Fibromyalgia: Proper Diagnosis is Half the Cure

Transcription

1 Presented by: Fibromyalgia: Proper Diagnosis is Half the Cure David Brady, ND, DC, CCN, DACBN, Human Nutrition Institute Associate Professor of Clinical Sciences University of Bridgeport, Conn. Produced by:

2 Contents Introduction...3 History of misunderstanding....4 Diagnosing fibromyalgia: Dos and don ts...5 Taking a history...5 Exam and lab work...6 New pain research illuminates fibromyalgia....7 Referred pain...7 Body-wide receptive fields of pain...8 Limbic system...8 Fibromyalgia treatments...9 Drug therapy...9 Sleep therapy...9 Biofeedback and cognitive behavioral therapy...10 Supplements...10 Fibromyalgia imposters Catching the fibromyalgia imposters...11 Conclusion...12 Biography

3 Fibromyalgia: Proper Diagnosis is Half the Cure David Brady, ND, DC, CCN, DACBN, Human Nutrition Institute Associate Professor of Clinical Sciences University of Bridgeport, Conn. Introduction Fibromyalgia has a reputation as a psychosomatic condition. For decades, doctors struggled to makes sense of the odd collection of pain, cognitive, and digestive symptoms in fibromyalgia patients, and why these symptoms didn t respond to standard treatments. Lost for an explanation, many health care providers began to wonder if fibromyalgia was just in a patient s head. Luckily, research in recent years has shown that fibromyalgia is, indeed, a physical issue, and led to the development of more effective treatments. David Brady, ND, is part of a growing group of fibromyalgia experts trying to change how patients and health care providers think about fibromyalgia. In this whitepaper, Brady explains the current scientific understanding of the nervous system and the unique type of pain fibromyalgia patients experience. Brady also details the link between the limbic system and the array of digestive, sleep, and cognitive fibromyalgia symptoms, as well as the best way to address these symptoms in treatment. Finally, Brady explains the various disorders that can masquerade as fibromyalgia, and guides doctors through the best practices in properly diagnosing this mysterious disease. 3

4 History of misunderstanding The first real mention of fibromyalgia in modern Western medical literature was made by the British physician and neurologist, Sir William Gowers, at the turn of the 20th century. Gowers described the syndrome as fibrositis, a term that reveals the early thinking about the disorder. Itis implies an inflammatory problem, and fibro implies inflammation of the fibrous tissues, such as the muscles, tendons, and fascia, rather than the bones and the joints. In fact, several of the myths surrounding fibromyalgia can be found in the terms doctors have used to describe it. One fibromyalgia myth to dispel is that fibromyalgia is inflammatory. Doctors are trained that inflammation drives pain, so it is not unreasonable to assume a painful syndrome is inflammatory. But people who actually meet the criteria for classic fibromyalgia don t tend to have high C-reactive protein (CRP), sedimentation (SED) rates, or any markers of global systemic inflammation. Fibromyalgia pain is not a classic, nociceptive, inflammatory pain. A second fibromyalgia myth is that pain originates from soft tissue. This, too, is a reasonable assumption at first glance, since soft tissue is where fibromyalgia pain is felt. However, soft tissue is not where fibromyalgia pain is emanating from. Therefore, all traditional therapies directed at inflamed, soft, compliant tissues aren t going to work. Experts in fibromyalgia now think that central allodynia may be a better term for the disorder, since fibromyalgia pain appears to originate in the brain and central nervous system. Fibromyalgia went through many different name changes since it was first discovered. In the 1950s, it was referred to as psychogenic rheumatism, implying a made-up rheumatic disorder. This attitude was only reinforced by the fact that fibromyalgia mostly strikes women, who already faced a stereotype of female hysteria at the time. Funding for fibromyalgia research languished for decades. As fibromyalgia was so difficult to treat, few researchers wanted to stake their career on it. That all started to change in the U.S. in 1987, when fibromyalgia got its first ICD-9 diagnostic code. After that, third-party reimbursement for dealing with the disorder was available, and research money started flowing in. However, early fibromyalgia studies were often muddled by misdiagnoses and research populations that resulted in inaccurate conclusions. ICD-9 FMS literature started soaring in the mid to late 80s Figure 1; Source: Mense S, Simons DG. Muscle Pain. Lippincott, William, & Wilkins; The first diagnostic criteria for fibromyalgia emerged in 1990 from the American College of Rheumatology. At the time, experts required that patients experience global pain and be hypersensitive at 18 distinct points across the body. Those points were a negotiated set of parameters from a committee, and meant to be a standard for enrolling patients in studies. Doctors searching for some kind of guidance on diagnosing fibromyalgia turned to these points. A few years later, the World Congress on Myofascial Pain in Fibromyalgia Syndrome had a big conference in Copenhagen, and some of the same experts got together and issued a refinement of the original criteria. In it, fibromyalgia was defined not as a widespread pain problem, 4 4

