Remarks to the Institute of Medicine Committee

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Last Updated: 29 January 2014 29 January 2014

Massachusetts CFIDS/ME and FM Association presentation to the Institute of Medicine Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

January 27, 2014
by Charmian Proskauer, President

Good afternoon, and thank you for inviting me to speak, and thank you for taking on this awesome responsibility. My name is Charmian Proskauer and I am president of the Massachusetts CFIDS/ME & FM Association. I am also a member of the Let’s Get It Right group. My written comments are more complete than these brief remarks and also include references to back up my statements.

I am here to speak on behalf of children and adolescents with this illness.

Children and Adolescents are an important group to consider separately (not merely as a “sub-group” of the adult illness).

For the last two years our Association been working to educate school nurses about ME/CFS in children and adolescents. School nurses can serve as gatekeepers to help identify ill children who may have ME/CFS and give information and support to their families and to the school.

There are several conditions that would alert a school nurse (or an informed pediatrician) to the possibility of an ME/CFS diagnosis.

• The clinical presentation, while variable, fits into patterns that are described by the existing case definition for pediatric ME/CFS.
• The illness often follows mononucleosis — 13% of mono cases develop into ME/CFS.
• As in adult ME/CFS, symptoms can wax and wane. A child who arrives at school and seems OK may need to go home by lunchtime. A pattern of variable symptoms over time may be an indication of ME/CFS.
• ME/CFS is the most frequent cause of prolonged absence from school, and it is this prolonged absence that often leads school officials down the wrong path of falsely labeling ill children with “school phobia” or taking the parents to court for Medical Child Abuse. Children with ME/CFS want to go to school — and will tell you that if you ask them!

A separate clinical definition for pediatric ME/CFS has been developed and should be added to the list of clinical definitions that you consider in your study.

• The adult definition is not appropriate for children and youth, as the initial presentation of symptoms may be quite different from that of adults. Also it may not be appropriate to ask an ill child to wait until the symptoms have persisted for 6 months (most of a school year) before receiving a diagnosis which will allow helpful management and treatments to be put in place.
• While the onset, symptoms and course of the illness in youth can be quite different from that in adults, as in adults the symptoms vary in nature and intensity on any given day. This variability can cause providers and others uninformed about the illness to believe the symptoms are psychological.
• Also as in adults, the illness is usually prolonged, lasting from several years to 10 or more. When a child changes schools, often the process of educating school officials has to start all over again.
• The range of issues needing to be dealt with is also different — important aspects for a child include educational needs and social development as well as physical health. Addressing these issues involves the school, the family, and the community as well as providers of health care.

Families with a chronically ill child already face many challenges. Caring for an ill child who does not have a recognized diagnosis, or with a diagnosis that family, friends, and school officials do not understand, is especially difficult. Without a diagnosis, the more severely ill a child is, the more likely the family will be under pressure from the school and the threat of legal action against them.

Pediatricians, at least in our state, have little knowledge of ME/CFS. When a school nurse recognizes a child with symptoms suggestive of ME/CFS, it is usually very difficult or impossible to find a pediatrician who can make the diagnosis which would allow the child to receive needed educational accommodations and begin appropriate treatment. Lacking a correct diagnosis, there is a significant risk, especially in the case of a severely ill child, that an incorrect diagnosis of Medical Child Abuse or Munchausen syndrome by proxy may be given, and the situation may escalate to the point where the child could be removed from the home or legally required to undergo an inappropriate treatment.

On the positive side, outcomes for youth, if good information, treatments, and social and educational support are provided promptly, seem to be better than outcomes for adults. However it should be noted that these studies do not include the most severely ill children, so we do not know the outcomes for them.

In summary:

• We urge this committee to give pediatric ME/CFS sufficient attention during your review.
• You should add the existing clinical definition for Pediatric ME/CFS to your scope of study.
  
• Your plan to educate physicians should explicitly address pediatricians and school nurses, as well as the providers of adult care. Pediatricians need to be confident in diagnosing this illness as a physical, not psychological, one.

Please do not defer this; great harm is done every day to children and families due to this lack of knowledge.

I would like to thank the NJ Chronic Fatigue Syndrome Association for their pioneering work with children and youth, and to the patient associations in NJ and CT for setting the model for providing support to children with ME/CFS and their families.

