What is the effect of non-invasive and invasive treatments for dysphagia in patients with inclusion body myositis (IBM)?

Wat is het effect van niet-invasieve en invasieve behandelingen voor slikstoornissen bij patiënten met idiopathische inclusion body myositis (IBM)?

Considerations – from evidence to recommendation

Pros and cons of the intervention and the quality of the evidence

A literature search was performed to investigate the effect of (non-)invasive treatment on dysphagia in patients with IIM, JDM and IBM. Improvement in swallowing function was defined as a primary outcome measure. Only two studies were identified that investigated interventions for dysphagia in patients with IBM, in particular treatment with IVIg. Unfortunately, these two studies had small sample sizes, insufficient external validity and poor methodological quality, causing bias and insufficient internal validity. As a result, the recommendations of this guideline module are based on observational studies and expert opinion.

Identification of patients with dysphagia

IBM-related dysphagia is often related to impaired bolus transport leading to oropharyngeal bolus residue, and/or to airway entrance of the bolus (penetration or aspiration). Usually, food boluses have to be swallowed repeatedly before passing through the esophagus sometimes accompanied by pharyngeal regurgitation, multiple clearing swallows a compensation to avoid bolus residue, or coughing due to penetration or aspiration. Other manifestations of dysphagia in patients with IBM include dysphonia with a wet gurgly voice, frequent clearing of the throat, drooling, and nasal regurgitation (Cox 2011). Patients often report a prolonged mealtime. Coincident respiratory muscle weakness is rare, but may affect the ability to cough and to expectorate a bolus in the event of penetration of aspiration.

Screening for dysphagia-related symptoms or complications starts with medical history-taking, usually by the neurologist and/or rehabilitation physician. For IBM the screening questions ‘Does food get stuck in your throat’ and ‘Do you have to swallow repeatedly in order to get rid of food’ reliably predict impaired bolus propulsion on VFSS and are an appropriate means in selecting patients with IBM for further swallowing evaluation (Cox 2011). In addition, dysphagia-specific self-report symptom questionnaires, for example the Eating Assessment Tool-10 (EAT-10), can be used in adults to identify patients at risk for dysphagia (Heijnen, 2016; Heijnen, 2020). It is important to note that the EAT-10 has not been validated for the screening of IBM-related dysphagia  and that it has a low positive predictive value.

Referral of patients with dysphagia

We recommend referring patients with dysphagia-related signs, symptoms or complications to a speech and language therapistand dietician in secondary or tertiary care facilities, preferably in a rehabilitation team with expertise in the treatment of neuromuscular disorders. We also recommend good oral hygiene following mealtimes and regular visits to the dentist and dental hygienist.

Speech and language therapists can clinically assess the type and severity of dysphagia and initiate treatment. If further in-depth instrumental assessment of dysphagia is needed, the patient can be referred to an experienced otolaryngologist within an interdisciplinary dysphagia team. If indicated, endoscopic evaluation of swallowing (FEES) and/or a videofluoroscopic swallow study (VFSS), performed in collaboration with the speech and language therapist of the interdisciplinary dysphagia team, can determine the nature and severity of the swallowing difficulties and exclude or confirm other reasons for dysphagia apart from the IBM.

Several interventions may improve dysphagia in patients with IBM. Treatment of dysphagia aims to:

1. improve health-related quality of life through enabling the patients amongst other to eat and drink that they enjoy, improving independence from caregivers, reducing socially undesirable swallowing sounds or actions while eating, reducing the fear of choking, cutting down on mealtime, etc., without eating and drinking consuming the majority of the day.
2. improve the overall condition of the patients by preventing involuntarily weight loss and by providing nutritional support, i.e., oral nutritional supplements, meeting their energy and protein requirements.
3. prevent complications such as aspiration pneumonia or cachexia.

