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Making a Firm Diagnosis of Fibromyalgia and Understanding its Pathophysiology

Making a Firm Diagnosis of Fibromyalgia and Understanding its Pathophysiology

Identifying symptoms of fibromyalgia is important for an accurate diagnosis. There are some difficulties in diagnosing fibromyalgia due to other concomitant ailments and insufficient site tender points. However, currently, the term FMS, or fibromyalgia, collectively applies to both primary and concomitant types. Fortunately, we describe clinical features, diagnosis, and pathophysiology in this article.

Diagnosis and Symptoms of Fibromyalgia!

In this Article:

Fibromyalgia Definition and Statistics!

Chronic musculoskeletal aches and pains, as well as multiple tender points on palpation by an examiner, characterize fibromyalgia syndrome (FMS) in the diagnosis of fibromyalgia. It’s more common in women than men; about 90 percent of patients are women. The most common age of presentation is between 30 and 60 years. However, FMS has been well described among juveniles.

FMS is a common condition. It encountered among 2.1 percent, 5 percent, and 10 to 20 percent of patients seen in family practice, internal medicine clinic, and rheumatic disease clinic, respectively. Scientists found the prevalence of FMS in a community at between 2 percent in Wichita, Kansas, and 3.3 percent in London and Ontario, Canada.

Primary Fibromyalgia Meaning!

The prevalence increases with age until 65 to 79 years. In a Canadian study, more than 7 percent of women had FMS in the 55 to 64 age group, and in the 60 to 79 age group in a U.S. study. The term primary fibromyalgia is used when a significant underlying or concomitant condition that may contribute to pain is absent in the diagnosis of fibromyalgia. FMS may be classified as concomitant when another condition, such as rheumatoid arthritis (RA), osteoarthritis, or hypothyroidism is present and may contribute to the pain or fatigue of FMS.

Fibromyalgia Symptoms Checklist!

Fibromyalgia Symptoms Checklist | Making a Firm Diagnosis of Fibromyalgia and Understanding Its Pathophysiology | Early Symptoms Of Fibromyalgia

Early Symptoms of Fibromyalgia!

  • Widespread pain
  • Fatigue and poor sleep
  • Subjective swelling of soft tissues and sometimes of the joints
  • Paresthesia: a sensation of tingling, tickling, prickling, or burning of a person's skin
  • Cognitive dysfunction, and symptoms of other associated conditions such as headaches
  • Irritable bowel syndrome or IBS
  • Restless legs syndrome and temporomandibular dysfunction.

There is no significant correlation between subjective swelling or subjective numbness and psychological status.

Fibromyalgia Symptoms Tender Points!

Common sites of pain or stiffness are the lower back, neck, shoulder region, arms, hands, knees, hips, thighs, legs, and feet. Chest pain is not uncommon and tender points in the chest wall usually accompany it.

Fibromyalgia and Fatigue!

Fatigue is common among the symptoms of fibromyalgia and may be the presenting feature in some cases because of its severity. Several factors may contribute to, or aggravate, fatigue and pain in FMS:

  • Nonrestorative sleep
  • Deconditioning
  • Overwork
  • Psychological factors
  • Poor coping skills
  • Sensitivity to environmental stimuli such as noise

Signs of Fibromyalgia!

Patients with FMS look healthy, but often they seem fatigued and in pain. Examination of the joints shows no objective swelling (unless there is concomitant arthritis), But some patients have marked joint tenderness on palpation. Despite neurologic symptoms, such as weakness and numbness, neurologic examination in FMS is normal in the diagnosis of fibromyalgia.

Fibromyalgia Diagnosis Checklist!

Fibromyalgia Diagnosis Checklist | Making a Firm Diagnosis of Fibromyalgia and Understanding Its Pathophysiology | Early Symptoms Of Fibromyalgia

The American College of Rheumatology 1990 Criteria for the Classification of FMS:

1. History of Widespread Pain (for at least three months)!

Pain is considered widespread when all of the following are present:

  • Pain in the left side of the body
  • Pain on the right side of the body
  • Pain above the waist
  • Pain below the waist
  • Axial skeletal pain: cervical spine or anterior chest or thoracic spine or low back

In this definition, shoulder and buttock pain are considered as pain for each involved side. Lower back pain is considered lower segment pain. Thus, pain at three widespread sites (for example, right arm, low back, and left leg) will satisfy the criterion of widespread pain.

