International Journal of Rheumatic Diseases 2015
CORRESPONDENCE
ANCA-positive crescentic glomerulonephritis in a patient with rheumatoid arthritis treated with anti-tumor necrosis factor alpha Dear Editor, Anti-tumor necrosis factor alpha (anti-TNF-a) are widely used antibodies to treat aggressive cases of rheumatoid arthritis (RA). Although these agents are well tolerated, serious side-effects such as reactivation of tuberculosis, heart failure, hematologic diseases and flare of vasculitis have been reported.1–3 More recently, a few case reports of glomerulonephritis resulting from treatment with these agents have been reported.3–5 Here we report on the clinical course of a patient with rheumatoid arthritis who developed myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA) associated glomerulonephritis.
CASE REPORT A 30-year-old female patient was diagnosed with rheumatoid factor-positive erosive RA at the age of 14 years. She received several drugs, including prednisone, hydroxychloroquine and methotrexate with poor response. She had never received penicillamine or auranofin. She had no extra-articular manifestations. Her kidney function was normal, but the urine analysis showed microscopic hematuria and trace proteinuria that was never quantified. Two months prior to her admission she was started on etanercept, an anti-TNF-a. She presented with acute kidney injury associated with hematuria and nephrotic range proteinuria. She had no abdominal pain. On examination she looked pale and had facial puffiness. She was alert and oriented with no acute distress. She was afebrile, with a blood pressure of 140/100 mmHg and a pulse of 92/min. There were no mucosal ulcers or skin rash. Cardiac, lung and neurological examinations were unremarkable. Examination of the extremities revealed mild symmetrical polyarticular synovitis involving the hands, wrists, elbows and ankles. There were deformities involving both hands and pitting edema in both lower extremities.
Laboratory findings were as follows: white cell count, 8.0 9 103/lL with 62% neutrophils, 25% lymphocytes, 10% monocytes and 2% eosinophils; Hemoglobin, 8.6 gm/dL; platelet count, 227 9 103/lL; serum creatinine, 4.9 mg/dL; blood urea nitrogen, 38 mg/dL; serum albumin, 2.6 gm/dL; normal electrolytes; negative antinuclear antibodies (ANA); normal complement levels, negative C-ANCA; positive P-ANCA and myeloperoxidase antibodies were positive with a titer of 0.5 units/L (normal < 0.4). Urine analysis revealed proteinuria > 300 mg/dL and large blood. Urine microscopy showed dysmorphic red blood cells (RBC) and scattered RBC casts. Urine protein over creatinine ratio was 11 mg/g. Light microscopy of the renal biopsy specimen showed 16 glomeruli, four of which were globally sclerosed. Eight glomeruli showed extensive fibrinoid necrosis associated with active and destructive crescents (Fig. 1). A few intact glomeruli showed mesangial proliferative changes. The arterial vessels showed focal mild intimal fibrosis and no thrombosis or vasculitis. Immunofluorescence studies demonstrated 2–3 positive granular mesangial staining for immunoglobulin A (IgA) along with trace IgM, 2–3 positive C3, one positive kappa light chain and 1–2 positive lambda light chains. IgG, C1q, albumin and fibrinogen were negative. Electron microscopy showed mesangial and segmental endocapillary proliferative changes along with segmental fibrin and obvious involvement by cellular crescents. Mesangial and paramesangial deposits were seen. No definitive subendothelial deposits or subepithelial deposits were identified and no tubuloreticular inclusion bodies were noted. Examination of the tubulointerstitial compartment showed mononuclear cell infiltrates but no tubular basement membrane deposits. No amyloid fibrils were identified (Fig. 2). The diagnosis of MPO-ANCA positive crescentic glomerulonephritis was made.
© 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd
Correspondence
Figure 1 Light microscopy of the renal biopsy showing the glomerular crescentic changes. Hematoxylin and eosin (H&E), trichrome and Jones stainings (9400).