The Dutch National Neuromuscular Diseases (NMD) Knowledge Network Speech-Language Therapy has issued a consensus document which included several recommendations on expert opinion level:

1. Dysphagia-education with regard to:
   1. The chewing- and swallowing process in dysphagia
   2. The relation between chewing- and swallowing activities and energy-saving strategies in this context (effects of fatigue, eating and drinking in social settings, eating and drinking without help)
   3. First aid in case of choking, including the Heimlich maneuver
   4. Coughing techniques (together with a physical therapist)
2. Optimizing head and body posture/compensatory strategies (together with anotolaryngologist, physiotherapist, or occupational therapist)
3. Adjusting bite- and swallow size
4. Using patient-tailored bolus modification (i.e., thickening of liquids) and/or modified texture diet based on the outcomes of clinical and instrumental swallowing assessment – FEES & VFSS (together with an otorhinolaryngologist and a dietician)
5. Using aids, e.g., adapted cutlery and cups (together with an occupational therapist)

Invasive treatment of cricopharyngeal muscle dysfunction

Several surgical and non-surgical interventions can be used to treat dysfunction of the cricopharyngeal muscle in IBM; cricopharyngeal myotomy, botulinum toxin, or balloon dilatation. The available evidence for these interventions is limited. Most studies are retrospective, include a very small number of IBM patients, include limited statistical information, and/or don’t include a control group (Houser, 1998; Oh, 2007; Dezoysa, 2013; Hoesseini, 2016; McMillan, 2021; Haapaniemi, 2001; Liu, 2004; Schrey, 2017; Di Pede, 2016). Specific interventions are discussed below.

Cricopharyngeal myotomy

Transcervical or endoscopic cricopharyngeal myotomy can alleviate dysphagia in well-selected patients with IBM. However, in a minority of cases cricopharyngeal myotomy can lead to serious complications such asaspiration pneumonia, esophageal perforation, mediastinitis, and death. Hence, careful selection of patients in whom benefit can be expected, timing of surgery, pre-operative swallowing assessment (FEES, VFSS, respiratory function), experience of the surgeon, surgical technique and approach, and discussion about the risks/benefit ratio are warranted. Consider pre-operative high-resolution manometry with impedance and a VFSS to optimize patient selection and to avoid cricopharyngeal myotomy in case of a normotonic cricopharyngeal muscle with hypotonic pharyngeal constrictor muscles. Also, gastro-esophageal reflux should be excluded before cricopharyngeal myotomy to avoid aspiration (pneumonia) of gastric content. Because of this, the working group recommends referring patients eligable for cricopharyngeal myotomy to an otorhinolaryngologist-board certified head-and-neck surgeon with a track record in cricopharyngeal myotomy, preferably in an IBM Center of Expertise. Despite the lack of high-quality evidence, the working group concludes that cricopharyngeal myotomy should be considered in carefully selected and well-assessed IBM patients with dysphagia due to cricopharyngeal dysfunction.

The largest study investigated 41 patients with IBM who underwent cricopharyngeal myotomy at the Mayo Clinic in Rochester between 1981 and 2020 (McMillan, 2021). Eighteen out of these 41 patients underwent transcervical cricopharyngeal myotomy (TCPM) and 23/41 underwent endoscopic CO₂ laser cricopharyngeal myotomy (ECPM). Mean age at intervention was 75 years. A previous intervention had been performed in 17/41 patients: esophageal dilation in 12/17 and cricopharyngeal myotomy at a different hospital in 5/17. The exact criteria to qualify for intervention were not defined in the study.

The degree of cricopharyngeal narrowing as measured by a dynamic barium swallowing study or VFSS significantly improved in both surgical groups (TCPM: pre-operative 73% narrowing; post-operative 3% narrowing. ECPM: pre-operative 80% narrowing; post-operative 20.2% narrowing). Dysphagia-specific questionnaires were administered in 12 patients, mainly in the ECPM group (11/12), and showed a significant pre- versus postintervention improvement (EAT-10; Reflux Severity Index (RSI); Functional Outcome Swallowing Scale (FOSS)). Recurrent dysphagia occurred in 11/41 (26.8%) patients and occurred immediately directly after the intervention in 6/11 patients. There was no difference in recurrence risk between the two surgical groups (TCPM versus ECPM). Postoperative complications occurred in 5/41 (12.2%) patients: 3/41 required a nasogastric tube due to subcutaneous emphysema, 1/41 required revision surgery due to hemoptysis, 1/41 developed aspiration pneumonia.

Cricopharyngeal injection of botulinum toxin

Transcervical or endoscopic administration of botulinum toxin in the cricopharyngeal muscle can be used as a diagnostic test prior to myotomy, or as a treatment of dysphagia in well-selected patients with IBM. Most studies concern single cases or small retrospective case series (N=1-17) that compare swallowing function before and after intervention (Haapaniemi, 2001; Liu, 2004; Schrey, 2017; Di Pede, 2016; Witting, 2022).

