Clin. luh. Ifurmut. 1992, 14, 327 330
CASE REPORT
The fifth cause of splenomegaly?-parvovirus B19 J.M. CURRIE, MRCP,* D.J.A. ADAMSON, MRCP,* T . B R O W N , BSc, P h D t & A . A . D A W S O N , M D , FRCP, FRCPath" *Ward 47, Aherdeen Royal Infirmary and ?Department of Medical Microbiology, Medical School, Foresterhill, Aherdeen , AB9 2 2 0 , UK Accepted for publication 3 February 1992 Keywords: human parvovirus B19, splenomegaly, anaemia
Two previously apparently healthy females were found to have severe anaemia associated with acute human parvovirus B19 infection (B19 virus). Both had splenomegaly at presentation which rapidly resolved. Neither splenomegaly nor a profound fall in haemoglobin has been reported to be associated with B19 virus infection in otherwise uncompromised patients. Case 1
An 18-year-old female presented with a 1-week history of generalized weakness, lethargy and dizziness. She was pale but otherwise looked well and no abnormality was found clinically. On investigation the haemoglobin was 5.4 g/dl, MCV 91 fl, MCH 36 pg, platelet count 576 x 109/1, and WBC 39.6 x 109/1(neutrophils 23.8, lymphocytes 5.6, eosinophils 1.2, monocytes 0.4, metamyelocytes 3.17, myelocytes 5.554, and reticulocyte count 302 x 109/l. The blood film showed normochromic RBC with minor spherocytosis. Direct antiglobulin test (DAGT) was negative, acidified glycerol lysis test at 37°C was normal, the transferrin was 2 g/1 and serum iron 9 pmol/l; serum biochemistry including bilirubin was normal; urinalysis showed no excess of urobilinogen. Although the spleen was not palpable, abdominal ultrasonography showed it to be bulky and of uniform consistency, measuring over 12 cm x 7 cm-abnormal for the size and sex of the patient. Because of her pathological fear of needles a bone marrow examination could not be done. Five days after transfusion with 5 units of packed red cells her haemoglobin was 10.7 g/dl, MCV 91 fl, platelet count 308 x 10y/l, and WBC 6.4 x 10y/l. There Correspondence: Dr Joanne M . Currie, Registrar, Ward 47, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, AB9 2ZB, UK.
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was no spherocytosis on the blood film. Abdominal ultrasound 4 weeks later showed a normal spleen. During follow-up over 6 months she remained well with a normal haemoglobin and white blood count. Viral titres assayed at presentation and 1 month later showed a fall in anti-B19 IgM ( > 100 to 4.1 RIA units) confirming recent B19 virus infection. No other infection, viral or bacterial, was detected.
Case 2 A 36-year-old female presented with a 10-day history of an influenza-like illness, associated epigastric discomfort and joint pains. There was no history of blood loss from the gastrointestinal tract, but she had minor menorrhagia (5 days' bleeding with clots on day 1). On examination she was very pale with soft nails. The spleen was enlarged 5 cm below the costal margin. Faecal occult blood was negative. Investigations were as follows: Hb 5.9 g/dl, MCV 59 fl, MCH 18 pg, WBC 4.5 x 10y/l,platelet count 263 x 109/1,and reticulocytes 6%. The blood film showed a hypochromic, microcytic anaemia, platelets and leucocytes normal; serum iron less than 5 pmol/l and transferrin 3 g/l; Kleihauer test negative; HbA, 1.5% and H b electrophoresis normal; DAGT was negative. The serum biochemistry, including bilirubin, was normal and urinalysis showed no excess of urobilinogen. Abdominal ultrasonography showed an enlarged spleen (1 7 cm in largest diameter) with a uniform internal echo pattern. She was treated with oral iron. Four weeks later she was asymptomatic and her splenomegaly had disappeared clinically. Repeat full blood count was Hb 10.4 g/dl, MCV 77 fl, WBC 5.5 x 10y/l and platelet count 277 x 109/l. Viral titres assayed at presentation and 1 month later showed a fall in anti-B19 IgM ( > 100 to 24 RIA units) and a rise in anti-B19 IgG (15 to > 100 RIA units) confirming recent B19 virus infection.
