Elevated sed rate and muscle weakness
Also, with muscle weakness one must differentiate muscle weakness that is due to damage to nerves (neuropathy) and weakness that is due to muscles.
When there is muscle weakness, a second distinction must be made. Are the muscles weak because of true damage to the muscle (myopathy) or are the muscles weak because of deconditioning? Let’s start out with a disorder that may present with weakness and achiness. Polymyalgia rheumatica (PMR) is a rheumatic disorder that is associated with moderate to severe muscle pain and stiffness in the neck, shoulder, and hip area. Stiffness is most noticeable in the morning. This disorder may develop rapidly--in some patients, overnight. In other people, polymyalgia rheumatica develops more gradually. The cause of polymyalgia rheumatica is not known; however, possibilities include immune system abnormalities and genetic factors. The fact that polymyalgia rheumatica is rare in people under the age of 50 suggests it may be linked to the aging process. With treatment, the symptoms of polymyalgia rheumatica are quickly controlled, but relapse if treatment is stopped too early. Giant cell arteritis, also known as temporal arteritis is a disorder that results in swelling of arteries in the head (most often the temporal arteries, which are located on the temples on each side of the head), neck, and arms. This swelling causes the arteries to narrow, reducing blood flow. Early treatment is critical for good prognosis.
It is unclear how or why polymyalgia rheumatica and giant cell arteritis are related, but an estimated 15 percent of people in the United States with polymyalgia rheumatica also develop giant cell arteritis. Patients can develop giant cell arteritis either at the same time as polymyalgia rheumatica or after the polymyalgia symptoms disappear. About half of the people affected by giant cell arteritis also have polymyalgia rheumatica. When a person is diagnosed with polymyalgia rheumatica, the doctor also should look for symptoms of giant cell arteritis because of the risk of blindness. With proper treatment, the disease is not threatening. Untreated, however, giant cell arteritis can lead to serious complications including permanent vision loss and stroke. Patients must learn to recognize the signs of giant cell arteritis, because they can develop even after the symptoms of polymyalgia rheumatica disappear. Patients should report any symptoms to the doctor immediately. White women over the age of 50 are most at risk of developing polymyalgia rheumatica and giant cell arteritis. Women are twice as likely as men to develop the conditions. Both conditions almost exclusively affect people over the age of 50. The average age at onset is 70 years. Polymyalgia rheumatica and giant cell arteritis are quite common. In the United States, it is estimated that 700 per 100,000 people in the general population over 50 years of age develop polymyalgia rheumatica. An estimated 200 per 100,000 people over the age of 50 develop giant cell arteritis. The primary symptoms of polymyalgia rheumatica are moderate to severe stiffness and muscle pain near the neck, shoulders, or hips. The stiffness is more severe upon waking or after a period of inactivity, and typically lasts longer than 30 minutes. People with this condition also may have flu-like symptoms, including fever, weakness, and weight loss. Early symptoms of giant cell arteritis also may resemble the flu. People are likely to experience headaches, pain in the temples, and blurred or double vision. Pain may also affect the jaw and tongue.
No single test is available to definitively diagnose polymyalgia rheumatica. To diagnose the condition, a physician considers the patient?s medical history, including symptoms that the patient reports, and results of laboratory tests that can rule out other possible diagnoses. The most typical laboratory finding in people with polymyalgia rheumatica is an elevated erythrocyte sedimentation rate, commonly referred to as the sed rate. This test measures how quickly red blood cells fall to the bottom of a test tube of unclotted blood. Rapidly descending cells (an elevated sed rate) indicate inflammation in the body. While the sed rate measurement is a helpful diagnostic tool, it alone does not confirm polymyalgia rheumatica. An abnormal result indicates only that tissue is inflamed, which also is a symptom of many forms of arthritis and/ or other rheumatic diseases. Before making a diagnosis of polymyalgia rheumatica, the doctor may perform additional tests to rule out other conditions, including rheumatoid arthritis, because symptoms of polymyalgia rheumatica and rheumatoid arthritis can be similar. The doctor may recommend a test for rheumatoid factor (RF). RF is an antibody sometimes found in the blood. (An antibody is a special protein made by the immune system.) People with rheumatoid arthritis are likely to have RF in their blood, but most people with polymyalgia rheumatica do not. If the diagnosis still is unclear, a physician may conduct additional tests to rule out other disorders. Doctors and patients both need to be aware of the risk of giant cell arteritis in people with polymyalgia rheumatica and should be on the lookout for symptoms of the disorder. Severe headaches, jaw pain, and vision problems are typical symptoms of giant cell arteritis. In addition, physical examination may reveal an abnormal temporal artery: tender to the touch, inflamed, and with reduced pulse. Because of the possibility of permanent blindness, a temporal artery biopsy is recommended if there is any suspicion of giant cell arteritis. In a person with giant cell arteritis, the biopsy will show abnormal cells in the artery walls. Some patients showing symptoms of giant cell arteritis will have negative biopsy results. In such cases the doctor may suggest a second biopsy.
