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Songtanin B, Chaisrimaneepan N, Mendóza R, Nugent K. Burden, Outcome, and Comorbidities of Extrahepatic Manifestations in Hepatitis B Virus Infections. Viruses 2024; 16:618. [PMID: 38675959 PMCID: PMC11055091 DOI: 10.3390/v16040618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Revised: 04/11/2024] [Accepted: 04/13/2024] [Indexed: 04/28/2024] Open
Abstract
Hepatitis B virus (HBV) infections affect approximately 296 million people around the world, and the prevalence of any past or present HBV infection during the years 2015-2018 was as high as 4.3%. Acute HBV infection often presents with nonspecific symptoms and is usually self-limited, but 5% of patients can have persistent infections leading to chronic HBV infection and the risk of turning into chronic HBV infection is significantly higher in babies with vertical transmission (95%). Patients with chronic HBV infection are usually asymptomatic, but 15 to 40% of chronic HBV carriers develop cirrhosis and/or hepatocellular carcinoma. In addition to liver-related disorders, HBV is also associated with several extrahepatic complications, including glomerulonephritis, cryoglobulinemia, neurologic disorders, psychological manifestations, polyarthritis, and dermatologic disorders. Making the diagnosis of HBV can be challenging since patients with chronic infections can remain symptom-free for decades before developing cirrhosis or hepatocellular carcinoma, and patients with acute HBV infection may have only mild, nonspecific symptoms. Therefore, understanding how this virus causes extrahepatic complications can help clinicians consider this possibility in patients with diverse symptom presentations. The pathophysiology of these extrahepatic disorders likely involves immune-related tissue injury following immune complex formation and inflammatory cascades. In some cases, direct viral infection of extrahepatic tissue may cause a clinical syndrome. Currently, the American Association for the Study of Liver Diseases recommends treatment of chronic HBV infections with interferon therapy and/or nucleos(t)ide analogs, and this treatment has been reported to improve some extrahepatic disorders in some patients with chronic HBV infection. These extrahepatic complications have a significant role in disease outcomes and increase medical costs, morbidity, and mortality. Therefore, understanding the frequency and pathogenesis of these extrahepatic complications provides important information for both specialists and nonspecialists and may help clinicians identify patients at an earlier stage of their infection.
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Affiliation(s)
- Busara Songtanin
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA (K.N.)
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Mazzaro C, Dal Maso L, Gragnani L, Visentini M, Saccardo F, Filippini D, Andreone P, Zignego AL, Gattei V, Monti G, Galli M, Quartuccio L. Hepatitis B Virus-Related Cryoglobulinemic Vasculitis: Review of the Literature and Long-Term Follow-Up Analysis of 18 Patients Treated with Nucleos(t)ide Analogues from the Italian Study Group of Cryoglobulinemia (GISC). Viruses 2021; 13:1032. [PMID: 34070832 PMCID: PMC8226459 DOI: 10.3390/v13061032] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 05/05/2021] [Accepted: 05/26/2021] [Indexed: 01/05/2023] Open
Abstract
Hepatitis B virus (HBV) chronic infection causes progressive liver damage, although about 20% of patients develop extrahepatic manifestations such as cryoglobulinemic vasculitis (CV). Clinical manifestations range from mild to moderate (purpura, asthenia, arthralgia) to severe (leg ulcers, peripheral neuropathy, glomerulonephritis, non-Hodgkin lymphoma). A comprehensive review of therapeutic options for HBV-related CV is lacking. Nucleos(t)ide analogues (NA) suppress HBV replication in 90-100% of cases and induce clinical response in most patients with mild-to-moderate CV. Plasma exchange can be performed in patients with severe CV and should be considered in severe or life-threatening cases combined with high doses of corticosteroids and antiviral treatment. A cautious use of rituximab can be considered only in association with NA treatment in refractory cases. A review of the literature and an analysis of data collected by six centers of the Italian Group for the Study of Cryoglobulinemia on 18 HBV-CV nucleotide/nucleoside analogues (NAs)-treated patients were carried out.
