P1810INFECTION TRIGGERS AS A COMPLEMENT-ACTIVATING STATE IN ATYPICAL HEMOLYTIC-UREMIC SYNDROME IN CHILDREN
Authors: Emirova Khadizha , Tolstova Evgeniya , Orlova Olga , Muzurov Alexandr , Pankratenko Tatiana , Abaseeva Tatiana , Generalova Galina , Mstislavskaya Sofya 
Published: June 2020

Background and Aims

Atypical hemolytic-uremic syndrome (aHUS) is a rare life-threatening disease, which is based on the dysregulation of the complement system. Different complement-activating factors is known for aHUS, including infections, vaccination, concomitant diseases, pregnancy, surgical interventions, transplantation, etc. In 24% of cases, a connection with diarrheal prodrome is revealed, in 18% - with acute respiratory infections. The diagnosis of aHUS is established if other forms of thrombotic microangiopathy (TMA) are rejected: HUS associated with Stx-producing strains of E. Coli and Shigella dysenteriae (STEC / Stx - HUS), TTP. We analyze the etiology of trigger events in children with aHUS.

Method

An analysis of 165 case histories of children with aHUS was carried out for the period from 2000 to 2019. Of these, 70 are boys and 95 are girls. The average age was 4.83 ± 3.84 years (from 2.5 months to 17.8 years). The diagnosis of aHUS was established on the basis of microangiopathic hemolysis, thrombocytopenia, organ dysfunction and recurrent TMA activity. 66 patients were genetically screened, among which mutations in genes encoding complement proteins were detected in 23 (34.9%) children.

Results

The prodromal period of patients with aHUS was characterized by fever (53.9%), weakness (42.4%), decreased appetite (27.3%), catarrhal symptoms (20.6%), nausea (17.6%), and vomiting ( 63%), abdominal syndrome (26.7%), diarrhea (38.8%), hemocolitis (12.1%). Among the trigger events, acute intestinal infections accounted for 44.2% of cases, acute viral infections - 26.0% (with catarrhal syndrome - 20.6%, intestinal - 5.4%), herpetic infection (CMV, VEB, HSV 1 type) was found in 3% of cases. In 10.3% of children, the TMA symptom complex developed after vaccination with mainly live attenuated vaccines, in 4.2% against other rare conditions (trauma, taking an unknown drug, tonsillitis, etc.). In 12.1% of cases, the disease manifested itself without a complement-activating state. E.coli was confirmed in 16 observations (EHEC - 12, EagEC - 2, EPEC - 2), shigellosis (Shigella Flexner 6) was detected in 1 case. The nature of viral diarrhea was identified in 8 patients: rotovirus RNA - 4, adenovirus DNA - 2, norovirus RNA - 2, type 5 Coxsackie RNA - 1. In the case of TMA after E.coli and shigella, the initial diagnosis was STEC / STx - HUS, which was subsequently transformed into aHUS due to the recurrent TMA activity with persistent dialysis-dependent AKI, and the addition of extrarenal symptoms not associated with volume overload.

Conclusion

Infectious diseases are the most common complement-activating condition for the implementation of aHUS in children. Among them, in most cases, diarrheal prodrome is associated with acute intestinal infections, which differs from population data (44.2% vs 24%). With the development of TMA in children with escherichiosis/shigellosis, repeated episodes of hemolysis, platelet consumption, the appearance of extrarenal symptoms with normalization of hematological parameters, the detection of pathogenic mutations in complement genes and the positive effect of complement blocking therapy (eculizumab) confirms the diagnosis of aHUS in this category of patients. To exclude or confirm aHUS in these cases, monitoring of clinical and laboratory data is necessary.