I now share three brief but very important points concerning your review of the research literature.

1) Reviewers need to focus carefully on the case definition used to select patients for the study, since this greatly influences the results of the study. A study group that is overly broad or heterogeneous will lead researchers to incorrect conclusions.

2) In any research which discusses psychiatric symptoms (such as depression) in the study group, a careful distinction must be made between pre-existing and post-illness manifestations of the condition. Depression following the onset of ME/CFS often occurs, as it does in many chronic illnesses. Any paper which does not clearly make this distinction is suspect and should be disregarded. Such flawed “research” is responsible for much of the misinformation about ME/CFS being a psychiatric illness not a medical illness, leading to recommendations of psychiatric care as the primary treatment instead of attempts to treat the underlying medical condition.

3) In closing I want to point out that over the years at least some mainstream journals have refused to even consider publishing papers on ME/CFS, regardless of their merit. This has forced ME/CFS researchers to sometimes seek less traditional avenues to publish their work, especially in years past. Please do not overlook these contributions just because they do not appear in the journals you may usually read.

Thank you.

Oral Complications in Sjögren's Syndrome and Chronic Dry Mouth

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Last Updated: 08 November 2015 08 November 2015

By R. Sanderson

Dry mouth and various oral and dental complications are problematic for many people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), or Fibromyalgia (FM). Persistent dryness of the mouth could indicate an autoimmune illness like Sjögren's, linked to poorly functioning or damaged salivary glands, or be the result of side effects associated with many medications. Either way, it is a problem that warrants prompt medical or dental attention.

Dental caries, which refers to localized disease that causes decay and cavities in teeth, and oral problems have a tendency to progress much more rapidly when there is poor salivation and ongoing dryness. The goal of this article is to provide information about the serious and often devastating consequences of persistent dry mouth and treatments that can help to protect teeth and restore oral health.

Ed. Note: This article features information about oral complications, research highlights, and guidelines for people living with Sjögren's Syndrome and chronic dry mouth. Most of the information used in this article is based on a lecture given by Dr. Athena Papas for the Greater Boston Sjögren's Syndrome Support Group held on December 5, 2013 at Tufts Medical Center, Sackler Building, in Boston, MA. Additional data is included in order to provide some background information and more resources for our readers.

This material was researched and prepared by a layperson with ME/CFS and Sjögren's. Every effort has been made to accurately convey the information delivered by Dr. Papas and represent the research of other scientists brought up in this material. As always, consult with your health care provider for advice and further evaluation of new or worsening symptoms. Please see our Disclaimer. 

The first part of the article discusses issues around diagnosing Sjogren's Syndrome. If you suffer from dry mouth and are more interested in issues/treatments for this general condition, you may want to skip to the part of the article beginning with "How to minimize oral complications and maximize oral health and comfort."

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Challenges of current diagnostic criteria and future screening methods

Athena Papas, DMD, PhD, is the Erling Johansen Professor of Research, the Co-Head of Geriatric Dentistry, and the Director of the Oral Medicine Department at Tufts University School of Dental Medicine. Dr. Papas has published numerous research papers based on her extensive clinical experience in Geriatric Dentistry, Sjögren's Syndrome, medically compromised patients, and xerostomia. At the December 2013 meeting, Dr. Papas discussed research updates and oral concerns and challenges of Sjögren's in her presentation titled, "Living with the Oral Complications of Sjögren's Syndrome."

Dr. Papas began her presentation with a short, educational video, "Does your patient have Sjögren's Syndrome?" released for dentists. The following is a brief description of Sjögren's taken from this video:

"Although hallmark symptoms are dry eyes and dry mouth, Sjögren's may also cause dysfunction of other organs such as kidneys, gastrointestinal system, blood vessels, lungs, liver, pancreas, and the central nervous system. Patients may also experience extreme fatigue and joint pain and about ten percent of patients develop lymphoma of their salivary glands. All instances of Sjögren's are systemic, affecting the entire body."

Sjögren's can exist alone, as a primary condition, or with another connective or autoimmune tissue disease such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma, and other conditions.

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Early diagnosis of Sjögren's remains a challenge

Sjögren's is one of the most commonly under-diagnosed autoimmune diseases, often taking 5 to 8 years before a diagnosis is made.