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Affiliation(s)
- Cesare Mazzaro
- Clinical Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico (CRO) IRCCS, 33081 Aviano, Italy;
| | - Luigino Dal Maso
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico (CRO) IRCCS, 33081 Aviano, Italy;
| | - Laura Gragnani
- MASVE Interdepartmental Center, Department of Experimental and Clinical Medicine, University of Florence, Center for Research and Innovation CRIA-MASVE, 50121 Firenze, Italy; (L.G.); (A.L.Z.)
| | - Marcella Visentini
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy;
| | - Francesco Saccardo
- Rheumatology Unit, Internal Medicine Unit, Presidio Ospedaliero di Saronno, ASST della Valle Olona, 21047 Saronno, Italy; (F.S.); (G.M.)
| | - Davide Filippini
- Rheumatology Unit, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy;
| | - Pietro Andreone
- Division of Internal Medicine, Department of Medical and Surgical Sciences, Maternal-Infantile and Adult, University of Modena and Reggio Emilia, 41124 Modena, Italy;
| | - Anna Linda Zignego
- MASVE Interdepartmental Center, Department of Experimental and Clinical Medicine, University of Florence, Center for Research and Innovation CRIA-MASVE, 50121 Firenze, Italy; (L.G.); (A.L.Z.)
| | - Valter Gattei
- Clinical Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico (CRO) IRCCS, 33081 Aviano, Italy;
| | - Giuseppe Monti
- Rheumatology Unit, Internal Medicine Unit, Presidio Ospedaliero di Saronno, ASST della Valle Olona, 21047 Saronno, Italy; (F.S.); (G.M.)
| | - Massimo Galli
- Infectious Diseases, L. Sacco Hospital, Department of Biochemical and Clinical Sciences, University of Milan, 20157 Milan, Italy;
| | - Luca Quartuccio
- Rheumatology Clinic, Department of Medicine (DAME), ASUFC, University of Udine, 33100 Udine, Italy
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Wang CR, Tsai HW. Human hepatitis viruses-associated cutaneous and systemic vasculitis. World J Gastroenterol 2021; 27:19-36. [PMID: 33505148 PMCID: PMC7789062 DOI: 10.3748/wjg.v27.i1.19] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Revised: 12/19/2020] [Accepted: 12/27/2020] [Indexed: 02/06/2023] Open
Abstract
Human hepatitis viruses (HHVs) include hepatitis A virus, hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis delta virus, and hepatitis E virus and can cause liver inflammation in their common human host. Usually, HHV is rapidly cleared by the immune system, following acute HHV invasion. The morbidities associated with hepatitis A virus and hepatitis E virus infection occur shortly after their intrusion, in the acute stage. Nevertheless, the viral infectious process can persist for a long period of time, especially in HBV and HCV infection, leading to chronic hepatitis and further progressing to hepatic cirrhosis and liver cancer. HHV infection brings about complications in other organs, and both acute and chronic hepatitis have been associated with clinical presentations outside the liver. Vascular involvement with cutaneous and systemic vasculitis is a well-known extrahepatic presentation; moreover, there is growing evidence for a possible causal relationship between viral pathogens and vasculitis. Except for hepatitis delta virus, other HHVs have participated in the etiopathogenesis of cutaneous and systemic vasculitis via different mechanisms, including direct viral invasion of vascular endothelial cells, immune complex-mediated vessel wall damage, and autoimmune responses with stimulation of autoreactive B-cells and impaired regulatory T-cells. Cryoglobulinemic vasculitis and polyarteritis nodosa are recognized for their association with chronic HHV infection. Although therapeutic guidelines for HHV-associated vasculitis have not yet been established, antiviral therapy should be initiated in HBV and HCV-related systemic vasculitis in addition to the use of corticosteroids. Plasma exchange and/or combined cyclophosphamide and corticosteroid therapy can be considered in patients with severe life-threatening vasculitis manifestations.