With treatment, however, symptoms disappear quickly, usually in 24 to 48 hours. If there is no improvement, the doctor is likely to consider other possible diagnoses. The treatment of choice is corticosteroid medication, usually prednisone. Polymyalgia rheumatica responds to a low daily dose of prednisone. The dose is increased as needed until symptoms disappear. Once symptoms disappear, the doctor may gradually reduce the dosage to determine the lowest amount needed to alleviate symptoms. The amount of time that treatment is needed is different for each patient. Most patients can discontinue medication after 6 months to 2 years. If symptoms recur, prednisone treatment is required again. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen also may be used to treat polymyalgia rheumatica. The medication must be taken daily, and long-term use may cause stomach irritation. For most patients, NSAIDs alone are not enough to relieve symptoms. Giant cell arteritis carries a small but definite risk of blindness. The blindness is permanent once it happens. A high dose of prednisone is needed to prevent blindness and should be started as soon as possible, perhaps even before the diagnosis is confirmed with a temporal artery biopsy. When treated, symptoms quickly disappear. Typically, people with giant cell arteritis must continue taking a high dose of prednisone for 1 month. Once symptoms disappear and the sed rate is normal and there is no longer a risk of blindness, the doctor can begin to gradually reduce the dose. When treated properly, giant cell arteritis rarely recurs. People taking low doses of prednisone rarely experience side effects. Side effects are more common among people taking higher doses. But all patients should be aware of potential effects, which include: • fluid retention and weight gain Most people with polymyalgia rheumatica and giant cell arteritis lead productive, active lives. The duration of drug treatment differs by patient. Once treatment is discontinued, polymyalgia may recur; but once again, symptoms respond rapidly to prednisone. When properly treated, giant cell arteritis rarely recurs. Another disease that can cause elevated sed rate and muscle weakness is Sjogren’s disease. Neuromuscular manifestations occur in 10-20% of patients. The criteria for diagnosis of Sjogren's disease would be the following: 1. Primary Sjogren's symptoms and objective signs of ocular dryness with positive Schirmer's test and positive Rose-Bengal or fluorescein staining of cornea and conjunctiva. Twenty-five per cent of patients with rheumatoid arthritis have Sjogren's syndrome; 50% of patients with Sjogren's have rheumatoid arthritis. There can be associations with thyroiditis and myasthenia gravis. HIV infection can occur in combination with sicca syndrome which would be prominent in young males. In the HIV group there would be a lack of autoantibodies against SSA and SSB, and a positive test should be found for HIV.
Individuals with muscle problems may have pain on palpation or spontaneous pain (myalgias). They may be unable to climb stairs or carry things (weakness). Individuals may or may not have symptoms. Individuals may have fever, fatigue, arthralgias, myalgias, or lymphadenopathy. Weakness is more prominent proximally than distally. The course is generally mild and insidious. Weakness can occur in those with renal involvement, renal tubular acidosis, and hypokalemia. Muscle biopsy may show myositis, but positive biopsy can be found in the absence of clinical symptoms in 17-74% of patients. When Sjogren's syndrome is suspected in muscle, a sed rate and electromyography should be performed, and muscle and nerve biopsy should be considered. Muscle involvement has been reported to include myositis, muscle fiber necrosis, and elevated muscle enzymes. Neuropathies (damage to nerves) are characterized by paresthesias, which can be numbness and tingling or painful dysesthesias such as burning. The neurological examination may be normal, despite clinical complaints because of involvement of small fibers. The lower extremities are more involved than the upper extremities. Types of possible neuropathies include sensory neuropathy or dorsal root ganglioneuropathy. Individuals may present with ataxia, loss of vibration and position sense, or hyperalgesia (hypersensitivity to noxious stimuli). There also may be alterations in appreciation of pain and temperature with burning. Reflexes may be absent. Motor involvement can occur along with sensory involvement. Weakness may be subacute and symmetrical. There also can be a rapidly progressive course of weakness to include a mononeuritis multiplex. Asymmetrical findings as well as stocking glove distribution of findings have also been reported. Polyradiculoneuropathy may be present. This would be characterized by findings mimicking disc abnormalities with nerve root pain and weakness in a radicular distribution. Motor neuron disease has recently been reported in a number of patients who turn out to have sicca syndrome.