While there are several techniques to assess salivary gland and ocular involvement, tests for certain autoantibodies in serum, and methods to demonstrate tissue changes, no single test is specific and sensitive enough to make a diagnosis.

Lack of international consensus regarding what defined positive evidence of the illness and ways to differentiate the two variants of the illness were some of the reasons for revision of the classification criteria for Sjögren's.

In April 2012, the latest version of the classification criteria was released by a group of international experts which included new details, rules and thresholds for tests and how these need to performed and interpreted. (Source: The Kelley's Textbook of Rheumatology, 9th edition).

The new criteria was intended, in part, to help ensure uniformity in participants selected for research.

To meet the classification criteria, there must be objective evidence in 2 out of 3 tests. For example, one of these tests must show one or more sites of inflammation per 4 mm squared area of glandular tissue for a positive result, according to the National Institutes of Health's release of April 2012, "New classification criteria released for research on Sjögren's Syndrome."

Clinicians and researchers who treat Sjögren's patients find these criteria can only detect patients with an established disease, that is, when their glands have already become damaged.

Patients will typically need to consult with at least two clinical specialties for evaluation and testing before a diagnosis can be made. The high cost of diagnostic tests, risks and discomfort associated with some of the procedures, and amount of time required to complete the testing/diagnostic process causes significant delay in diagnosis.

Continued disagreement and proposed changes to the 2012 classification criteria has gotten in the way of research for new treatments. All of the aforementioned issues underscore the importance of finding new ways to diagnose Sjögren's at an early stage of the illness.

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Turning to saliva as a diagnostic tool

Saliva is often described by researchers and doctors as a mirror of the body and its well-being. It contains valuable diagnostic biomarkers which can help to screen for periodontal and other oral diseases, various cancers, systemic illnesses, and other conditions.

Other benefits of saliva-based tests are that they are less invasive and are rapid and cost-effective ways to screen for illness or detect early signs of illness.

Saliva analysis has been used, in some capacity, over the past 20 years to evaluate various medical problems; however, the field of research specifically devoted to disease detection and surveillance is called salivary diagnostics.

An investment made by the National Institute of Dental and Craniofacial Research (NIDCR) in saliva analysis over ten years ago, has generated significant advancement in salivary diagnostics. The NIDCR research initiative funded salivary diagnostic technology development at several research centers across the United States.

This research has led to discovery and development of a "diagnostic toolbox"— identification of components in human saliva, with biomarker profiles which can be used in the diagnosis of disease. (Source: A Primer on Salivary Diagnostics, published by the American Dental Association).

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The future of salivary diagnostics

One of pioneers in salivary diagnostics is David T.W. Wong, D.M.D., D.M.Sc., the Associate Dean of Research at the University of California-Los Angeles (UCLA). Dr. Wong is also the Director at the UCLA Center for Oral/Head & Neck Oncology Research and Director of the Dental Research Institute at UCLA. Dr. Wong and the UCLA Dental Research Institute group have been instrumental in the development of salivary diagnostic biomarker profiles, which include: proteome, transcriptome, microRNA, metabolome and microbe. The Wong Lab/UCLA has established a research base that can serve as the scientific foundation for future dental and biomedical studies.

The UCLA research group has also developed statistical and informatics tools for salivary biomarker detection and validation. A prototype of this technology is a portable, integrated system that can rapidly detect multiple salivary proteins and other substances. This is an example of "point-of-care" technology that can be used at a healthcare provider's office to analyze oral fluid samples for disease or early signs of disease, eventually leading to chairside screening. Before this becomes common practice, scientists need to further investigate the potential diagnostic value of saliva and develop reliable and feasible technologies with high detection sensitivity. The future use and integration of salivary diagnostic technology may strengthen interdisciplinary patient care by changing the role that dentists and dental practitioners will play in healthcare. (Sources: A Primer on Salivary Diagnostics, American Dental Association. Salivary Diagnostics, The Wong Lab/UCLA School of Dentistry, The Dental Research Institute website).

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Potential salivary biomarkers for Sjögren's

Research at the Department of General Dentistry at Tufts University School of Dental Medicine, Boston, MA has focused on both biomarkers and treatment of Sjögren's.

