For example, someone may be suffering more from rheumatoid arthritis even though they have FMS. Sometimes, the best way to determine which disease is primary is to ask someone which disease of the two they would rather not have – that is the primary disease.
A 2005 internet survey conducted by the National Fibromyalgia Association of 2,596 FMS patients found that more than 75% had seen more than three health care professionals prior to being diagnosed and approximately 25% had seen more than six. FMS remains undiagnosed in up to three out of four individuals for the average time of five years it requires to be identified. A study of 2,260 FMS patients from the United Kingdom found that prior to the year of diagnosis they had made an average of 25 visits to health care providers! A report of six patient focus groups found those patients reporting that the “road to the diagnosis of fibromyalgia was frequently long and stressful.”
These facts are startling and true. You may have had similar experiences in your own travels. If there are other reasons why it is important to have a physician experienced in the diagnosis of FMS and one willing to listen to your symptoms, you should email it to this web site, as we cannot think of one at our end.
The single greatest risk factor for FMS is a family history, meaning you have a relative who has the syndrome. The closer the relative, the greater the risk – there is eight times the risk if that relative is your mother or father.
Let’s talk about some other conditions that frequently have FMS as an accompanying condition. Time to put on our rheumatology hat, (or lab coat).
Secondary FMS, by the 1990 ACR criteria can be present in up to 50% of two rheumatology diseases; one called Sjogren’s disease and another called primary systemic lupus erythematosus (SLE). It is also a common comorbidity in arthritic conditions with an average of 24% in psoriatic arthritis and a 12% to 15% co-occurrence with rheumatoid arthritis although one study reported 57%. Even though associated with other rheumatic diseases, there is no evidence that having FMS increases the risk of developing other conditions.
Rheumatoid arthritis (RA) has some interesting overlaps with FMS. Interestingly, 54.5% of patients presenting to a general rheumatology clinic with complaints of wrist and hand joint pain were subsequently diagnosed with FMS. Another confusing factor is that one of the most common presenting symptoms of RA is neck pain. RA is a systemic, autoimmune, inflammatory arthritis that resembles FMS in its early presentation as both have arthralgias, (joint-like pain), a female preponderance of similar age, and symptoms of pain and fatigue. About two million individuals suffer from RA with women three times more frequently affected than men.
A not uncommon presentation for a patient with RA would be significant generalized fatigue and several hours of morning stiffness that has been present for longer than three months. They may or may not have a family history of RA. The RA patient will describe more prolonged morning stiffness (>two hours), improvement of pain and stiffness with use, and usually have warm swollen joints. Patients with RA, unlike FMS, will begin to develop badly deformed joints at the junction of their fingers to the base of their hands and to the first joint of their fingers as you move outward toward to the tip. These joints are called the metacarpophalangeal and the proximal interphalangeal joints, respectively. The wrists bones and the bones of the feet are also affected.
In the past people have been tested by measuring something called the rheumatoid factor, but this is not a conclusive test. The reason the test is not conclusive is that rheumatoid factors can also be detectable in Sjogren’s syndrome, SLE, and a disease called scleroderma. A better test is called, anti-cyclic citrulinated peptide antibodies – anti-CCP. These are highly specific (90% - 95%) and sensitive for RA and may be detected years prior to the more overt manifestations of the disease.
Anti-CCP positive patients tend to have a more aggressive course than patients without these antibodies. If inflammation of synovial lining of the joint is to be documented the physician may order an ultrasound. This is the most sensitive test to use as less than 20% of patients who are ultimately diagnosed with RA will have abnormalities of the small joints of their hands or feet when they first see a doctor that can be detected by plain X-rays. RA patients may be asked to get X-rays of the hand which will be used to follow the progression of their disease – these are much more useful than those of the feet.
It is now recommended by the American College of Rheumatology that all patients with RA be seen by a rheumatologist to establish the diagnosis and begin the patients on what is called, “disease modifying medication therapy,” with specific medications. The earlier these medications are started the better the long-term outcome. Prednisone, which used to be a standard drug, is no longer used, or used at doses no greater than 5 mg to 10 mg daily. Initial medications are methotrexate (Rheumatrex®, Trexall®), the” gold standard,” and an NSAID such as naproxen with omeprazole (a medicine to protect the lining of the stomach) and daily folic acid. About 75% of patients show a response to this type of treatment. Folic acid has to be added because methotrexate interferes with some of the biochemical reactions involving folic acid. Other disease modifying agents include hydroxychloroquine (Plaquenil®) or sulfasalazine (Azulfidine®) and the newer oral agent leflunomide (Arava®).
There is also something called biologic therapy. This type of therapy uses drugs directed against specific molecules made by the body that are involved in inflammatory reactions such as cytokines (if you don’t recognize this term, read the short report on cytokines) and a molecule called tumor necrosis factor (again, in the short report on cytokines). Biologic therapies directed against inflammatory molecules include the drugs rituximab (Rituxan®), abatacept (Orencia®), etanercept (Enbrel®) or infliximab (Remicade®). Immunosuppressant drugs, which shut down the immune system, are used in very severe cases. Remember, RA is an auto-immune disease – the body is making antibodies against parts of itself.
