-IBIS-1.5.0-
tx
musculoskeletal system
fibromyalgia
diagnoses

definition and etiology

definition:
Widespread pain, tenderness and stiffness of muscles, tendons, ligaments of greater than 3 months duration, usually accompanied by fatigue and anxiety or depression.

Fibromyalgia is a complex syndrome with no known cause or cure. Its predominant symptom is severe muscle pain, although other symptoms, such as fatigue, headaches, chest pain, low grade fever, swollen lymph nodes, unrestful sleep or insomnia, frequent abdominal pain, irritable bowel syndrome, anxiety, and depression may be involved.

Fibromyalgia represents group of common nonarticular rheumatic disorders characterized by achy pain, tenderness, and stiffness of muscles, areas of tendon insertions, and adjacent soft-tissue structures. These may be primary and generalized or concomitant with another associated or underlying condition, or localized and often related to overuse or microtrauma factors. The term myalgia indicates muscular pain. In contrast, myositis is due to inflammation of muscle tissues and is an inappropriate term for fibromyalgia, when such inflammation is absent. Fibromyalgia indicates pain in fibrous tissues, muscles, tendons, ligaments, and other "white" connective tissues. Various combinations of these conditions may occur together as muscular rheumatism. Any of the fibromuscular tissues may be involved, but those of the occiput, low back (lumbago), neck (neck pain or spasm), shoulders, thorax (pleurodynia), and thighs (aches and spasms) are especially affected. There is no specific histologic abnormality, and the absence of cellular inflammation justifies the preferred terminology of fibromyalgia rather than the older terms of fibrositis or fibromyositis.

etiology:
Of the estimated three to six million people afflicted with this disorder, the majority are women between 25-45 years old, with females out-numbering males by 6:1. The patients tend to present as stressed, tense, depressed, anxious, and/or striving. It may be induced or intensified by physical or mental stress, chronic overwork, poor sleep or sleep disorders, physical or emotional trauma, depression, exposure to dampness or cold, and occasionally by a systemic, usually rheumatic, disorder. A viral or other systemic infection (e.g., Lyme disease) may precipitate the syndrome in an otherwise predisposed host. Patients often trace the onset of symptoms to an acute event or viral-like illness. Fibromyalgia may also be a complication of hypothyroidism. Men are more likely to develop localized fibromyalgia in association with a particular occupational or recreational strain or as a complication of sleep apnea. A minority of cases may be associated with significant psychogenic or psychophysiologic manifestations. Symptoms can be exacerbated by environmental or emotional stress, or by a physician who does not give proper credence to the patient's concerns and dismisses the distress as "all in the head."

A variety of metabolic factors have been presented as playing important roles in the causality of this syndrome. No conclusive pattern has been proven responsible for all occurrences of this disorder and a multifactorial causality is more likely predominant than the exception.

Some research now indicates that fibromyalgia patients may be deficient in certain compounds required for the synthesis of adenosine triphosphate (ATP). ATP synthesis requires the presence of oxygen, magnesium, substrate, ADP and phosphate. Optimal concentrations of each of these allows healthy mitochondrial respiration and the concomitant production of biological energy. Deficiencies, on the other hand can seriously slow the Krebs cycle, increase anaerobic glycolysis, increase lactic acid formation and cause a reduction of Max V02. This combination of factors can clearly lead to the symptoms of fatigue. depression and muscle pain.

Pain in fibromyalgia patients has been attributed to an unusually high degree of gluconeogenesis. This increased level of muscle tissue breakdown has been hypothesized as one of the main reasons for pain, aching and fatigue.

Serotonin and dopamine imbalances may constitute a major factor in fibromyalgia. Here, as in many other factors leading to fatigue and inflammation, increased permeability of the intestinal mucous membranes may play a crucial role; 80% of serotonin is produced in a healthy gut. Consequently a history of repeated courses of antibiotics, especially in the 6-12 months prior to onset, may be significant.

Aluminum toxicity may play a role in symptoms experienced by magnesium deficient fibromyalgia patients since magnesium is needed to help the body block the toxic effects of aluminum. This is especially important since aluminum inhibits glycolysis and oxidative phosphorylation, resulting in decreased intramitochondrial ATP production. Additionally, due to its high affinity for phosphate groups, aluminum blocks the absorption and utilization of phosphates vital to the synthesis of ATP. This further contributes to the problem of intramitochondrial phosphate deficiency.

