Scandinavian Journal of Rheumatology
ISSN: 0300-9742 (Print) 1502-7732 (Online) Journal homepage: http://www.tandfonline.com/loi/irhe20
Hepatitis C-associated glomerulonephritis mimicking systemic lupus erythematosus M Krajewska, D Rukasz, K Jakuszko, H Augustyniak-Bartosik, J Penar, Z Bednarz & M Klinger To cite this article: M Krajewska, D Rukasz, K Jakuszko, H Augustyniak-Bartosik, J Penar, Z Bednarz & M Klinger (2015) Hepatitis C-associated glomerulonephritis mimicking systemic lupus erythematosus, Scandinavian Journal of Rheumatology, 44:4, 343-344, DOI: 10.3109/03009742.2015.1027732 To link to this article: http://dx.doi.org/10.3109/03009742.2015.1027732
Published online: 25 Apr 2015.
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=irhe20 Download by: [University of California, San Diego]
Date: 10 November 2015, At: 22:41
Letters
343
7. Marie I, Ducrotte P, Denis P, Menard J-F, Levesque H. Small intestinal bacterial overgrowth in systemic sclerosis. Rheumatology (Oxford) 2009;48:1314–19. 8. Kayser C, Martini L, Pinheiro M, Szejnfeld V, Marighela TF. Evaluation of nutritional status and dietary intake in women with systemic sclerosis. Rheumatology (Oxford) 2012;51(Suppl 2):ii85–6.
Ariane L Herrick, Clinical Sciences Building, Salford Royal NHS Foundation Trust, Salford M6 8HD, UK. E-mail: [email protected] Accepted 3 March 2015
Hepatitis C-associated glomerulonephritis mimicking systemic lupus erythematosus
Downloaded by [University of California, San Diego] at 22:41 10 November 2015
M Krajewska, D Rukasz, K Jakuszko, H Augustyniak-Bartosik, J Penar, Z Bednarz, M Klinger Department and Clinic of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland
Hepatitis C virus (HCV) infection is known to be responsible for many autoimmune reactions but its association with systemic lupus erythematosus (SLE) has not yet been established. We present the case of young female patient infected with HCV, suspected of SLE accompanied by severe nephrotic syndrome (NS) treated effectively with antiviral agents. The 25-year-old female patient was admitted to the Internal Medicine Department presenting with weakness, hypertension, oliguria, and massive peripheral oedema. Laboratory tests showed anaemia, leucopenia, and thrombocytopenia, impaired renal function, and the features of severe NS with active urinary sediment. Immunological tests revealed the presence of a high titre of antinuclear antibodies (ANA) and anti-doublestranded DNA (anti-dsDNA) antibodies (Abs). Screening viral tests revealed HCV infection with active replication and genotype 1 was established. Serum cryoglobulins were negative. Laboratory data are shown in Table 1. Renal biopsy diagnosed lupus nephritis class IV (membranoproliferative glomerulonephritis). Immunosuppressive
treatment was introduced: pulses of methylprednisolone intravenously at a total dose of 1.5 g followed by oral methyloprednisolone at a dose of 48 mg every second day. As a result her kidney function improved and proteinuria decreased. Moreover, peripheral blood count normalized, ANA titre diminished, and anti-dsDNA Abs became negative. A liver biopsy revealed chronic hepatitis lesions (hepatitis chronica minimalis) without features of autoimmune hepatitis (AIH). For the next year the dose of methyloprednisolone was gradually decreased to 12 mg every second day. Serum albumin and protein concentrations increased slightly despite preserved nephrotic range proteinuria. In the 17th month of observation the patient was referred to the Nephrology Department. Laboratory tests showed normal serum creatinine, persistent NS, and slightly increased ANA and anti-dsDNA Abs. Low immunological activity with high daily proteinuria accompanied by high HCV replication led us to believe that the renal disease was secondary to HCV infection. We decided to implement antiviral therapy containing pegylated interferon α-2a treatment (180 μg/week) and
Table 1. Laboratory results. Serum Serum Serum Daily RBC Haemoglobin WBC PLT ALT GGTP creatinine protein albumin proteinuria HCV RNA ANA Month (106/μL) (g/L) (103/μL) (103/μL) (U/L) (U/L) (mmol/L) (g/L) (g/L) (g) (copies/mL) (titre) 0 3.93 5 4.78 12 4.75 17 5.42 21 5.08 29 3.31 37 4.05 54 5.78 Normal 4.2–5.4
10.2 12.9 14.6 14.5 14.3 10.4 12.9 13.7 12–16
2.4 4.8 6.6 4.8 6.76 4.2 2.3 4.77 4–10
93 10 15 208 36 61 239 39 53 189 37 38 232 44 78 162 19 44 140 22 75 296 34 97 140–440 0–35 0–38
129.6 83.9 91.5 100.7 88.5 72.4 70.9 70.9 62–99