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Affiliation(s)
- Chrong-Reen Wang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan
| | - Hung-Wen Tsai
- Department of Pathology, National Cheng Kung University Hospital, Tainan 70403, Taiwan
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Alfraji N, Upadhyaya VD, Bekampis C, Kuzyshyn H. Mixed Cryoglobulinemia Syndrome (MCS) due to untreated hepatitis B with uncommon presentation: case report and literature review. BMC Rheumatol 2020; 4:58. [PMID: 33292799 PMCID: PMC7672878 DOI: 10.1186/s41927-020-00159-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 08/17/2020] [Indexed: 01/28/2023] Open
Abstract
Background The mixed cryoglobulinemia (MC) syndrome is a systemic inflammatory syndrome that causes small-to-medium vessel vasculitis due to cryoglobulin-containing immune complexes most commonly caused by chronic hepatitis C virus (HCV), and rarely by chronic hepatitis B virus (HBV). Its clinical presentation is significantly varied, with manifestations ranging from purpura, arthralgia, and myalgia to more severe neurologic and renal involvement. Pulmonary involvement as organizing pneumonia, alveolar hemorrhage, and pulmonary vasculitis have been reported, but appear to be quite rare. Case presentation We report an uncommon case of a patient who presented with primary pulmonary syndrome without renal involvement in the setting of MC, due to untreated chronic hepatitis B infection. Early diagnosis and consequent institution of glucocorticoids, B-cell-depleting monoclonal antibody and antiviral therapy led to a favorable outcome and prevented any fatal sequelae. Conclusion Pulmonary compromise in MC syndrome is very uncommon and carries a high rate of mortality. Therefore, in patients with HBV presenting with hemoptysis, physicians must carry a high clinical suspicion for alveolar hemorrhage secondary to cryoglobulinemic vasculitis.
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Affiliation(s)
- Nasam Alfraji
- Department of Medicine, Jersey Shore University Medical Center, Neptune, NJ, 07753, USA. .,Internal Medicine Residency Program, Department of Medicine, Jersey Shore University Medical Center, Hackensack Meridian Health, Neptune, NJ, 07753, USA.
| | - Vandan D Upadhyaya
- Department of Medicine, Jersey Shore University Medical Center, Neptune, NJ, 07753, USA
| | - Christopher Bekampis
- Department of Medicine, Jersey Shore University Medical Center, Neptune, NJ, 07753, USA
| | - Halyna Kuzyshyn
- Department of Rheumatology, Jersey Shore University Medical Center, Neptune, NJ, 07753, USA
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Li C, Li H, Su W, Wen YB, Ye W, Ye WL, Cai JF, Qin XZ, Li XM, Li XW. Clinicopathological study of mixed cryoglobulinemic glomerulonephritis secondary to hepatitis B virus infection. BMC Nephrol 2020; 21:395. [PMID: 32928133 PMCID: PMC7490876 DOI: 10.1186/s12882-020-02057-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 09/06/2020] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Cryoglobulinemic glomerulonephritis (CryoGn) caused by hepatitis B virus (HBV) infection was rarely reported. Our study aimed to investigate the clinical features, renal pathology findings, and prognosis in patients with HBV related CryoGn. METHODS This was a retrospective study including seven Chinese patients with HBV related CryoGn in a tertiary referral hospital from April 2016 to March 2019. The clinical and pathological data were collected and analyzed. RESULTS Age at renal biopsy was 47 ± 12 years, with female/male ratio 3/4. Urine protein was 5.6 (3.0, 6.6) g/d and five cases presented with nephrotic syndrome. The baseline eGFR was 23.5 (20.2, 46.3) ml/min per 1.73m2. The extrarenal manifestations included purpura (n = 6), arthralgia (n = 1), peripheral neuropathy (n = 1), and cardiomyopathy (n = 1). Six cases had type II cryoglobulinemia with IgMκ, the other one had type III. The median cryocrit was 4.0 (1.0, 15.0) %. Renal pathologic findings on light microscopy: endocapillary proliferative glomerulonephritis (Gn) (n = 3), membranoproliferative Gn (n = 3), and mesangial proliferative Gn (n = 1). On immunofluorescence microscopy, the predominant type of immunoglobulin deposits was IgM (n = 5). HBsAg and HBcAg deposits were found in one case. Ultrastructural studies showed granular subendothelial and mesangial electron-dense deposits in all patients and microtubules in one case. All patients received antiviral medications. They were given corticosteroid alone (n = 2) or combined with cyclophosphamide (n = 4) or mycophenolate mofetil (n = 1). Two patients received plasmapheresis. The median follow-up time was 18 (6, 37) months. Four patients got remission, two patients died of pneumonia, and one progressed to end-stage renal disease (ESRD). At endpoint of follow-up, 24hUP was 2.1 (0.8-5.2) g/d, and eGFR was 55.3 (20.7, 111.8) ml/min per 1.73m2. The median cryocrit decreased to 1.0 (0, 5.75) %. CONCLUSIONS The etiology of mixed CryoGn should be screened for HBV infection. Endocapillary proliferative Gn and membranoproliferative Gn were the common pathologic patterns. Diagnosis and treatment in early stage benefit patients' renal outcomes. Immunosuppressive therapy should be considered for severe renal disease, based on efficient antiviral therapy.
