Incidence, risk factors, and severity of clinical manifestations of skin vasculitis in patients with HCV- and HCV/HIV-infection
https://doi.org/10.29001/2073-8552-2022-37-4-87-94
Abstract
Introduction. Several viruses including hepatitis C virus (HCV) and human immunodeficiency virus (HIV) can induce vasculitis.
Aim. We aimed to study the incidence, risk factors, and severity of skin vasculitis in patients with HCV and HCV/HIV coinfection.
Patients and Methods. The study group included 331 patients (254 patients with HCV and 77 patients with HCV/HIV coinfection) referred to a specialized hepatology center for antiviral therapy of HCV infection.
Results. Skin vasculitis was found in 21% (95% CI: 17–25%) of cases, n = 69/331. Skin vasculitis was observed in in 20% of patients infected with HCV (95% CI: 15–25%) and in 25% of HIV/HCV co-infected patients (95% CI; 16–35%), χ2 = 0,892, р = 0,345. Most patients with vasculitis infected with HCV had cryoglobulinemia (94%, n = 47/50), meanwhile, in HIV/HCV co-infected patients, cryoglobulinemia was found in 63% cases (n = 12/19), χ2 = 10.568, р = 0.001. Multiple regression analysis showed that skin vasculitis was related with cryoglobulinemia (OR = 6,928, 95% CI: 3.245–14.790, р < 0.001), liver cirrhosis (OR = 2.015, 95% CI: 1.062–3.824, р = 0.032), duration of overt HCV infection (OR = 1.057, 95% CI: 1.021–1.094, р = 0.002), patients age (OR = 1.029, 95% CI: 1.002–1.057, р = 0.033) and inversely related with plasma alanine transaminase (OR 0.433, 95% CI: 0.229–0.820, р = 0.010). The statistical model was normalized for gender, HIV-positivity and bilirubin levels, and regression equation constant was 4.398 (p < 0.001). The intensity of skin rashes was comparable in HCV infected and HCV/HIV co-infected patients (χ2 = 6.741, р = 0.081), and was highly correlated with cryoglobulin levels both in HCV infected (r = 0.788, p < 0.001), and HCV/HIV co-infected patients (r = 0.909, p = 0.001).
Conclusion. Skin vasculitis was found in 20–25% of cases among patients with HCV infection and HCV/HIV co-infection. Cryoglobulinemia was the main factor associated with skin vasculitis, and severity of skin lesions was closely related with cryoglobulin levels.
About the Authors
N. V. Dunaeva
Pavlov First Saint Petersburg State Medical University,;
Almazov National Medical Research Centre
Russian Federation
Russian Federation
Natalia V. Dunaeva, Cand. Sci. (Med.), Associate Professor, Senior Research Scientist, Laboratory of Chronic Viral Infections, Research Center, Pavlov First Saint Petersburg State Medical University, Saint Petersburg; Associate Professor, Department of Infectious Diseases, Almazov National Medical Research Centre
6/8 Lev Tolstoy str., Saint Petersburg, 197022;
2, Akkuratova str., Saint Petersburg, 197341
S. Yu. Romanova
Center for Prevention and Control of AIDS and Infectious Diseases
Russian Federation
Russian Federation
Svetlana Yu. Romanova, Cand. Sci. (Med.), Head of the Department, Department of Chronic Hepatitis
179, Obvodny kannal emb., Saint Petersburg, 190103
I. A. Dubina
Pavlov First Saint Petersburg State Medical University
Russian Federation
Russian Federation
Irina A. Dubina, M.D., Clinical Pathologist, Laboratory for Diagnostics of Autoimmune Diseases, Center for Molecular Medicine
6/8 Lev Tolstoy str., Saint Petersburg, 197022
S. V. Lapin
Pavlov First Saint Petersburg State Medical University
Russian Federation
Russian Federation
Sergey V. Lapin, Cand. Sci. (Med.), Head of the Laboratory, Laboratory for Diagnostics of Autoimmune Diseases, Center for Molecular Medicine
6/8 Lev Tolstoy str., Saint Petersburg, 197022
V. V. Rassokhin
Pavlov First Saint Petersburg State Medical University;
Institute of Experimental Medicine
Russian Federation
Russian Federation
Vadim V. Rassokhin, Dr. Sci. (Med.), Associate Professor, Professor, Department, Department of the Socially Significant Infections and Phthisiopulmonology, Pavlov First Saint Petersburg State Medical University, Saint Petersburg; Head of the Laboratory, Laboratory of the Chronic Viral Infections, Institute of Experimental Medicine
6/8 Lev Tolstoy str., Saint Petersburg, 197022;
12, Akademik Pavlov str., Saint Petersburg, 197022,
D. A. Gusev
Almazov National Medical Research Centre;
S.P. Botkin Clinical Infectious Diseases Hospital
Russian Federation
Russian Federation
Denis A. Gusev, Dr. Sci. (Med.), Professor, Chief Physician, S.P. Botkin Clinical Infectious Diseases Hospital; Head of the Department, Department of the Infectious Diseases, Almazov National Medical Research Centre
2, Akkuratova str., Saint Petersburg, 197341;
49, Piskarevskiy ave., Saint Petersburg, 195067
References
1. Belyaeva I.B., Zotkin E.G., Lila A.M., Mazurov V.I., Onushchenko I.A. Karlsberg P.L., Lee W.M., Casey D.L., Cockerell C.J., Cruz P.D. Jr. Cutaneous vasculitis and rheumatoid factor positivity as presenting signs of hepatitis C virus-induced mixed cryoglobulinemia. Arch. Dermatol. 1995;131(10):1119–1123.