Etanercept was discontinued and the patient was started on a combination therapy consisting of prednisone at 1 mg/kg body weight/day in conjunction with oral cyclophosphamide at a dose of 2 mg/kg body weight/day. Two weeks later, the kidney function started to recover and the serum creatinine normalized 6 weeks after initiation of treatment. There was a significant decrease in urine protein over creatinine ratio down to 0.3 mg/g.
DISCUSSION Our patient had RA for several years and was treated with multiple agents, the last one being etanercept. She developed renal failure associated with nephrotic range proteinuria. The kidney biopsy showed severe necrotiz-
2
ing crescentic glomerulonephritis associated with positive MPO-ANCA. The renal function recovered with the discontinuation of etanercept and institution of treatment with cyclophosphamide and corticosteroids. The timing of occurrence of the glomerulonephritis in relation to the introduction of etanercept and the rapid recovery after discontinuation of etanercept suggest that the glomerulonephritis was a complication of etanercept rather than a de novo disease. Rheumatoid arthritis is a chronic inflammatory disease that can progress to cause severe joint deformity and erosions. Proinflammatory cytokines such as TNF-a and interleukin-I are believed to play an important role in the pathogensis of RA.2 Biological therapy with antiTNF-a agents is now considered essential in the management of severe RA that does not respond to conven-
International Journal of Rheumatic Diseases 2015
Correspondence
2
1
3
2
5 4
4
5
Figure 2 Electron microscopy. 1, cellular crescent. 2, mesangial and paramesangial deposits with adjacent cellular proliferation. 3, capillary lumen. 4, segmental fibrin deposits. 5, mesangial deposits. See description in the text.
tional treatment with disease-modifying agents such as methotrexate. The most commonly used biological agents are: infliximab, a chimeric monoclonal antibody; adalimumab, a fully humanized monoclonal antibody; and etanercept, a synthetic human TNF receptor-Fc fusion protein that binds both TNF-a and TNF-b, preventing their interaction with the cell surface receptors.6
International Journal of Rheumatic Diseases 2015
The use of these agents has resulted in significant improvement of patients’ symptoms, and prevention and delay of radiological joint damage. The agents are well tolerated, and most of the side effects are related to headache, injection site reaction and gastrointestinal side effects such as diarrhea.1 Serious side effects such as infections and the development of autoimmune
3
Correspondence
diseases have been reported.6 Crescentic glomerulonephritis complicating the use of anti TNF-a is a rare phenomenon that has been recently observed. So far there are a few case reports and case series addressing this phenomenon.3,5,7–12 Some of these cases were associated with the appearance of MPO or proteinase-3 (PR3) ANCA. With discontinuation of anti TNF-a and treatment with corticosteroids and cyclophosphamide, there was either disappearance or significant decrease of the ANCA titers. Our patient had crescentic glomerulonephritis with positive MPO-ANCA. The recovery of renal function was rapid once etanercept was discontinued and treatment with cyclophosphamide and corticosteroids was initiated. It is not clear whether discontinuation of the offending agent without additional immunosuppressive agents would have been enough to control and reverse the inflammatory process that led to the development of crescentic glomerulonephritis. The significance of the IgA deposits is not very clear. There are three scenarios that can explain the clinical and pathological finding in our patient. The first possibility is that the patient had a de novo crescentic IgA glomerulonephritis that was induced by etanercept secondary to immune dysregulation. The second possibility is that the patient had an underlying mild IgA nephropathy prior to the administration of etanercept, and this is supported by the urinary finding of microscopic hematuria and mild proteinuria prior to the administration of etnercept. This may have been reactivated by the administration of etanercept and transformed into the more aggressive and crescentic type of IgA nephropathy. The third scenario, which we favor, is that the finding reflects a dual pathology consisting of MPO-ANCA-positive glomerulonephritis superimposed on a background IgA nephropathy. The patient did not have other criteria to make a diagnosis of Henoch-Sch€ onlein purpura (HSP). There are a few case reports describing HSP, a variant of IgA nephropathy, following treatment with etanercept in patients with RA.13–15 More recently, a case report was published where IgA nephropathy was diagnosed in a patient with psoriasis treated with adalimumab.16 The mechanism of anti-TNF-a induced autoimmunity and glomerulonephritis is not known. It has been suggested that anti TNF-a may up-regulate antibody production, form immune complexes, activate complements and mediate inflammation by switching the cytokine response from T-helper type 1 to type 2.17 It has been shown that administration of anti TNF-a leads to the induction of autoantibodies giving rise to lupus-like immune complex glomerulonephritis or
4
ANCA-related necrotizing and crescentic glomerulonephritis in susceptible individuals.5,18 In conclusion, etanercept can induce the development of crescentic glomerulonephritis and renal failure. RA patients undergoing therapy with anti-TNF-a agents should have routine renal function assessment, and those developing renal failure should undergo a kidney biopsy. The medical community should be vigilant about the renal complications of anti-TNF-a agents in order to prevent the catastrophic outcome associated with renal failure.