2. Fibromyalgia Tender Point Sites!

The pain must be present in at least 11 of the 18 tender point sites on digital palpation with an approximate force of 4 kg. Here are some of the tender point sites:

  • Occiput: bilateral, at the suboccipital muscle insertions
  • Low cervical: bilateral, at the anterior aspects of the intertransverse spaces at C5-7
  • Trapezius: bilateral, at the midpoint of the upper border
  • Supraspinatus: bilateral, at origins above the scapula spine near the medial border
  • Second rib: bilateral, at the second costochondral junctions, just lateral to the junctions on upper surfaces
  • Lateral epicondyle: bilateral, 2 cm distal to the epicondyles
  • Gluteal: bilateral, in upper outer quadrants of buttocks in anterior fold of muscle
  • Greater trochanter: bilateral, posterior to the trochanteric prominence
  • Knee: bilateral, at the medial fat pad proximal to the joint line

A patient with FMS may have many symptoms, but he or she needs only present with widespread pain and 11 or more tender points among the 18 sites specified in ACR criteria. Note that a patient with FMS may be tender in many more sites (including bones) besides these 18. Some patients have diffuse tenderness everywhere on palpation. Such a phenomenon does not necessarily imply high psychological distress. Such diffuse tenderness on palpation or a significant psychiatric disease does not influence a diagnosis of fibromyalgia (as long as a patient satisfies the ACR criteria).

For classification purposes, patients will be said to have FMS if both criteria (1 and 2) are satisfied. The presence of a second clinical disorder does not exclude the diagnosis of fibromyalgia.

ACR Criteria on Concomitant Conditions!

Despite a common notion, the diagnosis of fibromyalgia is disarmingly simple. It can, and should be, diagnosed by its own characteristics of widespread pain and multiple tender points. Another concomitant condition, such as arthritis or hypothyroidism, does not exclude the diagnosis of fibromyalgia, as stated by the American College of Rheumatology (ACR) criteria. Putting it another way, if a patient has FMS as well as RA, this patient has both FMS and RA. Although the ACR criteria are for the classification of FMS (so that researchers can use a uniform set of criteria for patient selection), these criteria have been found very useful for the diagnosis of fibromyalgia in clinical practice.

From Wolfe F et al. Arthritis Rheum. 1990

Fibromyalgia Test for Tender Points!

The most significant physical finding in FMS is the presence of multiple tender points in a widespread distribution. For the purpose of diagnosis of fibromyalgia, one needs to examine 18 specified sites, by application of a force of approximately 4 kg (roughly the pressure one needs to whiten the nail bed when pressing against a firm surface), using the index finger or the thumb. Note that practitioners must learn the proper way to examine a tender point, as in the case of examining other physical signs in medicine, such as hepatomegaly or splenomegaly. An underestimation of the number of tender points in a patient with FMS is the most important reason for missing a diagnosis of this disorder.

How to Diagnose Fibromyalgia!

It may surprise many physicians to learn that a diagnosis of FMS does not require any specific laboratory testing since ruling out does not apply to FMS. Practitioners should request laboratory tests, including radiology, only if they suspect another concomitant condition by careful history taking and physical examination. There's no reason to order tests of antinuclear antibodies or rheumatoid factor unless clinically indicated. However, a complete blood count and a chemistry panel with blood urea (Nitrogen, Creatinine) and hepatic enzymes are useful to monitor side effects of drugs either for FMS or a concomitant condition in the diagnosis of fibromyalgia.

Although the prevalence of hypothyroidism does not seem to increase in FMS compared with the normal population, we obtain T4 and thyroid-stimulating hormone levels in patients with significant fatigue, even in the absence of other features of hypothyroidism.

Fibromyalgia Without Tender Points in 11 Sites!

Now, a frequent question we hear from practicing physicians is should one diagnose FMS if a patient has widespread pain but not 11 tender points? For a clinical purpose, we suggest that a patient who has otherwise characteristic symptoms of FMS (e.g., fatigue, poor sleep, morning fatigue, and one or more associated conditions) but only 6 to 10 tender points should be treated for FMS.

Differential Diagnosis!

Several conditions may mimic FMS. As emphasized before, a patient may have FMS as well as any of the conditions listed above. For example, chest pain with localized tenderness in the chest wall in a patient with FMS would suggest the chest pain is part of FMS. However, this patient may also have a concurrent intrathoracic pathology the practitioner can diagnose by appropriate history, physical examination, and laboratory tests.

Fibromyalgia in Women Over 50!

In another example of concomitant disease, a 69-year-old female patient in our practice complained of pain and numbness in the legs when she first presented with FMS with a normal neurologic examination. Three years later, the pain, as well as numbness in the legs, became more intense. The pain was worse upon waking. This patient could no longer do her dishes standing because of bothering backache. Neurologic examination showed signs of L5-S1 root compression. A clinical diagnosis of spinal stenosis was made and we ordered an MRI scan of the lumbar spine. The MRI confirmed spinal stenosis that was treated surgically. The numbness and pain were substantially relieved following the surgery.