46 48 49 49 55 51 59 60 66–83
14 24 26 30 27 36 35 35–52
7.5 5.1 4.6 4.5 4.0 No data 2.0 Negative Negative
Positive 1.02 104 1.12 106 2.21 106 Negative Negative Negative Negative
1:1280 1:640 1:320 1:320 1:320 1:100 1:320 1:100 Negative
Anti-dsDNA Abs (IU/mL) 774.82 Negative Negative 104.67 162.83 52.14 80.16 63.77 < 100
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344
ribavirin at a daily dose of 1000 mg. At that time a dose of 24 mg of methyloprednisolone was given every second day. The treatment was provided under immunological and viral activity control for 12 months. In the fifth month of antiviral therapy (month 29), HCV replication was negative, kidney function, serum protein and albumin improved, and daily proteinuria diminished. Doses of glucocorticosteroids were lowered gradually until the treatment was completed a year later. Several months after the antiviral treatment had finished (month 54), the patient presented with normal renal function with no proteinuria and serum protein, and albumin concentrations at the low end of normal ranges. The ANA titre was 1:100 and anti-dsDNA Abs concentration did not exceed the normal range. HCV RNA remained undetectable. HCV infection can appear together with various autoantibodies, such as ANA, anti-dsDNA, anti-thyroid, anti-smooth muscle (anti-SMA), anti-liver/kidney/ microsomal type 1 (LKM1), rheumatoid factor (RF), or cryoglobulins. Its clinical manifestations may comprise systemic vasculitis, polyarthritis, mixed cryoglobulinaemia, and some types of glomerulonephritis, such as secondary membranous or membranoproliferative glomerulonephritis (1, 2). SLE is one of the most frequently diagnosed autoimmune diseases. Nephritis is presented in 35% cases at the time of diagnosis, increasing up to 60% of cases in the course of SLE (3). The connection between SLE and HCV is uncertain; however, in some cases the association is highly possible. In an Ibero-American study, SLE was accompanied by HCV infection in 11% of patients (4), and in an Egyptian population, where HCV was found in up to 14% of citizens, the occurrence of HCV was confirmed in 6.7% of SLE patients investigated (5). SLE in the course of HCV infection is characterized by less frequent skin involvement, lower ANA and anti-dsDNA antibodies, lower complement concentration (C4, CH50), and the more frequent incidence of cryoglobulin occurrence (2). Furthermore, lupus nephritis and coexisting HCV infection more frequently lead to end-stage renal disease compared to HCV negatives (6).
www.scandjrheumatol.dk
Letters
Furthermore, it has been noted that pegylated interferon per se may induce lupus-like syndrome and other autoimmune reactions (1). The use of interferon in the case of coexistence of autoimmune disease and HCV infection is debatable. Interferon-alpha overproduction underlies the development and progression of systemic lupus and can cause worsening of the disease and therefore is not recommended in these patients. In our patient, NS, which persisted despite immunosuppressive treatment, was related to active viral infection. Remission was achieved after interferon and ribavirin treatment. Given the described symptoms, the possibility of autoimmune reaction in response to HCV infection should always be considered.
References 1. McMurray RW, Elbourne K. Hepatitis C virus infection and autoimmunity. Semin Arthritis Rheum 1997;26:689–701. 2. Ramos-Casalam M, Jara LJ, Medina F, Rosas J, Calvo-Alen J, Mana J, et al. Systemic autoimmune diseases co-existing with chronic hepatitis C virus infection (the HISPAMEC Registry): patterns of clinical and immunological expression in 180 cases. J Intern Med 2005;257: 549–57. 3. Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, et al. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res 2012;64:797–808. 4. Ramos-Casalam M, Font J, Garcia-Carrasco M, Cervera R, Jimenez S, Trejo O, et al. Hepatits C virus infection mimicking systemic lupus erythematosus. Arthritis Rheum 2000;43:2801–6. 5. El Garf A, El Zorkany B, Gheith R, Sheba H, Abdel Moneim G, El Garf K. Prevalence and clinical presentations of hepatitis C virus among patients admitted to the rheumatology ward. Rheumatol Int 2012;32:2691–5. 6. Mitwalli AH, Hayat A, Alwakeel J, Hammad D. Effects of concomitant hepatitis C virus infection in patients with underlying lupus nephritis on long-term renal outcome. Nephrol Dial Transplant 2012;27:627–32.