Sjogren’s syndrome is the second most common autoimmune rheumatic disease in the U.S. and affects over 4 million people; 90% are women over 40 years of age. It also is an autoimmune disorder destroying the glands, called the exocrine glands, that produce saliva and tears resulting in sicca syndrome (sicca means dry in Latin – people have a dry mouth and eyes). Joint pain, swelling, stiffness, and fatigue are also common complaints. Although FMS patients have similar complaints the dry mucosal membranes are due to a dysfunction in the sympathetic nervous system. A physician can order laboratory tests that will clearly identify this disease.
Although primary Sjogren’s exists independently up to 25% of patients with RA later develop secondary Sjogren’s syndrome resulting in some patients having an overlap of FMS, Sjogren’s, and RA. Other conditions in which secondary Sjogren’s occurs are SLE and polymyositis. Medication management is with hydroxychloroquine and possibly methotrexate or cyclosporine; pilocarpine (Salagen®) and cevimeline (Evoxac®) are prescribed to increase saliva and tear production. A significant and underappreciated problem is dental decay from the lack of saliva.
SLE is an unpredictable, waxing and waning, chronic autoimmune disease with multi-organ involvement that primarily affects African American women. The auto-antibodies produced are directed against the cell’s nuclei. Clinical manifestation include arthritis, arthralgias, fatigue, pain disproportionate to the degree of inflammation, mucosal ulcers, multi-organ involvement (with 12% of patients having kidney disease when they finally make it to a doctor’s office), and a characteristic butterfly rash. Dr. Martinez-Lavin suggests that the dysautonomia of FMS may simulate several of the symptoms of lupus: diffuse arthralgias with a subjective feeling of swelling, a rash, fluttering heart episodes, profound fatigue, and “pseudo-Raynaud’s phenomenon.” Needless to say, this can be a confusing picture unless the physician is familiar with FMS.
Dr. Middleton examined SLE patients who met the ACR criteria for FMS as well as those who had clinical signs of FMS but did not fully meet all the classification criteria. FMS symptoms in SLE patients were more severe, occurred more frequently, and greatly impacted activities of daily living. These patients were also less likely to be employed, more likely to be divorced, and to be receiving some type of disability assistance. Clearly, having both FMS and SLE was not a good thing. Laboratory testing is highly specific for SLE, the diagnosis can rarely be missed.
Dr. Calvo-Alen and his group reviewed 230 charts of patients who were referred, followed up, or diagnosed with SLE at a university center. Upon an in-depth analysis only 39% met the 1982 ACR criteria for SLE (The ACR has criteria for diseases other than FMS, including SLE, and the one published in 1982 was used for this study). The definitive SLE patients had clinical arthritis, renal disease, and serositis. Serositis is an inflammation of the tissues that line the internal organs of the body, such as the heart and lung. What about the other patients? Well, 26% were found to have FMS!
The FMS patients showed up with myalgias, arthralgias, fatigue and had a positive laboratory study that would have been interpreted as SLE, which is known as a, “positive ANA” test. Drs. Yunus and Dinerman, experienced FMS researchers, in two separate studies, have shown that a positive ANA test could be found in 11.3% and 14% of female FMS patients with no evidence of any rheumatologic disease. Here was something else that confused the doctors. SLE patients have aching, tingling, burning, and “funny” feelings in both of their lower legs. Think about FMS who have restless legs syndrome and what they have – sound familiar? Given that some of these FMS patients had been seen for up to five years implies that medications were being prescribed for a disease (SLE) they did not have.
The consequences of not being able to diagnosis FMS can be quite substantial not to mention the emotional burden carried by the patient thinking they have one disease and then being told they were incorrectly treated and now have a different disease that was not helped by any of their past medical care and may have, in fact, progressed.
Polymyalgia rheumatica (PMR) has a somewhat similar presentation to FMS being characterized by widespread pain and morning stiffness in the cervical and shoulder regions and the pelvic girdles, as well as malaise, fatigue, and depression but differs with having an older age and associations with weight loss and fever. Pain is close to the central axis of the body affecting neck, shoulders, upper arms, thighs, and hips. The morning stiffness of PMR is also somewhat characteristic and lasts for at least 30 minutes. PMR patients tend to get shoulder bursitis which contributes to the general upper extremity discomfort. PMR rarely occurs in individuals under 50 yoa and has a peak onset after age 70. Women are affected twice as frequently as men, especially those of Northern European descent. Approximately 20% of individuals with PMR will develop a condition known as temporal cell arteritis. This is an inflammation of the temporal artery, which is the large artery you can usually see on the side of your head in front of your ear so patients are asked questions about new headaches, visual changes, or jaw pain. A clearly differentiating characteristic is the profound resolution of nearly all symptoms within 24 to 48 hours in PMR to a therapeutic trial of low dose prednisone.