Pathophysiologic Mechanisms of FMS!

Pathophysiologic Mechanisms of FMS | Making a Firm Diagnosis of Fibromyalgia and Understanding Its Pathophysiology | Early Symptoms Of Fibromyalgia

The pathogenesis of FMS is incompletely understood. Despite muscle pain, no histologic or biochemical abnormalities in the muscles have been demonstrated. It’s now known that pain and fatigue, as well as several other symptoms, are central in origin, the most important mechanism being central sensitization.

Central Sensitization!

Neurons in the CNS undergo structural, chemical, and functional changes following a peripheral noxious stimulus (such as mechanical, chemical, or thermal injuries), leading to the heightened sensitivity of the neurons both at spinal and supraspinal levels. The process is called central sensitization with the following characteristics:

  • Hyperalgesia: an exaggerated response to a peripheral stimulus that's normally painful
  • Allodynia: an experience of pain following a normally non-painful stimulus
  • Persistence of pain
  • Greater intensity of pain
  • Wider distribution of pain than the area of original stimulation

A phenomenon related to central sensitization is called wind-up in animal models and temporal summation in humans. N-methyl-D-aspartate (NMDA) receptors mediate this phenomenon. It’s characterized by a progressive increase in pain secondary with each brief but repeated peripheral stimulus of the C fibers at a certain interval, for example, two seconds. In the diagnosis of fibromyalgia, however, there's no obvious peripheral tissue injury except trauma-induced inflammation (for example, from automobile accidents) in some patients.

Suspected Causes of Fibromyalgia CNS!

So, the cause of nociceptor activation in a majority of these patients remains unclear. We have postulated that the CNS of some patients with FMS and similar disorders (such as headaches and IBS) are inherently hyper-responsive because of genetic susceptibility or childhood trauma (or both). An otherwise in-apparent (silent) source of peripheral nociception, such as mechanical stress in the cervical or lumbar spine, or such spinal stress generated by poor posture or degenerative disease, may now trigger central sensitization in these susceptible individuals.

Neurons Changing CNS!

Other sources of peripheral nociception, such as arthritis or a painful peripheral neurologic disease, may also initiate and perpetuate central sensitization. The presynaptic release of neurokinins mediate central sensitization, for example, Substance P (SP), and by excitatory amino acids, such as glutamate and aspartate that activate postsynaptic NMDA receptors. As a result, remarkable intramembranous and intracellular changes take place in the postsynaptic neurons, such as alteration of cell membrane permeability, an influx of calcium, and activation of second messengers, all of which contribute to orchestrate marked neuronal changes leading to central sensitization.

Inhibitory System in CNS!

Normally, there's also an inhibitory system that dampens hypersensitization. Serotonin, norepinephrine, endorphins, and other neurochemicals mediate the inhibitory activities. However, the inhibitory system may be dysfunctional in central sensitization.

Evidence for Central Sensitization in FMS!

Strong neurophysiologic evidence supports a state of central sensitization in FMS. One study demonstrated a significant reduction of the pain threshold in FMS patients compared with normal controls following an innocuous electro cutaneous stimulation that was associated with unpleasant pain, dysesthesia, and anatomical spread of pain. Other examples of central sensitization have been summarized and include temporal summation, decreased cerebral blood flow in the caudate nucleus and thalamus by single-photon emission computed tomography, and augmented pain processing.

CNS and Neurochemical Disturbances!

There is also central sensitivity-related neurochemical disturbance in FMS, such as increased SP and decreased 5-Hydroxyindole acetic acid (5-HIAA, a metabolite of serotonin) in the cerebrospinal fluid and decreased serum serotonin. Both increased SP and decreased serotonin help to explain increased pain sensitivity in the diagnosis of fibromyalgia.

Endocrine Aberrations!

Neuroendocrine abnormalities may play an important role in FMS. These include Hypothalamic-Pituitary-Adrenal (HPA) axis disturbance with an exaggerated adrenocorticotropic (ACTH) response to corticotropin-releasing hormone with normal cortisol response. Relative hypocortisolemia in FMS is not due to a primary failure of the adrenal cortex and seems to be of hypothalamic origin. Note that these findings are different from those found in depression where hyperreactivity of the HPA axis has been demonstrated at all levels, including hypercortisolemia that escapes dexamethasone suppression. Growth hormone (GH) deficiency in FMS may partly explain a lack of energy among patients with FMS. GH is secreted mostly during non-rapid eye movement (REM) sleep, which is disturbed in FMS.

Nonrestorative Sleep!

