Autoimmune Gastrointestinal Dysmotility: Symptoms, Pathogenesis and Treatment

Johns Hopkins University1 enrolled

Overview

Autoimmune gastrointestinal dysmotility syndromes are poorly understood, and often difficult to treat because the underlying pathogenesis is unclear. Refractory symptoms result in an impaired quality of life. The presence of positive serum autoantibodies to peripheral nervous system gangliosides and glycoproteins is suggestive of a possible mechanism. Immunomodulator treatments have shown benefit in case reports and case series but standardized data for treatment response is lacking. Therefore, our primary aims are to further characterize this syndrome in terms of symptoms, laboratory testing, pathology, and assess treatment response of immunomodulator therapy. Our research plan involves identifying this subset of patients with autoimmune gastrointestinal dysmotility and dysautonomia, and studying them as they are managed by their gastroenterologists.The study team will administer symptom-based questionnaires in a systematic manner to assess the clinical trajectory of this population and treatment response. The investigators will also analyze laboratory values (antibody titers, tilt testing, inflammatory markers) and study pathology specimens (enteric and skin biopsies) obtained from this cohort to gain a deeper understanding of the pathogenesis of their disease.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Dysmotility Syndrome Autoimmunity

Interventions

Eligibility

Sex: ALLMin age: 15 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Males and females, Aged\>15 * Evidence of enteric dysmotility with documented abnormality on objective testing which may include high resolution esophageal manometry, gastric emptying scintigraphy, SmartPill Wireless Motility Capsule, Sitz marker studies, antroduodenal manometry or anorectal manometry. * English proficiency and literacy sufficient to sign consent form and fill out questionnaires. * Previous Mayo paraneoplastic panel testing. * Referring gastroenterologist has recommended intravenous immunoglobulin (IVIg) therapy. Exclusion Criteria: * Non-autoimmune causes of enteric dysmotility (diabetes, adrenal insufficiency, Parkinson's, thyroid, electrolytes, drugs, malignancy). * Pregnancy as documented in EPIC with serum or urine Human chorionic gonadotropin (hCG) testing * If participants believe that they are pregnant, they will need to notify a study physician who will order a serum or urine hCG test for pregnancy within EPIC and remove them from the study if the test results come back positive. * Previous treatment with IVIg.

Outcomes

Primary Outcomes

Change in upper gastrointestinal symptom severity as assessed by the Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index

The Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) is composed of 20 items and 6 sub-scales: heartburn/regurgitation (7 items), nausea/vomiting (3 items), postprandial fullness/early satiety (4 items), bloating (2 items), upper abdominal pain (2 items), and lower abdominal pain (2 items). Sub-scale scores are calculated by averaging across items comprising the sub-scale; scores vary from 0 (none or absent) to 5 (very severe).

Time frame: Every two months up to 2 years.

Secondary Outcomes

Change in Quality of Life as assessed by the Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life scale

The effect of Autoimmune Dysmotility symptoms on quality of life assessed by the Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life (PAGI-QoL). The PAGI-QOL instrument consists of 30 items, each with response options based on a 6-point scale and with a recall period of the previous 2 weeks. The items are grouped into 5 dimensions: Daily Activities, Clothing, Diet and Food Habits, Relationship and Psychological Well-being and Distress. A score per dimension as well as a total score can be calculated. The PAGI-QOL scores range from 0 (lowest QoL) to 5 (highest QoL).