-1495Crossref PubMed Scopus (1348) Google Scholar, 4Cacoub P. Fabiani F.L. Musset L. Perrin M. Frangeul L. Leger J.M. Huraux J.M. Piette J.C. Godeau P. Mixed cryoglobulinemia and hepatitis C virus.Am J Med. 1994; 96: 124-132Abstract Full Text PDF PubMed Scopus (284) Google Scholar In addition, roughly 5% of patients with HCV-related MC develop symptomatic MC-related small-vessel vasculitis5Cacoub P. Poynard T. Ghillani P. Charlotte F. Olivi M. Piette J.C. Opolon P. MULTIVIRC Group Extrahepatic manifestations of chronic hepatitis C.Arthritis Rheum. 1999; 42: 2204-2212Crossref PubMed Scopus (574) Google Scholar, 6Vassilopoulos D. Calabrese L.H. Hepatitis C virus infection and vasculitis: implications of antiviral and immunosuppressive therapies.Arthritis Rheum. 2002; 46: 585-597Crossref PubMed Scopus (108) Google Scholar and less frequently necrotizing medium-vessel vasculitis (polyarteritis nodosa [PAN] like).7Cacoub P. Maisonobe T. Thibault V. Gatel A. Servan J. Musset L. Piette J.C. Systemic vasculitis in patients with hepatitis C.J Rheumatol. 2001; 28: 109-118PubMed Google Scholar Cardiac involvement has been rarely described in the setting of HCV-related vasculitis.8Karras A. Potier L. Reboux A.H. Coldea N. Perdrix L. Jacquot C. Mousseaux E. Cryoglobulin-induced cardiomyopathy.J Am Coll Cardiol. 2010; 55: e13Crossref PubMed Scopus (8) Google Scholar, 9Bragagni G. Baldini A. Bianconcini M. Heart failure as clinical onset of essential mixed cryoglobulinemia.Minerva Med. 1998; 89 ([article in Italian]): 283-286PubMed Google Scholar, 10Maestroni A. Caviglia A.G. Colzani M. Borghi A. Monti G. Picozzi G. Cannatelli G. Heart involvement in essential mixed cryoglobulinemia.Ric Clin Lab. 1986; 16: 381-383Crossref PubMed Scopus (9) Google Scholar Increased levels of circulating N-terminal pro–brain natriuretic peptide were found in 30% of patients with HCV-related MC compared to 7% of controls, findings that could indicate the presence of a subclinical cardiac dysfunction in patients with HCV-related MC.11Antonelli A. Ferri C. Ferrari S.M. Ghiri E. Galetta F. Franzoni F. Santoro G. Fallahi P. High circulating levels of N-terminal pro-brain natriuretic peptide and interleukin 6 in patients with mixed cryoglobulinemia.J Med Virol. 2010; 82: 297-303Crossref PubMed Scopus (9) Google Scholar However, the prevalence and the presentation of cardiac involvement related to HCV-related MC have not been evaluated to date. During primary systemic vasculitis, cardiac involvement has been mainly reported in Churg-Strauss syndrome (CSS), with a prevalence ranging from 13% to 75% of patients.12Keogh K.A. Specks U. Churg-Strauss syndrome: clinical presentation, antineutrophil cytoplasmic antibodies, and leukotriene receptor antagonists.Am J Med. 2003; 115: 284-290Abstract Full Text Full Text PDF PubMed Scopus (266) Google Scholar, 13Vinit J. Bielefeld P. Muller G. Pfitzenmeyer P. Bonniaud P. Lorcerie B. Besancenot J.F. Heart involvement in Churg-Strauss syndrome: retrospective study in French Burgundy population in past 10 years.Eur J Intern Med. 2010; 21: 341-346Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar In patients with PAN, cardiac involvement due to vasculitis of the coronary arteries or their branches with myocardial arteriolar infarcts was reported in 6% to 57% of patients when considering radiologic, electrocardiographic, or histopathologic studies. Congestive heart failure is the main clinical feature in PAN but usually less frequently than in CSS.14Bletry O. Godeau P. Charpentier G. Guillevin L. Herreman G. Cardiac manifestations of periarteritis nodosa. Incidence of non-hypertensive cardiomyopathy.Arch Mal Coeur Vaiss. 