5 but as a condition that encompasses a wider syndrome of headaches, irritable bowel symptoms, irritable bladder, dysmenorrhea, cold sensitivity, Raynaud s phenomenon, and restless legs. These experts went on to include a strong correlation between fibromyalgia and depression, anxiety, non-refreshing sleep, and fatigue. Despite all of these wideranging symptoms, many doctors still think of fibromyalgia as a muscle-related pain syndrome. Tender Points for Diagnosis of Fibromyalgia Figure 2 In the decades that followed, several proposed fibromyalgia etiologies rose to prominence. One was the possibility of ongoing, persistent stealth viral infections behind the symptoms. This idea was also floated as a cause behind chronic fatigue syndrome. Both conditions were considered difficult to diagnose and treat 20 or 30 years ago, and several of their symptoms overlap. However, these conditions aren t equivalent and now have very different diagnostic criteria. More recent research has been examining thyroid hormone, sleep disorders, psychological issues, and stress physiology as contributors to fibromyalgia. Research into neurotransmitters and pain-modulating peptides has also uncovered potential fibromyalgia causes. Diagnosing fibromyalgia: Dos and don ts Diagnosing fibromyalgia has never been easy. New research and new lab tests have made the process faster and more accurate, but fibromyalgia remains a diagnosis of exclusion. Every fibromyalgia diagnosis should start with a standard work-up of a patient history, exam, labs and imaging. Taking a history In terms of a patient s medical history, doctors should ask two cquestions: Is the patient female? Does the patient have pain over their entire body? If a patient doesn t meet these two criteria, it s unlikely that they have classic fibromyalgia. Often, the legacy of the 18 pressure points can get in the way of taking a history of global pain, when a patient has pain in several locations, but not pain that would be classified as fibromyalgia. Patients with fibromyalgia hurt across their body, mainly in their softer tissue of muscles, fascia, ligaments, and tendons. However, fibromyalgia patients don t have pain localized to several points over their bodies such as their shoulder, knee, or hip, nor do they have pain solely in their joints. Fibromyalgia patients usually have a set of similar personal traits and histories. Many fibromyalgia patients are perfectionistics, compulsive, very neat and orderly, and hypervigilant caretakers of the people around them. Fibromyalgia patients have histories of difficult childhoods with an abusive parent, or substance-abusing parent, in a household with a lot of conflict. 5 5

