Rainbow at shoreline

The Massachusetts ME/CFS & FM Association, a 501(c)3 founded in 1985, exists to meet the needs of patients with ME (Myalgic Encephalomyelitis), CFS (Chronic Fatigue Syndrome) or FM (Fibromyalgia), their families and loved ones. The Massachusetts ME/CFS & FM Association works to educate health-care providers and the general public regarding these severely-disabling physical illnesses. We also support patients and their families and advocate for more effective treatment and research.

Research articles

2014 Stanford ME/CFS Symposium: Advances in Clinical Care and Translational Research

By Rosamond Vallings
March 19, 2014

The day opened with a very good overview of the work being undertaken at Stanford: Â Jose Montoya; The Stanford ME/CFS initiative; a brief history of collaboration, innovation and discovery in the filed of infection-associated chronic diseases.

He talked of a large team working over 4 years. He described ME/CFS as a real illness affecting many lives.

He presented a case study initially of a patient who had HHV-6 in the blood and cerebrospinal fluid, treated with valganciclovir with a good response. The MRI had shown bright lesions in the right thalamus. Antivirals were again being considered after this patient relapsed later.

He then elaborated on the fact that there are subsets of this illness, and evolution of the illness over time. Stanford got involved as they came upon many patients face-to-face.

The Stanford Initiative is looking at the immune system, genes, neuroradiology, EEGs, cardiology and infectious diseases. He mentioned how some patients are bedridden and have extreme sensitivities. It is likely that there are infections triggering the illness or perpetuating it. Valganciclovir is helpful for HHV6 and EBV. But none of this is necessarily the full answer. Trials did demonstrate the effects of antiviral therapy, which also has an immunomodulatory effect. They are now looking at the effects of methylphenindate as a treatment plus a nutrient formula.

The underlying principles: much time and questions, a multidisciplinary team, clinical and translational research and methodology (double blinded, placebo controlled trials). There needs to be a candid and rigorous approach.

Their clinic has 600 patients currently and a waiting list of 300. They have a multidisciplinary team and have weekly meetings. 3 groups of trials are currently running: drug studies, longitudinal studies and case control studies—e.g., cytokine levels associated with severity. In this one, 13 cytokines are found to have an upward trend leading to many effects, and levels correlate with severity. In addition there are associations with autoimmune disease, and this may be consistent with an auto-immune process going on in ME/CFS. 2 cytokines are particularly higher in women: leptin and resistan. The LASSO method is used. TGFbeta correlates with duration of illness, is decreased and levels correlate with severity. This opens the door for treatment with antiinflammatory agents. Rest, good sleep and meditation are all options to be considered.

Beth Unger: Epidemiology of CFS–what have we learned?

She started by saying that there is often disagreement about terminology and definition, which can be confusing. I.e., Are CFS and ME synonyms or different?

There is consensus that the illness is characterized by severe fatigue unrelieved by rest, and accompanied by additional symptoms, such as post-exertional malaise and cognitive difficulty, etc. There may be other comorbid conditions. The key issue is the vicious circle of sleep, pain and fatigue leading to cognitive difficulties.

The areas of disagreement in the definitions seem to be duration, number of symptoms, exclusion conditions and whether post-exertional malaise is acquired or part of the disease. Most studies are based on the 1994 Fukuda definition and this is widely used. The findings can be extrapolated to other definitions. 80% of patients do have post-exertional malaise. Case definitions are inadequate to explain the actual experience of the illness. Patients and caregivers do however speak eloquently.

Epidemiology looks at demographics, prevalence, significance, prognosis and risk factors.

Prevalence: The highest prevalence is in the 40-50 year old age group. More females than males are affected. It does occur in children. Prevalence may be higher in some racial groups and the socially disadvantaged. Most CFS patients are ill for more than 5 years. 50% seek medical care.

When finding out how common the illness is, it depends where you look and how you ask. A meta-analysis of 14 adult studies showed a different picture with self-report of 3.2% and clinical assessment at 0.76%. Prevalence is likely about 0.31% in the USA, which equates to about 1 million sufferers. In teens the rate is between 0.4% and 2.4%. it is not rare.

Significance: Functional impairment is equivalent to that in MS, HIV, cancer, diabetes and lung disease. There is frequently inability to attend school. There is decreased working memory and motor speed. Various domains of the SF36 generate generally low scores. For fatigue, sleep and pain, the PROMIST scores are worse compared to other illnesses.

Economic burden: In the USA, $9-37billion is lost in productivity, (equivalent to 19% reduction in earnings) and $9-14billion in medical costs.

