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Dysregulation Spectrum Syndrome

It's time to get past the idea that any illness for which a physical cause can't be found must be a psychological problem, according to Muhammad B. Yunus, MD, a foremost fibromyalgia researcher and a board-certified rheumatologist, Professor of Medicine at the University of Illinois College of Medicine, Peoria, IL.

Speaking at the Fibromyalgia Alliance of America's Columbus '97 conference, Yunus introduced the Dysregulation Spectrum Syndrome (DSS), a concept that provides an umbrella for many common conditions often seen clustered together in the same patient group. Among disorders included in the DSS, in addition to fibromyalgia syndrome (FM), are irritable bowel syndrome (lBS), chronic fatigue syndrome (CFS), migraine, restless legs syndrome (RLS), and primary dysmenorrhea (pain during menstrual periods) - all familiar to people with FM. What they have in common Yunus said , is "a very similar, although not exactly the same, neuroendocrine abnormality." In other words, it's not all in your head, it's in your glandular secretions and the nervous system. "The nervous system is unusually vigilant in these disorders, causing various sensations to be amplified," he added.

Yunus said that the idea of grouping disorders is not new. Rheumatologists are accustomed to thinking of groups of illnesses - rheumatoid arthritis, lupus, scleroderma, polymyositis (called connective tissue d iseases); ankylosing spondylitis, Reiter's syndrome, psoriatic arthritis, and spinal arthritis with inflammatory bowel diseases (called spondyloarthropathies) - because they have overlapping features and are related through a common disease mechanism such as autoimmunity or the presence of the common genetic marker, HIA-B27. Looking at the DSS disorders in a similar way, because of their overlapping features and relationship through neuroendocrine dysregulation, is a logical way to think about them.

Yunus has been looking at the relationship among the DSS disorders for nearly 20 years. Inspired his experience with a patient whose FM pain grew worse when he had an attack of lBS, Yunus said, "This happened so many times and was so consistent that I became convinced of a common operative factor." In August 1981 Yunus and his colleagues published a paper in Seminars in Arthritis and Rheumatism showing results of the first controlled study that found some of FM's multiple symptoms - fatigue, poor sleep, a swollen feeling, numbness, IBS, and chronic headaches - are significantly more common in people with FM than in people of similar age and gender who do not have pain.1 This was the first paper to give credibility to FM as a real syndrome--a collection of symptoms that are more common than in the healthy population--and not just another name for hypochondria. Since the publication of that article, a couple of dozen controlled studies of people with FM have reported abnormalities in neurohormonal function.

Statistically, lBS, CFS, restless legs syndrome, headache, and menstrual pain problems occur in FM more commonly than in the general population; this occurrence is far greater than it would be by mere chance. Restless legs syndrome occurs in 31% of people wi th FM, 15% of people with rheumatoid arthritis, and 2% of the general population. lBS is more common in people with FM, and FM is found in 65% of people with lBS. This is not true of inflammatory bowel diseases such as Crohn's Disease and ulcerative coli t is. Yunus sees FM and its associated conditions as being triggered by stress in many cases, but he pointed out that not all stress is necessarily psychological in origin. Extremes of heat and cold, excessive physical activities, infection, physical trauma , and deprived sleep can all cause stress. He said he originally used the term "dysfunctional spectrum syndrome" but has dropped that because it has a negative psychological connotation, such as in dysfunctional families. He presented several arguments countering the view that FM is a manifestation of depression.

  • Depression is no more common in FM than it is in other chronic pain conditions of organic nature, such as rheumatoid arthritis.
  • Studies of serotonin and the hypothalamic-pituitary-adrenal axis show that FM and depression have different biochemical characteristics.
  • Fibromyalgia sleep disturbance is different from that found in depression.
  • The characteristics of cognitive dysfunction in FM differ from those found in depression.
  • People with FM respond to much smaller (loses of tricyclic agents than do people with depression.

Dr. Yunus prefers the term biophysiology to pathophysiology for these disorders since there is no pathology present in these conditions. Pathology, he explained , involves something that can be seen on physical examination, in X-rays, under the microscope, or in lab tests that show inflammation. None of this is the in the DSS ailments. "We must get used to a 'third model' of neuroendocrine dysregulation.," Yunus urged the audience, adding, "This is neither a pathology nor a psychiatric model." Unfortunately, some medical practitioners are wedded to the notion that the only true illnesses are those that demonstrate some form of pathology. "We must cut the cord with classical pathology if we want to understand DSS," Dr. Yunus emphasized. "An open mind is a good start," he added.