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Affiliation(s)
- Chao Li
- Nephrology Department, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Hang Li
- Nephrology Department, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences & Peking Union Medical College, Beijing, 100730, China.
| | - Wei Su
- Laboratory Department, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences & Peking Union Medical College, Beijing, 100730, China.
| | - Yu-Bing Wen
- Nephrology Department, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Wei Ye
- Nephrology Department, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Wen-Ling Ye
- Nephrology Department, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Jian-Fang Cai
- Nephrology Department, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Xu-Zhen Qin
- Laboratory Department, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Xue-Mei Li
- Nephrology Department, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Xue-Wang Li
- Nephrology Department, Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences & Peking Union Medical College, Beijing, 100730, China
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Mazzaro C, Dal Maso L, Visentini M, Ermacora A, Tonizzo M, Gattei V, Andreone P. Recent news in the treatment of hepatitis B virus-related cryogobulinemic vasculitis. Minerva Med 2020; 111:566-572. [PMID: 32573522 DOI: 10.23736/s0026-4806.20.06771-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Hepatitis B virus (HBV) is a hepatotropic virus that causes hepatitis, cirrhosis and hepatocellular carcinoma. Twenty percent of HBV patients may develop extra-hepatic manifestations, such as polyarthritis nodosa, glomerulonephritis, dermatitis, poly-arthralgia and arthritis, and aplastic anemia. The association of HBV and cryoglobulinemic vasculitis (CV) has been highlighted by several epidemiological investigations. CV can develop in 0.5-4% of HBV infected patients. It has been demonstrated that suppression of HBV replication by nucleot(s)ide analogues (NAs) effectively induces clinical response in most patients with mild to moderate CV, but low responses are seen in severe CV. Based on this evidence, NAs therapy represents the first line therapeutic option in subjects with mild or moderate HBV related CV. Peg-interferon-Alfa can be an alternative treatment for HBV related CV, but the few studies published so far have shown no encouraging results. In patients with severe vasculitis and/or skin ulcers, peripheral neuropathy and glomerulonephritis treatment with rituximab (RTX) and NAs should be considered as a first line treatment. The long-term administration of low-medium glucocorticoid doses has been widely used in few studies to control clinical symptoms, but it should be used as a second option, when RTX is ineffective or not tolerated and in association with NAs. This review focuses on novel treatments for HBV related CV.
