Varicella zoster virus induced haemolytic crisis in a child with congenital spherocytosis

Pierre TissieÁres á Yann Kernen á Alain Gervaix James Humbert á Susanne Suter Varicella zoster virus induced haemolytic crisis in a child with congenital spherocytosis Received: 7 December 1999 and in Revised form: 10 and 26 April 2000 / Accepted: 27 April 2000 Viral-induced haemolytic crisis in children with congenital spherocytosis is associated with parvovirus B19, cytomegalovirus, Epstein- Barr virus and human herpes virus but has never been described with varicella zoster virus. Congenital spherocytosis, an autosomal recessive disorder, is a common cause of haemolysis and haemolytic anaemia with a prevalence of approximately 1:5000 in northern Europe. Multiple mutations of cytoskeleton proteins induce decreased red blood cell deformability leading to splenic entrapment and premature destruction. Children with congenital spherocytosis are susceptible to aplastic crises due to parvovirus B19 and to hypoplastic crises associated with viral infections such cytomegalovirus CMV), Epstein-Barr virus EBV), and herpes simplex virus HSV). Accentuation of the baseline haemolytic process has been observed in congenital spherocytosis, but never in association with varicella zoster virus VZV). An 8-year-old boy, known to have congenital spherocytosis, presented with a mucocutaneous jaundice associated with varicella. Clinically, the patient was afebrile and in good physical condition. Neurological investigation was normal and no salicylate or phenothiazine class drug had been previously used by the patient. Abdominal examination revealed splenomegaly. Lymphadenopa- thy was absent. On admission, laboratory values outlined a haemolytic process: haemoglobin was 119 g/l reference range 115±155 g/l); haematocrit 31.4% reference range 35%±44%); reticulocyte count 556 g/l reference range 20±80 g/l) with a relative value to red cell count of 14.2% reference range 0.4%±1.6%); lactate dehydrogenase reached 835 IU/l reference range 187± 443 IU/l) and aspartate aminotransferase was 53 IU/l reference range 14±50 IU/l). Indirect hyperbilirubinaemia was observed with a total serum bilirubin of 199 lmol/l reference range 5±17 lmol/l) and an unconjugated serum bilirubin of 190 lmol/l. During the ongoing year, the baseline haemoglobin level SD) was 132 4 g/l and haematocrit 35.3 1.39%. Two weeks before the varicella manifested, the reticulocyte count was 348 g/l with a relative value of 8%. The patient's varicella was treated symp- tomatically. Eight days later, jaundice had resolved. Serum bilirubin, liver enzyme pro®le, haemoglobin and haematocrit reached baseline values. Reticulocyte count increased to 664 g/l with a relative value of 15.2%. B19 parvovirus, CMV and HSV serologies were negative. EBV mono-test was negative, whereas the viral capsid antigen VCA) IgG titre 1:160) and VCA IgM titre were positive. VZV ELISA was positive with an elevated IgG level of 1.32 negative <0.2), IgM level of 0.62 negative <0.2) and complement ®xation immunoglobin CF Ig) titre was 1:160. Six weeks later, EBV and VZV serologies were reassessed. Both IgM titres were negative. EBV IgG VCA titre was 1:160 and VZV IgG level 1.32. VZV CF Ig titre was 1:40. Glucose-6-phosphate dehydrogenase activity was normal as well as blood coagulation tests. VZV infected cells synthesise glycoproteins that not only provide structure for the virion but elicit both humoral and cell mediated immunity responses. Cell membrane molecular expression of VZV glycoproteins mimics the receptor for the C3b complement component and the IgG Fc fragment receptor [2]. Expression of the C3b receptor on erythrocytes activates the complement cascade and triggers a viral haemophagocytic syn- drome. Expression of the IgG Fc receptor on infected vascular endothelium potentiates erythrocyte aggregation and induces vasoclusive phenomena [1]. Although extremely rare in children, IgM mediated haemolysis has been described in a few patient with cold agglutinin auto-immune haemolysis [5]. These patho- physiological mechanisms may all potentially induce a haemolytic crisis in patients with congenital spherocytosis. Although varicella diagnosis was clinically established, both EBV and VZV serologies were positive. In children older than 4 years with primary EBV infection, IgM antibodies to VCA typically disappear within 2 to 3 months and VCA IgG persists for life [3]. In the published patient with EBV-induced haemolysis hampering congenital spherocytosis, haemolytic crisis occurred within 1 week following onset of mononucleosis symptoms [4]. In our patient, haemolytic crisis did not seem to be induced by EBV infection. Neither mononucleosis symptoms nor absolute lymph- ocytosis were observed and jaundice occurred simultaneously with varicella. VCA IgM disappeared within 6 weeks and the VCA IgG titre did not change, suggestive of a resolving infectious mononucleosis. In conclusion, VZV, a further member of the herpes family, is added to the list of triggers of haemolytic crisis in congenital spherocytosis. This report argues for the need of further study on the severity of VZV infection in children with congenital spherocytosis, with regard to evaluation of haemolysis prevention by VZV immunisation. References 1. Hebbel RP, Visser MR, Goodman JL, Jacob HS, Vercellotti GM 1987) Potentiated adherence of sickle erythrocytes to endothelium infected by virus. J Clin Invest 80: 1503±1506 2. Litwin V, Sandor M, Grose C 1990) Cell surface expression of varicella-zoster virus glycoproteins and Fc receptor. Virology 178: 263±272 3. Sumaya C, Ench Y 1985) Epstein-Barr virus infectious mononucleosis in children. II. Heterophile antibody and viral-speci®c responses. Pediatrics 75: 1011±1019 4. Taylor JJ 1973) Haemolysis in infectious mononucleosis: inapparent congenital spherocytosis. BMJ 4: 525±526 5. Terada K, Tanaka H, Mori R, Kataoka N, Uchikawa M 1998) Hemolytic anemia associated with cold agglutinin during chickenpox and a review of the literature. J Pediatr Hematol Oncol 20: 149±151 P. TissieÁres &) á Y. Kernen á A. Gervaix á J. Humbert á S. Suter Department of Paediatrics, Children's Hospital, 6, Rue Willy-DonzeÂ, 1211 Geneva 14, Switzerland e-mail: Pierre.TissieÁ[email protected]; Fax: +41-22-3824724 j Eur J Pediatr 2000) 159: 788±791 Ó Springer-Verlag 2000 RESEARCH LETTERS

Varicella zoster virus induced haemolytic crisis in a child with congenital spherocytosis

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