Dr. Athena Papas and Dr. Mabi Singh, who both treat high risk patients at the Tufts Dry Mouth Clinic, were two of several researchers from the Tufts University School of Dental Medicine to partake in a multi-center research study on salivary biomarkers. The aim of this study was to determine if biomarkers that could be used for diagnosis of Sjögren's are present in saliva.

"Discovery of putative salivary biomarkers for Sjögren's Syndrome using high resolution mass spectrometry and bioinformatics," published in the Journal of Oral Science, January 2012, found a biomarker that is unique to Sjögren's. They describe this biomarker as a "proteolytic peptide originating from human basic salivary proline-rich protein 3 precursor."

The research group concluded that the salivary biomarkers which they discovered, using the methods of detection and analysis detailed in the study, have the potential of serving as diagnostic/prognostic tools for Sjögren's Syndrome. A link to the full text of this research paper is provided at the end of this article.

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How to minimize oral complications and maximize oral health and comfort

Dr. Papas has served as the principal investigator of numerous clinical trials and co-investigator of many research studies. She also possesses clinical expertise in the oral healthcare of geriatric patients, patients who are medically compromised as well as those with Sjögren's Syndrome and chronic dry mouth. Her combined and extensive research and clinical knowledge is evident in Dr. Papas' appreciation for the difficulties and complications that patients experience with Sjögren's/chronic dry mouth.

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Common causes of tooth decay, dental problems, and oral pain

Saliva is essential for oral health. Once patients lose their saliva, they are at risk of losing their teeth. The effect of persistent dryness in the mouth may not always be understood by healthcare providers. Some, simply lacking knowledge in how to properly care for dry mouth, have given patients very poor advice. It is so important, but often very difficult, for patients to receive expert assistance at the early stages of their dental and oral complications. Many arrive at the Tufts Dry Mouth Clinic with teeth so eroded or broken that only jagged pieces protrude from the gums—the alarming discovery is many of these patients had extensive dental work, but it was no longer working. Dr. Papas tried to explained how this could happen.

Saliva is what keeps the enamel of teeth hard. Low amount of saliva production or loss of saliva leaves tooth enamel much more vulnerable to a wide range of dental problems. It is the weakening and erosion of tooth enamel which leads to many devastating complications.

The following list is a summary of the recognized as well as lesser known causes of tooth decay, deterioration, and erosion:

• Acid in foods and beverages can affect teeth by accelerating demineralization of teeth (i.e., removing vital minerals). Frequency of consumption also matters—it is better to drink an acidic beverage all at once, rather than to keep sipping on it.

• Acid reflux, found in at least half of Sjögren's patients, can cause stomach acids to backflow into the mouth, eat away at enamel, and even get at the pulp. Indications of acid backflow are soreness at the back of the throat, shiny amalgams, or signs of the enamel becoming eaten away around the amalgam. This acid can sometimes be so severe that it has completely worn away a person's teeth.

• Brushing too hard can wear the teeth down (referred to as toothbrush abrasion) and brushing immediately after consuming acidic foods or drinks can make matters worse, by stripping away enamel.

• Dryness cause teeth to dry out; when teeth dry out, they are much more likely to crack. Dryness can be the result of an underlying disease, like Sjögren's, or as a side effect from many drugs. Every effort needs to be made towards restoring moisture to the mouth.

• Failed dental work, even in patients who have undergone a lot of dental work, is greatly due to inadequate preventative care. Work done on teeth that are already weakened or in an unhealthy condition or in a mouth with chronic dryness will simply not hold!

• Fillings falling out of teeth often happens in teeth that are not hard enough. In most cases, it is not the filling but the teeth which have changed or deteriorated. This problem points back to causes of failed dental work. Getting a root canal or getting a tooth crowned does not eliminate future problems nor the need to continue protective therapy. In fact, teeth that have been worked on require even more attention and ongoing fluoride treatments or preventative measures. A tiny gap can easily develop along the edge of a crown and allow debris or bacteria to seep in.

• Inflammation can occur in salivary glands as well as in the gingival margins of the teeth. In Sjögren's, it usually does not go below the gum line, like in periodontal disease.

