Abstract: PUB240
Complement Mediated Hemolytic Uremic Syndrome After an Egyptian Vacation
Session Information
Category: Glomerular Diseases
- 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials
Authors
- Minev, Evgueni M., Nephrology Associates Of Northern Illinois and Indiana, Mount Prospect, Illinois, United States
- Eklund, Jamey E., Medical College of Wisconsin, Milwaukee, Wisconsin, United States
Introduction
Thrombotic microangiopathy (TMA) is characterized by intravascular hemolysis, low platelets, CNS & renal pathology. TTP is caused by congenital or acquired ADAMTS-13 deficiency, resulting in large vWF multimers and creation of platelet-rich thrombi. Enterohemorrhagic colitis causes HUS via shiga toxin, while complement dysregulation is an increasingly recognized cause of hemolytic-uremic syndrome (cHUS).
Case Description
A 24 year-old previously-healthy man presented with 3 days’ of bloody diarrhea, fever and abdominal cramps after returning from a 7-day trip to Egypt. He stayed in a hotel and ate meat in restaurants. He received ciprofloxicin but developed a rash, so he was then given IV Bactrim, Flagyl, and saline. Colonoscopy revealed presumed infectious pseudomembranous hemorrhagic colitis. On day 6 of symptoms, he developed AKI, thrombocytopenia, and anemia so nephrologist was consulted and TMA diagnosed.Labs listed below. Daily plasmapheresis with FFP replacement was started. Once ADAMTS13 resulted, PLEX was stopped. The patient suffered seizures and transient cortical blindness. Treatment with eculizumab was initiated with immediate symptom improvement, and complete recovery in 3 months. Genetic complement testing revealed one abnormal allele in exons 4 & 5 of CFHR5 gene. Eculizumab was successfully weaned after 6 months (monitoring by daily UA, weekly labs, CH50 monthly), and the patient remains in remission 3 years later.
Discussion
The majority of cHUS is mediated by abnormal regulatory factors (CFH, CFI, MCP); activation factors (C3 & CFB); and coagulation related factors (DGKE, THBD, PLG). Our patient had 2 abnormal alleles in the CFHR5, gene c622T>C, p.Cys208Arg in exon 5 and c480_481insA located in exon 4. While these mutations are described as variants with unknown significance (VUS), carriers of the double-mutated CFHR5 alleles have lower CFHR-5 levels. It is likely that the initial hemorrhagic colitis inflammatory milieu overwhelmed and shifted the alternative complement pathway into activated mode, leading to severe HUS, which improved only after eculizumab therapy.
Labs
| Serum | Stool | Complement |
| Platelets 19 | (-) Shiga toxin PCR | C3 70 |
| Creatinine 3 | (-) Shigella | C4 8 |
| (++) Schistocytes | (-) E Coli O157:H7 | CH50 79 |
| Haptoglobin <7.8 | C5-9 524 | |
| LDH 796 | CFH 19.6 | |
| ADAMTS13 activity 65% |