Liver (sclerosing cholangitis)
One of the most serious complications of hepatic LCH is cholestasis and sclerosing cholangitis. This usually occurs months after initial presentation, but on occasion may be present at diagnosis. The median age of children with this form of hepatic LCH is 23 months.
Patients with hepatic LCH present with hepatomegaly or hepatosplenomegaly, and elevated alkaline phosphatase, liver transaminases, and gamma glutamyl transpeptidase levels. While ultrasound and/or MRI-cholangiogram can be helpful in the diagnosis of this complication, liver biopsy is currently the only definitive way to determine whether active LCH or hepatic fibrosis is present. Biopsy results often show lymphocytes and biliary obstructive effects without LCH cells. Peribiliary LCH cells and, rarely, nodular masses of LCH, may also be present. It is thought that cytokines, such as transforming growth factor-beta (TGF)-beta, elaborated by lymphocytes during the active phase of the disease, leads to fibrosis and sclerosis around the bile ducts.
Seventy-five percent of children with sclerosing cholangitis will not respond to chemotherapy because the LCH is no longer active, but the fibrosis and sclerosis remain. Liver transplantation is the only alternate treatment when hepatic function worsens. In one series of 28 children undergoing liver transplantation, 78% survived and 29% had recurrence of LCH, but only two cases of recurrent LCH occurred in the transplanted liver, although other cases have been reported since the initial data was published. If at all possible, active LCH should be under control before transplant. The patients who undergo liver transplant for LCH may have a higher incidence of posttransplant lymphoproliferative disease.
Massive splenomegaly may lead to cytopenias because of hypersplenism and may cause respiratory compromise. Splenectomy typically provides only transient relief of cytopenias, as increased liver size and reticuloendothelial activation result in peripheral blood cell sequestration and destruction. Although rare, LCH infiltration of the pancreas and kidneys has been reported. Splenectomy is performed only as a life-saving measure.
Other gastrointestinal manifestations
Patients with diarrhea, hematochezia, perianal fistulas, or malabsorption have been reported.[20,21] Diagnosing gastrointestinal involvement with LCH is difficult because of patchy involvement. Careful endoscopic examination including multiple biopsies is usually needed.