Barriers to healthcare utilization: Over half the patients had at least one barrier. These included: accessibility, negative illness beliefs, the healthcare system itself.

Prognosis: Presentation of the illness may be sudden or gradual, and symptoms wax and wane. Good clinical management leads to increased wellbeing and functional improvement. The likelihood of recovery decreases with the severity of the illness. Recovery is more likely in children.

Associated factors: Infection, stressors, genetics. Work is usually done using case definitions as there is no biomarker. It is important to identify subgroups.

Future directions include: a multi-site study of CFS/ME and exploring the use of national surveys.

Jarred Younger–Daily fluctuations in cytokines in CFS/ME

This is a novel way of looking at the immune system. i.e—tracking symptom variability comparing good days and bad days and cytokine levels. We need to be able to track something in the blood, and this could be a potential target for new drugs. Cytokine levels may correlate with symptoms. Fluctuating levels may influence symptoms. There are now free programmes/apps to track symptoms over 25 days. Blood is then needed for 25 consecutive days, but with tiny needles and skilled phlebotomists, this need not be too difficult. Classic cytokines and chemokines can be measured.

His team had looked at 3 women with fibromyalgia, and found that leptin levels correlated in all three with symptoms. They then looked at 10 women with CFS/ME, and found that leptin levels correlated with fatigue in 6 of the 10. Comparing with 10 healthy women there was minimal correlation. A network analysis of all cytokines relating to fatigue was done, and leptin was the only one that significantly correlated.

Leptin was three times higher in females than males. It comes from the white fat tissue and is increased in stress and is very "inflammatory."

The microglia are the primary defence in the CNS. Firing leads to a pro-inflammatory state, which makes a person feel ill – this is a normal "sickness response." Microglia can be primed by aging, genetics etc and this can lead to over-expression. The astrocytes take over once the microglia are activated. Leptin crosses the blood-brain barrier and primes the microglia (lowers the threshold). If hit by TNFalpha, leptin increases the vulnerability of the microglia.

He then asked the question "What next?"—leptin antagonists—there are many possibilities, but this is not applicable yet. But cardiac hormones and some antihypertensives do have anti-leptin effects. He noted too that leptin suppresses the appetite. Leptin levels decrease with avoidance of stress.

Modulators of leptin include: naltrexone, minomycin, dextromethorphan, rimfampicin, ceftrixone. A number of natural compounds have the potential too such a tumeric, reservatrol and stinging nettle, but none have been tested.

A biobank is needed, so that more analyses can be done. He noted that leptin can be measured in saliva.

Amit Kaushal—Gene expression findings in CFS/ME

The approach by the Davis Lab was to look at phenotypes and gene expression. 200 patients and 400 healthy controls were assessed. MFI (20 scale) was used with 20 questions. This showed that the phenotypes of the patients were different from the controls. There was much variability in the CFS group—fatigue was far greater than in the controls. Looking at gene expression, whole blood was used looking at RNA activation, microarray overview etc. 47,000 genes can be measured simultaneously in patients versus controls. False positives are possible.

When looking at the sickest patients versus the healthiest of the controls there were more significant genes. There were a large number of genes showing significant different expression between patients and controls. Diseases with systemic inflammation were more highly correlated.

Limitations in the studies are whether there is significance of blood markers. But if there is a signal, the signal should be chased. He concluded that CFS/ME is a heterogeneous disease phenotypically, and there is genomic evidence for a chronic inflammatory state. The inflammation is associated with core intracellular components.

Mehdi Skhiri—Cardiovascular Aging in CFS/ME

He talked about 3 studies:

1. Small heart syndrome (Japan)—56 cases, 38 controls. There was significant difference between the CFS patients and controls using chest xray and echo, with patients having a smaller heart. However in the CFS group, only those with a low cardiac index were included, but this did not apply to controls.

2. Impaired cardiac function in CFS measured by MRI tagging—12 patients, 10 controls. The cardiac index (equivalent to output) was lower in CFS. Left ventricular volume was down, there were reduced cavity volumes, and reduced stroke volume and cardiac output. This correlated with a markedly reduced blood volume.

3. Evidence of diminished cardiac function. The study involved sedentary and non-sedentary controls and mild and severe CFS patients. 12 lead ECG was used. Cardiac index was down in patients who also had a possibly 15% decreased blood volume.

Problems noted: no data on vascular pathology, no study without some bias, cardiovascular matching is not easy to achieve.