Therapy is directed towards the vasculopathy associated with the neurological manifestations. These can include corticosteroids, azathioprine, cyclophosphamide, and IVIG. The true incidence and prevalence or neurological manifestations vary in various series reported in the literature. The neurological manifestations must be recognized early and aggressively treated so as to avoid long-term complications that would reduce the probability of success with treatment. Malignancy can produce neurologic symptoms. One syndrome that can be associated with elevated sed rate is lower extremity motor neuron syndrome (LEMS). Neurologic weakness can also be associated with malignancy. This is called paraneoplastic neuropathy. Chemotherapy can cause a drug-induced myopathy (eg. cyclosporine). Muscle weakness can be due to muscle damage from hypothyroidism, hyperthyroidism, Cushing's disease, dermatomyositis, and polymyositis. Damage to multiple nerves- called a polyneuropathy- may be due to rheumatoid arthritis, systemic lupus erythematosis, polyarteritis nodosa or cryoglobulinemia. An elevated sed rate suggests polymyositis, dermatomyostis or systemic lupus erythematosis or even infection. Lumbosacral plexopathy is an immune based problem that affects the large nerves leading from the low back to the legs. It comes on in older patients and is characterized by pain, lower extremity weakness, and a progressive course. EMG tests show denervation in the limbs and paraspinous muscles. Nerve biopsy reveals inflammatory cells around small epineurial blood vessels. An elevated sed rate is seen. Treatment consists of steroids an immune globulin.
Another cause of elevated sed rate and muscle weakness is microscopic polyangiitis or MPA. The first description of a patient with the illness now known as microscopic polyangiitis (MPA) appeared in the European literature in the 1920s. The concept of this disease as a condition that is separate from polyarteritis nodosa (PAN) and other forms of vasculitis did not begin to take root in medical thinking, however, until the late 1940s. Even today, some confusing terms for MPA (e.g., “microscopic poly arteritis nodosa ” rather than “microscopic poly angiitis ”) persist in the medical literature. Much of the explanation for the difficulty in separating MPA from other forms of vasculitis has stemmed from the numerous areas of overlap of MPA with other diseases. MPA, PAN, WG, CLA, the Churg-Strauss syndrome, and other disorders all share a variety of features but possess sufficient differences as to justify separate classifications.
MPA can affect individuals from all ethnic backgrounds and any age group. In the United States, the typical MPA patient is a middle-aged white male or female, but many exceptions to this exist. The disease may occur in people of all ages, both genders, and all ethnic backgrounds.
Many signs and symptoms are associated with MPA. This disease can affect many of the body's organ systems including (but not limited to) the kidneys, nervous system (particularly the peripheral nerves, as opposed to the brain or spinal cord), skin, and lungs. In addition, generalized symptoms such as fever and weight loss are very common. The FIVE most common clinical manifestations of MPA are: 1. Kidney inflammation (~ 80% of patients).
A carefully analyzed urine specimen should be obtained at the initial visit (and every follow-up visit!) to maintain vigilance for either the development or the progression of kidney involvement. A computed tomography (CT) scan of the chest may also be performed to detect the presence of lung involvement. A tissue biopsy may be needed to make the diagnosis of MPA, and is taken from an organ that seems to be involved at the time. Sometimes an electromyography/nerve conduction (EMG/NCV) study may need to be done to identify a site for biopsy or to detect findings consistent with a mononeuritis multiplex (see classic symptoms section above). Tissues that might be biopsied are kidney, skin, nerve, muscle, and lung.
A steroid (usually prednisone) in combination with a cytotoxic agent [usually starting with cyclophosphamide (CYC)] is typically the first combination of medications to be prescribed. Prednisone is usually taken every day along with CYC. Both of these medications are administered generally in tablet form in MPA (prednisone only comes in a tablet formulation). After control of the disease – usually around 4 - 6 months of treatment – CYC is then typically switched to azathioprine (AZA) or methotrexate (MTX). Prednisone is usually discontinued after approximately 6 months.
|
