Polymyositis is a rare systemic rheumatic disease characterized by a degenerative inflammatory process of the muscles.
“The inflammatory myopathies, commonly described as idiopathic, are the largest group of acquired and potentially treatable myopathies. On the basis of unique clinical, histopathological, immunological, and demographic features, they can be differentiated into three major and distinct subsets: dermatomyositis, polymyositis, and inclusion-body myositis. Use of new diagnostic criteria is essential to discriminate between them and to exclude other disorders.”1
“Polymyositis (PM) is an idiopathic inflammatory myopathy. It is a systemic disease that affects skeletal muscles and results in proximal muscle weakness. PM is associated with malignancy in 10–15% of patients. The 3 most commonly associated cancers are nasopharyngeal, lung, and breast cancer.4 Hepatocellular carcinoma (HCC)-associated PM is quite rare.”2
“Dermatomyositis (DM) and polymyositis (PM) are idiopathic inflammatory myopathies characterized by proximal skeletal muscle weakness and evidence of muscle inflammation. DM, unlike PM, is characterized by the presence of various cutaneous manifestations. DM and PM may also be associated with inflammatory arthritis, interstitial lung disease, Raynaud phenomenon, and the presence of autoantibodies.”3
Rheumatic diseases are those that affect the musculoskeletal system and generally are autoimmune, in which the body confuses its own tissue with is foreign ones, triggering an immunological reaction where the organism attacks its own structures.
“Rheumatic diseases are a diverse group of conditions. The main focus of rheumatologists is on inflammatory arthritides, as opposed to non-inflammatory conditions, such as osteoarthritis (OA). The most common autoimmune rheumatic diseases include rheumatoid arthritis (RA), spondyloarthritides, such as ankylosing spondylitis (AS), psoriatic arthritis (PsA), and other systemic connective tissue diseases, such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Sjögren syndrome (SS). All these conditions share several common features: they are all chronic conditions, they all cause joint inflammation and destruction, and they may all involve internal organs, which is associated with progressive disability and may be the direct cause of death. Their etiology is still not completely clear, and they cannot be effectively prevented. RA is the most prevalent and best understood rheumatic disease, and awareness of it in society is the highest among these diseases. It is estimated that the risk of RA is affected by genetic factors, which increase that risk by about 50–60%. Women are more commonly affected than men (with the male-to-female ratio being 3: 1), and the mean age at diagnosis is between 30 and 50 years of age. Population studies have shown that within 20 years of onset, 19% of patients with RA become completely disabled and 35% die.”4
Although there is no reliable data on the prevalence of polymyositis, it can develop at any age. However, it is more common in people around 50 years old and in children between the ages of 5 and 15 years of age. It occurs more frequently in women than in men.
The exact cause of this disease is unknown. However, since it’s an autoimmune reaction, the probability of suffering from it increases in an individual that is genetically susceptible. What do we mean when we talk about a genetically susceptible individual? To understand this, we must first discuss the system of human leukocyte antigens (HLA). This is also known as the major histocompatibility complex (MHC) and refers to the genes that code these antigens.
“The term HLA refers to the Human Leucocyte Antigen System, which is controlled by genes on the short arm of chromosome six. The HLA loci are part of the genetic region known as the Major Histocompatibility Complex (MHC). The MHC has genes (including HLA) which are integral to normal function of the immune response. The essential role of the HLA antigens lies in the control of self-recognition and thus defense against microorganisms. The HLA loci, by virtue of their extreme polymorphism ensure that few individuals are identical and thus the population at large is well equipped to deal with attack. Because some HLA antigens are recognized on all of the tissues of the body (rather than just blood cells), the identification of HLA antigens is described as ‘Tissue Typing’ or ‘HLA Typing’.”5
The HLA system is basically a set of molecules that are found on the surface of practically all the human body’s cells. The function of this system is to discern between what is ‘self’ and what is foreign. Each individual presents a unique HLA constituted by the combination of a set of antigens. When we speak of individuals genetically susceptible, we refer to those whose HLA is formed by at least one subtype of antigen which predisposes the individual to suffer from autoimmune diseases. These subtypes are: DR3, DR52 and DR6.
This does not imply that individuals whose HLA is constituted by any of these antigenic subtypes will suffer an autoimmune disease. For this to happen, a triggering phenomenon must take place, such as a muscular inflammation due to a viral infection or an underlying cancer. In fact, there are studies that talk about similar pathologies in animals triggered by viruses. However, the exact type of trigger virus is not known.
