Can treatment of malabsorption in Shwachman-Diamond syndrome improve prognosis?

Abstract

Intractable diarrhea is a rare disease that often results from congenital malabsorption due to congenital defects in luminal and brush border processing, absorption in the intestinal mucosa, or transport into circulation. Shwachman–Diamond syndrome (SDS), is a congenital malabsorption disease; it is an autosomal recessive multi-system disorder associated with exocrine pancreatic insufficiency, bone marrow dysfunction, and skeletal abnormalities.1 SDS is caused by a mutation in SBDS, on chromosome 7q11. Given that SDS is a rare inherited syndrome,2 clinical practice guidelines for the management of this disorder are limited.3 Growth failure with malnutrition is a common feature in the first year of life due to various factors, including inadequate nutrient intake with or without feeding difficulties, pancreatic insufficiency, and recurrent infections. The clinical response to enzyme treatment in patients with SDS is usually excellent, although growth restriction may continue due to skeletal abnormalities. In this issue of the Journal, Ikuse et al. have developed consensus guidelines to improve clinical practice for intractable diarrhea, using a nationwide survey in Japan as well as a systematic review.4 The survey identified 24 patients with SDS (median age, 10.4 years; male, n = 15). The systematic review was based on the Medical Information Network Distribution Service (Minds) Handbook for Clinical Practice Guideline Development 2014 from the Japan Council for Quality Health Care,5 and Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria.6 The Minds project aims to help medical practitioners to fully utilize information related to evidence-based medicine (EBM) in their practice, and the GRADE working group has developed a common, sensible, and transparent approach to grading quality (or certainty) of evidence and strength of recommendations. To identify the relationship between internal interventions and outcomes (development, ordinary school attendance rate, working experience rate, necessity of treatment, quality of life and life expectancy), the clinical question was identified as follows: can internal treatment of malabsorption improve prognosis in patients with SDS? The sample size, however, was small, and only limited information was obtained from the survey. Furthermore, the systematic review did not identify any high-quality evidence from randomized controlled trials (RCT) or meta-analyses. Based on case reports, expert opinions, and clinical information from patients with SDS in Japan, however, there is evidence for the efficacy of internal medicine interventions such as enzyme replacement and vitamin supplementation. As such, the authors concluded that the answer to the clinical question was as follows: internal medicine interventions for malabsorption in patients with SDS should be performed to improve fat absorption and stool condition, but it was not clear whether these treatments improve the prognosis of the underlying malabsorption or not. The author declares no conflict of interest. J.M. designed and wrote the editorial.