ACKNOWLEDGEMENT The authors acknowledge the use of Johns Hopkins Aramco Healthcare (JHAH) facilities for research data used in this article. Opinions expressed in this article are those of the authors and not necessarily of JHAH.
CONFLICT OF INTEREST None. Ahmed M. ALKHUNAIZI1 and Mohamad F. DAWAMNEH2 1
Nephrology Section, Internal Medicine Services Division, and 2Division of Pathology, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia
Correspondence: Ahmed M. Alkhunaizi MD, FACP, FASN email: [email protected]
REFERENCES 1 Khanna D, McMahon M, Furst DE (2004) Safety of tumour necrosis factor-alpha antagonists. Drug Saf 27, 307–24. 2 Klinkhoff A (2004) Biological agents for rheumatoid arthritis: targeting both physical function and structural damage. Drugs 64, 1267–83. 3 Hirohama D, Hoshino J, Hasegawa E et al. (2010) Development of myeloperoxidase-antineutrophil cytoplasmic antibody-associated renal vasculitis in a patient receiving treatment with anti-tumor necrosis factor-alpha. Mod Rheumatol 20 (6), 602–5. 4 Chen TJ, Yang YF, Huang PH, Lin HH, Huang CC (2010) Permanent renal loss following tumor necrosis factor alpha antagonists for arthritis. Rheumatol Int 30, 1077–9. 5 Stokes MB, Foster K, Markowitz GS et al. (2005) Development of glomerulonephritis during anti-TNF-alpha therapy for rheumatoid arthritis. Nephrol Dial Transplant 20, 1400–6.
International Journal of Rheumatic Diseases 2015
Correspondence
6 Alonso-Ruiz A, Pijoan JI, Ansuategui E et al. (2008) Tumor necrosis factor alpha drugs in rheumatoid arthritis: systematic review and metaanalysis of efficacy and safety. BMC Musculoskelet Disord 9, 52. 7 Simms R, Kipgen D, Dahill S, Marshall D, Rodger RS (2008) ANCA-associated renal vasculitis following antitumor necrosis factor alpha therapy. Am J Kidney Dis 51, e11–4. 8 Ashok D, Dubey S, Tomlinson I (2008) C-ANCA positive systemic vasculitis in a patient with rheumatoid arthritis treated with infliximab. Clin Rheumatol 27 (2), 261–4. 9 Doulton TW, Tucker B, Reardon J, Velasco N (2004) Antineutrophil cytoplasmic antibody-associated necrotizing crescentic glomerulonephritis in a patient receiving treatment with etanercept for severe rheumatoid arthritis. Clin Nephrol 62, 234–8. 10 Kaneko K1, Nanki T, Hosoya T, Mizoguchi F, Miyasaka N (2010) Etanercept-induced necrotizing crescentic glomerulonephritis in two patients with rheumatoid arthritis. Mod Rheumatol 20(6), 632–6. 11 Broshtilova V, Iliev E, Gantcheva M (2013) Etanerceptinduced Wegener granulomatosis in a patient with rheumatoid arthritis. Dermatol Ther 26 (1), 73–6.