2. Karlsberg P.L., Lee W.M., Casey D.L., Cockerell C.J., Cruz P.D. Jr. Cutaneous vasculitis and rheumatoid factor positivity as presenting signs of hepatitis C virus-induced mixed cryoglobulinemia. Arch. Dermatol. 1995;131(10):1119–1123.
3. Cacoub P., Poynard T., Ghillani P., Charlotte F., Olivi M., Piette J.C. et al. Extrahepatic manifestations of chronic hepatitis C. MULTIVIRC Group. Multidepartment Virus C. Arthritis Rheum. 1999;42(10):2204– 2212. DOI: 10.1002/1529-0131(199910)42:10<2204::AID-ANR24>3.0.CO;2-D
4. Cacoub P., Renou C., Rosenthal E., Cohen P., Loury I., LoustaudRatti V. et al. Extrahepatic manifestations associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. The GERMIVIC. Groupe d’Etude et de Recherche en Medecine Interne et Maladies Infectieuses sur le Virus de l’Hepatite C. Medicine (Baltimore). 2000;79(1):47–56. DOI: 10.1097/00005792-20000100000005.
5. Stefanova-Petrova D.V., Tzvetanska A.H., Naumova E.J., Mihailova A.P., Hadjiev E.A., Dikova R.P. et al. Chronic hepatitis C virus infection: prevalence of extrahepatic manifestations and association with cryoglobulinemia in Bulgarian patients. World J. Gastroenterol. 2007;13(48):6518– 6528. DOI: 10.3748/wjg.v13.i48.6518.
6. Ramos-Casals M., Forns X., Brito-Zerón P., Vargas A., Ruiz M., Laguno M. et al. Cryoglobulinaemia associated with hepatitis C virus: influence of HCV genotypes, HCV-RNA viraemia and HIV coinfection. J. Viral. Hepat. 2007;14(10):736–742. DOI: 10.1111/j.1365-2893.2007.00866.x.
7. Aguiar M.F., Faria-Janes A.L., Garcia-Brandes G.I., Takemi-Emori C., Ferraz M.L.G., Andrade L.E.C. et al. Prevalence of cryoglobulinemia and cryoglobulinemic vasculitis in chronically HCV-infected Brazilian patients. Ann. Hepatol. 2019;18(5):685–692. DOI: 10.1016/j.aohep.2019.04.010.
8. Della Rossa A., Tavoni A., D’Ascanio A., Catarsi E., Marchi F., Bencivelli W. et al. Mortality rate and outcome factors in mixed cryoglobulinaemia: the impact of hepatitis C virus. Scand. J. Rheumatol. 2010;39(2):167–170. DOI: 10.3109/03009740903313639.
9. Terrier B., Sène D., Dechartres A., Saadoun D., Ortonne N., Rouvier P. et al. Systemic vasculitis in patients with hepatitis C virus infection with and without detectable mixed cryoglobulinemia. J. Rheumatol. 2011;38(1):104–110. DOI: 10.3899/jrheum.100191.
10. Dammacco F., Lauletta G., Vacca A. The wide spectrum of cryoglobulinemic vasculitis and an overview of therapeutic advancements. Clin. Exp. Med. 2022:1–18. DOI: 10.1007/s10238-022-00808-1.