Discussion
Fifth disease (erythema infectiosum or slapped cheek disease) is perhaps the best known manifestation of B19 virus infection. Since its chance discovery in the serum of blood donors (Cossart et al. 1975) it has been noted to be predominantly a subclinical infection, with IgG antibodies indicating past infection in 60% of certain populations (Eriksson, Stromberg & Kreuger 1988). Severe erythroid hypoplasia leading to a rapid-onset and profound anaemia has been associated with B19 virus infection in compromised individuals such as those with hereditary spherocytosis (Eriksson et al. 1988), red cell enzyme defects or haemoglobinopathies (Bentley I986), bone marrow transplant recipients (Weiland rt ul. 1989), combined immunodeficiency with immunoglobulins (Kurtzman et al. 1987) and acute lymphoblastic leukaemia in remission (Takahashi et al. 1991). It has also been reported to be associated with anaemia during the course of other infections
The Jifth cause of splenornegaly.7
329
such as malaria (Jones et al. 1990), and AIDS (Mitchell et ul. 1990). In vitro work has suggested that B 19 virus causes anaemia and reticulocytopenia by infecting the bone marrow and propagating there with a direct cytotoxic effect on progenitors at the erythrocyte burst-forming unit/colony-forming unit [BFU-E/CFU-El stage of differentiation (Kurtzman et al. 1987). Although normal volunteers infected with B19 virus show a small fall (1-2 g/dl) in their haemoglobin (Pattison 1990), there have been no reports of infected normal individuals having severe anaemia, except perinatally (Belloy et al. 1990) when the red-cell kinetics are very different from later life (Gray, Davidson & Anand 1987). We report 2 cases of severe anaemia and splenomegaly which appeared to be induced by acute infection with B19 virus. We suggest that the reticulocytosis evident in both cases was a recovery phenomenon following virally-induced progenitor cell maturation arrest. In case 2 there was underlying iron deficiency and perhaps the marrow stress accompanying this made the patient’s erythroid progenitors especially vulnerable to B19 virus infection but in case 1 the patient did not have any of the above recognized predisposing factors to B19 virusinduced aplastic crisis. It seems likely, therefore, that this virus can be sufficiently cytotoxic in the marrow of ‘normal’ individuals to cause a significant anaemia. Although minor splenomegaly is rarely associated with long-standing severe iron deficiency anaemia, here it seems more likely to us that even in apparently normal subjects it is a feature of B19 virus infection.
Acknowledgement
We are grateful for the assistance of the Virus Reference Laboratory, Colindale.
References BCLLOYM., MORINET F., BLONDIN G., COUROUCE A.M., PEYROL Y. & VILMERE. (1990) Erythroid hypoplasia due to chronic infection with parvovirus B19. N. Engl. J. Med. 322, 633-634 BENTLEY D.P. (1986) Hyperplastic anaemia and parvovirus infection. B.M.J. 293, 836 COSSAKT Y.E., FIELD A.M., CANTB. & WIDDOWSD. (1975) Parvovirus-like particles in human ser. Lancet i, 72-73 EKIKSSON B.-M., STROMBERG A. & KREUGEK A. (1988) Human parvovirus B19 infection with severe anaemia affecting mother and son. Scand. J. Inject. Dis. 20, 335-337 GRAYE.S., DAVIDSON R.J.L. & ANANDA. (1987) Human parvovirus and fetal anaemia. Lancer i, 1144 JONESP.H., PICKETT L.C., ANDERSON M.J. & PASVOLG. (1990) Human parvovirus infection in children and severe anaemia seen in an area endemic for malaria. J . Trop. Med. Hyg. 93, 67-70 KURTZMAN G.J., OZAWAK., COHEN B., HANSONG., OSEASR. & YOUNGN.S. (1987) Chronic bone marrow failure due to persistent B1Y parvovirus infection. N. Engl. J . Med. 317, 287 294 MITCHELL S.A., WELCHJ.M., WESTON-SMITH S., NICHOLSON F. & BRADBEER C.S. (1990) Parvovirus infection and anaemia in a patient with AIDS: case report. Genitourin. Med. 66, 95-96 PATTISON J.R.(1990) The pathogenesis of diseases associated with B19 virus. Behring Inst. Mitt. 85, 55-59