Patients with inflammation of their muscle tissues, termed inflammatory myostis, can have two major diseases known as polymyositis and dermatomyositis. These patients will also have complaints of fatigue but greater degrees of symmetrical (equal of both sides of the body) muscle weakness and usually lesser emphasis on pain than individuals with FMS. As the disease progresses proximal (in other words, closer to the body) muscle weakness exceeds pain as the limiting symptom, especially in the hip muscles making it difficult to arise from a chair or ascend stairs; difficulty swallowing can also occur in up to 33% of patients as can Raynaud’s phenomenon – the bluish discoloration of the fingers and toes with cold or stressful events. Females between the ages of 30 to 50 are primarily affected. Patients are treated with steroids for this condition.
Now, were going to consider an area of considerable contention. Dr. Lowe and his group in 2006 have shown that FMS patients, compared to normal people, have almost a 25% lower resting metabolic rates. The metabolic rate is controlled by the thyroid gland. People with lower resting metabolic rates usually have a thyroid which is not functioning to full capacity – something called subclinical hypothyroidism. The thyroid is stimulated by thyroid stimulating hormone (TSH) made by the pituitary gland to make two hormones: thyroxine (T4) and tri-iodothyronine (T3), which are primarily responsible for the regulation of metabolism. TSH is made when the pituitary is stimulated by the hypothalamus in the brain which secretes thyrotropin releasing hormone (TRH).
The major form of thyroid hormone in the blood is T4 which although having a longer half-life than T3 is only one-third to one-quarter as potent as T3. The ratio of T4 to T3 released into the blood is roughly 20 to 1. Thyroxine is converted to the active T3 within cells by deiodinases , e.g. 5'-iodinase. Two studies suggested that FMS patients have an impaired pituitary response given they showed a decreased secretion of TSH in response to TRH that was given them. There was another study that also found lower T3 levels compared to normal people. There was also a poor response in the secretion of both free tri-iodothyronine (T3) and free T4 by the thyroid gland. Two researchers suggest this may reflect a failure to de-iodinate T4 to T3 in the outside tissues.
However, the question as to the degree of hypothyroidism in FMS has generated contentious opinions. Given the range of normal laboratory thyroid panel values there is a school of thought that FMS patients may exhibit subclinical hypothyroidism even if their tests show low normal levels of the different hormones. A 1997 letter to the editor in the British Medical Journal by an English Physician suggested that a low dose of thyroxine be started and continued for at least three months in patients with clinical signs of hypothyroidism even though free thyroxine and thyroid stimulating hormone (TSH) values may be within normal limits.
The responses to this letter were quite varied and numerous, evidently because of lay press coverage. At one extreme were physicians who decried any such prescription because of some of the dangers of using thyroid hormones which include a heart irregularity called atrial fibrillation and osteoporosis which is a disease of bones that leads to increased fractures. Conversely, word came from physicians who harkened back to the days before the TSH test when treatment consisted of providing “one of the safest medications,” levothyroxine, at a dose that alleviated symptoms. The side effects mentioned above were noted to occur rarely and at higher doses. Criticisms were levied at physicians who were now are treating lab results with “normal” values that have a ten-fold range.
There are no clinical trials on the use of tri-iodothyroxine in FMS patients although if you look at the numerous web sites that FMS physicians or chat groups have posted you will see there are numerous posts attesting to its benefit as well as the use of Armour Thyroid. Armour Thyroid is a preparation of pork thyroid that contains both T4 and T3. Unfortunately, the question of whether hypothyroidism is a driving factor in FMS patients is still unanswered. Consequently, thyroid supplementation, at this point, is the personal predilection of the treating physician as there are simply no studies to support or exclude its use.
It may be useful in this short report to discuss one of the most useful tools used in FMS, the Fibromyalgia Impact Questionnaire. (FIQ) The Fibromyalgia Impact Questionnaire is a ten item self-administered questionnaire originally developed and validated by Drs. Burckhardt, Clark, and Bennett in 1991. The FIQ includes items for physical functioning, work status, depression, anxiety, sleep, pain, stiffness, and fatigue, and well-being. It is a very effective measuring tool in discriminating and evaluating the impact of FMS on the quality of life. The FIQ is also more able to assess the severity of FMS than trigger point counts or pain ratings. However, it does have its limitations. For example, it is directed towards higher levels of disability and does not assess the amount of effort required to complete a physical task, which is an important component in FMS. Neither does it assess the impact of FMS on social and occupational functioning. All the more reason you need to describe to your physician the full impact of FMS on your life.
Well, there you have it: a tour through the rheumatologic “differential diagnoses” of what diseases and conditions may have resembled FMS, sometimes closely, sometimes not so closely. Conversely, you can see how some diseases have looked so much like FMS that people have been treated for that disease for quite a bit of time. It only goes to show that medicine is not an exact science and relies considerably on the ability of patients being able to express themselves and explain their symptoms as best possible. The heart of treatment is the doctor-patient relationship, and in the case of FMS best had with a physician who understands the nuances of FMS.