The Case | A patient with antineutrophil cytoplasmic antibody–positive vasculitis on treatment with fever and leucopenia
Authors: Maya Kemps, Jacobien C. Verhave, Mark A.A. Claassen, Janneke Ruinemans-Koerts, Ellen van der Spek
Journal: Kidney International (2017)

A 71-year-old man presented with severe acute renal failure, erythrocyturia, with dysmorphic erythrocytes and proteinuria (2.9 g/24 h). Sonography showed normal-sized kidneys. His antineutrophil cytoplasmic antibody was positive (myeoperoxidase 80 E/ml). Kidney biopsy showed a necrotizing crescentic glomerulonephritis with acute tubular necrosis. The patient was treated for crescentic antineutrophil cytoplasmic antibody–positive vasculitis with prednisone, cyclophosphamide, and plasmapheresis (8 sessions). Also, hemodialysis was started because of worsening kidney function. After 2 weeks, plasmapheresis and dialyses were stopped because kidney function had improved (Supplementary Figure S1). Two weeks later, the patient was readmitted with pulmonary embolism. At that time, he had fever, leucopenia (3.3 × 106), elevated liver enzymes, and a serum ferritin of 18,569 ug/l (Table 1). Leucopenia was first attributed to cyclophosphamide and this immunosuppression was stopped. However, leucopenia, fever, and elevated liver enzymes persisted.Table 1Serum laboratory valuesParameterResultsNormal valuesHemoglobin8.413.5–17.4 g/dlLeukocytes3.34–11 × 109/lLymphocytes< 0.01Thrombocytes130150–400 × 109/lCreatinine6.2< 1.2 mg/dlBilirubin0.9< 1.2 mg/dlAlkaline phosphatase387< 120 U/lGGT1440< 55 U/lASAT78< 35 U/lALAT196< 45 U/lLDH465< 250 U/lCRP29< 10 mg/lFerritin18,56920–300 ug/lALAT, alanine aminotransferase; ASAT, aspartate aminotransferase; CRP, C-reactive protein; GGT, gamma-glutamyl transferase; LDH, lactate dehydrogenase. Open table in a new tab ALAT, alanine aminotransferase; ASAT, aspartate aminotransferase; CRP, C-reactive protein; GGT, gamma-glutamyl transferase; LDH, lactate dehydrogenase. What is the clinical diagnosis? In this patient, because of persistent fever and leucopenia despite stopping cyclophosphamide, and the patient’s continued elevated liver enzymes, we suspected viral reactivation. Cytomegalovirus titers were sent and found to be high (3 × 106 copies/ml). Epstein–Barr virus serology was negative. The elevated ferritin was suggestive for hemophagocytic lymphohistiocytosis, which was confirmed by bone marrow aspirate (Figure 1a and b). Table 2 shows the diagnostic criteria and the items present in the patient.1Jordan M.B. Allen C.E. Weitzman S. et al.How I treat hemophagocytic lymphohistiocytosis.Blood. 2011; 118: 4041-4052Crossref PubMed Scopus (679) Google Scholar Hemophagocytic lymphohistiocytosis is a life-threatening overstimulation of the immune system causing inflammation and multiorgan failure. Activation of macrophages and histiocytes cause phagocytosis of the blood elements. The patient was treated with intravenous ganciclovir (1.25 mg/kg after each dialysis) for the cytomegalovirus reactivation. Anakinra (interleukin 1 receptor antagonist) 400 mg/3 d i.v. was administered for 10 days to limit the excessive inflammation cascade and inhibit phagocytosis.2Netea M.G. van Deuren M. van der Meer J.W. Case 10-2011: fever, confusion and liver failure.N Engl J Med. 2011; 365: 186PubMed Google Scholar Hemodialysis was restarted in view of worsening renal function. The patient recovered from his acute illness but remained on dialysis.Table 2Diagnostic criteria hemophagocytic lymphohistiocytosis (HLH-2004 trial)1Jordan M.B. Allen C.E. Weitzman S. et al.How I treat hemophagocytic lymphohistiocytosis.Blood. 2011; 118: 4041-4052Crossref PubMed Scopus (679) Google ScholarDiagnosis in case of 5 of 8 criteriaPresent in patientFever> 38.5°CYesSplenomegalyNoCytopeniaYesHypertriglyceridemia> 265 mg/dlYesHemophagocytosisBone marrowYesOr spleen/liver/lymph nodeLow natural killer cell activity?Ferritin> 500 ug/lMore indicative > 3000 ug/lYesElevated soluble CD252 SD above normalYes Open table in a new tab Although leucopenia is a common complication of cyclophosphamide therapy, one should consider an alternative diagnosis. Leucopenia may be an expression of an opportunistic infection such as cytomegalovirus.3Tollitt J. O’Riordan Poulikakos D. CMV disease complicating induction immunosuppressive treatment for ANCA-associated vasculitis.BMJ Case Rep. 2016;Feb 23; 2016PubMed Google Scholar Furthermore, viral infections including cytomegalovirus are known triggers for precipitating hemophagocytic lymphohistiocytosis. Finally, when the suspicion of hemophagocytic lymphohistiocytosis is high, immediate treatment is indicated because the mortality rate is high.4Dhote R. Simon J. Papo T. et al.Reactive hemophagocytic syndrome in adult systemic disease: report of twenty-six cases and literature review.Arthritis Rheum. 2003; 49: 633-639Crossref PubMed Scopus (241) Google Scholar All the authors declared no competing interests. Download .docx (.06 MB) Help with docx files Figure S1Kidney function (estimated glomerular filtration rate by Modification of Diet in Renal Disease) over time.