A further phenotyping study was presented, with 82 patients. Exclusion included, obesity, athletes, Ehlers danlos, any cardiac condition and those unable to exercise. Results showed: cardiac remodeling in patients, with smaller cavities (because of different levels of fitness), no clear differences between L and R ventricular function and no signs of early cardiovascular aging or increased risks.

Michael Zeineh—MRI findings in CFS/ME

He is a neuro-radiologist. He had looked at 14 CFS patients and 15 controls. He outlined his 3T imaging protocol, looking at volume, grey/white matter and perfusion. Grey matter in CFS was similar to controls, white matter was lower in CFS than controls, and the thalamic volume was slightly down in CFS compared to controls. He also looked at cortical thickness, which thins in dementia. The cortex was thicker in 5 regions in patients and the differences were more noticeable in younger patients. There are many tracts in the brain, and these are affected by handedness. There was no difference in Arterial Spin Labelling perfusion, but there was increased cortical thickening along the endpoints of both arcuate tracts. In patients there was increased phosphatidic acid in the arcuate and inferior longitudinal fasciculus.

Marcie and Mark Zinn—EEG/LORETA (low-resolution brain electromagnetic tomography) studies suggesting cortical pathology in ME/CFS

They looked at 50 patients and 50 controls, using a standard EEG. Peak frequency is associated with cognitive function. The CFS patients showed reduced PAFs over 58% of the cortex, This was significant, and suggests brain pathology. They then looked at the effects of fatigue, and this predicted the PAFs well. The implications are that there are interruptions in goal-directed behaviour. This leads to mental status changes (cognitive problems) affecting alertness and attention, memory and temporal organisation of behaviour. These findings could help confirm the diagnosis, monitor disease progression and monitor treatment response.

They then determined whether LORETA can be applied to the understanding of cognitive impairment in CFS, and to examine the underlying neurological underpinning of CFS. CFS patients had widespread delta sources mainly in the left frontal lobes. Axial slices showed depth and abnormalities.

The implications mean disruptions in transmission of information. This includes: destabilisation of ascending arousal system mechanisms, inhibition of faster brain rhythms—thus more basic generalised functional processing takes place, deficits in language production and syntax, pathophysiological CNS conditions: grey/white matter lesions etc. There are also lower beta-2 sources in CFS, primary motor deficits, sensory ataxia and pain sensation disturbances. Speech deficits occur as a result of abnormalities around Broca's area. There may be behavioural effects such as apathy. All this is a possible indicator of limbic encephalomyelitis.

The implications are that there is central fatigue and brain fog with no psychiatric comorbidity. In summary there is hypoactivation in CFS and LORETA shows this link.

Anthony Komaroff—Medical care of ME/CFS patients

An overview of management of patients with this illness was presented. Age range is 5 – 65 years. 65% patients are female. It affects all socio-economic groups, but is more common in Afro-Americans and Latinos. 50% patients are "shut-in" or bedridden much of the time. Average duration of illness is 14 years (4-36 year range). Post-exertional malaise (PEM) is characteristic and not seen in any other illness. Cognitive impairment is common. The SF-36 shows low scores in all areas. 10% patients achieve full remission, 23% end up with an alternative diagnosis.

This is not depression, as SSRIs do not fix it. There are abnormalities in the HPA, and neurological and immunological abnormalities are not seen in depression. However with psychological assessment, 50% patients have a diagnosis of depression after onset. Prolactin is often elevated in CFS, and decreased in depression.

Abnormalities found include: neuro-endocrine dysfunction, cognitive deficit, autonomic dysfunction, abnormalities on MRI,Spect and EEG, lactate abnormalities in the CSF, striking differences in immune system. There is evidence of abnormal energy metabolism. Infectious agents implicated include HHV6 in 90-95% patients (the receptor is the complement receptor).

Treatment options discussed:

  • CBT helps patients cope with the illness and reduces symptoms.
  • Gradual exercise plan which should be gentle to avoid PEM
  • Trazadone for sleep
  • Rituximab—as possible autoimmune disease

Final words were that case definitions may encompass several different subsets or other illnesses.

Jose Montoya–Circulating cytokines in ME/CFS patients reveal a novel inflammatory and autoimmune profile

Flu-like symptlms are ongoing, but conventional markers are seldom elevated. There is an associated TH-2 shift. He presented a controlled study of 197 cases and 300 controls. MFI20 and FSS scores were measured to assess severity, followed by statistical analysis. Included was the LASSO technique, and also "random forest". In the results, patients and controls were well matched. The CFS patients almost all had PEM. 26 cytokines were found to decline with age. 4 had differences between males and females: Leptin. IL-1alpha, ENA78 and resistan.