International Journal of Rheumatic Diseases 2015
12 Ortiz-Sierra MC, Echeverri AF, Tob on GJ, Ca~ nas CA (2014) Developing of Granulomatosis with Polyangiitis during Etanercept Therapy. Case Rep Rheumatol 2014, 210108. 13 Lee A, Kasama R, Evangelisto A, Elfenbein B, Falasca G (2006) Henoch-Schonlein purpura after etanercept therapy for psoriasis. J Clin Rheumatol 12, 249–51. 14 Asahina A, Ohshima N, Nakayama H et al. (2010) Henoch-Schonlein purpura in a patient with rheumatoid arthritis receiving etanercept. Eur J Dermatol 20, 521–2. 15 Duffy TN, Genta M, Moll S, Martin PY, Gabay C (2006) Henoch Schonlein purpura following etanercept treatment of rheumatoid arthritis. Clin Exp Rheumatol 24(Suppl 41), S106. 16 Wei SS, Sinniah R (2013) Adalimumab (TNF alpha Inhibitor) Therapy Exacerbates IgA Glomerulonephritis Acute Renal Injury and Induces Lupus Autoantibodies in a Psoriasis Patient. Case Rep Nephrol 2013, 812781. 17 Guillevin L, Mouthon L (2004) Tumor necrosis factoralpha blockade and the risk of vasculitis. J Rheumatol 31, 1885–7. 18 Ziolkowska M, Maslinski W (2003) Laboratory changes on anti-tumor necrosis factor treatment in rheumatoid arthritis. Curr Opin Rheumatol 15, 267–73.
5
CORRESPONDENCE
ANCA-positive crescentic glomerulonephritis in a patient with rheumatoid arthritis treated with anti-tumor necrosis factor alpha Dear Editor, Anti-tumor necrosis factor alpha (anti-TNF-a) are widely used antibodies to treat aggressive cases of rheumatoid arthritis (RA). Although these agents are well tolerated, serious side-effects such as reactivation of tuberculosis, heart failure, hematologic diseases and flare of vasculitis have been reported.1–3 More recently, a few case reports of glomerulonephritis resulting from treatment with these agents have been reported.3–5 Here we report on the clinical course of a patient with rheumatoid arthritis who developed myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA) associated glomerulonephritis.
CASE REPORT A 30-year-old female patient was diagnosed with rheumatoid factor-positive erosive RA at the age of 14 years. She received several drugs, including prednisone, hydroxychloroquine and methotrexate with poor response. She had never received penicillamine or auranofin. She had no extra-articular manifestations. Her kidney function was normal, but the urine analysis showed microscopic hematuria and trace proteinuria that was never quantified. Two months prior to her admission she was started on etanercept, an anti-TNF-a. She presented with acute kidney injury associated with hematuria and nephrotic range proteinuria. She had no abdominal pain. On examination she looked pale and had facial puffiness. She was alert and oriented with no acute distress. She was afebrile, with a blood pressure of 140/100 mmHg and a pulse of 92/min. There were no mucosal ulcers or skin rash. Cardiac, lung and neurological examinations were unremarkable. Examination of the extremities revealed mild symmetrical polyarticular synovitis involving the hands, wrists, elbows and ankles. There were deformities involving both hands and pitting edema in both lower extremities.
