#3740 AFTER ALL A TYPICAL HUS
Authors: Vidal Helena , Menezes Maria Do Mar , Fonseca Nuno Moreira , Jorge Cristina 
Published: June 2023

Abstract

Background and Aims
Typical Hemolytic Uremic Syndrome (HUS) is a thrombotic microangiopathy (TMA) characterized by the triad of acute renal failure, hemolytic anemia and thrombocytopenia. TMAs are classified into: Inherited or primary acquired (atypical HUS), secondary or infection associated. Infection with Shiga-toxin–producing Escherichia coli (E. coli), mainly of serotype O157:H7, is the most common cause of typical HUS, but other serotypes have been rarely associated such as Enteroagregative Escherichia coli (EAEC) serotype O104:H4.

Method
Case Report

Results
We report a case of a 51-years-old male with past medical history of arterial hypertension (treated with Perindopril) and IgGk Multiple Myeloma (MM) diagnosed 10 years prior submitted to two bone marrow autotransplants (9 and 4 years prior) and multiple chemotherapy agents including Carfilzomib-Pomalidomide-Dexamethasone (last cycle 4 days before the onset of symptoms). One week after returning from a trip to Brazil, he was admitted to the emergency department with a two-day history of non-bloody diarrhea (4-5 liquid stools per day) and asthenia, with similar positive familiar epidemiology. He denied abdominal pain, fever, nausea or vomiting. At physical examination, he was hypertensive (177/90 mmHg), anuric (12,5 ml/h), dehydrated and apyretic. Abdominal palpation was painless and there were no signs of peritoneal irritation. Laboratory tests showed hemoglobin 10.5 g/dl, new onset thrombocytopenia (261 000/uL » 21 000/uL), kidney disfunction (serum creatinine (sCr) 0.74 mg/dL to 9 mg/dL and serum urea (sU) 41 mg/dL to 260 mg/dL), hyperkaliemia (6 mEq/L) and metabolic acidosis (pH 7,39 and bicarbonate 18.4 mEq/L). LDH was 1949 U/L, C-reactive protein 30.6 mg/L, procalcitonin 3.77 ng/mL, haptoglobin &lt;0.07 g/L and with normal complement levels (C3 and C4). Schistocytes were present in peripheral blood smear. The diagnosis of Acute Kidney Injury related with TMA was established and the patient was transferred to the Nephrology ward and urgent hemodialysis was started. Exhaustive study was performed showing normal renal ultrasound, non-nephrotic proteinuria (1.6 g/g), urinalysis showed leukocyturia and erythrocyturia. Autoimmune study including PR3-ANCA, MPO-ANCA, anti-GBM antibody, Anti-dsDNA antibody, anti-beta 2-glycoprotein I antibodies, anticardiolipin antibodies, anti-ADAMTS13 antibodies and ADAMTS13 activity, as well as study of complement C5, C'3, C'4, factor B, H and I, anti-factor H ac, AH 50 and CH50b were unremarkable. Blood and urine culture and antistreptolysin O titers were negative. Specific stool cultures for E. coli O157, Shigella, Salmonella, Yersinia and Campylobacter were negative. Stool evaluation for parasites were also negative. Viral serology for HIV, HBV, HCV and Plasmodium tests were negative. PCR stool was required due to high suspicion of E.coli infection. The suspicion of a Carfilzomib induced TMA was also raised, while molecular techniques results were awaited. MM was stable and treatment was held until recovery of kidney function. During hospitalization the patient recovered diuresis and creatinine decreased. On the 11th day of hospitalization, he was discharged but still depended on hemodialysis. Finally, stool PCR techniques identified aatA and aggR genes associated with EAEC O104:H4 allowing the diagnosis of acquired infectious HUS rather than drug-related TMA. One week after discharge, the dialysis was stopped due to sCr 3 mg/dL. Four months later, he resumed Carfilzomib and kidney function remained stable with sCr 0.9 mg/dL, despite sustained proteinuria of 1.2 g.

Conclusion
The authors emphasize the importance of considering other causes of TMA when E.coli O157 infection is excluded, namely drug-related causes (as Carfilzomib) or less frequent infectious agents such as EAEC O104:H4. This case reveals the importance of requesting PCR in the stool even when the E.coli test is negative. This is of particular relevance in immunosuppressed patients. This diagnosis allowed continuing MM treatment.