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TAKAHASHI M., MORIYAMA Y . , SHIBATA A,, TAKAI K . & SANADAM . (1991) Anaemia caused by parvovirus in an adult patient with acute lymphoblastic lcukacmia in complete remission. Eur. J. Haematol. 46, 41 WEILANDH.T., SALIMANS M.M.M., FIBBEW.E., KLUINP.M. & COHENB.J. (1989) Prolonged parvovirus B19 infection with severe anaemia in a bone marrow transplant rccipient. Br. J. Haemutol. 71, 300
CASE REPORT
The fifth cause of splenomegaly?-parvovirus B19 J.M. CURRIE, MRCP,* D.J.A. ADAMSON, MRCP,* T . B R O W N , BSc, P h D t & A . A . D A W S O N , M D , FRCP, FRCPath" *Ward 47, Aherdeen Royal Infirmary and ?Department of Medical Microbiology, Medical School, Foresterhill, Aherdeen , AB9 2 2 0 , UK Accepted for publication 3 February 1992 Keywords: human parvovirus B19, splenomegaly, anaemia
Two previously apparently healthy females were found to have severe anaemia associated with acute human parvovirus B19 infection (B19 virus). Both had splenomegaly at presentation which rapidly resolved. Neither splenomegaly nor a profound fall in haemoglobin has been reported to be associated with B19 virus infection in otherwise uncompromised patients. Case 1
An 18-year-old female presented with a 1-week history of generalized weakness, lethargy and dizziness. She was pale but otherwise looked well and no abnormality was found clinically. On investigation the haemoglobin was 5.4 g/dl, MCV 91 fl, MCH 36 pg, platelet count 576 x 109/1, and WBC 39.6 x 109/1(neutrophils 23.8, lymphocytes 5.6, eosinophils 1.2, monocytes 0.4, metamyelocytes 3.17, myelocytes 5.554, and reticulocyte count 302 x 109/l. The blood film showed normochromic RBC with minor spherocytosis. Direct antiglobulin test (DAGT) was negative, acidified glycerol lysis test at 37°C was normal, the transferrin was 2 g/1 and serum iron 9 pmol/l; serum biochemistry including bilirubin was normal; urinalysis showed no excess of urobilinogen. Although the spleen was not palpable, abdominal ultrasonography showed it to be bulky and of uniform consistency, measuring over 12 cm x 7 cm-abnormal for the size and sex of the patient. Because of her pathological fear of needles a bone marrow examination could not be done. Five days after transfusion with 5 units of packed red cells her haemoglobin was 10.7 g/dl, MCV 91 fl, platelet count 308 x 10y/l, and WBC 6.4 x 10y/l. There Correspondence: Dr Joanne M . Currie, Registrar, Ward 47, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, AB9 2ZB, UK.
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was no spherocytosis on the blood film. Abdominal ultrasound 4 weeks later showed a normal spleen. During follow-up over 6 months she remained well with a normal haemoglobin and white blood count. Viral titres assayed at presentation and 1 month later showed a fall in anti-B19 IgM ( > 100 to 4.1 RIA units) confirming recent B19 virus infection. No other infection, viral or bacterial, was detected.
Case 2 A 36-year-old female presented with a 10-day history of an influenza-like illness, associated epigastric discomfort and joint pains. There was no history of blood loss from the gastrointestinal tract, but she had minor menorrhagia (5 days' bleeding with clots on day 1). On examination she was very pale with soft nails. The spleen was enlarged 5 cm below the costal margin. Faecal occult blood was negative. Investigations were as follows: Hb 5.9 g/dl, MCV 59 fl, MCH 18 pg, WBC 4.5 x 10y/l,platelet count 263 x 109/1,and reticulocytes 6%. The blood film showed a hypochromic, microcytic anaemia, platelets and leucocytes normal; serum iron less than 5 pmol/l and transferrin 3 g/l; Kleihauer test negative; HbA, 1.5% and H b electrophoresis normal; DAGT was negative. The serum biochemistry, including bilirubin, was normal and urinalysis showed no excess of urobilinogen. Abdominal ultrasonography showed an enlarged spleen (1 7 cm in largest diameter) with a uniform internal echo pattern. She was treated with oral iron. Four weeks later she was asymptomatic and her splenomegaly had disappeared clinically. Repeat full blood count was Hb 10.4 g/dl, MCV 77 fl, WBC 5.5 x 10y/l and platelet count 277 x 109/l. Viral titres assayed at presentation and 1 month later showed a fall in anti-B19 IgM ( > 100 to 24 RIA units) and a rise in anti-B19 IgG (15 to > 100 RIA units) confirming recent B19 virus infection.