Histological Findings of PM Muscular Tissue
“In PM the characteristic feature is presence of CD8 T cells and macrophages in the myofibers. Compared with healthy muscles, MHC I is up regulated in myofibers of PM. The expression of MHC I on myositis muscle suggest that these cells may be killed byCD8 T cells which contain perforin, a pore forming protein that mediates the entry of cytotoxic proteases and calcium into target cells. In confocal microscopic studies it has been found that these perforin containing granules are oriented toward muscle fibers, consistent with a cytotoxic mechanism of cell death in PM. Although MHC I has been proposed to mediate cell death in PM, but it is also expressed in DM patients mainly on perifascicular fibers.”6
“The first symptoms are usually painless weakness of the pelvic and proximal lower extremity muscles, which can result in difficulty walking and climbing stairs or in getting up after sitting in a chair. Often the next muscles affected are those of the neck and shoulder girdle. The degree of weakness may vary from mild to near paralysis. Weakness usually develops slowly over weeks to months, although in rare cases weakness may progress more rapidly.
Other PM symptoms include:
- Difficulty swallowing (dysphasia)
- Difficulty speaking
- Shortness of breath
The predominant symptom of PM is muscle weakness. Weakness is symmetric, affecting the proximal muscles of the extremities as well as the neck flexors. Weakness of the distal muscles is rare, and when present should warrant consideration of another type of myopathy, such as inclusion body myositis. PM patients may occasionally experience pain and tenderness in the muscles, which can mimic the symptoms of polymyalgia rheumatica. Involvement of the striated muscles of the oropharynx and upper esophagus occurs in 10-15% of patients, is a poor prognostic indicator, and may lead to dysphagia, regurgitation, and aspiration pneumonia. Interstitial lung disease occurs in 5-10% of patients. In addition, there may be ventilatory dysfunction due to involvement of the diaphragm and intercostal muscles. Cardiac involvement is most often asymptomatic, but may result in conduction disturbances, myocarditis, or congestive heart failure. Raynaud’s phenomenon, non-erosive arthritis, and systemic symptoms of morning stiffness, fatigue, weight loss, and fever all may be present during the course of PM.”7
The pathophysiology of polymyositis has common aspects to many other autoimmune diseases, including muscular atrophy, where the loss of muscle tissue releases substances, triggering an inflammatory process whose severity is directly proportional to the seriousness of the disease. Muscular atrophy usually affects all the muscles of the body. However, the muscles of the extremities and face seem to be the least affected. If not treated properly, the involvement of the muscles of the esophagus, pharynx and / or heart can compromise the function of these organs, resulting in fatal consequences for the individual.
The symptoms of this disease can appear in a short period of time, but it can also appear gradually. The main symptom is joint and muscle pain, characteristic of almost any inflammatory disease. Muscle weakness is a direct consequence of polymyositis. It becomes more evident when the immune system has destroyed almost half of the individual’s muscle fibers, a symptom of advanced polymyositis.
In the most severe of cases, the patient may lose the ability to walk and be forced to use mobility aids, especially if the neck muscles have been affected to such an extent that the patient is unable to hold their own head. Joint pain, known as polyarthralgia (when present in more than five joints) is another consequence of the inflammatory process that polymyositis causes. Generally, the individual is forced to take analgesics and anti-inflammatories to be able to enjoy a normal life.
“Once a rheumatic pain syndrome has been localized to one or more joints, additional historical data are required. First determine whether or not other signs of inflammation (of the joint) have been observed by the patient. Redness, warmth (“fever”), and especially swelling should be specifically addressed. The nature of the onset should be established early in the interview. If the arthralgia began recently and was rapid in onset, the syndrome can be considered acute and a specific differential diagnosis is suggested. Regardless of the nature of the onset, arthralgia that has persisted for a month or longer can be considered chronic or persistent, and other differential diagnoses are suggested, depending on whether one joint or more than one joint has been symptomatic.”8
What happens to someone with polymyositis?
“Although PM, DM and IBM have certain features in common, they differ in significant ways. PM is more common in females than males and usually begins after age 20. Over a period of weeks or months, several muscles become weak and gradually get weaker. Most affected are the muscles of the hips and thighs, the upper arms, the top part of the back, the shoulder area and the muscles that move the neck. Many people with PM have pain or tenderness in the affected areas. The person may have trouble extending the knee, stepping down or climbing stairs. Lifting things, fixing the hair or putting things on a high shelf may be difficult. It can be hard to raise the head off the bed when lying down. Swallowing muscles can be affected as well, leading to poor intake of food and weight loss. PM also can affect the heart muscle, causing a condition called inflammatory cardiomyopathy. The muscles involved in breathing may be affected and a few patients develop some inflammation of the lung tissues themselves, another respiratory complication.
