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Correspondence
In view of this very promising response, bosentan might be a viable option for the treatment of severe arterial cutaneous ulcers associated with disorders of the vasculature,4 such as those characteristic of CUA. Indeed, bosentan seems effective in the treatment of systemic sclerosis-associated digital ulcers.5 While ‘traditional’ proposed treatments for CUA include sodium thiosulfate,6 hyperbaric oxygen,7 and infusion of tissue plasminogen activator,8 none of these have be subjected to rigorous randomized controlled trials. While not constituting an approved use of the drug, CUA, or syndromes closely resembling CUA, may be amenable to treatment with endothelin-1 receptors antagonists, a prospect which in our view warrants further investigation.
ACKNOWLEDGEMENTS The authors thank Luis Sánchez-Grande Alarcón, MD and Wesley E. Chang, MD, for helpful insights on the radiologic findings, and Rafael Abellón-Carsi, MD, for important contributions facilitating the writing and translation of the manuscript. Disclosures: The authors have no conflicts of interest to declare. Sources of Funding: None. Accepted for publication 9 February 2014. doi:10.1111/nep.12218
CHYLOUS PERICARDIAL EFFUSION IN GRANULOMATOSIS WITH POLYANGIITIS Nicholas Larkins,1 Kevin C Harris,2 Kimberly Morishita3 and Douglas G Matsell1, 1 Division of Nephrology, Department of Pediatrics, 2Division of Cardiology, Department of Pediatrics, and 3Division of Rheumatology, Department of Pediatrics, University of British Columbia, Vancouver, Canada
We describe a 15-year-old girl known to have granulomatosis with polyangiitis (GPA) who presented during follow-up with a large chylous pericardial effusion. Her initial presentation 2 months prior was with pulmonary haemorrhage requiring admission to the intensive care unit. At that time, her urine sediment was active despite a normal serum creatinine (42 μmol/L). An elevated anti neutrophil cytoplasmic antibody titre was demonstrated (1:320), with an elevated proteinase 3 (1:80) and normal myeloperoxidase titre (1:2). A renal biopsy demonstrated pauci-immune, focal segmental fibrinoid necrosis with cellular crescents. She was treated with pulse methylprednisolone and intravenous (IV) cyclophosphamide, to which her pulmonary disease responded well. However, her renal disease remained active despite continued cyclophosphamide and prednisone. On review she had symptoms of increased cough and shortness of breath despite normal vital signs. A chest X-ray (CXR) demonstrated significant cardiomegaly (Fig. 1), which was not present on CXR performed 2 weeks prior. An echocardiogram demonstrated a large pericardial effusion
REFERENCES 1. Weenig RH, Sewell LD, Davis MD et al. Calciphylaxis: Natural history, risk factor analysis, and outcome. J. Am. Acad. Dermatol. 2007; 56: 569–79. 2. Ross EA. Evolution of treatment strategies for calciphylaxis. Am. J. Nephrol. 2011; 34: 460–67. 3. Nigwekar SU, Wolf M, Sterns RH et al. Calciphylaxis from nonuremic causes: A systematic review. Clin. J. Am. Soc. Nephrol. 2008; 3: 1139–43. 4. Kaoukis A, Deftereos S, Raisakis K et al. The role of endothelin system in cardiovascular disease and the potential therapeutic perspectives of its inhibition. Curr. Top. Med. Chem. 2013; 13: 95–114. 5. Humbert M, Cabane J. Successful treatment of systemic sclerosis digital ulcers and pulmonary arterial hypertension with endothelin receptor antagonist bosentan. Rheumatology 2003; 42: 191–3. 6. Salmhofer H, Franzen M, Hitzl W et al. Multi-modal treatment of calciphylaxis with sodium-thiosulfate, cinacalcet and sevelamer including long-term data. Kidney Blood Press. Res. 2013; 37: 346–59. 7. Podymow T, Wherrett C, Burns KD. Hyperbaric oxygen in the treatment of calciphylaxis: A case series. Nephrol. Dial. Transplant. 2001; 16: 2176–80. 8. el-Azhary RA, Arthur AK, Davis MD et al. Retrospective analysis of tissue plasminogen activator as an adjuvant treatment for calciphylaxis. JAMADermatol. 2013; 149: 63–7. © 2014 Asian Pacific Society of Nephrology
Fig. 1 Marked cardiomegaly due to a large pericardial effusion.