In addition to the absence of an obvious pathology and to the relationship to various varieties of stress, DSS disorders have other characteristics in common, Yunus noted. Most sufferers are women, most have fatigue and a problem with sleep, and all have a heightened sensitivity to pain. "A genetic factor may well be involved," he said, citing his study of 40 families with multiple members having FM. But further studies in that area need to be done, he emphasized.

Yunus postulated three models of the DSS, any of which may apply in a particular case. The first he called the Neuroendocrine Dysregulation Model alone (which he nick-named NED). This model recognizes that neuroendocrine dysfunction alone can amplify pain, and that pain in turn can cause neuroendocrine changes. (However, the pure NED patients may have psychological distress later as a result of chronic pain.) For example, I. Jon Russell, MD, has shown in a study that the neuropeptide Substance P, the chemical that transmits pain sensation, is more plentiful in people who have been in chronic pain from FM for years compared with those normal controls without pain.

Fibromyalgia, Yunus explained, is a prototype of the NED model. People with FM have heightened pain not only in the musculoskeletal system, but also in other areas such as the bowels. Daniel Clauw, MD, for example, has demonstrated greater sensitivity in FM patients to pain in the esophagus and other researchers have shown similar hypersensitivity in the rectum. "Chronicity may further aggravate this sensitivity as I had suggested in my 1992 proposed model," Yunus said. The lesson in this, according to Yunus, is that efforts should focus on stopping the chronicity of pain to prevent further alterations in neuroendocrine function.

The second model combines NED and psychological factors. Pain always has a psychological component. "There is no way you can get away from [that fact]," he noted. Still, he said, "neither lBS nor FMS [has] anything to do with psychological problems alone." The fact that mood-altering drugs can help people with fibromyalgia does not indicate that FM is a psychiatric illness, he insisted. Plaquenil, an antimalarial drug, has been found useful in treating rheumatoid arthritis, but that doesn't mean that rheumatoid arthritis is caused by the malaria parasite. He noted that the prevalence of depression among people with fibromyalgia is similar to that in other chronic diseases of organic nature having classical pathology such as rheumatoid arthritis.

The third model combines NED and pathology. Psychological factors may be operative here, too, by virtue of chronic illness. Noting that 30% of people in his study of RA patients have FM, Yunus offered the hypothesis that inflammation and/or the stress of chronic illness makes changes in the neuroendocrine system that cause a lowered pain threshold and increased perception of pain. He suspects this is why so many people with an inflammatory arthritis develop FM although the reverse isn't generally true: FM does not predispose people to arthritis although some may develop arthritis purely by chance.

Yunus said that it is valid to ask what difference it makes if these conditions for which no pathology can be found are actually related to each other. His answer: "The knowledge of associations between members [of this class of disorder] is diagnostically helpful and avoids unnecessary investigation." This way of looking at things suggests it is not necessary to spend huge sums on money on tests for a person with lBS, FM, headaches, and CFS for example. Secondly, a clue of biophysiology in one may be true of the other. Thirdly, dealing with the neuroendocrine problem provides a logical and efficient way to treat the whole spectrum of symptoms. "If a satisfactory treatment is found in one, it is likely that treatment will work in others as well," he said.

As to what to do about general treatment of DSS disorders, Yunus had three suggestions: promotion of restful sleep, exercise, and cognitive behavioral therapy (CBT). CBT is valuable because pain can cause stress and depression, and depression can aggravate pain. CBT can help people change their perception of what is happening to them, reduce their anxiety and stress, and help them to help themselves through a better understanding of the nature of their illness. Yunus noted that a study of people with FM by Robert Bennett, MD, showed that a combination of CBT and regular exercise produces significant improvement in pain, tender points, quality of life, anxiety, and depression. Of the importance of sleep, he said, "We do know that sleep is important in all of [the DSS disorders]. For example, data suggest there is a definite correlation between poor sleep quality and the symptoms of lBS the next morning."

The goal of research in DSS disorders, he asserted, should be to find the specific neuroendocrine abnormality and tailor a drug to fix it. Even now, he pointed out , the drugs that work best with FM work through the neuroendocrine system (mostly the central nervous system). If you view DSS as one group of illnesses, then it is the most common medical condition known to medicine, with millions of sufferers. "Proportionally to the number of people who suffer from DSS in one form or another, the amount of research funding we get for this condition is so minuscule, it's just pathetic" Yunus said. He drew applause when he urged his listeners "to make noise and write to your congressman and your senators. Tell them that we need more money for research, because this is the number one cause of human suffering anywhere in the world."

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