Rare case of Atypical hemolytic uremic syndrome: a report

Dr B. M. D. B. Basnayake at Department of Nephrology and Renal Transplant, Teaching Hospital Kandy, Kandy, Sri Lanka and colleagues have reported a rare case of Atypical hemolytic uremic syndrome. The case has appeared in the Journal of Medical Case Reports.

Thrombotic microangiopathy is a pathological condition comprised of microvascular thrombosis involving any organ of the body leading to thrombocytopenia, Coombs-negative hemolytic anaemia, and end-organ damage. The most common forms of thrombotic microangiopathies are Shiga toxin-producing Escherichia coli-mediated hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and atypical hemolytic uremic syndrome. The atypical hemolytic uremic syndrome occurs due to genetic and acquired mutations in complement regulatory factors and to complement activation factors in the immune system, mainly the alternative pathway. The atypical hemolytic uremic syndrome is a rare disease entity requiring a high index of suspicion to diagnose.

A 15-year-old, previously healthy Sri Lankan girl with no significant medical history or family history of hypertension or diabetes mellitus was admitted to a peripheral hospital with fever and skin rash of 2 weeks’ duration that was treated as chickenpox. The diagnosis of chickenpox was confirmed by a dermatologist. She developed severe lower abdominal pain. She was oliguric and tachycardic (pulse rate of 102 beats per minute), and her blood pressure was elevated to 180/100 mm Hg. Her temperature was 38.1 °C. The result of her neurological examination was normal. Her serum creatinine was 210 μmol/L (normal range 80–130 μmol/L), and she had active urinary sediments (urine full report, red cells 100–150 with 50% dysmorphic red cells). She was clinically diagnosed with acute appendicitis, confirmed with ultrasound findings and complicated with sepsis-induced acute kidney injury. She was initiated on intravenous cefuroxime 750 mg 8-hourly and intravenous metronidazole 500 mg 8-hourly and was transferred to the nephrology unit of Teaching Hospital Kandy for specialized care.

She was referred to the surgical unit, where an appendectomy was performed while she was under general anesthesia. Her appendix was inflamed, but it was not perforated. Both intravenous cefuroxime 750 mg 8-hourly and intravenous metronidazole 500 mg 8-hourly were continued. In preoperative assessment, her blood pressure was 150/94 mmHg, and her serum creatinine level was high (226 μmol/L) with hyperkalemia (5.8 mmol/L), which was corrected with a potassium-lowering regimen prior to induction of anesthesia. During the surgery, her blood pressure was under control, and her recovery was also uneventful. Later, the diagnosis of appendicitis was confirmed with the histological findings.

On postsurgery day 1, she was anuric and severely acidotic, and her creatinine level further inclined. Urgent hemodialysis was offered, and input-output was strictly monitored. A renal biopsy was performed.

On postsurgery day 3, she developed high-grade fever again, and therefore surgical site infection or femoral vascular catheter infection was suspected. Intravenous antibiotics were changed; intravenous flucloxacillin 500 mg 6-hourly was added according to the microbiology team’s opinion. The vascular catheter was removed, and catheter tip and blood samples, which were taken with aseptic non touch technique, were sent for cultures. The culture results were negative for aerobic and anaerobic bacteria and fungi, and surgical site infection was also excluded. Findings of an echocardiogram ruled out infective endocarditis.

The patient’s full blood count showed haemoglobin of 7.6 g/dl, platelet count of 68 × 109/L, and white cell count of 19.5 × 109/L. Blood film revealed features of microangiopathic hemolytic anemia. The patient’s serum creatinine was 312 μmol/L. Her liver enzymes were within the normal range. Her coagulation profile was normal, including the thromboelastogram. Her lactate dehydrogenase (LDH) level was 3124 U/L. Her reticulocyte count was 7.27%. Her D-dimer was negative at 0.78 mg/L (< 1). Her Coombs test result was negative. With the blood film evidence and other test result findings, together with unexplained fever, TTP was suspected. She was admitted to the intensive care unit (ICU) and was initiated on therapeutic plasma exchange (TPE) together with cryo-poor plasma as the replacement fluid.

Her ICU stay was complicated with pulmonary haemorrhage with lower respiratory tract infection followed by respiratory failure requiring mechanical ventilation, and intravenous antibiotics were upgraded to meropenem 1 g 12-hourly and levofloxacin 500 mg once per day. Initially, plasma exchange was carried out daily (for 14 days) and then every other day (for 28 days). She was offered hemodialysis every other day for 14 days, every third day for 21 days, and every fourth day for 24 days. Hemodialysis was stopped following the improvement of urine output.

Histological examination of renal biopsy revealed fibrinoid necrosis of small arteries. The patient’s complement C3 was 57.6 mg/dl (normal range 90–180), and her complement C4 was 17.4 mg/dl (10–40). Results of tests for antineutrophil cytoplasmic antibodies, antinuclear antibody, and double-stranded deoxyribonucleic acid (DNA) were negative. Test results for hepatitis B surface antigen, hepatitis C antibody, human immunodeficiency virus and VDRL (Venereal Disease Research Laboratory) were negative. Blood culture results were negative for E. coli. Investigation findings together with hypertension, blood picture features of microangiopathic hemolytic anaemia, kidney injury, and pulmonary haemorrhage associated with respiratory failure prompted the diagnosis of the atypical hemolytic uremic syndrome. ADAMTS-13 level and genetic studies were not done, owing to the unavailability of resources.

As the long-term management plan, the patient was offered long-term plasma exchange in a tapering regimen. Initially, two cycles per week were arranged. She gradually responded to treatment, and investigation results were improving. She stayed in the ICU for 14 days and was discharged from the hospital after a total of 69 days with two antihypertensive agents and a tapering regimen of oral prednisolone.

She was regularly followed up in the nephrology clinic, and TPE was offered once per week for 6 months and then tapered to once in 2 weeks, 4 weeks, 6 weeks, and 8 weeks. Following a total TPE course of 30 months, plasma exchange therapy was omitted. Her haemoglobin, platelet count, serum creatinine, LDH, reticulocyte count, and blood film were all within normal ranges.

Journal of Medical Case Reports

For more details click on the link: https://doi.org/10.1186/s13256-019-2334-y