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Affiliation(s)
- Cesare Mazzaro
- Unit of Clinical Experimental Onco-Hematology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Pordenone, Italy -
| | - Luigino Dal Maso
- Unit of Cancer Epidemiology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Pordenone, Italy
| | - Marcella Visentini
- Depatment of Clinical Medicine, Laboratory affiliated to Pasteur Italia Institute - Cenci Bolognetti Foundation, Sapienza University, Rome, Italy
| | - Anna Ermacora
- Department of Internal Medicine, Hospital of Pordenone, Pordenone, Italy
| | - Maurizio Tonizzo
- Department of Internal Medicine, Hospital of Pordenone, Pordenone, Italy
| | - Valter Gattei
- Unit of Clinical Experimental Onco-Hematology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Pordenone, Italy
| | - Pietro Andreone
- SMECHIMAI Department, University of Modena and Reggio Emilia, Modena, Italy.,Department of Internal and Metabolic Medicine, University Hospital of Modena, Modena, Italy
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Macroglobulinemia de Waldenström presentándose como glomerulonefritis membranoproliferativa crioglobulinémica tipo II. Nefrologia 2018; 38:439-441. [DOI: 10.1016/j.nefro.2017.09.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Accepted: 09/04/2017] [Indexed: 12/22/2022] Open
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Li SJ, Xu ST, Chen HP, Zhang MC, Xu F, Cheng SQ, Liu ZH. Clinical and morphologic spectrum of renal involvement in patients with HBV-associated cryoglobulinaemia. Nephrology (Carlton) 2018; 22:449-455. [PMID: 27062412 DOI: 10.1111/nep.12795] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Revised: 04/01/2016] [Accepted: 04/03/2016] [Indexed: 12/30/2022]
Abstract
AIM Cryoglobulinaemic glomerulonephritis related to hepatitis B virus (HBV) infection has been rarely reported. The aim of this study was to investigate the clinical features, renal biopsy findings in patients with HBV-associated cryoglobulinaemia. METHODS Twelve patients with HBV-associated cryoglobulinaemia were identified in this study. The demographic, clinical, pathological characteristics, treatment and follow-up data were analyzed. RESULTS Renal involvement was characterized by nephrotic range proteinuria with microscopic haematuria in all patients, and impaired renal function in nine patients (75%). Purpuric rash was the main extrarenal manifestation (58.3%). Type II cryoglobulinaemia was presented in three patients and type III in nine patients. Hypocomplementaemia and positive of rheumatoid factors were present in all patients. Membranoproliferative glomerulonephritis (MPGN) was observed in all kidney specimens. Seven patients also had evidence of prominent cryoglobulins thrombi on renal biopsy, but only three patients had HBV antigen deposits in renal tissues. Antiviral and steroids or immunosuppressive agents have been used in most of patients. During follow-up, two patients died, and four reaching end-stage renal disease; three patients had complete remission, and three patients had renal function improved after therapy. CONCLUSIONS Nephrotic syndrome with haematuria and renal insufficiency are the main clinical manifestation; cryoglobulinaemic glomerulonephritis are the main renal lesion in patients with HBV-Associated cryoglobulinaemia; half of patients have poor outcome even with antiviral and immunosuppressive therapy. The results of this study indicate that cryoglobulins should be detected in hepatitis B virus-Associated nephropathy in endemic area.
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Affiliation(s)
- Shi-Jun Li
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Shu-Tian Xu
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Hui-Ping Chen
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Ming-Chao Zhang
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Feng Xu
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Shui-Qin Cheng
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Zhi-Hong Liu
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
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Ostojic P, Jeremic IR. Managing refractory cryoglobulinemic vasculitis: challenges and solutions. J Inflamm Res 2017; 10:49-54. [PMID: 28507447 PMCID: PMC5428757 DOI: 10.2147/jir.s114067] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Cryoglobulinemia is thought to be a rare condition. It may be an isolated disorder or secondary to a particular disease. According to immunoglobulin composition, cryoglobulinemia is classified into three types. In mixed cryoglobulinemia (types II and III), vascular deposition of cryoglobulin-containing immune complexes and complement may induce a clinical syndrome, characterized by systemic vasculitis and inflammation – cryoglobulinemic vasculitis (CryoVas). Most common clinical manifestations in CryoVas are skin lesions (orthostatic purpura and ulcers), weakness, peripheral neuropathy, Raynaud’s phenomenon, sicca syndrome, membranoproliferative glomerulonephritis, and arthralgia and seldom arthritis. In patients with mixed cryoglobulinemia, prevalence of anti-hepatitis C virus (HCV) antibodies and/or HCV RNA, detected by polymerase chain reaction (PCR), is reported to be up to 90%, indicating a significant role of HCV in the development of this condition. The goals of therapy for mixed cryoglobulinemia include immunoglobulin level reduction and antigen elimination. CryoVas not associated with HCV infection should be treated according to treatment recommendations for small-vessel vasculitides. CryoVas associated with chronic HCV infection should be treated with antivirals along with immunosuppressive drugs, with or without plasmapheresis, depending on disease severity and organ involvement. Patients who do not respond to first-line therapy may achieve remission when treatment with rituximab is started as second-line therapy. In HCV-related CryoVas, antiviral therapy should be given along with rituximab in order to achieve complete or partial remission. Moreover, rituximab has proven to be a glucocorticoid-sparing medication. Other potential therapies for refractory CryoVas include mycophenolate mofetil and belimumab, while tumor necrosis factor (TNF) inhibitors are not effective.