1980; 73 ([article in French]): 1027-1036PubMed Google Scholar In these patients, cardiac involvement has been identified as an independent factor associated with poor outcomes.15Guillevin L. Lhote F. Gayraud M. Cohen P. Jarrousse B. Lortholary O. Thibult N. Casassus P. Prognostic factors in polyarteritis nodosa and Churg-Strauss syndrome. A prospective study in 342 patients.Medicine (Baltimore). 1996; 75: 17-28Crossref PubMed Scopus (904) Google Scholar, 16Guillevin L. Pagnoux C. Seror R. Mahr A. Mouthon L. Le Toumelin P. The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort.Medicine (Baltimore). 2011; 90: 19-27Crossref PubMed Scopus (664) Google Scholar The aims of this study were to describe the presentation and outcomes of patients with cardiac involvement and to compare them to patients with HCV-related vasculitis without cardiac involvement. Data from 165 consecutive patients with HCV-related systemic vasculitis (76 mean, 89 women; median age 62 years, range 31 to 85) followed from January 1, 1993, to January 1, 2010, by the same physician (P.C.) in the Department of Internal Medicine at Groupe Hospitalier Pitié-Salpétrière (Paris, France) were retrospectively reviewed by the same physician (B.T.). For each patient, clinical and biologic data were recorded at the time of the initial evaluation, during follow-up, and at the end of follow-up. All patients were HCV ribonucleic acid positive at initial presentation of vasculitis. Patients were considered to have HCV-related vasculitis if they had, in association with clinical manifestations of vasculitis (purpura or cutaneous ulcers, arthralgia, myalgia, peripheral neuropathy, renal involvement, cerebral vasculitis, gastrointestinal involvement, cardiac involvement), (1) histologically proved vasculitis (n = 103) (required for all patients without detectable MC) and/or (2) detectable MC with at least purpura as a clinical manifestation (n = 62). Patients without histologically proved vasculitis but with purpura and detectable MC were considered to have small-vessel vasculitis on the basis of previously defined clinical and biologic criteria.17Gorevic P.D. Kassab H.J. Levo Y. Kohn R. Meltzer M. Prose P. Franklin E.C. Mixed cryoglobulinemia: clinical aspects and long-term follow-up of 40 patients.Am J Med. 1980; 69: 287-308Abstract Full Text PDF PubMed Scopus (702) Google Scholar, 18Jennette J.C. Falk R.J. Small-vessel vasculitis.N Engl J Med. 1997; 337: 1512-1523Crossref PubMed Scopus (1211) Google Scholar Cryoglobulin levels were measured and classified as previously described.19Musset L. Diemert M.C. Taibi F. Thi Huong Du L. Cacoub P. Leger J.M. Boissy G. Gaillard O. Galli J. Characterization of cryoglobulins by immunoblotting.Clin Chem. 1992; 38: 798-802Crossref PubMed Scopus (216) Google Scholar Patients who were MC positive were defined as having MC in their serum that was >0.05 g/L on ≥2 occasions. The type of vasculitis for each patient was classified according to the Chapel Hill criteria.18Jennette J.C. Falk R.J. Small-vessel vasculitis.N Engl J Med. 1997; 337: 1512-1523Crossref PubMed Scopus (1211) Google Scholar According to these criteria and to the American College of Rheumatology criteria,20Lightfoot Jr., R.W. Michel B.A. Bloch D.A. Hiunder G.G. Zvaifler N.J. McShane D.J. Arend W.P. Calabrese L.H. Leavitt R.Y. Lie J.T. The American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa.Arthritis Rheum. 