Discussion
Fifth disease (erythema infectiosum or slapped cheek disease) is perhaps the best known manifestation of B19 virus infection. Since its chance discovery in the serum of blood donors (Cossart et al. 1975) it has been noted to be predominantly a subclinical infection, with IgG antibodies indicating past infection in 60% of certain populations (Eriksson, Stromberg & Kreuger 1988). Severe erythroid hypoplasia leading to a rapid-onset and profound anaemia has been associated with B19 virus infection in compromised individuals such as those with hereditary spherocytosis (Eriksson et al. 1988), red cell enzyme defects or haemoglobinopathies (Bentley I986), bone marrow transplant recipients (Weiland rt ul. 1989), combined immunodeficiency with immunoglobulins (Kurtzman et al. 1987) and acute lymphoblastic leukaemia in remission (Takahashi et al. 1991). It has also been reported to be associated with anaemia during the course of other infections
The Jifth cause of splenornegaly.7
329
such as malaria (Jones et al. 1990), and AIDS (Mitchell et ul. 1990). In vitro work has suggested that B 19 virus causes anaemia and reticulocytopenia by infecting the bone marrow and propagating there with a direct cytotoxic effect on progenitors at the erythrocyte burst-forming unit/colony-forming unit [BFU-E/CFU-El stage of differentiation (Kurtzman et al. 1987). Although normal volunteers infected with B19 virus show a small fall (1-2 g/dl) in their haemoglobin (Pattison 1990), there have been no reports of infected normal individuals having severe anaemia, except perinatally (Belloy et al. 1990) when the red-cell kinetics are very different from later life (Gray, Davidson & Anand 1987). We report 2 cases of severe anaemia and splenomegaly which appeared to be induced by acute infection with B19 virus. We suggest that the reticulocytosis evident in both cases was a recovery phenomenon following virally-induced progenitor cell maturation arrest. In case 2 there was underlying iron deficiency and perhaps the marrow stress accompanying this made the patient’s erythroid progenitors especially vulnerable to B19 virus infection but in case 1 the patient did not have any of the above recognized predisposing factors to B19 virusinduced aplastic crisis. It seems likely, therefore, that this virus can be sufficiently cytotoxic in the marrow of ‘normal’ individuals to cause a significant anaemia. Although minor splenomegaly is rarely associated with long-standing severe iron deficiency anaemia, here it seems more likely to us that even in apparently normal subjects it is a feature of B19 virus infection.
Acknowledgement
We are grateful for the assistance of the Virus Reference Laboratory, Colindale.
References BCLLOYM., MORINET F., BLONDIN G., COUROUCE A.M., PEYROL Y. & VILMERE. (1990) Erythroid hypoplasia due to chronic infection with parvovirus B19. N. Engl. J. Med. 322, 633-634 BENTLEY D.P. (1986) Hyperplastic anaemia and parvovirus infection. B.M.J. 293, 836 COSSAKT Y.E., FIELD A.M., CANTB. & WIDDOWSD. (1975) Parvovirus-like particles in human ser. Lancet i, 72-73 EKIKSSON B.-M., STROMBERG A. & KREUGEK A. (1988) Human parvovirus B19 infection with severe anaemia affecting mother and son. Scand. J. Inject. Dis. 20, 335-337 GRAYE.S., DAVIDSON R.J.L. & ANANDA. (1987) Human parvovirus and fetal anaemia. Lancer i, 1144 JONESP.H., PICKETT L.C., ANDERSON M.J. & PASVOLG. (1990) Human parvovirus infection in children and severe anaemia seen in an area endemic for malaria. J . Trop. Med. Hyg. 93, 67-70 KURTZMAN G.J., OZAWAK., COHEN B., HANSONG., OSEASR. & YOUNGN.S. (1987) Chronic bone marrow failure due to persistent B1Y parvovirus infection. N. Engl. J . Med. 317, 287 294 MITCHELL S.A., WELCHJ.M., WESTON-SMITH S., NICHOLSON F. & BRADBEER C.S. (1990) Parvovirus infection and anaemia in a patient with AIDS: case report. Genitourin. Med. 66, 95-96 PATTISON J.R.(1990) The pathogenesis of diseases associated with B19 virus. Behring Inst. Mitt. 85, 55-59
330
J . M . Currie et al.
TAKAHASHI M., MORIYAMA Y . , SHIBATA A,, TAKAI K . & SANADAM . (1991) Anaemia caused by parvovirus in an adult patient with acute lymphoblastic lcukacmia in complete remission. Eur. J. Haematol. 46, 41 WEILANDH.T., SALIMANS M.M.M., FIBBEW.E., KLUINP.M. & COHENB.J. (1989) Prolonged parvovirus B19 infection with severe anaemia in a bone marrow transplant rccipient. Br. J. Haemutol. 71, 300