6 Exam and lab work A well-trained doctor can use a physical examination to determine whether a patient truly feels the global pain of fibromyalgia, or is experiencing another sort of pain. Start with a good general physical examination, as well as a basic orthopedic and neurological exam, to make sure the patient does not have joint pain or another health issue. The goal is to ensure that the patient actually perceives the pain all over their body. The diagnostic criteria for fibromyalgia no longer includes the original pain points across the body. However, doctors can, and should, do an examination by hand to challenge and test the type of pain a patient reports. Start by systematically applying firm digital pressure into major muscle groups. Include pressure in the gastrocnemius, front and back of the legs, and the gluteal areas, work up around the body, and squeeze the upper arm and forearm. During the exam, watch the patient s response to see if they have an exaggerated, wincing pain response to pressure. This response should not be limited to one location, but found all over the body. enough to be considered fibromyalgia. The patient s responses are calculated into a final score from 0-31 points, and a person must score 13 or more points to meet the diagnostic criteria for fibromyalgia. Doctors may get hung up on scored questionnaires. While these tools can be useful, fibromyalgia requires an in-depth and logical exploration of each patient s symptoms that includes exams, labs, and a probing history. Unfortunately, there are several disorders and diseases that can masquerade as fibromyalgia, leading to a growing number of misdiagnosed fibromyalgia patients. One of the rationales for removing the pressure points in fibromyalgia diagnostic criteria was actually because physicians practicing today do not always complete physical exams. Today s physicians are much more comfortable ordering diagnostic tests than putting their hands on patients to do structural and musculoskeletal exams. FM Pain Diagram Figure 3 FMS and /or Soma,za,on Disorder Regional Myofascial Pain Syndrome Instead of encouraging doctors to become more competent in a physical exam, the new fibromyalgia diagnostic criteria includes a patient survey to rate each symptom on a sliding scale of severity. The checklist includes questions on whether the patient has fatigue, trouble with cognitive function, or unrefreshed sleep. It also delves into the patient s threemonth history of possible fibromyalgia-related symptoms, such as pain or cramps in the lower abdomen, depression, and headache. The questionnaire is designed to catch symptoms, severity, and whether symptoms are chronic The propensity to misdiagnose fibromyalgia is welldocumented in medical literature. In a 2003 study in the journal, Rheumatology, researchers sent a group of patients to be reviewed by an expert panel of rheumatologists who had special training in fibromyalgia. All the patients had been diagnosed with fibromyalgia by family physicians, internal medicine doctors, and rheumatologists before being referred to a rheumatology center. The expert panel assessed each patient to see how many diagnoses could be confirmed. The accuracy rate was 34 percent, with 66 percent diagnosed incorrectly. 6 6

7 New pain research illuminates fibromyalgia Biopsyand Electromyography (EMG) studies have consistently shown there is no discernable physical difference between muscle tissues or soft tissues in healthy patients and fibromyalgia patients. In fact, research indicates that fibromyalgia pain is actually generated from the central nervous system, rather than from the soft tissues where a patient perceives the pain. A 2015 study in the journal, Brain, showed evidence of neuroinflammation in key regions of the brain in chronic pain patients. Referred pain To understand how fibromyalgia pain is experienced, remember the role of the spinal cord in pain perception. Many doctors learned to think of the brain as the central processing unitof the body, and the spinal cord as the wires coming from it, like an electrical diagram. Our bodies are much more complex. The spinal cord is not a bundle of wires, but rather a little peripheral brain with gray matter, white matter, and the ability to make decisions. The spinal cord can modify the response to pain and other conditions through associative conditioning or learning. There is a very complex, inter-neuronal pool in the spinal cord, particularly in the dorsal horn. To visualize how the spinal cord plays a role in fibromyalgia pain, first imagine a pin prick to a muscle. Pricking a muscle will hit a nociceptive pain receptor that fires an impulse through the innervating nerve, through the posterior nerve root, and into the posterior or dorsal horn of the spinal cord synapse. That s the first transfer of information. Then, the signal crosses the midline, goes up through ascending spinal tracts in this case, the spinothalamic tract stops at the thalamus, and gets distributed to the area of the cortex that is assigned to that real estate in the body, according to the homunculus. This is a classic example of localized pain. Fibromyalgia patients who experience muscle pain aren t experiencing a pin prick sensation, but rather they are experiencing referred pain through secondary pain pathways. In this case, pricking a muscle will cause the neuron to fire up the dorsal horn, crossing the midline and up the spinal spinothalamic tract until the brain registers the pain. However, if that initial stimulus is severe enough in amplitude, or if it becomes chronic, the person will experience a secondary pathway firing. When the brain registers this, it does not know where the source of pain is, and a referred pain pattern begins. This is called a widening of the receptive fields of pain, and typically occurs in injuries. To understand widening of receptive fields of pain, think of a shoulder injury. If a person injures themselves at the gym and sees a doctor the next day, they can often point out the injured shoulder as the source of the pain. But if someone suffers from an old, untreated chronic shoulder injury, a whole region of the body hurts, not just the injury site, and they may develop pain across their whole back or side. This person experienced a widening of the receptive fields of pain. Fibromyalgia is almost always a body-wide opening up of the receptive fields of pain. The Muscle Pain Pathway: Spinothalamic Tract Figure 4 Tricyclics SSNRI Norepinephrine *Seems to have benefit for limited amount of time in about 25% of subjects 7 7

