Chronic fatigue syndrome. 1: Etiology and pathogenesis.

Chronic fatigue syndrome (CFS) is a disorder of unknown etiology characterized by debilitating fatigue and other somatic and neuropsychiatric symptoms. A range of heterogeneous clinical and laboratory findings have been reported in patients with CFS. Various theories have been proposed to explain the underlying pathophysiologic processes but none has been proved. Research findings of immunologic dysfunction and neuroendocrine changes suggest the possible dysregulation of interactions between the nervous system and the immune system. Without a clear understanding of its etiopathogenesis, CFS has no definitive treatment. Management approaches have been necessarily speculative, and they have evolved separately in a number of medical and nonmedical disciplines. The results of several controlled treatment studies have been inconclusive. An accurate case definition identifying homogeneous subtypes of CFS is needed. The integration of medical and psychologic treatment modalities and the use of both biologic and psychologic markers to evaluate treatment response will enhance future treatment strategies.

Tophaceous deposition in the finger pads without gouty arthritis.

Tophi are rarely observed in patients without a prior history of gouty arthritis. We describe four patients whose initial manifestation of gout was tophaceous deposition in an unusual location, the finger pad. None of these patients had a history of acute gouty arthritis and none had tophi elsewhere. All four patients were postmenopausal women with decreased renal function; all were taking diuretics. We conclude that tophaceous gout without arthritis may be more common than previously recognized and that tophi may deposit in the finger pad. We recommend prompt aspiration and crystal analysis of white subcutaneous finger pad deposits in hyperuricemic patients even without a history of gouty arthritis.

Arthritic manifestations of inflammatory bowel disease.

Rheumatologic conditions associated with inflammatory bowel disease may be divided into four clinical categories. First, a unique form of peripheral arthritis occurs in 15-20% of patients with inflammatory bowel disease. The incidence is higher in Crohn's disease than in ulcerative colitis. This is a self-limited, nondeforming, seronegative arthritis that waxes and wanes with bowel flares. It characteristically involves knees and ankles. Persistent erosive monoarthritis is described. Second, spondylitis clinically and radiographically indistinguishable from idiopathic ankylosing spondylitis occurs in 3-6% of patients with inflammatory bowel disease. HLA-B27 positivity occurs in 53-75% of cases, fewer than in idiopathic spondylitis. Third, a bilateral, symmetrical sacroiliitis is seen in 4-18% of patients. This may not progress to clinical spondylitis. The fourth category encompasses rheumatologic complications of inflammatory bowel disease. These include granulomas of bones and joints, granulomatous vasculitis, clubbing, periostitis, amyloidosis, osteoporosis, osteomalacia, septic arthritis, and complications of corticosteroid therapy.

Relief of morning stiffness: a comparative study of naproxen and ibuprofen.

Morning stiffness in 75 patients with mild to moderate rheumatoid arthritis was treated with 1600 mg ibuprofen 4-times daily or 750 mg naproxen twice daily after a placebo-induced flare of this symptom. With the final daily dose of each drug administered at bedtime, both drugs significantly reduced the duration and severity of morning stiffness compared to baseline values but, on average, duration of morning stiffness tended to be shorter for naproxen patients than for ibuprofen patients. No corresponding between-drug difference was found for severity of morning stiffness.

Four-way, multicenter, crossover trial of ibuprofen, fenoprofen calcium, naproxen, and tolmetin sodium in osteoarthritis: comparative clinical profiles.

One hundred forty-one subjects with osteoarthritis completed this double-blind, multicenter, crossover trial comparing four nonsteroidal anti-inflammatory (NSAI) agents after single-blind aspirin stabilization. Preferences of both patients and physicians showed the following rank order from most to least preferable: tolmetin sodium, naproxen, ibuprofen, fenoprofen calcium. By all but three of more than 20 measures of efficacy, tolmetin sodium and naproxen were the more effective pair and fenoprofen calcium and ibuprofen the less effective pair of the four. Eight of nine measures of tolerability suggested the following rank order from best to worst tolerated: ibuprofen, naproxen, tolmetin sodium, fenoprofen calcium, aspirin. Few differences among the newer NSAI agents compared in this study achieved statistical significance. Nevertheless, the tolerability-efficacy relationships that emerge from studies of this type can help to define rational approaches to the use of these drugs in rheumatic diseases.

