Stephen Paget, MD: I am the Chairman of Division of Rheumatology and Medicine at the Hospital for Special Surgery. We are pleased today to have one of our experts, Dr. Larry Kagen, who is a Professor of Medicine at the Weill Medical College of Cornell University and an attending physician at the NewYork-Presbyterian Hospital and the Hospital for Special Surgery, to talk about muscle disease.
Dr. Kagen, what are the various types of muscle diseases that patients can present with?
Lawrence J. Kagen, MD: Beyond the usual sprains and strains of everyday life and the difficulties that people have with their muscles in connection with overexertion and lack of training, in the summer time, the kinds of real illnesses that we see in the hospital are largely related to inflammatory muscle diseases occurring in connective tissue disorders. These are diseases like dermatomyositis, polymyositis, inclusion body myositis, or myositis in association with certain of the other connective tissue disorders, such as rheumatoid arthritis or scleroderma.
Stephen Paget, MD: How do patients' usually present when they come in with a muscle disorder of an inflammatory type?
Lawrence J. Kagen, MD: The usual presentation is muscle weakness. Sometimes it can be rather insidious, and patients may not even notice that they are becoming weaker; in particular, older patients often ascribe weakness that they may have to the effects of age. But in general, weakness of the upper arms, difficulty in combing the hair, hanging up an overcoat, weakness in the lower extremities, difficulty in going up the stairs, that sort of thing is what presents.
Stephen Paget, MD: When they present to the doctor, either the primary care physician or eventually for example a rheumatologist, how will that doctor make the diagnosis?
Lawrence J. Kagen, MD: Sometimes it's difficult because patients often don't use a vocabulary that is as precise as we might like it to be. That is to say, they may say they are fatigued or that they are weak, but it may be hard to understand actually that their muscles are not functioning well. But, in general, once we understand that the patient's muscles are not functioning well, we tend to ask questions designed to indicate the severity of the problem. We then do a physical examination to corroborate the historical information that we have gotten from our interview, and then there are laboratory tests. We test for the muscle enzymes which may be elevated and, if need be, there are specialized tests. Electromyography, imaging studies, magnetic resonance imaging, and ultrasonography can be used and finally, if need be, a muscle biopsy can actually reveal by histological analysis what the status of the muscle is.
Stephen Paget, MD: What are the different types of myositis and what causes them?
Lawrence J. Kagen, MD: Well I wish I knew. We don't know the final cause or approximate cause of the inflammatory muscle diseases, but we do know that inflammation within the muscle may be associated with death of myofibers, which leads to weakness and sometimes leads to pain. So our therapy is largely aimed at reducing inflammation to preserve the strength that the patient has and to prevent the further loss of muscle tissue.
Stephen Paget, MD: How do polymyositis and dermatomyositis differ from each other, clinically and pathologically?
Lawrence J. Kagen, MD: The patient with dermatomyositis has muscle weakness and inflammation in muscle just as the patient with polymyositis does. The patient with dermatomyositis also has a rash, which can be quite prominent and which may actually be the first manifestation of the illness before there is any experience of muscle weakness. There are some subtle changes and differences which can be perceived on the muscle biopsy. There is more involvement of blood vessels in patients with dermatomyositis, and there are in certain patients with dermatomyositis the presence of occult tumors or malignancies, especially in adults.
Stephen Paget, MD: Could you tell us a little bit more of what types of tumors?
Lawrence J. Kagen, MD: The types of tumors that have been described are those in general that afflict the population in the geographical area that is being seen. So that here tumors of the lung and of the gastrointestinal tract would probably be the most common. There have been several series of patients which indicate that some patients have occult ovarian tumors. For this reason, patients with dermatomyositis may be subjected to examinations to evaluate this point; that is to say, their physicians may require that certain studies be done to make certain that the patient does not have an underlying tumor.
Stephen Paget, MD: Is that done in everyone or only people over a certain age?
Lawrence J. Kagen, MD: It is usually done in adults with dermatomyositis, although depending on the clinical queues and clinical situation, the patient's treating physician may elect to do it in other circumstances as well.
Stephen Paget, MD: Certainly an age appropriate malignancy assessment is always appropriate, right?
Lawrence J. Kagen, MD: Yes, I think so.
Stephen Paget, MD: Tell us about inclusion body myositis. It's a little bit different. How is it different?
Lawrence J. Kagen, MD: Inclusion body myositis is a relatively more recently recognized illness which occurs in older people. It is often very insidious, and it often does not respond well to therapy. In addition to the proximal muscle weakness, that is weakness of the large muscles of the upper arm and of the thigh, there may be weakness of distal muscles which may occur early in inclusion body myositis particularly the flexors of the forearm. That is something a little bit different from what is usually seen in the other forms of inflammatory myopathy. Also the laboratory studies are not as vivid. That is to say that the enzymes may not be as high and the response to therapy is not as good.
Stephen Paget, MD: Is there the same relationship to malignancy?
Lawrence J. Kagen, MD: We really don't know that quite yet, but I think we feel that, in general, there have been malignancies that have been described, including occult malignancies in patients with inclusion body myositis. They are probably not quite as common as in dermatomyositis, but we do not have the large fund of data needed to be certain of that.
Stephen Paget, MD: So once patients have been diagnosed as having myositis, how do you treat them?
Lawrence J. Kagen, MD: The major aim of therapy is to suppress and bring about a cessation in inflammation, and we use a number of medications to try to achieve that. I would think the most common medication now in use are the corticosteroids, that group of medications of which prednisone is probably the most commonly used. There are other cytostatic or so-called immunosuppressive agents that have and can be used and can be successful: methotrexate (Rheumatrex) and azathioprine (Imuran) are probably the most common in that group. There are others as well. There have been recent studies, indicating the value of intravenous infusions of gamma-globulin, and there has been a lot of interest recently in certain of the newer modalities. We don't have enough information about the newer medications, that is the anti-cytokine therapies, to be able to know what their place in therapy will be, but there is some preliminary information that indicates that they have been helpful.
Stephen Paget, MD: Are there masqueraders of muscle inflammation or certain underlying disorders or chemical changes that actually may make muscle weakness worse?
Lawrence J. Kagen, MD: That is an excellent question. I think every physician who cares for a patient with muscle symptoms and with weakness has to be certain that we have a good history that relates to medications and to exogenous toxins. For example; alcohol is an exogenous toxin which can be myopathic. Among the medications we use, the statins rarely can have side effects related to dysfunction of muscle, and penicillamine rarely may have that side effect as well. There are infectious diseases that can mimic inflammatory muscle disease that we have been talking about; viral disease may be an example of that. There are endocrine disorders, for example; hypothyroidism and hyperthyroidism both may be associated with muscle weakness. So what is required is the same thing that is required in any patient that one sees: a good history and physical examination and a good evaluation of just the kind of things that you are talking about.
Stephen Paget, MD: In general, what is the prognosis given our current therapeutic modalities?
Lawrence J. Kagen, MD: It probably has been improving. The original reports, dating back decades, indicated the myositis can be a very serious and progressive disabling disorder, and that still is true for many patients. Particularly it seems to be true where there is a long period of time between the onset of symptoms and the onset of therapy. That has been true in every study that has been done. That is a particular problem in patients with inclusion body myositis because there may be a long period of time before the patient or the family or the friends recognize that something is organically the matter.
Lawrence J. Kagen, MD: If patients are seen early and treated early, I think the overall outlook may be good.
Stephen Paget, MD: Thank you very much, Dr. Kagen.
Learn more about the Myositis Education and Support Group at HSS
From an interview with Dr. Lawrence J. Kagen by Dr. Stephen A. Paget