J Clin Pathol: first published as 10.1136/jcp.41.11.1242-a on 1 November 1988. Downloaded from JClin Pathol 1988;41:1242-1246 tion in patients with sickle cell anaemia, fi- Letters to the Editor thalassaemia, pyruvate kinase deficiency, Severe aplastic anaemia after parvovirus and hereditary , but the course I Plummer FA, Hammond GW, Forward K, et in the absence of underlying is benign and the virus has not been al. An erythema infectiosum-like illness haemolytic anaemia implicated in severe aplastic anaemia in caused by human parvovirus infection. N normal or abnormal people. When healthy Engl J Med 1985;313:74-9. Infection with human parvovirus (HPV), the adult volunteers underwent intranasal 2 Anderson MJ, Higgins PG, Davis LR, et al. causative agent of erythema infectiosum,' is inoculation with HPV the ensuing mild Experimental parvoviral infection in a well recognised precipitant of marrow humans. JInfect Dis 1985;152:257-65. febrile illness was followed by transient 3 Mortimer PP, Humphries RK, Moore JG, aplasia in patients with a haemoglobin- reticulocytopenia, mild anaemia, neutro- Purcell RH, Young NS. A human opathy and may unmask hereditary penia and a fall in the platelet count. It was parvovirus-like virus inhibits haematopoeitic spherocytosis in otherwise asymptomatic also noted that after two or three weeks three colony formation in vitro. Nature 1983; patients. We describe a patient with no red of the four initially seronegative volunteers 302:426-9. cell abnormalities who has had progressive developed rash and arthralgia consistent 4 Kurtzman GJ, Ozawa K, Cohen B, Hanson G, bone marrow failure after an erythema infec- with a diagnosis oferythema infectiosum.2 Oseas R, Young NS. Chronic bone marrow tiosum-like illness and HPV seroconversion. Serum from patients with recent HPV failure due to persistent B19 parvovirus infec- A 20 year old caucasian woman tion. N Engl J Med 1987;317:287-94. presented infection has been shown to inhibit normal 5 Van Horn DK, Mortimer PP, Young N, Han- with a one month history ofa rash on her legs red cell colony growth in vitro,3 but the son GR. Human parvovirus-associated red and arthralgia. She was otherwise well and association ofconfirmed recent infection and cell aplasia in the absence of underlying receiving no medication. On examination, the development of severe aplastic anaemia hemolytic . Am J Pediatr Hematol bruising and a vasculitic rash on her shins does not establish a causative link without Oncol 1986;8:235-9. were noted. There was fusiform swelling over the presence of the virus in the marrow. In the proximal interphalangeal and metacar- view of the documented in vivo and in vitro pophalangeal joints of the hands, but no suppression of haemopoiesis being directly other abnormal findings. Investigations related to the virus it is likely that this could showed a haemoglobin concentration of 10-8 occur. Aplasia has been described in g/dl, a count of less than 5 x immunodeficient patients. A child with com- HIV detection by DNA ampl3fication 109/l, a white cell count of 3-8 x 109/l bined immunodeficiency with immuno- (neutrophils 1 3 x 109/1), a platelet count of globulins (Nezelof's syndrome) had a 15 HIV-1 carriers are routinely detected by the 59 x 109/l. There was no evidence of month history of relapsing-remitting presence of antibodies to HIV-L.' The haematinic deficiency and the blood film, antibody test may give uncertain results in marrow failure. HPV DNA was isolated copyright. haemoglobin electrophoresis, osmotic from the patient's serum at each deteriora- cases where infection has occurred but fragility and sucrose lysis test all yielded tion and HPV capsid protein and DNA were seroconversion has not, and in neonatal normal results. There was no evidence of shown in the bone marrow.4 Similarly, blood samples from infected mothers, where immunological disorder or deficiency. Bone aplasia was described in a 3 year old boy with the presence of maternal antibody does not marrow aspirate and a trephine biopsy acute lymphoblastic leukaemia in remission prove that the fetus is affected. specimen were hypocellular. Initial and con- following an upper respiratory tract infec- I describe a DNA detection technique of valescent sera for HPV IgM and IgG titres tion associated with a papular rash over the high sensitivity. Evidence of HIV-1 DNA in were consistent with primary virus exposure face and chest. His serum was positive for the peripheral cells in cases of HIV-1 of two to four weeks before her initial HPV antigen and after three months when antibody positive haemophiliacs was presentation. HPV DNA was not detected in his blood counts had returned to normal he obtained using the polymerase chain reac- either sample. developed a clinically important anti-HPV tion (PCR)2 with the heat stable DNA http://jcp.bmj.com/ Her fiance's HPV serology was also cons- IgG titre, having previously been sero- polymerase from Thermus aquaticus. As far istent with recent infection. Over the follow- negative.5 In both these cases impaired host as I am aware this is the first report ofdirect ing 18 months her haemoglobin deteriorated immunity could have permitted the contin- detection of HIV-1 DNA from peripheral to 7-0 g/dl, white cells to 2 5 x 109/l (neutro- ued presence of HPV with subsequent blood without the use ofmolecular hybridis- phils 0-7 x 109/1), and platelets to 13 x 109/l. marrow failure. ation. A repeat bone marrow examination again These cases and our own suggest that Twelve asymptomatic, HIV-l-sero- showed hypocellularity. In the absence of an severe aplasia may develop in conjunction positive heamophiliacs aged between 22 and

HLA compatible donor for bone marrow with HPV infection and that the marrow 47, who were known to have seroconverted on October 1, 2021 by guest. Protected transplantation she received treatment with failure may be prolonged. We therefore between three and five years before sample horse anti-lymphocyte globulin and corti- suggest that HPV infection be considered in collection, were studied. DNA was extracted costeroids. This led to a transient patients with severe aplastic anaemia even in from peripheral blood and amplified using improvement in the blood counts and she has normal subjects. two 20 base primers whose sequence was continued to require blood product support. MD HAMON taken from a region of the HIV-l pol gene3 Severe aplastic anaemia has an identifiable AC NEWLAND conserved over a wide variety of isolates, cause in only 50% of cases and in most of MJ ANDERSON* including more recently isolated African these it is drug related. Infectious causes are Department ofHaematology, HIV-1 strains. These primers (OLIGO-A2: rare but there is an association with infec- The London Hospital, 5'-CAGTAGTAATACAAGATAAT OLI- tious hepatitis, non-A non-B hepatitis, Eps- Whilechapel El JBB GO-B3: 5'-ATCCTCATCCTGTCTAC- tein-Barr virus, and *Department ofMedical Microbiology, TTG) are complementary to opposite . Transient marrow failure is an Middlesex Hospital School ofMedicine. strands of the HIV-I pol gene separated by acknowledged complication of HPV infec- London WCIE6JJ 80 bases of DNA, which was the target for