Laboratory findings were as follows: white cell count, 8.0 9 103/lL with 62% neutrophils, 25% lymphocytes, 10% monocytes and 2% eosinophils; Hemoglobin, 8.6 gm/dL; platelet count, 227 9 103/lL; serum creatinine, 4.9 mg/dL; blood urea nitrogen, 38 mg/dL; serum albumin, 2.6 gm/dL; normal electrolytes; negative antinuclear antibodies (ANA); normal complement levels, negative C-ANCA; positive P-ANCA and myeloperoxidase antibodies were positive with a titer of 0.5 units/L (normal < 0.4). Urine analysis revealed proteinuria > 300 mg/dL and large blood. Urine microscopy showed dysmorphic red blood cells (RBC) and scattered RBC casts. Urine protein over creatinine ratio was 11 mg/g. Light microscopy of the renal biopsy specimen showed 16 glomeruli, four of which were globally sclerosed. Eight glomeruli showed extensive fibrinoid necrosis associated with active and destructive crescents (Fig. 1). A few intact glomeruli showed mesangial proliferative changes. The arterial vessels showed focal mild intimal fibrosis and no thrombosis or vasculitis. Immunofluorescence studies demonstrated 2–3 positive granular mesangial staining for immunoglobulin A (IgA) along with trace IgM, 2–3 positive C3, one positive kappa light chain and 1–2 positive lambda light chains. IgG, C1q, albumin and fibrinogen were negative. Electron microscopy showed mesangial and segmental endocapillary proliferative changes along with segmental fibrin and obvious involvement by cellular crescents. Mesangial and paramesangial deposits were seen. No definitive subendothelial deposits or subepithelial deposits were identified and no tubuloreticular inclusion bodies were noted. Examination of the tubulointerstitial compartment showed mononuclear cell infiltrates but no tubular basement membrane deposits. No amyloid fibrils were identified (Fig. 2). The diagnosis of MPO-ANCA positive crescentic glomerulonephritis was made.
© 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd
Correspondence
Figure 1 Light microscopy of the renal biopsy showing the glomerular crescentic changes. Hematoxylin and eosin (H&E), trichrome and Jones stainings (9400).
Etanercept was discontinued and the patient was started on a combination therapy consisting of prednisone at 1 mg/kg body weight/day in conjunction with oral cyclophosphamide at a dose of 2 mg/kg body weight/day. Two weeks later, the kidney function started to recover and the serum creatinine normalized 6 weeks after initiation of treatment. There was a significant decrease in urine protein over creatinine ratio down to 0.3 mg/g.
DISCUSSION Our patient had RA for several years and was treated with multiple agents, the last one being etanercept. She developed renal failure associated with nephrotic range proteinuria. The kidney biopsy showed severe necrotiz-
2
ing crescentic glomerulonephritis associated with positive MPO-ANCA. The renal function recovered with the discontinuation of etanercept and institution of treatment with cyclophosphamide and corticosteroids. The timing of occurrence of the glomerulonephritis in relation to the introduction of etanercept and the rapid recovery after discontinuation of etanercept suggest that the glomerulonephritis was a complication of etanercept rather than a de novo disease. Rheumatoid arthritis is a chronic inflammatory disease that can progress to cause severe joint deformity and erosions. Proinflammatory cytokines such as TNF-a and interleukin-I are believed to play an important role in the pathogensis of RA.2 Biological therapy with antiTNF-a agents is now considered essential in the management of severe RA that does not respond to conven-
International Journal of Rheumatic Diseases 2015
Correspondence
2
1
3
2
5 4
4
5
Figure 2 Electron microscopy. 1, cellular crescent. 2, mesangial and paramesangial deposits with adjacent cellular proliferation. 3, capillary lumen. 4, segmental fibrin deposits. 5, mesangial deposits. See description in the text.
