Morphea See scleroderma

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MRI See magnetic resonance imaging in Appendix II.

multicentric reticulohistiocytosis A rare disorder in which cells called histiocytes and multinu-cleate giant cells are filled with fat and infiltrate into tissues, especially skin and joints. It is mostly a disease of middle age but can occur at any age. In 60 percent of patients the arthritis starts before the skin is involved and diagnosis is then very difficult. The typical appearance in the skin is of nodules up to 2 cm in diameter, reddish in color, and numbering from a few to several hundred. Hands, ears, face, chest, lips, and the inside of the mouth and throat can all be involved. The arthritis resembles that of rheumatoid arthritis, except that the joints at the ends of the fingers (distal interphalangeals) are often involved. It is often a highly destructive arthritis.

other organs, including the lungs, heart, stomach, thyroid, and bone marrow may be affected. There may be a mild anemia, raised ESR, and moderately high cholesterol, but none of these help with the diagnosis. X rays show destructive joint lesions that are difficult to differentiate from rheumatoid arthritis. Biopsy of the skin nodules or joint lining (synovium) shows the typical fat-filled cells. Many conditions are associated with multicentric reticulo-histiocytosis. Nearly 50 percent of patients react positively to a skin test for tuberculosis (TB), and a few patients have had active TB. About a third have other skin lesions, suggesting raised cholesterol (xanthelasma), and a number have had autoimmune diseases. About a quarter have had cancers of various kinds. These have included cancer of the breast, stomach, lung, bowel, cervix, ovary, and blood and also melanoma.

Treatment is difficult. Successful treatment of a number of cancers and TB has improved the joint and skin disease in a few patients. However, lowering cholesterol levels, corticosteroids, and other medications used for rheumatoid arthritis as well as blind treatment for TB (i.e., without a definite diagnosis) have not been particularly useful. The powerful immunosuppressants cyclophosphamide and chlorambucil have improved or halted the disease most consistently and are used for severe disease. Because of their potential side effects, however, mild disease is sometimes best treated symptomatically with painkillers or NSAIDs.

myasthenia gravis An autoimmune disorder that results in muscle weakness and is caused by antibodies against receptors for a chemical messenger, acetylcholine, that transmits messages from nerves to muscles. Myasthenia affects about 10 people out of 100,000 and, although it can occur at any age, most often affects young or middle-aged adults and women more often than men.

Cause

Although about 80 percent of patients with myas-thenia gravis have antibodies against acetylcholine receptors, the underlying cause of myasthenia is not known. Individual patients form antibodies against slightly different parts of the acetylcholine receptor, so it is not a case of a unique antibody causing the disease. The approximately 20 percent of patients who do not have antibodies against acetylcholine receptors by standard tests may have them if a more sensitive assay is used or may have antibodies against other muscle enzymes or receptors. There is an increased risk of myasthenia in patients with other autoimmune disorders such as thyroid disease, rheumatoid arthritis, and SLE. The reason for this is not known. one possibility is that T lymphocytes that have been activated by an underlying autoimmune disease stimulate B lymphocytes to produce antibodies against acetylcholine receptors. The thymus gland, an organ that lies just underneath the sternum (breastbone), seems to play an important role in the cause of myasthenia. This observation was first made when physicians noticed that patients with a tumor of the thymus gland, called a thy-moma, developed myasthenia much more often than other people did. The thymus plays an important role in programming lymphocytes to react, or not react, against various antigens. Another clue to the cause of myasthenia may be that penicillamine, a drug that was previously used to treat rheumatoid arthritis but has now been replaced by more modern drugs, can cause myasthenia as a side effect. The way in which penicillamine causes myasthenia is not clear, but it can also cause other autoimmune diseases such as glomerulonephritis, suggesting that it somehow activates autoimmune responses.

Symptoms

The key symptom of myasthenia is weakness that comes on, or gets worse, when a muscle is used repetitively. Myasthenia often starts in a few muscles, a type of disease called localized myasthenia, and at this stage patients may not realize that symptoms are related to use. For example, myasthenia often starts in the muscles that move the eye or those that carry out the act of swallowing, and therefore a patient early in the illness may notice only occasional double vision, droopy eyelids, or difficulty swallowing. In about 80 percent of patients with myasthenia the first symptoms affect the eyes, but over time most develop generalized disease with symptoms in many muscles. In about 20 percent of patients the illness remains localized to a few muscle groups.

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