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with a scleroderma-like appearance of the skin and exion contractures at the knees and elbows associated with hyperglobulinemia, elevated sedimentation rate, and eosinophilia Biopsy revealed greatly thickened fascia, extending from the subcutaneous tissue to the muscle and in ltrated with plasma cells, lymphocytes, and many eosinophils; the muscle itself appeared normal and the skin lacked the characteristic histologic changes of scleroderma One of Shulman s patients recovered in response to prednisone The many reports that followed have fully substantiated and ampli ed Shulman s original description The disease predominates in men, in a ratio of 2:1 Symptoms appear between the ages of 30 and 60 years in most cases and are often precipitated by heavy exercise (Michet et al) Initially there may be low-grade fever and myalgia, followed by the subacute development of diffuse cutaneous thickening and limitation of movement of small and large joints In some patients, proximal muscle weakness and eosinophilic in ltration of muscle can be demonstrated (Michet et al) Repeated examinations of the blood disclose an eosinophilia in most but not all patients Usually, the disease remits spontaneously or responds well to corticosteroids A small number relapse and do not respond to treatment, and some have developed aplastic anemia and a form of lympho- or myeloproliferative disease Eosinophilic Monomyositis Painful swelling of a calf muscle or, less frequently, some other muscle has been the chief characteristic of this disorder A painful mass forms within the muscle Biopsy discloses in ammatory necrosis and edema of the interstitial tissues; the in ltrates contain variable numbers of eosinophils This disorder is typi ed by one of our patients a young woman who developed such an in ammatory mass rst in one calf and then, 3 months later, in the other The response to prednisone in this patient was dramatic; the swelling and pain subsided in 2 to 3 weeks, and power of contraction was then found to be normal When the connective tissue and muscle are both damaged, a chaotic regeneration of broblasts and myoblasts may occur, forming a pseudotumor mass that may persist inde nitely Eosinophilic Polymyositis Layzer and associates described a third form of eosinophilic disorder, which they classi ed as a true subacute PM Their patients were adults in whom predominantly proximal weakness evolved over several weeks The other features of the muscle disorder were also typical of PM except that the in ammatory in ltration was predominantly eosinophilic and the muscles were swollen and painful Moreover, in each case the muscle disorder was part of a severe and widespread systemic illness typical of the hypereosinophilic syndrome The systemic manifestations included a striking eosinophilia of the blood (20 to 55 percent of the white blood cells), cardiac involvement (conduction disturbances and congestive failure), vascular disorder (Raynaud phenomenon, subungual hemorrhages), pulmonary in ltrates, strokes, anemia, neuropathy, and hypergammaglobulinemia There was a favorable response to corticosteroids in two patients, but in a third the outcome was fatal within 9 months Layzer and coworkers noted that a lack of necrotizing arteritis distinguished this process from polyarteritis nodosa and Churg-Strauss disease No infective agent could be isolated An allergic mechanism seems a likely cause of the lesions, and in the present authors view one cannot exclude an angiitis as a cause of all of the lesions The last two of these previously mentioned syndromes (eosinophilic monomyositis and PM) have overlapping features, as shown by Stark s cases, in which a monomyositis was accompanied by several of the systemic features described by Layzer et al.

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Eosinophilia-Myalgia Syndrome Beginning in 1980, a number of sporadic reports documented a lingering systemic illness characterized by severe generalized myalgia and eosinophilia of the peripheral blood following the ingestion of L-tryptophan In late 1989 and early 1990, there occurred a massive outbreak of this eosinophilia-myalgia syndrome, as the illness came to be called Over 1200 cases were reported to the Centers for Disease Control (Medsger), and we examined several of them The outbreak was ultimately traced to the use of nonprescription L-tryptophan tablets supplied by a single manufacturer and contaminated by a ditryptophan-aminal of acetaldehyde (Mayeno et al) The onset was relatively acute, with fatigue, low-grade fever, and eosinophilia ( 1000 cells per cubic millimeter) Muscle pain and tenderness, cramps, weakness, paresthesias of the extremities, and induration of the skin were the main clinical features A severe axonal neuropathy with slow and incomplete recovery was associated in some cases Biopsies of the skin fascia, muscle, and peripheral nerve disclosed a microangiopathy and an in ammatory reaction in connective tissue structures changes like those observed in scleroderma, eosinophilic fasciitis, and the toxic oil syndrome The latter syndrome, caused by the ingestion of contaminated rapeseed oil (in Spain, 1981), gave rise to a constellation of clinical and pathologic changes that were similar if not identical to those caused by contaminated L-tryptophan (Ricoy et al; page 1134) The two toxins are also closely linked chemically The cutaneous lesions and eosinophilia of this syndrome responded to treatment with prednisone and other immunosuppressive drugs, but other symptoms did not The severe axonal neuropathy in our patients has improved incompletely over several years, leaving one of our patients chairbound with severe distal atrophic weakness Acute Orbital Myositis Among the many cases of orbital in ammatory disease (pseudotumor of the orbit, page 234), there is a small group in whom the in ammatory process appears to be localized to the extraocular muscles To this latter group the term acute orbital myositis has been applied The abrupt onset of orbital pain that is made worse by eye motion, redness of the conjunctiva adjacent to the muscle insertions, diplopia caused by restrictions of ocular movements, lid edema, and mild proptosis are the main clinical features It may spread from one orbit to the other The erythrocyte sedimentation rate is usually elevated and the patient may feel generally unwell, but only rarely can the ocular disorder be related to a connective tissue disease or any other speci c sys-.

What, exactly, constitutes something living, which makes it different from something nonliving This has been one of the great questions of science throughout history In some cultures, life is ascribed to things that Americans think of as inanimate One definition of artificial life involves the ability of a human-made thing to reproduce itself Suppose you were to synthesize a new kind of molecule in a beaker and

temic disease Computed tomography and MRI have proved to be particularly useful in demonstrating the swollen ocular muscles or muscle and separating orbital myositis from the many other remitting in ammatory orbital and retro-orbital conditions (Dua et al) As a rule, acute orbital myositis resolves spontaneously in a matter of a few weeks or a month or two, although it may recur in the same or the opposite eye Administration of steroids appears to hasten recovery

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