Alagille syndrome is more than an insufferable itch.
Parents and caregivers of children with Alagille syndrome describe pruritus as the most challenging symptom, citing the anxiety, sleep deprivation, fatigue, and emotional distress associated with unrelenting itching and scratching.2-4
In addition to unrelenting itching and scratching, cholestatic pruritus leads to skin damage, bleeding, scarring, cutaneous mutilation, sleep disturbances, disrupted school activities, and more.1-4
Furthermore, many children with Alagille syndrome encounter significant growth deficits and a failure to thrive.2,4,5
We end up with bloody bed sheets, wounds on his face, and him wanting to tear his skin off. –Robigaile B.
While pruritus is considered the most unbearable symptom associated with cholestatic liver disease in Alagille syndrome, xanthomas are also common, affecting 30% to 42% of patients and usually appearing at a median of 20 months to 48 months of age. In patients with a native liver, the presence of xanthomas is associated with a worse 10-year survival rate than in those without.2,6
Out of a group of children with Alagille syndrome who had xanthomas (36%)3:
Xanthomas are also associated with poor long-term hepatic outcomes.7
Malnutrition and growth deficiencies are common in Alagille syndrome, and these may be related to the impaired absorption of fat and fat‑soluble vitamins. Children may have growth hormone resistance, and their short stature may be because of cholestasis, cardiovascular abnormality, and/or defective bone development.7,8
Previously, treatment options were very limited.1 Therapy was focused on the consequences of liver disease, as well as the surgical and medical treatment of congenital heart defects.9 While several off-label, unapproved medications are frequently used to treat cholestatic pruritus or other symptoms of cholestatic liver disease, including rifampin, ursodiol, cholestyramine, naltrexone, and antihistamines, these approaches may not be entirely effective.1,9
We run 14 syringes of medication through his G-tube every morning, night, and midnight. Still, he itches and scratches all the time. –Chad H.
As a result of medical management shortcomings, surgery becomes the only viable option to treat the signs and symptoms of cholestatic pruritus in Alagille syndrome.
Indications for liver transplant include1,10,11:
Therefore, there is a high unmet need in Alagille syndrome for more pharmacologic strategies to limit the progression of liver disease and need for surgical interventions, including liver transplant.1
...Knowing our son might one day need a liver transplant, we worried and had many questions. –Maribel V.