tional treatment with disease-modifying agents such as methotrexate. The most commonly used biological agents are: infliximab, a chimeric monoclonal antibody; adalimumab, a fully humanized monoclonal antibody; and etanercept, a synthetic human TNF receptor-Fc fusion protein that binds both TNF-a and TNF-b, preventing their interaction with the cell surface receptors.6
International Journal of Rheumatic Diseases 2015
The use of these agents has resulted in significant improvement of patients’ symptoms, and prevention and delay of radiological joint damage. The agents are well tolerated, and most of the side effects are related to headache, injection site reaction and gastrointestinal side effects such as diarrhea.1 Serious side effects such as infections and the development of autoimmune
3
Correspondence
diseases have been reported.6 Crescentic glomerulonephritis complicating the use of anti TNF-a is a rare phenomenon that has been recently observed. So far there are a few case reports and case series addressing this phenomenon.3,5,7–12 Some of these cases were associated with the appearance of MPO or proteinase-3 (PR3) ANCA. With discontinuation of anti TNF-a and treatment with corticosteroids and cyclophosphamide, there was either disappearance or significant decrease of the ANCA titers. Our patient had crescentic glomerulonephritis with positive MPO-ANCA. The recovery of renal function was rapid once etanercept was discontinued and treatment with cyclophosphamide and corticosteroids was initiated. It is not clear whether discontinuation of the offending agent without additional immunosuppressive agents would have been enough to control and reverse the inflammatory process that led to the development of crescentic glomerulonephritis. The significance of the IgA deposits is not very clear. There are three scenarios that can explain the clinical and pathological finding in our patient. The first possibility is that the patient had a de novo crescentic IgA glomerulonephritis that was induced by etanercept secondary to immune dysregulation. The second possibility is that the patient had an underlying mild IgA nephropathy prior to the administration of etanercept, and this is supported by the urinary finding of microscopic hematuria and mild proteinuria prior to the administration of etnercept. This may have been reactivated by the administration of etanercept and transformed into the more aggressive and crescentic type of IgA nephropathy. The third scenario, which we favor, is that the finding reflects a dual pathology consisting of MPO-ANCA-positive glomerulonephritis superimposed on a background IgA nephropathy. The patient did not have other criteria to make a diagnosis of Henoch-Sch€ onlein purpura (HSP). There are a few case reports describing HSP, a variant of IgA nephropathy, following treatment with etanercept in patients with RA.13–15 More recently, a case report was published where IgA nephropathy was diagnosed in a patient with psoriasis treated with adalimumab.16 The mechanism of anti-TNF-a induced autoimmunity and glomerulonephritis is not known. It has been suggested that anti TNF-a may up-regulate antibody production, form immune complexes, activate complements and mediate inflammation by switching the cytokine response from T-helper type 1 to type 2.17 It has been shown that administration of anti TNF-a leads to the induction of autoantibodies giving rise to lupus-like immune complex glomerulonephritis or
4
ANCA-related necrotizing and crescentic glomerulonephritis in susceptible individuals.5,18 In conclusion, etanercept can induce the development of crescentic glomerulonephritis and renal failure. RA patients undergoing therapy with anti-TNF-a agents should have routine renal function assessment, and those developing renal failure should undergo a kidney biopsy. The medical community should be vigilant about the renal complications of anti-TNF-a agents in order to prevent the catastrophic outcome associated with renal failure.
ACKNOWLEDGEMENT The authors acknowledge the use of Johns Hopkins Aramco Healthcare (JHAH) facilities for research data used in this article. Opinions expressed in this article are those of the authors and not necessarily of JHAH.