367
Correspondence
with features of tamponade. Pericardiocentesis drained 450 mL of milky white fluid. Fluid chemistry confirmed the diagnosis of chylopericardium with a triglyceride concentration of 9.19 mmol/L, lactate dehydrogenase 354 U/L, and predominance of lymphocytes. Ultrasound of the internal jugular, subclavian and brachiocephalic veins and magnetic resonance imaging of the thorax ruled out thrombosis as a cause of her chylopericardium. There was ongoing pericardial drainage for three days after which IV octreotide was started. The drainage subsided and the drain was removed on day four. On follow-up the effusion did not recur and there has been no further cardiac involvement 6 months later. Unfortunately, the patient’s renal disease has remained recalcitrant to treatment including rituximab. Her current serum creatinine is 459 μmol/L. A recent renal biopsy demonstrated widespread glomerulosclerosis. Cardiac involvement in GPA is uncommon, affecting 6–9% of children and adults with the disease.1,2 Pericarditis is the most common form of cardiac involvement, although coronary arteritis is equally common at autopsy.3 Less frequent manifestations include endocarditis, valvular lesions and arrhythmia.4 We believe this to be the first report of chylous
368
pericardial effusion in GPA. The case highlights the diversity and seriousness of cardiac disease that may occur in this condition. As such patients need to be carefully followed for cardiac involvement, in particular pericarditis, during the course of their disease. No disclaimers or conflict of interest. Accepted for publication 8 April 2014. doi:10.1111/nep.12262
REFERENCES 1. Hoffman GS, Kerr GS, Leavitt RY et al. Wegener granulomatosis: An analysis of 158 patients. Ann. Intern. Med. 1992; 116: 488–98. 2. Rottem M, Fauci AS, Hallahan CW et al. Wegener granulomatosis in children and adolescents: Clinical presentation and outcome. J. Peditr. 1993; 122: 26–31. 3. Forstot JZ, Overlie PA, Neufeld GK, Harmon CE, Forstot SL. Cardiac complications of Wegener granulomatosis: A case report of complete heart block and review of the literature. Semin. Arthritis Rheum. 1980; 10: 148–54. 4. Grant SCD, Levy RD, Venning MC, Ward C, Brooks NH. Wegener’s granulomatosis and the heart. Br. Heart J. 1994; 71: 82–6.
© 2014 Asian Pacific Society of Nephrology
Correspondence
In view of this very promising response, bosentan might be a viable option for the treatment of severe arterial cutaneous ulcers associated with disorders of the vasculature,4 such as those characteristic of CUA. Indeed, bosentan seems effective in the treatment of systemic sclerosis-associated digital ulcers.5 While ‘traditional’ proposed treatments for CUA include sodium thiosulfate,6 hyperbaric oxygen,7 and infusion of tissue plasminogen activator,8 none of these have be subjected to rigorous randomized controlled trials. While not constituting an approved use of the drug, CUA, or syndromes closely resembling CUA, may be amenable to treatment with endothelin-1 receptors antagonists, a prospect which in our view warrants further investigation.
ACKNOWLEDGEMENTS The authors thank Luis Sánchez-Grande Alarcón, MD and Wesley E. Chang, MD, for helpful insights on the radiologic findings, and Rafael Abellón-Carsi, MD, for important contributions facilitating the writing and translation of the manuscript. Disclosures: The authors have no conflicts of interest to declare. Sources of Funding: None. Accepted for publication 9 February 2014. doi:10.1111/nep.12218
CHYLOUS PERICARDIAL EFFUSION IN GRANULOMATOSIS WITH POLYANGIITIS Nicholas Larkins,1 Kevin C Harris,2 Kimberly Morishita3 and Douglas G Matsell1, 1 Division of Nephrology, Department of Pediatrics, 2Division of Cardiology, Department of Pediatrics, and 3Division of Rheumatology, Department of Pediatrics, University of British Columbia, Vancouver, Canada