A Danish study prospectively described the outcomes of cricopharyngeal injection of botulinum toxin in 10 IBM patients with subjective dysphagia and an abnormal cold-water swallow test (Witting, 2022). Scores on a non-validated dysphagia questionnaire improved in 9/10 patients (Cox, 2009). The results of the cold-water swallow test did not show a statistically significant improvement.

Based on the current literature and the significant limitations of the above-mentioned studies – i.e., retrospective observational studies or prospective case series, no standardization of outcome methods, no validated swallowing measurements, limited objective findings, small intervention groups – the working group concludes that there is insufficient evidence to support cricopharyngeal injection of botulinum toxin as a treatment for dysphagia in patients with IBM.

Cricopharyngeal balloon dilatation

Balloon dilatation is mainly used in patients with fibrosis of the cricopharyngeal muscle, often as the result of radiotherapy for malignancies of the head and neck. The working group concludes that there is insufficient evidence to support balloon dilatation as a treatment for dysphagia in patients with IBM.

Percutaneous gastrostomy

Endoscopic or radiological gastrostomy can be considered in patients with IBM and severe dysphagia, in whom other treatment options for dysphagia have yielded no or insufficient effect and in whom a (re-)myotomy is not possible.

Intravenous immunoglobulins

Two studies have investigated the effect of IVIg on dysphagia in patients with IBM (Dalakas, 1997; Dobloug, 2012). Both studies did not find any clinically relevant or statistically significant effect of IVIg on dysphagia in patients with IBM. The level of evidence of these studies is poor. Due to the methodological flaws of the study design and the lack of statistical information in the results of these studies, it is not possible to draw reliable conclusions from these findings. Based on the available literature, the working group does not recommend IVIg to treat dysphagia in patients IBM.

Values and preferences of patients

Dysphagia is a common feature of IBM with significant impacts on daily life, social participation, physical, and psychological quality of life (Senn, 2022). A large survey among 510 patients with IIM also including IBM asked patients to rank the importance of their symptoms (Mecoli, 2019). Dysphagia was ranked 8^th out of 24 domains, following muscle-related symptoms, fatigue, impaired levels of physical activity, medication-related side effects, pain, skin-related symptoms, and respiratory/pulmonary symptoms. Examples of domains that were considered less important than dysphagia included increased risk of infection, reduced work ability, cognitive impact, joint-related symptoms, and sleep disorders. Timely identification of dysphagia may not only reduce complications, but also increase health-related quality of life.

Costs

IBM is associated with a significant increase in healthcare resource utilization, which is mainly driven by an increase in office visits, but also by increased visits to the Emergency Room and hospital admissions (Capkun, 2017). Prevalence of pneumonia and aspiration pneumonia was twice the prevalence in the healthy community, and other studies identified pneumonia as the cause of death in up to 28% of patients with IBM. However, considering the significant morbidity associated with dysphagia due to pulmonary infections, hospital admissions with IV antibiotics, and invasive procedures such as nasogastric tube placement or PEG/PRG, it seems reasonable to assume that timely detection and treatment of dysphagia may reduce costs of healthcare resource utilization and work loss.

Acceptability, feasibility and implementation

Adequate dysphagia care for patients with IBM is best provided in an interdisciplinary team experienced in neuromuscular disorders. Rehabilitation teams with expertise in neuromuscular disorders are not available in all hospitals. Referral to Myositis Centers of Expertise may provide barriers due to travel time, costs and logistics associated with travel, and preferences of patients to be treated in their local community hospital.

Furthermore, neurologists need to be aware of the signs, symptoms and potential complications of dysphagia in IBM to ensure early identification and subsequent referral to rehabilitation specialists for treatment and, if appropriate, advance care planning. Speech and language therapists and otolaryngologists should be aware that dysphagia is a common feature of IBM, and should have knowledge of the appropriate diagnostic assessment and treatment methods for this patient popularion, preferably in an interdisciplinary dysphagia team.

Cricopharyngeal myotomy should be considered in carefully selected and well-assessed IBM patients with dysphagia due to cricopharyngeal dysfunction. Cricopharyngeal myotomy can greatly improve health-related quality of life in patients with IBM and should be carried out by an otorhinolaryngologist-board certified head-and-neck surgeon with a track record in cricopharyngeal myotomy, preferably in an IBM Center of Expertise.