Of course, the heart, respiratory and swallowing problems are the most serious effects of PM and need close monitoring.
Treatment of PM
The first drug used in the treatment of PM is usually a corticosteroid, such as prednisone. The treatment may involve high-dose oral prednisone on a daily, every other day, or other schedule; or intermittent, short courses of intravenous corticosteroids. Sometimes, prednisone is stopped and then has to be restarted several times during the course of the disease.
Prednisone is usually very effective at bringing inflammation under control, restoring for the most part the person’s strength, as well as swallowing, breathing and heart functions.
But prednisone has many side effects, including unwanted weight gain, redistribution of fat to the face and abdomen and away from the limbs, thinning of the skin, bone loss, cataracts and psychological problems. For this reason, if long-term treatment is necessary, most doctors (and patients) want to lower the dose of prednisone as quickly as possible. This can be accomplished by adding one or more other medications to suppress the damage being caused by the immune system.
These medications include azathioprine, methotrexate, cyclosporine, cyclophosphamide — all ‘traditional’ immunosuppressants that have been used for many years; and some newer drugs, such as mycophenolate mofetil and tacrolimus.
Although most people tolerate these medications without difficulty, they carry their own risks, such as flulike symptoms, a lowered white blood cell count (which can predispose the patient to infection) and liver toxicity. Many are associated with an increased risk of cancer.
Some patients have responded well to intravenous infusion of antibodies culled from donors. This treatment — known as intravenous immunoglobulins, or IVIg, may seem strange in a disease that’s probably caused by an immune response in the first place, but the extra antibodies seem to ‘confuse’ the immune system and at least temporarily alleviate the attack on muscle.
Gently progressive physical therapy, such as that taken in a swimming pool, can be very helpful in maintaining strength. Range-of-motion exercise (putting a joint through its normal movement range), particularly of the shoulders, is helpful in keeping the joints supple.
Some people may need a cane, walker or even a wheelchair during acute flareups of PM. Many people eventually recover much or all of their muscle strength and function, although they may relapse and lose function if they stop taking medications.
Plasmapheresis, a ‘blood-cleansing’ process to remove antibodies, was at one time used in PM and DM, but is rarely used in these diseases today. Immunosuppressant drugs and/or IVIg treatments are now considered more effective.”9
(1) Dalakas, M. C., & Hohlfeld, R. (2003). Polymyositis and dermatomyositis. The Lancet, 362(9388), 971-982. Available online at https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(03)14368-1/fulltext
(2) Thanapirom, K., Aniwan, S., & Treeprasertsuk, S. (2014). Polymyositis associated with hepatitis B virus cirrhosis and advanced hepatocellular carcinoma. ACG case reports journal, 1(3), 167. Available online at https://pdfs.semanticscholar.org/a150/81c0a1b49e266df1a66c9a5dc43aecbc175d.pdf
(3) Miller, M. L., Targoff, I. N., & Shefner, J. M. (2012). Malignancy in dermatomyositis and polymyositis. UpToDate, Waltham, MA. Available online at https://www.uptodate.com/contents/malignancy-in-dermatomyositis-and-polymyositis?topicRef=15653&source=see_link
(4) Kwiatkowska, B., Raciborski, F., Kłak, A., Maślińska, M., & Gryglewicz, J. (2015). Early diagnosis of rheumatic diseases: an evaluation of the present situation and proposed changes. Reumatologia, 53(1), 3. Available online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847309/
(5) Shankarkumar, U. (2004). The human leukocyte antigen (HLA) system. International Journal of Human Genetics, 4(2), 91-103. Available online at https://pdfs.semanticscholar.org/9b34/7ce8f4880f75f3591819ec522244b73effcb.pdf
(6) Raychaudhuri, S. P., & Mitra, A. (2012). Polymyositis and dermatomyositis: disease spectrum and classification. Indian journal of dermatology, 57(5), 366. Available online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482799/
(7) Hunter, K., & Lyon, M. G. (2012). Evaluation and management of polymyositis. Indian journal of dermatology, 57(5), 371. Available online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482800/
(8) Hardin, J. G. (1990). Arthralgia. In Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Butterworths. Available online at https://www.ncbi.nlm.nih.gov/books/NBK303/
(9) Chavez, R. (2009). Facts about Inflammatory Myopathies (Myositis). Available online at https://www.mda.org/sites/default/files/publications/Facts_Inflamm_Myopathies_P-199.pdf