1990; 33: 1088-1093Crossref PubMed Scopus (969) Google Scholar patients were classified as having MC-type small-vessel vasculitis and PAN-like medium-vessel vasculitis. Liver biopsy specimens were evaluated according to the previously validated METAVIR scoring system.21The French METAVIR Cooperative Study Group Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C.Hepatology. 1994; 20: 15-20Crossref PubMed Scopus (1873) Google Scholar Cardiac involvement was defined as (1) cardiac manifestations present at the time of vasculitis and responding to vasculitis treatment, after exclusion of other causes of cardiac involvement, and (2) cardiac manifestations occurring during a relapse of vasculitis, diagnosed on the basis of extracardiac features of vasculitis and/or immunologic features, responding to vasculitis treatment, after exclusion of other causes of cardiac involvement. The following manifestations were considered to be cardiac manifestations: thoracic pain; heart failure; acute pulmonary edema; myocardial ischemia or infarction; abnormalities in serum troponin and brain natriuretic peptide levels; and abnormal findings on electrocardiographic, ultrasonography, scintigraphy, coronary angiography, and/or cardiac magnetic resonance imaging. Dilated cardiomyopathy was characterized by dilation and impaired contraction of 1 or both ventricles. Clinical response of vasculitis to antiviral treatment was defined by analyzing the course of cardiac involvement (clinical, biologic, and radiologic improvement). Relapse was defined as the reappearance of clinical signs of vasculitis. Data are presented as mean ± SD or as median (range), as appropriate for continuous variables, and as frequency (percentage) for qualitative variables. Fisher's exact tests were used to compare qualitative variables, and nonparametric Mann-Whitney U tests were used to compare continuous variables. Multivariate analysis using logistic regression was used to determine the variables independently associated with cardiac involvement. Variables associated with cardiac involvement at the 0.20 level were considered in the multivariate analysis. Variable selections were performed using a backward procedure on the basis of a p value cutoff of 0.05. A p value <0.05 was considered significant. Statistical analyses were performed using GraphPad Prism version 4.0 and Instat version 3.0 for Windows (GraphPad Software, San Diego, California). The main characteristics of the 165 patients with HCV-related systemic vasculitis according to the presence of cardiac involvement are listed in Tables 1 and 2. Cardiac involvement was present in 7 of 165 patients (4%), at the diagnosis of vasculitis in 3 patients (43%), and during clinical relapses of vasculitis in 4 patients (57%), including 2 patients without virologic relapse. No cardiac biopsy was available.Table 1Baseline epidemiologic and virologic features of the 7 patients with and 158 patients without hepatitis C virus–related vasculitis cardiac involvementFeatureAll Patients (n = 165)No Cardiac Involvement (n = 158)Cardiac Involvement (n = 7)p ValueEpidemiologic features Age (yrs)62 (31–85)62 (31–85)61 (40–76)0.93 Women89 (54%)85 (54%)4 (57%)1.00Virologic features HCV genotype0.02†Statistically significant (p <0.05).192 (61%)89 (62%)3 (42%)225 (17%)25 (17%)0 (0%)314 (10%)12 (8%)2 (29%)413 (9%)11 (8%)2 (29%)57 (5%)7 (5%)0 (0%)Not available14140 HCV ribonucleic acid level (log10 IU)5.9 (3.3–7.9)5.8 (3.3–7.9)6.0 (5.0–7.0)0.69 Median duration of infection (yrs)21 (3–48)21 (3–48)19 (16–28)0.57 Liver METAVIR score∗Liver biopsy specimens were evaluated according to the previously validated METAVIR scoring system.Activity score1 (0–3)1 (0–3)1 (0–2)0.38Fibrosis score2 (0–4)2 (0–4)2 (0–4)0.70Fibrosis score ≥348/142 (34%)46/135 (34%)2 (29%)1.00Alanine aminotransferase (times upper limit of normal)1.5 (0.5–7)1.5 (0.5–7)1 (0.5–1.5)0.008†Statistically significant (p <0.05).Data are expressed as median (range) or as number (percentage).