CONFLICT OF INTEREST None. Ahmed M. ALKHUNAIZI1 and Mohamad F. DAWAMNEH2 1
Nephrology Section, Internal Medicine Services Division, and 2Division of Pathology, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia
Correspondence: Ahmed M. Alkhunaizi MD, FACP, FASN email: [email protected]
REFERENCES 1 Khanna D, McMahon M, Furst DE (2004) Safety of tumour necrosis factor-alpha antagonists. Drug Saf 27, 307–24. 2 Klinkhoff A (2004) Biological agents for rheumatoid arthritis: targeting both physical function and structural damage. Drugs 64, 1267–83. 3 Hirohama D, Hoshino J, Hasegawa E et al. (2010) Development of myeloperoxidase-antineutrophil cytoplasmic antibody-associated renal vasculitis in a patient receiving treatment with anti-tumor necrosis factor-alpha. Mod Rheumatol 20 (6), 602–5. 4 Chen TJ, Yang YF, Huang PH, Lin HH, Huang CC (2010) Permanent renal loss following tumor necrosis factor alpha antagonists for arthritis. Rheumatol Int 30, 1077–9. 5 Stokes MB, Foster K, Markowitz GS et al. (2005) Development of glomerulonephritis during anti-TNF-alpha therapy for rheumatoid arthritis. Nephrol Dial Transplant 20, 1400–6.
International Journal of Rheumatic Diseases 2015
Correspondence
6 Alonso-Ruiz A, Pijoan JI, Ansuategui E et al. (2008) Tumor necrosis factor alpha drugs in rheumatoid arthritis: systematic review and metaanalysis of efficacy and safety. BMC Musculoskelet Disord 9, 52. 7 Simms R, Kipgen D, Dahill S, Marshall D, Rodger RS (2008) ANCA-associated renal vasculitis following antitumor necrosis factor alpha therapy. Am J Kidney Dis 51, e11–4. 8 Ashok D, Dubey S, Tomlinson I (2008) C-ANCA positive systemic vasculitis in a patient with rheumatoid arthritis treated with infliximab. Clin Rheumatol 27 (2), 261–4. 9 Doulton TW, Tucker B, Reardon J, Velasco N (2004) Antineutrophil cytoplasmic antibody-associated necrotizing crescentic glomerulonephritis in a patient receiving treatment with etanercept for severe rheumatoid arthritis. Clin Nephrol 62, 234–8. 10 Kaneko K1, Nanki T, Hosoya T, Mizoguchi F, Miyasaka N (2010) Etanercept-induced necrotizing crescentic glomerulonephritis in two patients with rheumatoid arthritis. Mod Rheumatol 20(6), 632–6. 11 Broshtilova V, Iliev E, Gantcheva M (2013) Etanerceptinduced Wegener granulomatosis in a patient with rheumatoid arthritis. Dermatol Ther 26 (1), 73–6.
International Journal of Rheumatic Diseases 2015
12 Ortiz-Sierra MC, Echeverri AF, Tob on GJ, Ca~ nas CA (2014) Developing of Granulomatosis with Polyangiitis during Etanercept Therapy. Case Rep Rheumatol 2014, 210108. 13 Lee A, Kasama R, Evangelisto A, Elfenbein B, Falasca G (2006) Henoch-Schonlein purpura after etanercept therapy for psoriasis. J Clin Rheumatol 12, 249–51. 14 Asahina A, Ohshima N, Nakayama H et al. (2010) Henoch-Schonlein purpura in a patient with rheumatoid arthritis receiving etanercept. Eur J Dermatol 20, 521–2. 15 Duffy TN, Genta M, Moll S, Martin PY, Gabay C (2006) Henoch Schonlein purpura following etanercept treatment of rheumatoid arthritis. Clin Exp Rheumatol 24(Suppl 41), S106. 16 Wei SS, Sinniah R (2013) Adalimumab (TNF alpha Inhibitor) Therapy Exacerbates IgA Glomerulonephritis Acute Renal Injury and Induces Lupus Autoantibodies in a Psoriasis Patient. Case Rep Nephrol 2013, 812781. 17 Guillevin L, Mouthon L (2004) Tumor necrosis factoralpha blockade and the risk of vasculitis. J Rheumatol 31, 1885–7. 18 Ziolkowska M, Maslinski W (2003) Laboratory changes on anti-tumor necrosis factor treatment in rheumatoid arthritis. Curr Opin Rheumatol 15, 267–73.
5