Dagna Rukasz, Department and Clinic of Nephrology and Transplantation Medicine, Wroclaw Medical University, 213 Borowska Street, 50-556 Wrocław, Poland E-mail: [email protected] Accepted 6 March 2015
ISSN: 0300-9742 (Print) 1502-7732 (Online) Journal homepage: http://www.tandfonline.com/loi/irhe20
Hepatitis C-associated glomerulonephritis mimicking systemic lupus erythematosus M Krajewska, D Rukasz, K Jakuszko, H Augustyniak-Bartosik, J Penar, Z Bednarz & M Klinger To cite this article: M Krajewska, D Rukasz, K Jakuszko, H Augustyniak-Bartosik, J Penar, Z Bednarz & M Klinger (2015) Hepatitis C-associated glomerulonephritis mimicking systemic lupus erythematosus, Scandinavian Journal of Rheumatology, 44:4, 343-344, DOI: 10.3109/03009742.2015.1027732 To link to this article: http://dx.doi.org/10.3109/03009742.2015.1027732
Published online: 25 Apr 2015.
Submit your article to this journal
Article views: 61
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=irhe20 Download by: [University of California, San Diego]
Date: 10 November 2015, At: 22:41
Letters
343
7. Marie I, Ducrotte P, Denis P, Menard J-F, Levesque H. Small intestinal bacterial overgrowth in systemic sclerosis. Rheumatology (Oxford) 2009;48:1314–19. 8. Kayser C, Martini L, Pinheiro M, Szejnfeld V, Marighela TF. Evaluation of nutritional status and dietary intake in women with systemic sclerosis. Rheumatology (Oxford) 2012;51(Suppl 2):ii85–6.
Ariane L Herrick, Clinical Sciences Building, Salford Royal NHS Foundation Trust, Salford M6 8HD, UK. E-mail: [email protected] Accepted 3 March 2015
Hepatitis C-associated glomerulonephritis mimicking systemic lupus erythematosus
Downloaded by [University of California, San Diego] at 22:41 10 November 2015
M Krajewska, D Rukasz, K Jakuszko, H Augustyniak-Bartosik, J Penar, Z Bednarz, M Klinger Department and Clinic of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland
Hepatitis C virus (HCV) infection is known to be responsible for many autoimmune reactions but its association with systemic lupus erythematosus (SLE) has not yet been established. We present the case of young female patient infected with HCV, suspected of SLE accompanied by severe nephrotic syndrome (NS) treated effectively with antiviral agents. The 25-year-old female patient was admitted to the Internal Medicine Department presenting with weakness, hypertension, oliguria, and massive peripheral oedema. Laboratory tests showed anaemia, leucopenia, and thrombocytopenia, impaired renal function, and the features of severe NS with active urinary sediment. Immunological tests revealed the presence of a high titre of antinuclear antibodies (ANA) and anti-doublestranded DNA (anti-dsDNA) antibodies (Abs). Screening viral tests revealed HCV infection with active replication and genotype 1 was established. Serum cryoglobulins were negative. Laboratory data are shown in Table 1. Renal biopsy diagnosed lupus nephritis class IV (membranoproliferative glomerulonephritis). Immunosuppressive
treatment was introduced: pulses of methylprednisolone intravenously at a total dose of 1.5 g followed by oral methyloprednisolone at a dose of 48 mg every second day. As a result her kidney function improved and proteinuria decreased. Moreover, peripheral blood count normalized, ANA titre diminished, and anti-dsDNA Abs became negative. A liver biopsy revealed chronic hepatitis lesions (hepatitis chronica minimalis) without features of autoimmune hepatitis (AIH). For the next year the dose of methyloprednisolone was gradually decreased to 12 mg every second day. Serum albumin and protein concentrations increased slightly despite preserved nephrotic range proteinuria. In the 17th month of observation the patient was referred to the Nephrology Department. Laboratory tests showed normal serum creatinine, persistent NS, and slightly increased ANA and anti-dsDNA Abs. Low immunological activity with high daily proteinuria accompanied by high HCV replication led us to believe that the renal disease was secondary to HCV infection. We decided to implement antiviral therapy containing pegylated interferon α-2a treatment (180 μg/week) and
Table 1. Laboratory results. Serum Serum Serum Daily RBC Haemoglobin WBC PLT ALT GGTP creatinine protein albumin proteinuria HCV RNA ANA Month (106/μL) (g/L) (103/μL) (103/μL) (U/L) (U/L) (mmol/L) (g/L) (g/L) (g) (copies/mL) (titre) 0 3.93 5 4.78 12 4.75 17 5.42 21 5.08 29 3.31 37 4.05 54 5.78 Normal 4.2–5.4
10.2 12.9 14.6 14.5 14.3 10.4 12.9 13.7 12–16
2.4 4.8 6.6 4.8 6.76 4.2 2.3 4.77 4–10
93 10 15 208 36 61 239 39 53 189 37 38 232 44 78 162 19 44 140 22 75 296 34 97 140–440 0–35 0–38
129.6 83.9 91.5 100.7 88.5 72.4 70.9 70.9 62–99