Fatigue is one of the most prominent features of fibromyalgia syndrome, and studies show that both chronic fatigue syndrome and fibromyalgia may have a common link in manganese-dependent neuroendocrine changes, especially along the hypothalamic-pituitary thyroid axis. The cycle begins with hypothalamic production of thyrotrophin-releasing hormone (TRH). TRH stimulates the pituitary gland to produce thyroid stimulating hormone (TSH), which in turn stimulates thyroid production of thyroxin.

Several studies conducted in Sweden on patients with fibromyalgia reported appear to have microcirculation disturbances, along with mitochondrial damage and abnormally low phosphate counts - strongly suggesting an energy deficient state in the muscle tissues. At the conclusion of the study, scientists hypothesized that fibromyalgia might be the result of any condition that could lead to constant muscle hypoxia, specifically through the establishment of abnormal motor patterns.

signs and symptoms

Fibromyalgia is commonly a diagnosis of exclusion.
The patient feels incapable of performing normal activities, and even minor exertion aggravates pain and increases fatigue, yet objective signs of inflammation are usually absent and conventional laboratory studies normal.

Key Signs and Symptoms:
• Tenderness of specific anatomical sites ("trigger points")
• Chronic aching
• Stiffness
• Sleep disturbances, unrestful sleep or insomnia; decreased REM
• Pain
• Numbness and paresthesias
• Subjective soft tissue swelling

Common Signs and Symptoms:
• Chronic Fatigue, especially on waking, also 3-5 pm; worsened by muscle spasm and fatigue
• Low grade fever
• Swollen lymph nodes
• Anxiety, often anxiety attacks
• Depression
• Chronic headaches
• Gastrointestinal disturbances and frequent abdominal pain, commonly irritable bowel syndrome
• Chest pain and cardiovascular problems (dizziness, palpitations)

Lab:
Usually all normal. A detailed history and repeated physical examination can obviate the need for extensive laboratory testing.
• ESR may be elevated
• CDSA (Complete Digestive Stool Analysis) can help determine the presence and severity of intestinal dysbiosis and excessive mucous membrane permeability.
• Adrenal Stress index (ASI) or other tests of adrenal function, especially cortisol levels and cycles, can reveal much about the role of stress-induced fatigue and inflammation.

Physical Examination:
Patients usually appear healthy and physical examination is normal except for "trigger points" of pain produced by palpation. Tender points can range from mildly irritating to completely debilitating and are located over muscles and tendinous insertions, such as the trapezius, the medial fat pad of the knee, the lateral epicondyle of the elbow, iliac crest, and lumbar spine (see graphic).Tender Point Count (i.e. sensitivity in at least 11 of 18 points) has become the primary diagnostic factor for fibromyalgia and may be key in differentiating the syndrome from chronic fatigue syndrome.

course and prognosis

Fibromyalgia may remit spontaneously (in milder cases) with decreased stress. Most patients have chronic symptoms that are constant or recur at frequent intervals. With treatment, however, many do eventually resume increased activities. Progressive or objective findings may not develop. Deeper resolution usually requires addressing issues of nutrition, metabolic efficiency, intestinal permeability, adrenal and thyroid function, and, most importantly, stress reduction and lifestyle modification.

Conventional treatment, at best, usually involves reassuring the patient of the "benign" nature of the syndrome and recommending stretching exercises, local applications of heat, gentle massage. Quite often, low- dose tricyclic agents at bedtime (e.g., amitriptyline 10 or 25 mg) are prescribed to provide some short-term relief, such as promoting deeper sleep; however, the drug’s efficacy in this regard is variable and only symptomatic; it is also known to have adverse side effects, including myocardial infarction, stroke, arrhythmia, coma, seizure and alopecia. Long-term effects of the drug are still not known. Any use of tricyclic antidepressant drugs should be in the lowest effective dose and must be monitored for side effects. Other controlled studies have tested the effects of Aspirin 650 mg orally q 3 to 4 h or other NSAIDs, specifically, Ibuprofen (Motrin, Advil, Nuprin), and found them to be no more beneficial than a placebo. Opioids and corticosteroids are ineffective and should never be used. Nevertheless, it is not uncommon to see treatment with injections of 1% lidocaine solution, 1 or 2 ml alone or in combination with a 40-mg hydrocortisone acetate suspension in an attempt to incapacitate areas of focal tenderness. Ultimately, all of the conventional treatment modalities that have been tested on fibromyalgia patients have yielded unsatisfactory results. Even so, functional prognosis is usually favorable with a comprehensive, supportive program, although some degree of symptoms tends to persist.