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Affiliation(s)
- Predrag Ostojic
- Institute of Rheumatology, School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Ivan R Jeremic
- Institute of Rheumatology, School of Medicine, University of Belgrade, Belgrade, Serbia
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Kinetics of Rituximab Excretion into Urine and Peritoneal Fluid in Two Patients with Nephrotic Syndrome. Case Rep Nephrol 2017; 2017:1372859. [PMID: 28243475 PMCID: PMC5294364 DOI: 10.1155/2017/1372859] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2016] [Revised: 12/26/2016] [Accepted: 12/28/2016] [Indexed: 01/27/2023] Open
Abstract
Clinical observations suggest that treatment of Rituximab might be less effective in patients with nephrotic range proteinuria when compared to nonnephrotic patients. It is conceivable that the reason for this is that significant amounts of Rituximab might be lost in the urine in a nephrotic patient and that these patients require a repeated or higher dosage. However, this has not been systematically studied. In this case report we describe two different patients with nephrotic range proteinuria receiving Rituximab. The first patient received Rituximab for therapy resistant cryoglobulinemic membranoproliferative glomerulonephritis and the other for second line treatment of Felty's syndrome. We employed flow cytometry to determine the amount of Rituximab excretion in both urine and peritoneal fluid specimens in these patients following administration of Rituximab. We found that a significant amount of Rituximab is lost from the circulation by excretion into the urine. Furthermore we saw a close correlation of the excretion of Rituximab to the excretion of IgG molecules suggesting selectivity of proteinuria as the determining factor of Rituximab excretion. Further larger scale clinical studies could have the potential to evaluate an optimal cut-off value of IgG urinary loss before a possible administration of Rituximab therefore contributing to a more individualized treatment approach in patients with nonselective and nephrotic range proteinuria.
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11
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Ryu A, Shimamura Y, Hasegawa K, Moniwa N, Takizawa H, Kang JH, Sakai H, Ogawa Y. [Case Report; Hepatitis B virus-associated cryoglobulinemia with membranoproliferative glomerulonephritis]. ACTA ACUST UNITED AC 2016; 103:2807-9. [PMID: 27522822 DOI: 10.2169/naika.103.2807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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Lymphoproliferative disease-related mixed cryoglobulinemia treated with rituximab and prednisolone. CEN Case Rep 2015; 4:6-13. [PMID: 28509274 DOI: 10.1007/s13730-014-0130-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2013] [Accepted: 05/28/2014] [Indexed: 10/23/2022] Open
Abstract
Mixed cryoglobulinemia is often associated with hepatic C virus infection and is less common with hepatitis B virus infection, and it often progresses into lymphoproliferative diseases. Rituximab is known to achieve systemic B-cell depletion and clinical remission of the systemic effects of cryoglobulins in hepatitis C virus-associated cryoglobulinemia. Conversely, there are few reports regarding the use of rituximab in hepatitis B virus-associated cryoglobulinemia. We report here the case of a 65-year-old Japanese female who presented with lymphoproliferative disease-related cryoglobulinemia with hepatitis B virus, including membranoproliferative glomerulonephritis with renal failure. The vasculitis was refractory to conventional and antiviral therapy, but rituximab use led to control the disease. Our case highlights the benefit and efficacy of rituximab in association with antiviral therapy in small vessel vasculitis related to lymphoproliferative disease-related cryoglobulinemia with hepatitis B virus.