• Thick saliva; the watery part of saliva is the first to go in Sjögren's. Advanced dryness caused by the lack of saliva or damaged glands in Sjögren's can be so profound that a wooden tongue depressor will remain stuck on a patient's tongue.

• Tooth Decay, particularly in Sjögren's, often occurs at the gum line, especially as gums start to recede. The root is much more sensitive to decay than the crown of the tooth. When there is a lot of tooth decay along the gum line, the tooth can shear right off.

• Triggers of oral pain, sensitivity, and burning sensations

- Candidiasis: As saliva decreases, the development of candidiasis increases. A significant percentage (60%) of Sjögren's patients have candidiasis, especially the erythematous variant. This will present as red, irritated oral tissues and a red, raw tongue. It causes a lot of soreness and sensitivity inside the mouth. It can also develop as cracks at the corners of the mouth.

- Burning tongue/burning mouth: The lack of lubrication in the mouth can make the tongue become dry and rough due to friction against teeth and causes burning sensations. An interesting finding is that women have more taste buds than men. This difference may point to early means of survival that women were born with as they were the ones to determine if plants or foods were safe to eat by tasting them for their bitterness. When nerve endings on all of these extra taste buds become dry, irritated or inflamed, the patient will experience a burning mouth.

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Treatments that make a difference and reduce tooth decay

Dr. Papas reviewed many treatment options which can help to minimize oral complications and maximize overall comfort and well-being. While there are many over-the-counter products advertised for dry mouth, she cautioned these products are primarily for comfort. They can be used, but they will not treat or protect the mouth or teeth. Treatments that make a difference, many times a prescription product, will help to stimulate salivation, restore moisture, protect and restore tooth enamel, and prevent anticipated complications.

The most important treatments and techniques for patients to start with are listed below:

• Fluoride toothpaste – prescription-strength: Daily use of prescription-strength fluoride toothpaste is recommended (brand name, Colgate PreviDent). Research has shown that Sjögren's /dry mouth patients had less tooth decay with regular use of fluoride (i.e., as toothpaste, oral rinses, treatments provided by the dentist).

• Fluoride varnishes: New ways to deliver fluoride, as a clear film that gets brushed on by the dentist. Discuss this option with your dentist.

• Brushing techniques: Be sure to brush your teeth correctly. Don't scrub. Power toothbrushes with sonic technology are recommended for Sjögren's /dry mouth patients. These are found to more thoroughly remove plaque from teeth and gums.

• Night-time routine: This should include brushing teeth with a prescription-strength toothpaste, followed by an application of MI Paste™ over the teeth, and then going to sleep (without rinsing). This regimen serves as an overnight treatment that will help remineralize and protect teeth.

• Remineralize teeth by using a topical cream like MI Paste™ that contains calcium and phosphate. Place a small dab on a fingertip and spread it over teeth. Note: MI Paste contains RECALDENT™, a special milk-derived protein which helps to release the active ingredients. It may not be suitable for people with milk protein allergies. It is usually provided or sold by a dentist or an oral specialist, although it is sold at several online stores. Discuss this treatment option with your dentist.

• Increase salivation with use of sialogogues: Sialogogues are agents or drugs that help to increase/stimulate salivation. Two of the most commonly used systemic sialogogues are pilocarpine (brand name, Salagen) and cevimeline (brand name, Evoxac). These are prescription drugs and may cause side effects in some patients. Research has shown that patients who had used Salagen for 4 years had much less tooth decay.

• Increase salivation by chewing: Chewing gum can also help to stimulate production of saliva. Xylitol gum is preferred because it helps to generate moisture in the mouth. Too much xylitol can cause diarrhea; therefore, the recommended consumption is no more 8 pieces per day.

• Improve salivation by massaging glands: See massage techniques to relieve painful or swollen salivary glands, described in detail, at the end of this list.

• Chlorhexidine: an antimicrobial oral rinse, available by prescription (brand name, Peridex, Periogard) is used to treat swollen or infected gums.

• Anti-inflammatories, like Celebrex, have been shown to reduce inflammation in periodontal disease. A short course may help Sjögren's/dry mouth during a flare.

• Omega 3 fatty acids can help to reduce inflammation and improve salivation.

• Lubricate the inside of your mouth with extra virgin olive oil or vitamin E capsules.