differential diagnosis

• Myofibrositis
• Chronic Fatigue Syndrome
• Generalized Osteoarthritis
• Rheumatoid arthritis and systemic lupus erythematosus:these conditions virtually always present with objective physical findings or abnormalities on routine testing, including the erythrocyte sedimentation rate.
• Hypothyroidism :Thyroid function tests are useful, since hypothyroidism can produce a secondary fibromyalgia syndrome.
• Polymyositis produces weakness rather than pain. The diagnosis of fibrositis probably should not be made in a patient over age 50 and should never be invoked to explain fever, weight loss, or any other objective signs.
• Polymyalgia rheumatica produces shoulder and girdle pain, is associated with anemia and an elevated sedimentation rate, and occurs after age 50.
• Psychogenic muscle pain and spasm


footnotes

Abraham, G. Flechas, J. Management of fibromyalgia:Rationale for the use of magnesium and malic acid. J. Nutr. Med. 1992;3:49-59.

Carette, S, et al. Comparison of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia:A randomized, double-blind clinical trial. Arthritis Rheum. 1994;37:32. (Both more effective than placebo, but only one-third significantly improved after 6 months of therapy.)

Carette, S. Fibromyalgia 20 years later:What have we really accomplished? J. Rheum. 1995;22(4):590-594.

Carlsen, BD, Synthesis of Malate from Phosphenol Pyruvate by Rabbit Liver Mitochondria Implications for Lipogenesis. Bio et Bophysica Acta. 1988;965:1-8.

Domingo, JL, et at. Citric, Malic and Succinic Acids as Possible Alternatives to Deferoxamine in Aluminum Toxicity. Clin. Tox. 1988;26(1,2):67-79.

Eisinger, J, Zakarian, H, Plantamura, A, et al. Studies of transketolase in chronic pain. J. Adv. Med. 1992;5:105-113.

Eisinger, J, Bagneres, D, Arroyo, et al. Effects of magnesium, high energy phosphates. piracetam, and thiamin on erythrocyte transketolase. Magnesium Research. 1994;7(1):59-61.

Goldzer RC, et al. Hyperkalemia associated with indomethacin. Arch. Intern. Med. 1982; 141:802-4.

Granges, G, Zilko, P, Littlejohn, GO. Fibromyalgia syndrome:Assessment of the severity of the condition 2 years after diagnosis. J. Rheumatol. 1994;21:523. (Twenty-four percent remitted in 2 years.)

Is fibromyaIgia caused by a glycolysis impairment? Nutr. Reviews. 1994;52(7):248-250.

MacCarthy EP, et al. Indomethacin induced hyperkalemia. Med. J. Austral. 1979:1:550.

Mengshail, AM, Komnaes, HIB, Forre, O. The effects of 20 weeks of physical fitness training in female patients with fibromyalgia. Clin. Exp. Rheum. 1992;10:345-349.

Russell, J, Michalek, J, Flechas, J, et al. Treatment of fibromyalgia syndrome with SuperMalic:A randomized, double-blind, placebo-controlled, crossover pilot study. J. Rheum. 1995;22(5):953-957.

Steinherg, CL, The tocopherols (vitamin E) in the treatment of primary fibrositis. J. Bone Joint Surg. 1942;24:411-423.

Tan, SY, et al. Indomethacin-induced prostaglandin inhibition with hyperkalemia. Ann. Intern Med. 1979; 90:783-5.

Wilke, W, Fibromyalgia:Recognizing and addressing the multiple interrelated factors. Postgraduate Med. 1996:100(1):153-170.

Wolfe, F, Ross, K, Anderson, J, Russell, J. Aspects of fibromyalgia in the general population:Sex, pain threshold, and FM symptoms. J. Rheum. 1995;22(1):151-155.