We describe a 15-year-old girl known to have granulomatosis with polyangiitis (GPA) who presented during follow-up with a large chylous pericardial effusion. Her initial presentation 2 months prior was with pulmonary haemorrhage requiring admission to the intensive care unit. At that time, her urine sediment was active despite a normal serum creatinine (42 μmol/L). An elevated anti neutrophil cytoplasmic antibody titre was demonstrated (1:320), with an elevated proteinase 3 (1:80) and normal myeloperoxidase titre (1:2). A renal biopsy demonstrated pauci-immune, focal segmental fibrinoid necrosis with cellular crescents. She was treated with pulse methylprednisolone and intravenous (IV) cyclophosphamide, to which her pulmonary disease responded well. However, her renal disease remained active despite continued cyclophosphamide and prednisone. On review she had symptoms of increased cough and shortness of breath despite normal vital signs. A chest X-ray (CXR) demonstrated significant cardiomegaly (Fig. 1), which was not present on CXR performed 2 weeks prior. An echocardiogram demonstrated a large pericardial effusion
REFERENCES 1. Weenig RH, Sewell LD, Davis MD et al. Calciphylaxis: Natural history, risk factor analysis, and outcome. J. Am. Acad. Dermatol. 2007; 56: 569–79. 2. Ross EA. Evolution of treatment strategies for calciphylaxis. Am. J. Nephrol. 2011; 34: 460–67. 3. Nigwekar SU, Wolf M, Sterns RH et al. Calciphylaxis from nonuremic causes: A systematic review. Clin. J. Am. Soc. Nephrol. 2008; 3: 1139–43. 4. Kaoukis A, Deftereos S, Raisakis K et al. The role of endothelin system in cardiovascular disease and the potential therapeutic perspectives of its inhibition. Curr. Top. Med. Chem. 2013; 13: 95–114. 5. Humbert M, Cabane J. Successful treatment of systemic sclerosis digital ulcers and pulmonary arterial hypertension with endothelin receptor antagonist bosentan. Rheumatology 2003; 42: 191–3. 6. Salmhofer H, Franzen M, Hitzl W et al. Multi-modal treatment of calciphylaxis with sodium-thiosulfate, cinacalcet and sevelamer including long-term data. Kidney Blood Press. Res. 2013; 37: 346–59. 7. Podymow T, Wherrett C, Burns KD. Hyperbaric oxygen in the treatment of calciphylaxis: A case series. Nephrol. Dial. Transplant. 2001; 16: 2176–80. 8. el-Azhary RA, Arthur AK, Davis MD et al. Retrospective analysis of tissue plasminogen activator as an adjuvant treatment for calciphylaxis. JAMADermatol. 2013; 149: 63–7. © 2014 Asian Pacific Society of Nephrology
Fig. 1 Marked cardiomegaly due to a large pericardial effusion.
367
Correspondence
with features of tamponade. Pericardiocentesis drained 450 mL of milky white fluid. Fluid chemistry confirmed the diagnosis of chylopericardium with a triglyceride concentration of 9.19 mmol/L, lactate dehydrogenase 354 U/L, and predominance of lymphocytes. Ultrasound of the internal jugular, subclavian and brachiocephalic veins and magnetic resonance imaging of the thorax ruled out thrombosis as a cause of her chylopericardium. There was ongoing pericardial drainage for three days after which IV octreotide was started. The drainage subsided and the drain was removed on day four. On follow-up the effusion did not recur and there has been no further cardiac involvement 6 months later. Unfortunately, the patient’s renal disease has remained recalcitrant to treatment including rituximab. Her current serum creatinine is 459 μmol/L. A recent renal biopsy demonstrated widespread glomerulosclerosis. Cardiac involvement in GPA is uncommon, affecting 6–9% of children and adults with the disease.1,2 Pericarditis is the most common form of cardiac involvement, although coronary arteritis is equally common at autopsy.3 Less frequent manifestations include endocarditis, valvular lesions and arrhythmia.4 We believe this to be the first report of chylous
368
pericardial effusion in GPA. The case highlights the diversity and seriousness of cardiac disease that may occur in this condition. As such patients need to be carefully followed for cardiac involvement, in particular pericarditis, during the course of their disease. No disclaimers or conflict of interest. Accepted for publication 8 April 2014. doi:10.1111/nep.12262
REFERENCES 1. Hoffman GS, Kerr GS, Leavitt RY et al. Wegener granulomatosis: An analysis of 158 patients. Ann. Intern. Med. 1992; 116: 488–98. 2. Rottem M, Fauci AS, Hallahan CW et al. Wegener granulomatosis in children and adolescents: Clinical presentation and outcome. J. Peditr. 1993; 122: 26–31. 3. Forstot JZ, Overlie PA, Neufeld GK, Harmon CE, Forstot SL. Cardiac complications of Wegener granulomatosis: A case report of complete heart block and review of the literature. Semin. Arthritis Rheum. 1980; 10: 148–54. 4. Grant SCD, Levy RD, Venning MC, Ward C, Brooks NH. Wegener’s granulomatosis and the heart. Br. Heart J. 1994; 71: 82–6.
© 2014 Asian Pacific Society of Nephrology