15 cytokines behaved differently in CFS compared to controls. 13 out of the 15 were significant differences, and these were the pro-inflammatory cytokines. Mild cases tend to fall below the controls, severe cases tend to fall above the controls.

Activation of B-cells suggests the possibility of autoimmune disease.

IL-17 is associated with psoriasis, IBD, Arthritis and MS. Leptin and resistan are associated with female sex. Lowered TGF-beta is associated with duration of illness—it is a powerful anti-inflammatory cytokine, whose capacity gets lost. The body thus feels inflamed.

Ian Lipkin–Microbial diagnostics and discovery in ME/CFS

He said they were still able to use the earlier XMRV samples. He explained how one started with a hunt for "possible" microbes and then moved onto the "probable" when one could consider treatment options, followed by the "confirmed" when one looked at drugs and vaccines. He told us how emerging diseases usually came from animal sources.

He explained how micro-array techniques moved onto unbiased sequencing. There are 24 million peptide micro-arrays needed to investigate the vertebrate organism. He discussed as an example Kawasaki Disease, an autoimmune condition in children. Often diseases are due to an immunological response to an environmental trigger.

He then went on to discuss the human microbiome—abnormalities of which can create gastrointestinal symptoms, which in children are sometimes predictors for autism. He is interested in this relation to autism. There may be reduced enzyme and transporter RNA. The organism suterella is increased in autism and there may be an antibiotic cause, and a lack of the gene affecting gastrointestinal metabolism.

He then talked about his involvement with the Chronic Fatigue Initiative, who are doing multiplex assays. He is working closely with Montoya looking at viruses. HHV-6 has been found in the plasma of 4 out of 6 cases. Looking for HHV-6 in PBMCs, 13% were positive in patients and 11% positive in controls. Annellovirus was found in 75% of the samples—this may not be useful, but negative findings are as important as positive.

Looking immunologically at CFS/ME IL-17 was elevated in the first 3 years and then decreased. Lower levels were found in the CFS/ME patients' cerebrospinal fluid. They are doing RNA sequencing looking at biomarkers in 100 cases compared to 100 controls. This equates to 117million reads divided into 3 "libraries". But there is a need to control for library effects, as the "library" construction reflected the results – ie processing may be different.

They are also looking for chemicals produced by bacteria which may have systemic effects. He confirmed that there was zero evidence now for XMRV. Contamination is always a problem and contaminants must be eliminated prior to any analysis.

Jose Montoya closed the symposium remarking that this had been a most successful and exciting day.

Oral Complications in Sjögren's Syndrome and Chronic Dry Mouth

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."

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.

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.

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).

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).

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.

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.

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.

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.

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.

 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.


"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.

Dr. Anthony Komaroff Fall 2013 Lecture Video

The Massachusetts CFIDS/ME & FM Association was pleased and honored to welcome back Anthony Komaroff, M.D., Simcox-Clifford-Higby Professor of Medicine at Harvard Medical School, Clinician and Researcher, as the keynote speaker at our Fall 2013 Educational Lecture. The title of Dr. Komaroff's talk was "CFS Research: Recent Progress and Challenges." The lecture took place on Saturday, November 2, 2013 at the Morse Institute Library in Natick, MA.

YouTube links (YouTube versions can be only be accessed from this site or from the direct links; the videos are not searchable on YouTube):

Dr. Komaroff's 2013 lecture "The Latest Research on CFS" (56 minutes)

Dr. Komaroff's 2013 lecture Questions & Answers (37 minutes)

Some of the highlights from Dr. Komaroff's talk included advancements in gene technology and other methods which have improved the ability to research CFS and other illnesses. Dr. Komaroff explained that every gene can now be identified, but even more important, researchers can determine whether genes are turned on or off and detect changes or abnormalities in this process—these differences are what really matter because they may provide the link to the development of disease. He also reviewed several new treatments that have been studied scientifically and have shown encouraging results. Lastly, Dr. Komaroff emphasized the growing interest in CFS by scientists around the world.


Notice about names

The Massachusetts ME/CFS & FM Association would like to clarify the use of the various acronyms for Chronic Fatigue Syndrome (CFS), Chronic Fatigue & Immune Dysfunction Syndrome (CFIDS) and  Myalgic Encephalomyelitis (ME) on this site. When we generate our own articles on the illness, we will refer to it as ME/CFS, the term now generally used in the United States. When we are reporting on someone else’s report, we will use the term they use. The National Institutes of Health (NIH) and other federal agencies, including the CDC, are currently using ME/CFS. 

Massachusetts ME/CFS & FM Association changed its name in July, 2018, to reflect this consensus.