8 Body-wide receptive fields of pain Experts are beginning to understand the misfires and feedback loops in the body s nervous system that can lead to the body-wide, receptive fields of pain found in fibromyalgia. Normally, when there are continued stimuli, there s a mechanism to turn off those stimuli. Fibromyalgia patients may suffer from a dysfunction of this mechanism, by way of a glitch in the descending antinociceptive system. If a muscle is pricked, and a neuron fires, it comes in the spinal cord, crosses the midline, and goes up through the spinothalamic tract to the cortex to tell the brain where the pain originated. A secondary pathway on the spinomesencephalic tract sends the stimulus to the mesencephalon, and an area called the periaqueductal gray, after which a descending inhibitory stimulus begins. nervous system kept sendingthat message all day, a person would go crazy. The body knows how to differentiate between an initial stimuli and a continued, or repeat, stimuli. The T descending antinociceptive system turns off this notification and the control mechanism, and helps people ignore stimuli. In fibromyalgia, the failure of the descending antinociceptive system is one of the prime mechanisms that can constitute an ongoing, never-ending, body-wide pain. Researchers are still trying to understand why it fails, but one substance in play is a pain-modulating peptide called substance P. The more substance P available, the more easily secondary association neurons fire. Other studies indicate the limbic system might have a hand in fibromyalgia pain, as well as fibromyalgia symptoms of fatigue, sleep disturbances, and irritable bowel syndrome. Limbic System Hypo-Thalamus Periaqueductal (PAG) Gray Ma>er SEROTONIN (5-HT) Nucleus Raphe (NRM) Magnus Descending Antinociceptive System Figure 5 & 6 Limbic system: emo.onal brain, can block pain or facilitate pain FMS pa.ents may have significant psychological factors affec.ng the limbic system, which may dampen the DANS. Spinal Cord The descending inhibitory stimulus stops off in the medulla, then in the nucleus raphe magnus, until it is distributed to the same segmental level where the initial stimulus came in, where the descending inhibitory stimulus shuts off the initial stimulus. This process happens every day. When a person gets out of the shower and puts a shirt on, their nervous system works in concert to tell the brain they are dressed. However, if their Limbic system When the limbic system fails due to injury or disease, a slew of conditions can follow, which mirror many fibromyalgia symptoms. People with limbic system problems may experience ascending arousal syndromes, hypervigilance, sleep disorders, or unrefreshed sleep. Irritable bowel and irritable bladder have also been linked to the limbic system, 8 8

9 as has parasympathetic imbalances with a tendency towards sympathetic dominance, and changes in the hypothalamic pituitary adrenal (HPA) axis, symptoms which seem to fit with fibromyalgia. The limbic system helps to control the descending antinociceptive system, through the hypothalamus. One of the main messengers that modulate the system is serotonin, or 5-HT Serotonin is a neurotransmitter modulator that plays a role in a number of processes linked to fibromyalgia. Serotonin helps regulate and drive the HPA axis, and alters substance P levels, which, in turn, alter the perception of pain. Serotonin initiates stage-four sleep, and sleep dysfunction is a big part of fibromyalgia. Many fibromyalgia patients are experience a cycle of poor sleep, fatigue, stress, and pain. Every Symptom of FM! 5. HPA Axis Figure 7 Limbic System - Increased corasol, ACTH, adrenaline 1. Ascending Arousal System - Hypervigilance, sleep disorders 2. SympatheAcs & ParasympatheAcs 3. DANS - Irritable Everything - InhibiAon of sensory samuli 4. ReAcular FormaAon - Increased skeletal muscle tone Fibromyalgia treatments The medical industry is a long way from discovering a fibromyalgia cure, but new understanding into the mechanisms driving its symptoms has opened up new treatment opportunities. Drug therapy Current FDA-approved drugs for fibromyalgia include selective serotonin-norepinephrine reuptake inhibitors (SSNRIs), antiepileptic drugs (alpha 2-delta ligands), and tricyclic antidepressants. Both types of drugs act centrally and peripherally on the nervous system. SSNRIs block the reuptake of serotonin from the distal synapse to the proximal, so there is more serotonergic effect for the amount of serotonin the person is producing. However, this drug relies onthe person making a reasonable baseline level of serotonin. Several large meta-analysis studies of SSNRIs have shown these drugs can significantly help a fraction of fibromyalgia patients, but a large fraction of patients do not see much improvement. Moreover, there s often a significant drop-off in the positive benefit of the medication after three months. Low-dose naltrexone (LDN) is gaining popularity as a treatment for fibromyalgia and other global pain syndromes. Though LDN works through a blockade of neuronal opioid receptors, which don t affect global pain syndromes, the drug does have the ability to lower micro-inflammation. Sleep therapy Early sleep studies identified a specific type of sleep dysfunction in fibromyalgia patients. Although the patients may appear to be sleeping fine, they do not get into a stage three or four delta-wave sleep, which is crucial for growth hormone output and restoration. This sleep dysfunction also appears to be bidirectional, where sleep deprivation will cause allodynia, increased pain perception, and resulting increased pain will cause sleep dysfunction. This is one reason why sleep therapy should be a treatment target for fibromyalgia patients. 9 9