46 48 49 49 55 51 59 60 66–83
14 24 26 30 27 36 35 35–52
7.5 5.1 4.6 4.5 4.0 No data 2.0 Negative Negative
Positive 1.02 104 1.12 106 2.21 106 Negative Negative Negative Negative
1:1280 1:640 1:320 1:320 1:320 1:100 1:320 1:100 Negative
Anti-dsDNA Abs (IU/mL) 774.82 Negative Negative 104.67 162.83 52.14 80.16 63.77 < 100
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Downloaded by [University of California, San Diego] at 22:41 10 November 2015
344
ribavirin at a daily dose of 1000 mg. At that time a dose of 24 mg of methyloprednisolone was given every second day. The treatment was provided under immunological and viral activity control for 12 months. In the fifth month of antiviral therapy (month 29), HCV replication was negative, kidney function, serum protein and albumin improved, and daily proteinuria diminished. Doses of glucocorticosteroids were lowered gradually until the treatment was completed a year later. Several months after the antiviral treatment had finished (month 54), the patient presented with normal renal function with no proteinuria and serum protein, and albumin concentrations at the low end of normal ranges. The ANA titre was 1:100 and anti-dsDNA Abs concentration did not exceed the normal range. HCV RNA remained undetectable. HCV infection can appear together with various autoantibodies, such as ANA, anti-dsDNA, anti-thyroid, anti-smooth muscle (anti-SMA), anti-liver/kidney/ microsomal type 1 (LKM1), rheumatoid factor (RF), or cryoglobulins. Its clinical manifestations may comprise systemic vasculitis, polyarthritis, mixed cryoglobulinaemia, and some types of glomerulonephritis, such as secondary membranous or membranoproliferative glomerulonephritis (1, 2). SLE is one of the most frequently diagnosed autoimmune diseases. Nephritis is presented in 35% cases at the time of diagnosis, increasing up to 60% of cases in the course of SLE (3). The connection between SLE and HCV is uncertain; however, in some cases the association is highly possible. In an Ibero-American study, SLE was accompanied by HCV infection in 11% of patients (4), and in an Egyptian population, where HCV was found in up to 14% of citizens, the occurrence of HCV was confirmed in 6.7% of SLE patients investigated (5). SLE in the course of HCV infection is characterized by less frequent skin involvement, lower ANA and anti-dsDNA antibodies, lower complement concentration (C4, CH50), and the more frequent incidence of cryoglobulin occurrence (2). Furthermore, lupus nephritis and coexisting HCV infection more frequently lead to end-stage renal disease compared to HCV negatives (6).
www.scandjrheumatol.dk
Letters
Furthermore, it has been noted that pegylated interferon per se may induce lupus-like syndrome and other autoimmune reactions (1). The use of interferon in the case of coexistence of autoimmune disease and HCV infection is debatable. Interferon-alpha overproduction underlies the development and progression of systemic lupus and can cause worsening of the disease and therefore is not recommended in these patients. In our patient, NS, which persisted despite immunosuppressive treatment, was related to active viral infection. Remission was achieved after interferon and ribavirin treatment. Given the described symptoms, the possibility of autoimmune reaction in response to HCV infection should always be considered.
References 1. McMurray RW, Elbourne K. Hepatitis C virus infection and autoimmunity. Semin Arthritis Rheum 1997;26:689–701. 2. Ramos-Casalam M, Jara LJ, Medina F, Rosas J, Calvo-Alen J, Mana J, et al. Systemic autoimmune diseases co-existing with chronic hepatitis C virus infection (the HISPAMEC Registry): patterns of clinical and immunological expression in 180 cases. J Intern Med 2005;257: 549–57. 3. Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, et al. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res 2012;64:797–808. 4. Ramos-Casalam M, Font J, Garcia-Carrasco M, Cervera R, Jimenez S, Trejo O, et al. Hepatits C virus infection mimicking systemic lupus erythematosus. Arthritis Rheum 2000;43:2801–6. 5. El Garf A, El Zorkany B, Gheith R, Sheba H, Abdel Moneim G, El Garf K. Prevalence and clinical presentations of hepatitis C virus among patients admitted to the rheumatology ward. Rheumatol Int 2012;32:2691–5. 6. Mitwalli AH, Hayat A, Alwakeel J, Hammad D. Effects of concomitant hepatitis C virus infection in patients with underlying lupus nephritis on long-term renal outcome. Nephrol Dial Transplant 2012;27:627–32.
Dagna Rukasz, Department and Clinic of Nephrology and Transplantation Medicine, Wroclaw Medical University, 213 Borowska Street, 50-556 Wrocław, Poland E-mail: [email protected] Accepted 6 March 2015