• Increase dental cleanings/exams plus fluoride treatments—ideally, four times per year to effectively manage and care for Sjögren's /chronic dry mouth.

• Check for early signs of lymphoma, very important to do in Sjögren's as lymphoma is detected in about 10% of patients— don't ignore little things—a warning by Dr. Papas.

• Dental implants, consider implants if all else fails. There have been 200 implants done at the Tufts Dental Specialty Clinic with a 97% success rate. Implants can also serve as a base for dentures.

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Massage techniques to relieve painful or swollen salivary glands

The parotid glands are located in the upper part of each cheek, close to the ear, and secretions from the glands have to pass through a complex pattern of ductwork. The parotid glands are encapsulated and have a thick fibrous coating. These glands can become obstructed with a mucus plug or stones in the ducts and cause swelling, pain and damage to the ducts.

Therefore, it is very important to keep the flow of saliva moving and good way to encourage flow of saliva is by massaging the glands.

For parotid glands, place two fingers behind the ear and slide them forward along cheek, while applying gentle pressure.

For the submandibular/sublingual glands, place two fingers under the jaw and slide them forward, along the edge of the jaw line to promote flow of saliva into floor of the mouth.

These are self-applied massage techniques that can help to keep saliva flowing. Warm compresses can be used to soothe painful glands.

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 A promising treatment for dry mouth is in the pipeline

Dr. Papas ended her presentation with encouraging news about her work with Dr. Howard Green, at Harvard Medical School, who had developed artificial skin for severely burned patients. They have conceived a treatment plan for a moisturizing agent that would be delivered by way of a mucoadhesive film (attached to the mucosa) into the oral cavity. They have asked the Forsyth Institute in Cambridge, MA to help them create this product, and it has shown an interest in it.

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References

"A Primer on Salivary Diagnostics", American Dental Association, 2009. 

"New classification criteria released for research on Sjögren's Syndrome," National Institutes of Health's New & Events, Release of April 11, 2012: http://www.nih.gov/news/health/apr2012/nidcr-11.htm.

Shiboski SC et al, "American College of Rheumatology classification criteria for Sjögren's syndrome: A data-driven, expert consensus approach in the Sjögren's International Collaborative Clinical Alliance Cohort", Arthritis Care & Research 64, no. 4 (2012): 475–487, doi: 10.1002/acr.21591. Full text of this article (Wiley Online Library) as PDF: http://onlinelibrary.wiley.com/doi/10.1002/acr.21591/pdf.

Spielmann N and Wong DT, "Saliva: diagnostics and therapeutic perspectives," Oral Disease 17, no. 4 (2011): 345–354, doi:10.1111/j.1601-0825.2010.01773.x. Full text of article as NIH Public Access Author Manuscript: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056919/. 

St. Clair, EW. "Sjögren's Syndrome," in The Kelley's Textbook of Rheumatology, 9th ed. Gary S. Firestein, M.D., et al (Philadelphia: Elsevier/Saunders, 2012), Ch. 73.

Zoukhri D  et al, "Discovery of putative salivary biomarkers for Sjögren's syndrome using high resolution mass spectrometry and bioinformatics," Journal of Oral Science 54, no. 1 (2012). Full text of this article: https://www.jstage.jst.go.jp/article/josnusd/54/1/54_1_61/_pdf.

 

For additional information on salivary diagnostics/salivaomics

Dr. David T. Wong extends an invitation to anyone who would like to explore more of research done by the UCLA School of Dentistry, Dental Research Institute to visit their website, Salivary Diagnostics. 

A chart that illustrates the scientific development of salivary diagnostic toolboxes can be seen at: Salivaomics Knowledge Base (The Wong Lab, at the UCLA School of Dentistry, Dental Research Institute).

Listen to an informative Podcast by the American Association for Clinical Chemistry, September 2012 issue, that features Dr. David T. Wong. In this 15 minute interview, Dr. Wong reviews one of his recent research papers and explains how the evaluation of RNA in saliva has the potential of becoming an emerging diagnostic technology in disease detection: "The Human Salivary RNA Transcriptome Revealed by Massively Parallel Sequencing." The link for this podcast can also be accessed on the Home page of The Wong Lab /UCLA Dental Research website.