10 Biofeedback and cognitive behavioral therapy Figure 8 Fortunately, there are plenty of easily-accessible sleep therapies for fibromyalgia patients. An overall goal to get better sleep is to improve sleep hygiene, or maintaining a physical environment and personal habits that foster better sleep. For example, when a person experiences bright natural light during the day and darkness in the evening, their body will naturally release melatonin to help them fall asleep. However, nighttime exposure to bright blue lights from computer screens and other electronics will interfere with this melatonin release and disrupt sleep. Fibromyalgia patients may be able to improve sleep, decrease anxiety, and relieve some of their pain through non-pharmaceutical treatments, such as cognitive behavioral therapies and biofeedback with real-time electroencephalogram (EEG). These therapies can help people control their physical reactions to strong emotion or stimuli, and may directly control their physical state. With a trained professional, fibromyalgia patients can start to learn how to control their heart rate, and get back into more calming brain patterns. Supplements Health care providers must be careful about recommending supplements for fibromyalgia. Some supplements that help other conditions, like chronic fatigue, may hurt someone with fibromyalgia. One recommended fibromyalgia supplement is 5-HTP, which is a byproduct of the proteinbuilding block, L-tryptophan, and can boost serotonin levels. People take 5-HTP for sleep disorders, migraines, anxiety, and a host of other symptoms. Doctors should use caution when combining 5-HTP and SSRIs, and be sure to monitor the serotonin levels of their patients. Fibromyalgia patients struggling to sleep may try avoiding screens before bedtimes, or use amber lenses or devices to change the color of their screens to pull the blue light out. Other good sleep hygiene practices include keeping a consistent sleep schedule and limiting distracting activities, like reading or watching TV in bed. TRP 5-HTP Re-uptake of 5-HT by neurons 5-HT MAO Inhibitors 5-HIAA SSRIs/SSNRIs Excre/on Biochemistry of Serotonin Figure

