Parvovirus B19 infection associated with myelosuppression and cutaneous polyarteritis nodosa

R. Durst, N. Goldschmidt1 and A. Ben Yehuda

Internal Medicine Division and
1 Hematological Department, Hadassah Medical Center, Jerusalem 91120, Israel

SIR, Parvovirus B19 is an agent that causes several clinical manifestations, the most common being erythema infectiosum in children. It has also been associated with bone marrow suppression, most commonly transient red cell aplasia in patients with chronic haemolysis [1]. Several reports have linked parvovirus with necrotizing vasculitis disorders [29]. We report a unique case of a patient who developed vasculitis and myelosuppression simultaneously during the course of an acute parvovirus B19 infection.

A 70-yr-old man was hospitalized for the evaluation of fever and maculonodular rash in his legs. The patient was a tourist in the USA and Canada for 3 weeks and came back to Israel 3 days prior to his hospitalization. During his stay in the USA he developed a fever of 32.8–38.5°C and fatigue that was treated with an NSAID and lasted for 3 days. When he came home he noticed a skin rash on his legs and he was admitted for further evaluation.

The patient's medical history was notable for non-insulin-dependent diabetes mellitus and hyperlipidaemia that had been treated with diet and glibenclamide 5 mg daily for 5 yr.

On examination, the patient had a temperature of 38.5°C, blood pressure 130/80 mmHg and a pulse rate of 65/min. His neck was supple. No jaundice was noticed. His cardiorespiratory examination was normal. His abdomen was not tender and no splenic or liver enlargement was noticed. No lymphadenopathy was noticed. Non-tender erythematous nodular lesions of diameter 0.5–1 cm with ill-defined circumference were noticed on both legs, mainly on the extensor surfaces.

His white blood cell count was 2400/mm3 with 44% lymphocytes and 39% granulocytes. Haemoglobin was 14.2 mg% with mean corpuscular volume 88 mm3, haematocrit 41% and reticulocyte count 1.8%. On the peripheral blood smear, the red blood cell line showed unisocytosis. The granulocytes had pale cytoplasm and the lymphocytes showed mild atypia. Thrombocytopenia of 64 000/mm3 was noticed, with large variance in platelet size. The bone marrow aspirate showed hypercellularity, megakaryocytosis, reduced granulocyte count with megaloblastosis, and lymphocytes with mild atypia. Bone marrow biopsy revealed hypercellularity, with representation of all cell lines. Relative hypertrophy of the myeloid cell line with left shift and no apparent malignancy was noticed. Bone marrow leukaemic markers (chromosome aberrations) were negative. Blood chemistry, liver function tests and renal function tests were all within normal limits. Urine sediment was normal. ANA, cryoglobulin and cytoplasmic pattern ANCA were negative. Complement C3 level was within normal limits. Peripheral pattern ANCA was slightly elevated above the threshold value. Four blood cultures as well as sputum culture and urine culture were negative. Serology for human immune deficiency, syphilis, rickettsial diseases (Q fever, spotted fever and murine typhus) and hepatitis B and C viruses were negative. Serology for measles virus, Epstein–Barr virus and cytomegalovirus was compatible with past exposure. Parvovirus B19 serology was positive for immunoglobulin (Ig) M antibodies and negative for IgG. Skin biopsy showed a medium-sized artery with inflammatory infiltrate and necrosis of the vessel wall, a finding compatible with polyarteritis nodosa (PAN). The patient was treated with prednisone 1 mg/kg for 3 weeks with improvement in the skin rash, but anaemia of 8 mg% developed and no change occurred in the white blood cell and platelet counts. He was then treated with intravenous Ig (IVIG) 2 g/kg. After this regimen, approximately 2 months after his initial admission, his parvovirus serology was positive for IgG and negative for IgM. This was accompanied by an improvement in white blood cell count, but anaemia persisted for 12 months. He required repeated packed cell transfusions. After 12 months he suffered a massive cerebrovascular accident and died.

We describe a 70-yr-old man who presented with bicytopenia and later with pancytopenia, vasculitis compatible with cutaneous polyarteritis nodosa and evidence for recent parvovirus B19 infection. The seroprevalence of parvovirus in adults ranges between 30 and 60% [10]. Thus, primary infection with the virus can occur at any age. Several diseases might explain the clinical presentation in this case. Primary necrotizing vasculitides are unlikely because they generally do not cause bone marrow suppression. Systemic lupus erythematosus is also unlikely as he was negative for ANA and the C3 level was normal. Acute bacterial endocarditis is unlikely because of the repeated negative blood cultures. Myelodysplastic syndrome (MDS) with cutaneous paraneoplastic manifestations, including vasculitis, has been reported [11, 12]. The clinical course of this patient, together with the need for recurrent red blood cell transfusion, is somewhat suggestive of MDS. However, the acute onset of the disease accompanied by fever and rash does not support this diagnosis. Also, the lack of chromosomal aberrations in the bone marrow is not compatible with MDS. Indeed, It is possible that the patient had subclinical MDS that was exacerbated by parvovirus infection.

Several reports have related parvovirus infection and necrotizing vasculitides (Table 1Go) [29]. In four cases it was associated with Wegener's granulomatosis, in eight with polyarteritis nodosa and in one with temporal arteritis. In none of these cases did an immunocompromising disease exist. Parvovirus has been reported to persist in immune-competent hosts [13]. Most of the patients reported survived the infection with little or no sequelae [38]. Only two cases, the present one and a previously reported case of PAN, have died [9]. Although in most reported cases the treatment consisted of immunosuppressive therapy and IVIG, two reports noted clinical recovery only after IVIG therapy [6]. In one case the parvovirus infection was diagnosed early, hence IVIG was the only therapy given [8]. In the other case, the resolution of symptoms occurred only after IVIG had been added to the immunosuppressive therapy [6]. It is thus suggested that clinical recovery might coincide with the clearance of viraemia. The development of autoimmune phenomena during parvovirus infection is probably related to a poor host response and might be associated with immune complex formation. Such a mechanism has been suggested as the cause of vasculitides in chronic hepatitis B infections [14]. This hypothesis is supported by cases in which the resolution of symptoms occurred only after IVIG treatment. In only one of the cases reported previously was the vasculitis associated with myelosuppression (case 3 in [6]). Although red cell aplasia is the classical presentation of the effect of parvovirus on bone marrow, leucopenia and myelosuppression have been associated with chronic parvovirus infection [1, 15]. In the case reported here, the serological findings compatible with recent infection with parvovirus, accompanied by myelosuppression and vasculitis, is strongly suggestive of a cause-and-effect relationship. The serology tests for parvovirus have low sensitivity but high specificity for infection [16]. We believe that the clinical presentation of myelosuppression and vasculitis were caused by persistent parvovirus infection. Although the patient was not immunocompromised, his poor immunological response to the virus might have been related to his age or to underlying MDS that was not diagnosed earlier. This is the second case of vasculitis and concurrent myelosuppression due to parvovirus B19 infection. This case adds to the increasing evidence for a possible association of vasculitis with parvovirus infection.


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TABLE 1. Clinical features, means of diagnosis and treatment leading to resolution of symptoms in reported cases of necrotizing vasculitis and parvovirus infection

 

Notes

Correspondence to: R. Durst. Back

References

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Accepted 16 April 2002





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