Most patients with FMS sleep poorly and wake up tired in the morning. Alpha intrusion of non-REM sleep in FMS indicates arousals during the restorative phase of sleep architecture. Phasic alpha sleep, in particular, is associated with increased pain and tender points the next morning. However, routine sleep electroencephalographic testing has no practical utility unless other sleep problems, such as REM sleep behavior disorder and sleep apnea, are clinically suspected. Poor sleep the previous night predicts pain the next day.

Psychological Factors!

Psychological distress aggravates pain and fatigue in FMS. Most studies have shown an increased frequency of present and lifetime anxiety, stress, and depression in patients with FMS compared with normal as well as RA control groups. Poor coping skills may also perpetuate pain. However, It's clear that psychological factors aren't necessary for causing FMS. Only about 30 to 40 percent of patients have psychological disturbances, and in many of these cases, distress may be secondary to chronic pain itself.

Genetic Factors!

Genetics is quite likely to play a role in FMS. There's familial aggregation in FMS. Genetic markers include T102C polymorphism of the 5-HT2-A receptor gene and a probable linkage with the HLA. Genome mapping of multicast families with FMS is currently in progress.

Summary of Pathophysiologic Mechanisms!

FMS is a multifactorial condition with many triggering or interacting factors, such as genetics, neuroendocrine aberrations, psychological distress, trauma, peripheral sources of nociception (such as inflammation), poor sleep, deconditioning, or over activities, which may initiate and sustain central sensitization leading to chronic pain and exaggerated response to various stimuli. It’s now clear that FMS symptoms may be explained by biological and Psychosocial-Behavioral factors, with much variability in the relative contributions of these elements in an individual patient.

Central Sensitivity Syndromes (CSS)!

Yunus was the first to postulate and demonstrate that several common chronic illnesses, such as fibromyalgia, IBS, headaches, and primary dysmenorrhea, are related conditions with many similar features with common pathophysiology. These are currently called functional somatic syndromes, an intriguing name for a group of disorders that manifest as dysfunction in the neuroendocrine systems. It now seems that the common binding pathophysiologic glue of these conditions is central sensitization; Hence the term central sensitivity or CSS. CSS include FMS, IBS, chronic fatigue syndrome, myofascial pain syndrome, restless legs syndrome, temporomandibular dysfunction syndromes, multiple chemical sensitivity, post-traumatic stress disorder, depression, and other similar conditions.

Article Source!

We have not modified the factual content from the article by By Sule Arslan, MD, Gaziosmanpasa University, and Muhammad B. Yunus, MD, University of Illinois. This content is syndicated news that you can use for your research, and we hope that it can help your productivity. This content is strictly for educational purposes and is not made for any kind of the commercial purpose of this blog.

Clinical Highlights!

  • Common sites of pain or stiffness are the low back, neck, shoulder region, arms, hands, knees, hips, thighs, legs, and feet. Chest pain is not uncommon and tender points in the chest wall usually accompany it. Fatigue is a frequent manifestation and may be the presenting feature in some patients because of its severity.
  • The diagnostic finding in FMS is multiple tender points (11 or more among the 18 sites specified by the American College of Rheumatology [ACR] criteria). However, if a patient with characteristic symptoms, such as pain in many sites, fatigue, poor sleep, morning fatigue, has only 6 to 10 tender points, treat that patient as if he or she has FMS.
  • Examination of the joints shows no objective swelling; however, some patients have marked joint tenderness on palpation. Neurologic examination results are normal in FMS.
  • Psychological factors alone do not cause FMS, although anxiety, stress, and depression may contribute to, or exacerbate, pain and fatigue. In many patients, distress may be secondary to chronic pain.
  • Laboratory testing isn't required to make the diagnosis of FMS, because the disorder is identifiable by using ACR criteria that state that FMS is not a disease of exclusion. Order laboratory tests such as radiographs, antinuclear antibody, or a rheumatoid factor only if the history and physical examination results suggest a concomitant condition.

Fibromyalgia is an ailment that can turn into a chronic condition without proper treatment. However, before treatment, an accurate diagnosis of this disease must be performed with the necessary laboratory tests and physical examination. Complications may arise in the diagnosis due to the presence of other concomitant diseases or not enough tender point sites affected, but if your physician follows the ACR criteria, the higher the chances of your condition being diagnosed correctly. So always make sure to keep this article in mind the next time you go to your doctor's appointment.

Have you been diagnosed with fibromyalgia? What was your experience with these symptoms of fibromyalgia? Share your thoughts and experience with us in the comments sections below!

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Editor’s Note - This post was originally published on October 11, 2017, and has been updated for quality and relevancy.
Disclaimer: These statements have not been evaluated by the Food and Drug Administration. None of the nutritional products mentioned is intended to Diagnose, Treat, Cure or Prevent any Disease.