11 All can be associated with fa1gue and muscle tenderness Patients with fibromyalgia may also benefit from calming nutraceuticals, such as gamma-aminobutyric acid (GABA), L-Theanine, inositol, and magnesium. Ashwagandha, German chamomile, valerian, passionflower, and lemon balm are all calming herbal supplements that can help fibromyalgia patients with stress and anxiety management. Certain nutrients considered to have calming adrenal properties, such as methylated folate, B-12, and vitamin C, may also help fibromyalgia. Insufficient vitamin D levels can contribute to fibromyalgia. Vitamin D is a pain modulator, and activates the transcription of the serotonin-synthesizing gene, tryptophan hydroxylase 2, which is the enzyme that converts 5-HTP to 5-HT. Supplementing vitamin D in some patients may make 5-HTP supplements more effective and help relieve pain. Classic FMS - Sleep disorder - Anxiety - Depression - Altera3ons of CNS chemistry - Neuro-endocrine imbalances Fibromyalgia Syndrome Clinical Reasoning Guide Figure 10 Organic - Anemia - Lyme disease - Hypothyroidism - Inflammatory arthri3des - Dysglycemia - Occult carcinoma - Mul3ple sclerosis Pseudo - FMS The various disorders that are misdiagnosed as FMS 1) Organic diseases 2) Func3onal disorders 3) Musculoskeletal disorders Func3onal - Mitochodrial dysfunc3on - Toxicity - GI dysbiosis - Nutri3onal deficiencies Musculoskeletal - Mul3ple TrPs - Joint dysfunc3on - Muscle imbalance - Postural distor3on - Undiagnosed disc/ facet lesions Fibromyalgia imposters Fibromyalgia symptoms tend to overlap with symptoms of unrelated medical conditions, which require very different types of treatment. Be mindful of fibromyalgia imposters, such as suboptimal thyroid function, myofascial pain syndrome,e and suboptimal mitochondrial function. Learning how to recognize these frequently-confused conditions will help providers more accurately diagnose fibromyalgia patients. Catching the fibromyalgia imposters Suboptimal thyroid function is often mistaken for fibromyalgia, but unfortunately commonly missed by doctors. Many symptoms of fibromyalgia and thyroid dysfunction overlap. While there are lab tests to check thyroid levels, most doctors only test thyroid-stimulating hormone (TSH) levels for thyroid function. However, TSH is generally controlled with a feedback loop from circulated T4 levels, and a TSH reading doesn t reveal how T4 is converted to T3 in the periphery, or how it s acting at the peripheral receptor. A more thorough thyroid lab test is enough to help distinguish a thyroid problem from fibromyalgia. Myofascial pain syndrome is also often mistaken for fibromyalgia. Many practitioners think they are successfully treating fibromyalgia, when they are likely treating myofascial pain syndrome. Both myofascial pain syndrome and fibromyalgia patients will have tender points on their bodies. However, the tender point in myofascial pain syndrome is due to a muscle contraction the muscle doesn t shorten, but there s a contracted sarcomere nodule with an area of compensating elongated sarcomeres. Physically manipulating a myofascial trigger point can relieve pain, but since there s nothing wrong with a muscle in a fibromyalgia tender point, applying physical medicine to a patient would only cause pain

12 Elongated sarcomeres TrP nodule = focus of contracted sarcomeres symptoms. Fibromyalgia patients aren t suffering from a systemic inflammation issue, but a smoldering, microinflammation in their brain that produces body-wide symptoms. Now that doctors know fibromyalgia is a centrally-mediated problem and a hypervigilance issue, they can start treating fibromyalgia patients more effectively. However, providers must ensuring that each patient is properly diagnosed for new treatments to be effective. Fibromyalgia Syndrome Clinical Reasoning Guide Figure 11 Mitochondrial problems can also masquerade as fibromyalgia, and must be ruled out. Organic acid workups can catch mitochondrial dysfunction. Providers should check neurotransmitter metabolites and the Krebs cycle intermediates. There is mitochondrial support through supplements if someone is suffering from mitochondrial dysfunction, including high-dose CoQ10, carnitine, ribose, nicotinamide, riboside, and lipoic acid. Conclusion Normal sarcomeres Diagnosing fibromyalgia is a long and arduous process. No single lab or imaging test can confirm the diagnosis, and a number of conditions can masquerade as fibromyalgia. Since effective fibromyalgia treatments are often different from the treatments for other conditions, providers must be careful when diagnosing patients. Better education among health care providers, and ongoing research, will hopefully continue to improve fibromyalgia care in coming decades. Biography Dr. David Brady, ND, has more than two decades of experience as an integrated physician and an academic in health science. Dr. Brady currently serves as vice president for the Division of Health Science and director of the Human Nutrition Institute at the University of Bridgeport in Connecticut. He maintains a private practice, Whole Body Medicine, in Fairfield, Connecticut. Dr. Brady is chief medical officer for Designs for Health and Diagnostic Solutions Laboratory, and author of new book, The Fibro Fix. Fibromyalgia patients have long-suffered from a lack of scientific research on their disease. For decades, fibromyalgia symptoms defied what doctors thought they knew about the origin of pain, digestive issues, anxiety, and depression. A complete understanding of fibromyalgia is a long way off, but new research has opened up hope for treatments. Recent advances in neurological research has uncovered possible explanations for the wide array of fibromyalgia