∗ Liver biopsy specimens were evaluated according to the previously validated METAVIR scoring system.† Statistically significant (p <0.05). Open table in a new tab Table 2Baseline clinical, biologic, and histologic features of the 7 patients with and 158 patients without hepatitis C virus–related vasculitis cardiac involvementFeatureAll Patients (n = 165)No Cardiac Involvement (n = 158)Cardiac Involvement (n = 7)p ValueMedian duration between diagnosis of vasculitis and treatment (mo)12 (1–192)12 (1–192)1 (1–6)0.0002∗Statistically significant (p <0.05).Clinical features Deterioration of the general health status36 (22%)31 (20%)5 (71%)0.006∗Statistically significant (p <0.05). Purpura117 (71%)111 (70%)6 (86%)0.67 Arthralgia87 (53%)85 (54%)2 (29%)0.26 Myalgia23 (14%)21 (13%)2 (29%)0.25 Peripheral neuropathy122 (74%)119 (75%)3 (43%)0.08 Renal involvement56 (34%)50 (32%)6 (86%)0.007∗Statistically significant (p <0.05). Central nervous system involvement15 (9%)14 (9%)1 (14%)0.49 Gastrointestinal involvement12 (7%)9 (6%)3 (43%)0.009∗Statistically significant (p <0.05). B-cell lymphoma26 (16%)21 (13%)5 (71%)0.001∗Statistically significant (p <0.05).Biologic features Median C-reactive protein (mg/L)2 (0–158)2 (0–158)11 (1–89)0.10 Median C4 (mg/L)0.06 (0.01–0.41)0.06 (0.01–0.41)0.02 (0.01–0.04)0.0005∗Statistically significant (p <0.05). Rheumatoid factor positivity109/141 (77%)102/134 (76%)7 (100%)0.35Characteristics of MC Detectable MC149 (90%)142 (90%)7 (100%)1.00 Median MC level (g/L)0.76 (0.05–7.00)0.70 (0.05–7.00)1.25 (0.61–3.44)0.08 Type II MC1231167 Type III MC26260Histologic features0.61 MC vasculitis135 (82%)130 (82%)5 (71%) PAN-like vasculitis30 (18%)28 (18%)2 (29%)Data are expressed as median (range) or as number (percentage).∗ Statistically significant (p <0.05). Open table in a new tab Data are expressed as median (range) or as number (percentage). Data are expressed as median (range) or as number (percentage). The comparison of patients with and without cardiac involvement is listed in Tables 1 and 2. Cardiac involvement was significantly associated with higher rates of deterioration of the general health status, renal and gastrointestinal involvement, and B-cell non-Hodgkin lymphoma (B-NHL). Median serum C4 complement fraction level was significantly higher in patients with than those without cardiac involvement, while median MC levels tended to be higher in patients with cardiac involvement. In multivariate analysis, the presence of B-NHL (odds ratio 18.1, 95% confidence interval 2.8 to 116.7, p = 0.0023) and gastrointestinal involvement (odds ratio 14.6, 95% confidence interval 2.0 to 104.9, p = 0.0078) were independently associated with cardiac involvement. The individual characteristics of the 7 patients with cardiac involvement are listed in Tables 3 and 4. None of the patients had histories of cardiomyopathy. Thoracic pain was present in 4 patients (57%), and congestive heart failure manifestations were noted in 4 patients (57%), including acute pulmonary edema in 4 and massive lower limb edema in 2 patients. Electrocardiography showed negative or flattened T waves in 6 patients (involving the inferior territory in 3, the lateral territory in 2, leads V1 to V6 in 2, the apical territory in 1, and the septal territory in 1), associated with ST-segment depression in 1 (involving the inferior and septal territories). Cardiac ultrasound revealed abnormalities in all cases: dilated cardiomyopathy in 5 