11. Clinical recommendations. HIV infection in adults. URL: https:// cr.minzdrav.gov.ru/recomend/79_1. (In Russ.).
12. Neustroeva Iu.A., Tikhomirova T.A., Dunaeva N.V., Lapin S.V., Totolian A.A. Optimization of semiquantitative method for detection of cryoglobulins in a clinical diagnostic laboratory. Klinicheskaya Laboratornaya Diagnostika. 2007;(1):37–41. (In Russ.).
13. Konstantinova N.A. Cryoglobulins and pathology. Мoscow: Меditsina; 1999:176. (In Russ.).
14. Muratori L., Gibellini D., Lenzi M., Cataleta M., Muratori P., Morelli M.C. et al. Quantification of hepatitis C virus-infected peripheral blood mononuclear cells by in situ reverse transcriptase-polymerase chain reaction. Blood. 1996;88(7):2768–2774.
15. Bernardin F., Tobler L., Walsh I., Williams J.D., Busch M., Delwart E. Clearance of hepatitis C virus RNA from the peripheral blood mononuclear cells of blood donors who spontaneously or therapeutically control their plasma viremia. Hepatology. 2008;47(5):1446–1452. DOI: 10.1002/hep.22184.
16. Toubi E., Gordon S., Kessel A., Rosner I., Rozenbaum M., Shoenfeld Y. et al. Elevated serum B-Lymphocyte activating factor (BAFF) in chronic hepatitis C virus infection: association with autoimmunity. J. Autoimmun. 2006;27(2):134–139. DOI: 10.1016/j.jaut.2006.07.005.
17. Liao T.L., Chen Y.M., Hsieh S.L., Tang K.T., Chen D.Y., Yang Y.Y. et al. Hepatitis C Virus-Induced Exosomal MicroRNAs and Toll-Like Receptor 7 Polymorphism Regulate B-Cell Activating Factor. mBio. 2021;12(6):e0276421. DOI: 10.1128/mBio.02764-21.
18. Brouet J.C., Clauvel J.P., Danon F., Klein M., Seligmann M. Biologic and clinical significance of cryoglobulins. A report of 86 cases. Am. J. Med. 1974;57(5):775–788. DOI: 10.1016/0002-9343(74)90852-3.
19. Minopetrou M., Hadziyannis E., Deutsch M., Tampaki M., Georgiadou A., Dimopoulou E. et al. Hepatitis C virus (HCV)-related cryoglobulinemia: cryoglobulin type and anti-HCV profile. Clin. Vaccine Immunol. 2013;20(5):698–703. DOI: 10.1128/CVI.00720-12.
20. Dunaeva N.V., Mazing A.V., Lapin S.V., Gusev D.A. Incidence of mixed cryoglobulinemia and its significance in the development of extrahepatic manifestations in chronic hepatitis C and co-infection chronic hepatitis C/HIV infection. Infectious Diseases: News, Opinions, Training. 2022;11(2):69–76. (In Russ.). DOI: 10.33029/2305-3496-2022-11-2-69-76.21.
21. Sansonno D., Tucci F.A., Ghebrehiwet B., Lauletta G., Peerschke E.I., Conteduca V. et al. Role of the receptor for the globular domain of C1q protein in the pathogenesis of hepatitis C virus-related cryoglobulin vascular damage. J. Immunol. 2009;183(9):6013–6020. DOI: 10.4049/jimmunol.0902038.
22. Sansonno D., Carbone A., De Re V., Dammacco F. Hepatitis C virus infection, cryoglobulinaemia, and beyond. Rheumatology (Oxford). 2007;46(4):572–578. DOI: 10.1093/rheumatology/kel425.
23. Saadoun D., Terrier B., Semoun O., Sene D., Maisonobe T., Musset L. et al. Hepatitis C virus-associated polyarteritis nodosa. Arthritis Care Res. (Hoboken). 2011;63(3):427–435. DOI: 10.1002/acr.20381.
24. Ramos-Casals M., Robles A., Brito-Zerón P., Nardi N., Nicolás J.M., Forns X. et al. Life-threatening cryoglobulinemia: clinical and immunological characterization of 29 cases. Semin. Arthritis Rheum. 2006;36(3):189–196. DOI: 10.1016/j.semarthrit.2006.08.005.
Review
For citations:
Dunaeva N.V., Romanova S.Yu., Dubina I.A., Lapin S.V., Rassokhin V.V., Gusev D.A. Incidence, risk factors, and severity of clinical manifestations of skin vasculitis in patients with HCV- and HCV/HIV-infection. Siberian Journal of Clinical and Experimental Medicine. 2022;37(4):87-94. (In Russ.) https://doi.org/10.29001/2073-8552-2022-37-4-87-94
Views:
330
.png)
Email this article 