Pharmacokinetics of Mycophenolic Acid and Dose Optimization in Children After Intestinal Transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (MPS) is now commonly used in pediatric intestinal transplantation (Tx), but to date, no clear recommendations regarding the dosing regimen have been made in this population. The aim of this study was to determine the MMF/MPS dosage required to achieve an area under the plasma concentration-time curve from 0 to 12 hours (AUC0-12) for mycophenolic acid (MPA) greater than 30 mg·h·L in children after intestinal transplantation. METHODS: A pharmacokinetic study was conducted in 8 children (median, 9.4 years; range, 0.75-15.8 years) at a median time of 113 months (range, 1.5-160 months) after intestinal transplantation. RESULTS: MMF was initially introduced at a low median starting dose of 687 mg·m·d (range, 310-1414 mg·m·d). One of the 3 patients who received MPS and 2 of the 6 patients who received MMF had an MPA AUC0-12 value below 30 mg.h.L. The median MMF dosage had to be increased by 91% (1319 mg·m·d versus 687 mg·m·d) to reach AUC0-12 values above the defined target level of 30 mg·h·L. CONCLUSIONS: When used in combination with tacrolimus and steroids, an initial MMF dose of 600 mg/m twice a day would be recommended to children after intestinal transplantation to achieve MPA exposure similar to those observed in adults and children after the transplantation of other organs. Further studies are required to recommend a suitable dosage for pediatric intestinal transplant recipients who receive MPA.

A patient with Simpson-Golabi-Behmel syndrome, biliary cirrhosis and successful liver transplantation.

Simpson-Golabi-Behmel syndrome type 1 (SGBS1) -OMIM 312870- is a rare X-linked inherited overgrowth syndrome caused by a loss of function mutation in the GPC3 gene. Affected patients present a variable phenotype with pre- and post-natal macrosomia, distinctive facial dysmorphism, organomegaly, and multiple congenital anomalies. Intellectual disability is not constant. About 10% of patients have an increased risk of developing embryonic tumors in early childhood. Only one case of biliary disease has been described so far. GPC3 is localized on Xq26. It encodes for glypican 3, a heparan sulfate proteoglycan, which among its different known roles, negatively regulates liver regeneration and hepatocyte proliferation. This report concerns a male with a SGBS1, carrier of a GPC3 pathogenic mutation, and neonatal liver disease, who developed an early biliary cirrhosis. Together with the associated risk of cancer and developmental delay, liver transplantation was discussed and then successfully performed at the age of 19 months. A hypothesis on the role of GPC3 in the patient's liver disease is also proposed.

Refractory rheumatoid factor positive polyarthritis in a female adolescent already suffering from type 1 diabetes mellitus and Hashimoto's thyroiditis successfully treated with etanercept.

Type 1 diabetes mellitus may be associated with many autoimmune diseases with the common autoimmune pathogenesis. We describe the case of a girl suffering from Type 1 diabetes mellitus and autoimmune Hashimoto's thyroiditis since the childhood and, due to the onset of Juvenile Idiopathic Arthritis during adolescence, for three years practiced therapy with an anti-TNF drug, etanercept . Currently her inflammatory markers are normal, arthritis is inactive and diabetes is well controlled. During the treatment with anti-TNF drug we observed a significative reduction of insulin dose, probably due to an increased tissue sensitivity secondary to the suppression of the activity of TNF-alpha. Several clinical trials that have evaluated the effect of immunomodulatory agents in diabetic patients, especially in those with recent onset of disease, were already performed but further studies of longer duration on a larger population are needed to assess the role of biologic drugs and immunotherapy in this group of patients.

Refractory vasculitic ulcer of the toe in an adolescent suffering from systemic lupus erythematosus treated successfully with hyperbaric oxygen therapy.

Skin ulcers are a dangerous and uncommon complication of vasculitis. We describe the case of a teenager suffering from Systemic Lupus Erythematosus with digital ulcer resistant to conventional therapy, treated successfully with Hyperbaric Oxygen Therapy. The application of hyperbaric oxygen, which is used for the treatment of ischemic ulcers, is an effective and safe therapeutic option in patients with ischemic vasculitic ulcers in combination with immunosuppressive drugs. Further studies are needed to evaluate its role as primary therapy for this group of patients.