GI Symptoms Are an Important Component of DM Disease Burden
The involvement of gastrointestinal functions in all types of myotonic dystrophy is well documented (see MDF’s summary at: http://www.myotonic.org/what-dm/how-dm-affects-your-body/gastrointestinal-system). Common GI symptoms include difficulties in chewing or swallowing, GI reflux, abdominal or chest pain, gallstones, constipation, diarrhea, impaired/painful bowel movements, and incontinence. GI manifestations have been treated by repurposing existing drugs (e.g., mexiletine, metoclopramide, cholestyramine) or behavioral modifications. Awareness of the types and breadth of GI manifestations from appropriately powered studies is vital to inform patient management.
Report on GI Manifestations from a Registry-based Study
James Hilbert and colleagues have reported findings of the frequency, progression and management of GI manifestations using data from the National Registry of Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Patients and Family Members. The investigators evaluated Gi manifestations in a cohort of adult patients (913 DM1 and 180 DM2) enrolled in a patient-reported registry, analyzing data collected between 2002 and 2016, with annual updates on registrants.
GI Manifestations Represent a Substantial Factor in the Burden of Disease.
GI involvement was already prevalent among registrants at initial data entry, as 79% of DM1 and 77% of DM2 registrants reported one or more manifestations. Less than 2% of DM1 and none of the DM2 patients reported GI involvement as the first sign of their disease. In order of descending frequency, trouble swallowing, acid reflux, and constipation were most commonly reported for DM1, while constipation, acid reflux, and trouble swallowing were most commonly reported for DM2. Abnormal liver problems were in sufficient numbers (6-8% of DM1 and DM2) to potentially be a factor for clinical trials. As in prior reports of gender differences, female sex was associated with a higher frequency of GI manifestations in both DM1 and DM2 (constipation and gallbladder problems in this study)Analysis of management practices for GI manifestations included 59 medications used in DM1 and 28 medications in DM2.
Analysis of disease progression in this studied was based on the approximately 50% of DM1 and DM2 registrants with data available at baseline and year 5. For DM1, trouble swallowing (the most frequent symptom at baseline) and acid reflux were the most frequently reported manifestation not previously present at baseline. Likewise, for DM2, manifestations of constipation and swallowing (the first and third most frequent symptoms, respectively, at baseline) were most frequent new reports at year 5.
Better Understanding of Causes, Consequences and Treatment of GI Manifestations Will Require International Collaboration
The research team notes that GI manifestations have complicating consequences for disease management and patient quality of life. Disease duration was associated with GI manifestations, confirming prior findings in DM1. The pathogenic mechanisms and putative biomarkers for many of the GI manifestations are poorly understood—this group noted no association with repeat length—and treatments are symptomatic. Often symptomatic treatments haven’t been systematically studied in DM. Finally, these researchers note the importance of data sharing to assess GI manifestations, and their progression and treatment, across a larger, better powered cohort.
Hilbert JE, Barohn RJ, Clemens PR, Luebbe EA, Martens WB, McDermott MP, Parkhill AL, Tawil R, Thornton CA, Moxley RT 3rd; National Registry Scientific Advisory Committee/Investigators.
Neurology. 2017 Aug 30. pii: 10.1212/WNL.0000000000004420. doi: 10.1212/WNL.0000000000004420. [Epub ahead of print]