Developing aHUS complicates baby’s HUS recovery, but drug helps
Prompt use of approved treatment leads to boy's full recovery
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Developing atypical hemolytic uremic syndrome (aHUS) complicated the recovery of a baby boy with typical hemolytic uremic syndrome (HUS) — a related condition caused by an infection — but prompt treatment with the approved infusion med Soliris (eculizumab) led to a complete recovery.
That’s according to a case report from Italy, in which genetic testing done in the infant revealed variations in genes encoding proteins of the complement system, a part of the immune system that becomes overactive in aHUS. Such genetic variants are not uncommon in the general population, the researchers noted, and may predispose patients — such as this 11-month-old boy — toward aHUS when another trigger is present.
For this child, that trigger was an infection with Shiga toxin-producing Escherichia coli (STEC), the researchers noted. But Soliris can, as seen in this case, suppress the overactivation of the immune system, and prove to be an effective treatment.
The bigger question for researchers here was “whether the patient experienced aHUS triggered by STEC infection or [a type of HUS] followed by … aHUS.” The team noted that “these cases generate a diagnostic and interpretative dilemma with potentially serious consequences.”
“Variants in complement regulatory genes … may be responsible for complement dysregulation in patients with STEC-HUS [STEC-associated HUS],” also known as typical HUS, the researchers wrote.
In this baby with STEC-HUS, aHUS was suspected after levels of platelets, the cell fragments responsible for blood clotting, unexpectedly dropped even with supportive care for STEC-HUS.
“The novelty of the present case report resides in the proposal of using the day-by-day course of platelet count as a reference that may facilitate the early recognition of aHUS in patients with documented STEC infection,” the researchers wrote.
The study, “Typical or atypical hemolytic uremic syndrome? That is the question,” was published in the journal Pediatric Nephrology.
In aHUS, uncontrolled activation of the complement system causes blood clots to form in small blood vessels, leading to red blood cell destruction, called hemolysis, kidney damage, and a low platelet count.
While most patients have inherited aHUS-predisposing mutations in genes that encode proteins of the complement system, a trigger such as an infection is typically needed for aHUS to develop.
Typical HUS, or STEC-HUS, is marked by similar symptoms, but caused by Shiga toxins produced by E. coli bacteria. A diagnosis of aHUS typically involves exclusion of STEC-HUS and other rare conditions with similar symptoms.
Still, “STEC infection may occasionally trigger aHUS in genetically predisposed individuals,” the researchers wrote, making the two conditions difficult to distinguish.
Worsening HUS in baby raised suspicion of overlapping condition
Now, a team of researchers in Milan detailed the case of this small boy whose STEC-HUS was complicated by the development of aHUS.
The baby was admitted to the hospital with a fever and diarrhea that did not contain blood. He fed poorly, his hands and feet were swollen, and his kidneys did not function properly, per the report. Blood tests revealed signs of hemolysis and low platelets counts.
A stool test detected Shiga toxins that are released by a type of E. coli bacteria, confirming a diagnosis of STEC-HUS. Treatment focused on supportive care, the researchers noted, with the child receiving intravenous, or into-the-vein, fluids to maintain hydration, an antibiotic to treat the infection, and blood transfusions.
Despite supportive treatment, however, the infant’s kidney function continued to worsen, and he was started on dialysis, a treatment that temporarily removes waste and excess fluid from the blood when the kidneys cannot do so. This resulted in an improvement of his condition.
Urine output had increased, platelet count had returned to normal, kidney function was gradually recovering, and blood pressure, which had increased due to his kidney problems, was well-controlled with appropriate medications, per the report. Altogether, these findings suggested that the acute phase of STEC-HUS was resolving.
However, the boy’s recovery soon became unusual. Instead of remaining stable or increasing, his platelet count unexpectedly halved. This pattern differed from the normal recovery seen in more than 140 children with STEC-HUS treated at the same hospital over the previous decade, “raising suspicion of an overlapping condition,” the researchers wrote.
Case raised question of which condition triggered the other
Given the low platelet count and an additional finding of low levels of C3, a protein of the complement system, doctors suspected aHUS triggered by STEC. The boy thus was given Soliris, an aHUS-approved therapy that suppresses complement activation by blocking the complement protein C5.
His platelet count sincreased and his kidney function returned to normal. He received a second dose of Soliris before being discharged 23 days after admission.
Genetic testing later identified two variants in the CFH and CFI genes, which encode two proteins that regulate the complement system. Both were classified as variants of uncertain significance, meaning there was not enough evidence to determine whether they can cause disease.
Because the diagnosis remained uncertain — was aHUS triggered by STEC infection or was STEC-HUS followed by complement-mediated aHUS? — and the boy had fully recovered, treatment with Soliris was discontinued, the report noted.
A little more than three months later, after developing a fever and an upper respiratory infection, the boy experienced another episode of aHUS. Soliris was restarted immediately using an individualized treatment schedule, and all signs of aHUS resolved within about two weeks, the researchers reported.
“Careful monitoring of platelet count using disease-specific reference trajectories may represent a clinically useful tool to detect early deviation from classical STEC-HUS evolution and prompt timely [C5 suppressor treatment], preventing severe consequences,” the researchers wrote, calling this a “particularly challenging differential diagnosis.”
“Platelet count during recovery from STEC-HUS follows a regular course [toward normalization]. Any derangement from the regular course of platelet count should be regarded as a complication, such as infectious complications, … or aHUS,” the team concluded.
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