Primary HIV infection presenting as haemolytic crisis in a patient with previously undiagnosed glucose 6-phosphate dehydrogenase deficiency

Abstract

In a recent comprehensive review article about glucose 6-phosphate dehydrogenase (G6PD) deficiency by Cappellini and Fiorelli [1], different infections are listed as a possible cause for acute haemolysis in patients with G6PD deficiency. We would like to add another infectious cause for haemolysis, which, to the best of our knowledge, has not been described in the literature yet. A 26-year-old African male, who was born in Burkina Faso and had been living in Germany since 2002, was admitted with a history of generalized weakness, temperature greater than 39°C, diarrhoea, nausea and vomiting for about 1 week. He reported progressive darkening of his urine, and was anuric since the day prior to admission. The patient denied the use of illicit drugs or any other medication and had not travelled abroad since 2002. Except for slightly enlarged but nontender cervical and inguinal lymph nodes, physical examination revealed no abnormalities. A routine abdominal ultrasound showed no pathological findings, except a slightly enlarged spleen. A chest radiograph was normal on admission. The initial laboratory analysis showed a mild normochromic and normocytic anaemia [haemoglobin (Hb) 10.8 g/dl (Hb had dropped from 14 g/dl 3 days prior to admission), mean corpuscular volume 90.2 fl, mean corpuscular haemoglobin 30.5 fl], 2.07% reticulocytes, a leukopenia (total white cells 2.9 × 109 l−1) and a thrombocyte count of 160 000 μl−1. Additional laboratory tests revealed an elevated bilirubin (2.4 mg/dl, direct bilirubin 0.3 mg/dl), an elevated creatinine (3.5 mg/dl), elevated liver enzymes (aspartate aminotransferase 1981 U/l, alanine aminotransferase 219 U/l, gamma-glutamyl transpeptidase 1131 U/l) as well as a C-reactive protein within normal limits. Haemoglobinuria and the combination of elevated lactate dehydrogenase (LDH) (4846 U/l), creatinine kinase (449 U/l), low haptoglobin [0.21 g/l (0.3–2.0 g/l)] and low haemopexin [<0.05 g/l (0.5–1.5 g/l)] confirmed the diagnosis of an acute haemolytic crisis. We immediately started treatment with intravenous fluids to prevent kidney failure. Due to the lymphopenia and a low CD4+ helper cell count (244 μl−1), HIV serologies and PCR were obtained. Although initial HIV ELISA and immunobloting tests performed were considered indeterminate according to the Centres for Disease Control guidelines, the HIV viral load of greater than 50 000 000 copies/ml (strain CRF02-AG) and a full serological conversion of the confirmatory HIV western blot tests performed 1 week later confirmed the diagnosis of primary HIV infection [2]. In order to reveal other possible causes of haemolysis in the presence of an acute HIV infection, a comprehensive panel of serologic tests were performed. Tests for hepatitis A virus (HAV), hepatitis C virus, cytomegalovirus (CMV), Epstein–Barr virus, Parvo-B19-Virus, Mycoplasma pneumoniae, Treponema pallidum, Leptospira interrogans, Brucella spp., Toxoplasma gondii, Schistosomiasis and Leishmaniasis were consistently negative. Several thick films for malaria were negative. Immunoglobulin (Ig) G antibodies against HAV, CMV and T. gondii were interpreted as past infections. Testing for Legionella antigen in the urine yielded a negative result. Blood, stool and urine cultures were all negative. IgG, IgM and IgA serum levels were normal, irregular autoreactive antibodies, cold or warm agglutinins could not be detected, and direct and indirect Coombs tests were negative. Other screening tests for autoimmune diseases including antinuclear antibody, antids-DNA, anti-U1RNP, anti-SM, anti-Sjögren's syndrome A, anti-Sjögren's syndrome B, anti-systemic sclerosis 70, anticentromere and anti-Jo1 were not contributory. A haemoglobin electrophoresis did not yield any abnormal findings. A QuantiFERON-TB-Gold test was positive (acid fast sputum stains and culture were negative). Bone marrow aspiration cytology showed no pathologic results but signs of precipitous erythropoesis. Accessory findings included a chronic, low replicating hepatitis B infection (hepatitis B surface antigen positive, hepatitis core antibody positive, hepatitis B e antibody positive, hepatitis B surface antibody negative, hepatitis B e antigen negative with a viral load below the detection level). A test for G6PD deficiency (performed during this episode) showed a rest activity of 0.8 U/g Hb (normal: 7.0–17.0 U/g Hb), which proved the presence of G6PD deficiency with a low rest activity. Upon further questioning, the patient did not remember any similar illnesses in the past. We discharged the patient 2 weeks later in good health, with a Hb level of 9.2 mg/dl (minimum 8.6 mg/dl), a nearly normalized creatinine, falling LDH and normalized liver enzymes. As extensive virological and microbiological diagnostic tests including several blood and stool cultures [3] did not yield a positive result and inflammation markers were negative in this patient throughout this hospital stay, we hypothesize that the haemolytic crisis in this G6PD-deficient patient was triggered by the primary HIV infection. Rhabdomyolysis with acute kidney failure has been reported as a first manifestation of primary HIV infection [4]; however, the creatinine kinase levels were only mildy elevated and quickly normalized in the patient described here. Although HIV and G6PD are independently seen as important contributors to anaemia in Africa [5,6], few studies have looked at anaemia in G6PD-deficient HIV-positive patients, even though early in-vitro laboratory work and clinical studies revealed a possible link between oxidative stress, glutathione metabolism and HIV infection [7–10]. A study of 323 HIV-positive men in Sardinia did not find a negative impact of G6PD on survival. However, only men with the Mediterranean G6PD variant were tested [11]. More than 15 000 patients are infected with the HIV virus every day. As G6PD deficiency is very common in many parts of the world [1], it is surprising that acute haemolysis has not been described as a complication in primary HIV infection more often. It remains unclear whether we describe a rarity or whether a systematic review of cohorts that show a high prevalence of G6DP deficiency (e.g. Sub-Saharan Africa) will reveal that haemolysis is a more common, yet easily overlooked complication of primary HIV infection.