patients (71%), global hypokinesia with left ventricular ejection fractions <40% in 4 (57%), pericardial effusion in 2 (29%) and acute hypertrophic cardiomyopathy with a left ventricular mass index of 123 g/m2 in 1 patient. Cardiac magnetic resonance imaging was performed in 5 patients, showing dilated left ventricles in 4 patients (Figure 1), hypokinetic left ventricles in 3, hypertrophic cardiomyopathy in 1 (Figure 1), and late gadolinium enhancement in 3 patients (including diffuse nodular enhancement in 2 and subendocardial enhancement in 1) (Figure 1). Four patients underwent coronary angiography, which revealed no coronary stenosis, but the presence of microaneurysms on right and left coronary arteries was noted in 1 patient (Figure 2). Myocardial scintigraphy, performed in 2 patients, showed abnormal myocardial defects in both patients.Table 3Individual demographic, clinical, biologic, and histologic characteristics of extracardiac involvement in the 7 patients with hepatitis C virus vasculitis–related cardiomyopathyPatientAge at Diagnosis of Vasculitis (yrs)Age at Diagnosis of Cardiac Involvement (yrs)GenderMedical HistoryVasculitis InvolvementLymphoma CharacteristicsBiologic FeaturesHistologic FeaturesCardiovascular Risk FactorsCardiovascular DrugsPurpuraPeripheral NeuropathyRenalCentral Nervous SystemGastrointestinalAge at Diagnosis (yrs)TypeMC TypeMC Level (g/L)C4 Level (mg/L)Rheumatoid Factor14040M00+0+0+40SLVLII1.200.01+MC24647MTobacco0++00046MZLII1.300.03+PAN35456FHT0++++054SLVLII3.440.01+MC46161F00+0+0+——II0.610.04+PAN56263F0ACE inhibitor0++00——II1.050.02+MC67575F00+0+0+75MZLII1.980.01+MC77576MHTACE inhibitor+0+0076MZLII0.250.02+MCACE = angiotensin-converting enzyme; HT = arterial hypertension; MZL = marginal zone lymphoma; SLVL = splenic lymphoma with villous lymphocytes. Open table in a new tab Table 4Individual characteristics of cardiac involvement, treatment, and outcomes of the 7 patients with hepatitis C virus vasculitis–related cardiomyopathyPatientCardiac InvolvementTroponin Level (μg/L)BNP Level (ng/L)Hb Level (g/L)ECGUltrasonographyCMRCoronary angiographyTreatmentUS LVEFCMR LVEFOutcomeT-Wave AbnormalitiesST-Segment AbnormalitiesDCHypokinesiaPericardial EffusionCoronary StenosisCoronary Artery Microaneurysms0 Months6 Months12 Months0 Months6 Months12 Months1Myocardial ischemia0.93—105+0000—00IFN, CTC, CYC5560————Death (7 mo)2Myocardial ischemia, DC2.101,320105+0++0DC, diffuse nodular LGE0+CTC, RTX, CYC, plasmapheresis, peg-IFN/RBV395160284966Death (24 mo)∗Death by suicide.3HC 1 g/day, renal insufficiency (serum creatinine >140 μmol/L), specific cardiomyopathy, severe gastrointestinal involvement, and central nervous system involvement.15Guillevin L. Lhote F. Gayraud M. Cohen P. Jarrousse B. Lortholary O. Thibult N. Casassus P. Prognostic factors in polyarteritis nodosa and Churg-Strauss syndrome. A prospective study in 342 patients.Medicine (Baltimore). 1996; 75: 17-28Crossref PubMed Scopus (904) Google Scholar, 16Guillevin L. Pagnoux C. Seror R. Mahr A. Mouthon L. Le Toumelin P. The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort.Medicine (Baltimore). 