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13
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Grigorescu I, Dumitrascu DL. Spontaneous and antiviral-induced cutaneous lesions in chronic hepatitis B virus infection. World J Gastroenterol 2014; 20:15860-6. [PMID: 25400473 PMCID: PMC4229554 DOI: 10.3748/wjg.v20.i42.15860] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 03/03/2014] [Accepted: 06/13/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To describe spontaneous, or interferon (IFN)- or immunization-induced skin lesions in hepatitis B virus (HBV) infection. METHODS A comprehensive literature search of all the papers presenting case reports of dermatological lesions in patients with chronic HBV infection was carried out. We included only patients with histologically proven skin lesions that appeared in the normal course of hepatitis B infection, or after immunization for hepatitis B or antiviral treatment. RESULTS We found 44 papers on this topic, reporting 151 cases. About 2% of patients with hepatitis B infection, mainly men, presented with skin lesions. Among patients with chronic hepatitis B, vasculitis and essential mixed cryoglobulinemia seemed to be the most frequent skin lesion (53.3%), followed by papular changes, rashes and Gianotti-Crosti syndrome, skin carcinoma and Henoch-Schönlein purpura were rare. IFN treatment seemed to be effective against HBV-associated and immunoglobulin-complex-mediated disease (vasculitis). Two cutaneous lesions (lichen planus and granuloma annulare) were described after hepatitis B vaccination. Systemic lupus and lupus-like lesions were the most frequently encountered lesions after antiviral treatment. Immunosuppressive and steroid therapy ameliorates lichen planus lesions in 50% of cases. CONCLUSION Vasculitis was the most frequent spontaneous skin lesion found in chronic hepatitis B. Lichen planus was most frequent after immunization and lupus/lupus-like lesions after IFN.
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Viganò M, Martin P, Cappelletti M, Fabrizi F. HBV-Associated Cryoglobulinemic Vasculitis: Remission after Antiviral Therapy with Entecavir. Kidney Blood Press Res 2014; 39:65-73. [DOI: 10.1159/000355778] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/15/2014] [Indexed: 11/19/2022] Open
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Chay J, Donovan P, Cummins L, Kubler P, Pillans P. Experience with low-dose rituximab in off-label indications at two tertiary hospitals. Intern Med J 2014; 43:871-82. [PMID: 23919335 DOI: 10.1111/imj.12207] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2012] [Accepted: 05/01/2013] [Indexed: 01/14/2023]
Abstract
BACKGROUND Rituximab is a monoclonal antibody directed against B cells and is increasingly used to treat a variety of autoimmune conditions. Most published evidence reporting the successful use of rituximab in off-label indications has empirically used a high-dose regimen (either 375 mg/m(2) weekly for 4 weeks, or 1000 mg × 2), which is the approved course of treatment for lymphoma and rheumatoid arthritis patients. AIMS The aims of this report are to review the indications, outcomes and adverse events of low-dose (500 mg twice, given 1-2 weeks apart), off-label use of rituximab in our institutions, and to review the available evidence. METHODS We performed a retrospective audit of the off-label use of low-dose rituximab at two university teaching, tertiary referral hospitals, from mid-2008 until the end of 2011. RESULTS Off-label rituximab was given to 52 patients (53 indications) across a heterogeneous group of autoimmune conditions. Outcomes were known for 46 conditions (affecting 45 patients), and of these, complete responses were observed in 16 (35%) conditions and a further 19 (41%) had a partial response. There was no response to rituximab in 11 (24%) patients. There were eight significant adverse events, mostly related to infectious complications. CONCLUSION This case series suggests that low-dose courses of rituximab can be used off-label to treat several severe and/or refractory immunological disorders with a reasonable safety profile; however, further trials are required in many off-label indications.
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Affiliation(s)
- J Chay
- Department of Rheumatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
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Yang SH, Hsu C, Cheng AL, Kuo SH. Anti-CD20 monoclonal antibodies and associated viral hepatitis in hematological diseases. World J Hematol 2014; 3:29. [DOI: 10.5315/wjh.v3.i2.29] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2013] [Revised: 01/27/2014] [Accepted: 03/18/2014] [Indexed: 02/05/2023] Open
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