Dengue Fever-Induced Hemolytic Uremic Syndrome

To the Editor—Dengue virus infection is increasingly recognized as one of the world's major emerging infectious diseases [1]. Here, we present the description of, to our knowledge, the first case of a patient with acute renal failure as part of a hemolytic uremic syndrome induced by a dengue virus infection. A previously healthy 48-year-old man was admitted to the hospital with a high fever, blurred vision of the left eye, dyspnea, and cough with mild hemoptysis. Symptoms started the day after he returned from a 3-week visit to his native country, Suriname. The patient was moderately ill, with a temperature of 40.9°C, blood pressure of 190/98 mm Hg, a heart rate of 110 beats per minute, and a respiratory rate of 30 breaths per minute. Fundoscopic examination of the left eye showed cotton wool spots and peripapillary hemorrhages (figure 1). Aside from basal crackles on pulmonary auscultation, no other abnormalities were found on physical examination. Laboratory findings showed a hemoglobin level of 9.99 g/dL (6.2 mmol/L) with fragmentocytes in the blood smear, a WBC count of 6.3 × 103 cells/µL (6.2 × 109 cells/L), a platelet count of 63 × 103 platelets/µL (63 × 109 platelets/L), a creatinine level of 7.04 mg/dL (537 µmol/L), and a haptoglobin level of <0.2 mg/dL (<0.02 g/L), as well as a negative direct antiglobulin (Coombs) test result and proteinuria (urinary protein, 1.25 g per 24 h). Renal biopsy showed thrombotic microangiopathy with glomerular and arteriolar microthrombi (figure 1), and electron microscopy revealed the presence of microtubuloreticular structures, suggesting a viral infection. A diagnosis of hemolytic uremic syndrome was made. Further diagnostic examination excluded thrombotic thrombocytopenic purpura because of a normal von Willebrand factor—cleaving protease level (65%). A rapid strip test (Panbio) showed seroconversion to dengue virus IgM and IgG antibodies. Dengue virus ELISAs (Panbio) showed transient presence of IgM antibodies and high levels of IgG antibodies. Dengue fever was confirmed by a positive dengue virus type 2 PCR result on EDTA plasma. All other serological test and culture results remained negative. The patient was treated with plasmapheresis, hemodialysis, and antihypertensive drugs. Signs of dengue virus—induced hemolytic uremic syndrome. Cotton wool spots, diffuse retina edema, and peripapillary hemorrhage were observed in the left eye of the patient (A). These were the only hemorrhagic signs of dengue virus infection. Renal biopsy showed microthrombi in the glomeruli (B), electron lucent changes in the glomerular basement membrane (C), and virus-associated particles on electron microscopy (D) (hematoxylin-eosin staining; original magnification, ×200 [B and C]). Acute renal failure is rare in dengue fever, and it mainly presents as shock-induced acute tubular necrosis. It has been observed as a complication of dengue fever in French Guiana (the country east of Suriname) [2] and was found to occur in 0.3% of cases in a series of 6154 patients with dengue hemorrhagic fever [3]. The glomerular changes observed in dengue hemorrhagic fever have only been scarcely described and can include a variety of signs, including IgG, IgM, and/or C3 deposition and thickening of the glomerular basal membrane [4]. Our patient showed all the characteristics of acute renal failure, with both the clinical as histological signs of thrombotic microangiopathy. Of interest, next to mild hemoptysis, peripapillary hemorrhage was the only observed hemorrhagic sign. This is a finding that infrequently occurs in dengue hemorrhagic fever and may result in permanent visual impairment [2, 5]. In conclusion, to the best of our knowledge, this is the first description of dengue virus—induced hemolytic uremic syndrome. It could very well be possible that dengue virus—induced hemolytic uremic syndrome does occur much more frequently in regions of endemicity but is simply missed because of a lack of diagnostic possibilities, as well as a lack of awareness of this serious and potentially lethal complication. Also, clinicians in areas where the virus is not endemic will see and have to treat dengue virus infection, as well as its complications, in increasing numbers of travelers. Potential conflicts of interest. All authors: no conflicts.