2011; 90: 19-27Crossref PubMed Scopus (664) Google Scholar In HCV-related vasculitis, overall survival was also significantly associated with the presence of cardiac involvement. Early cardiac outcomes were favorable in all patients. The analysis of causes of death revealed that they were more frequently related to extracardiac manifestations. Cardiac involvement in patients with HCV-related vasculitis should be considered a severe manifestation, but probably in part because of extracardiac involvement. Nearly 3/4 of patients with cardiac involvement had overt B-NHL, suggesting that these patients should undergo extensive explorations for the early diagnosis of lymphoma. Last, regarding the therapeutic management of patients with HCV-related systemic vasculitis, the standard of care includes primarily an optimal antiviral therapy (pegylated interferon plus ribavirin) without the systematic use of immunosuppressive agents.29Cacoub P. Lidove O. Maisonobe T. Duhaut P. Thibault V. Ghillani P. Myers R.P. Leger J.M. Servan J. Piette J.C. Interferon-alpha and ribavirin treatment in patients with hepatitis C virus-related systemic vasculitis.Arthritis Rheum. 2002; 46: 3317-3326Crossref PubMed Scopus (168) Google Scholar, 30Saadoun D. Resche-Rigon M. Thibault V. Piette J.C. Cacoub P. Antiviral therapy for hepatitis C virus–associated mixed cryoglobulinemia vasculitis: a long-term followup study.Arthritis Rheum. 2006; 54: 3696-3706Crossref PubMed Scopus (219) Google Scholar However, cardiac involvement should be treated more aggressively. In the present study, most of our patients initially received a therapeutic regimen of short-term corticosteroids with rituximab, which seemed to be effective on short-term cardiac outcomes. In our experience, the long-term use of immunosuppressive agents in patients with HCV-related vasculitis is associated with significant morbidity and mortality,31Terrier B. Semoun O. Saadoun D. Sene D. Resche-Rigon M. Cacoub P. Prognostic factors in hepatitis C virus patients with systemic vasculitis.Arthritis Rheum. 2011; 63: 1748-1757Crossref PubMed Scopus (88) Google Scholar while short-term corticosteroids and/or rituximab do not seem to have a negative impact on survival. In the absence of contraindication or treatment failure, antiviral therapy should be initiated as soon as possible in all patients. Nevertheless, 2 patients experienced severe adverse events after rituximab, suggesting that this treatment should be administered with caution. The use of cytotoxic agents (i.e., cyclophosphamide or fludarabine) in case of B-NHL should also be used with caution, because these drugs that may cause cardiac problems in a small percentage of patients. Because of the retrospective nature of our study and the small number of patients with cardiac involvement, conclusions should be interpreted with caution. In addition, our study did not have a control group of HCV-infected patients without vasculitis. HCV infection has been associated with cardiomyopathy,32Matsumori A. Hepatitis C virus infection and cardiomyopathies.Circ Res. 2005; 96: 144-147Crossref PubMed Scopus (84) Google Scholar, 33Omura T. Yoshiyama M. Hayashi T. Nishiguchi S. Kaito M. Horiike S. Fukuda K. Inamoto S. Kitaura Y. Nakamura Y. Teragaki M. Tokuhisa T. Iwao H. Takeuchi K. Yoshikawa J. Core protein of hepatitis C virus induces cardiomyopathy.Circ Res. 2005; 96: 148-150Crossref PubMed Scopus (46) Google Scholar but despite the absence of a control group, the definition of cardiac involvement as manifestations present at the time of vasculitis or during a relapse of vasculitis and responding to vasculitis treatment, after the exclusion of other causes of cardiac involvement and without preexisting cardiomyopathy, strongly argues for a causal relation between vasculitis and cardiac involvement. However, these data represent the first analysis available, all patients were managed at the same center with long-term follow-up (except for patients who died), and none of these patients were lost to follow-up. The authors have disclosed no conflicts of interest.
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