A possible association between influenza vaccination and small-vessel vasculitis.

We describe two patients who experienced small-vessel vasculitic syndromes after influenza immunization. Their illnesses were characterized by fever, arthralgias, and myalgias; uveitis and optic neuritis occurred in one patient, while the other had palpable purpura, which histologically was proved to be a cutaneous necrotizing venulitis. No viral or bacterial infection, medications, or underlying systemic rheumatic disease could be implicated. To our knowledge, small-vessel vasculitis occurring after influenza vaccination has not been previously reported.

Rapid onset of lung involvement in progressive systemic sclerosis.

Lung involvement in progressive systemic sclerosis (PSS) is common but usually is of chronic onset late in the course. Skin changes usually antedate pulmonary findings. Presentation of PSS with rapid development of pulmonary interstitial fibrosis, without skin changes, has not previously been described. Such a case is discussed here and the radiologic and pathologic findings and course of pulmonary PSS are reviewed.

The effects of anti-inflammatory drugs on prostaglandin production by rheumatoid synovial tissue.

The effect of anti-inflammatory drugs on prostaglandin production by rheumatoid synovial tissue has been investigated. Synovial explants were maintained in tissue culture for periods up to six days and PGE2 concentrations in culture were determined by radioimmunoassay. The more potent nonsteroidal inhibitors of PGE2 production and their IC50 (micrometer) values were indomethacin 0.005, flufenamic acid 0.2, flurbiprofen 0.6, ibuprofen 2.0 , naproxen 6.0, phenylbutazone 10.0, and aspirin 20.0. Drugs with weak or insignificant effects were hydroxychloroquin, acetaminophen, azathioprine, chloroquin, penicillamine, gold Na thiomalate, and Na salicylate. Glucocorticoids were potent inhibitors; dexamethasone 0.003, prednisolone 0.01, hydrocortisone 0.03; while mineralocorticoids deoxycorticosterone and aldosterone were inactive at 1.0 micrometer. There is a reasonably good correlation between the IC50 concentrations of the nonsteroidal inhibitors and their peak free plasma concentration achieved during therapy in man. Inhibition of prostaglandin synthesis may contribute to the effects of many but not all anti-inflammatory drugs.

Urinary excretion of hydroxylysine and its glycosides as an index of collagen degradation.

Urimary excretion of hydroxyprolin (Hyp) is one index of total collagen degradation, from all sources. Since some of the Hyp released from collagen may be further metabolized before it is excreted, other markers are necessary to measure collagen breakdown. Excretion of the glycosides of hydroxylysine (Hyl), glucosyl galactosyl hydroxylysine (Hy1[Gl)cGa1]), and galactosyl hydroxylysine (Hyl[Ga)]), more accurately reflects collagen metabolism since these products occur in specificratios in different tissue collagens and are themselves metabolized only to a minor degree. The ratios of total Hy1/Hyp and Hyl(GlcGal)/Hyl(Ga1) were measured in the urine of norma. subjects and of patients with Paget's disease of bone, hyperphosphatasia, and extensive thermal burns. In patients with extensive thermal burns the pattern of urinary Hy1 and its glycosides was consistent with degradation of collagen in dermis and fascia. When bone collagen degradation was dominant, the pattern of urinary metabolites reflected that source. Pagetic bone collagen has an amino acid composition similar to normal bone and Hy1(G1cGa1/Hyl(G1) of 0.396-0.743,vs. normal of 0.474+/-0.088. In untreated patients with severe Paget's disease of bone or hyperphosphatasia (urinary Hyp greater than 2.0 micronmol/mg creatinine) urinary Hyl/Hyp averaged 0.052+/-0.042 (0.042+/-0.009 in normal bone) and Hy1(G1cGa1)/Hy1(Ga1) 0.601+/-0.017 (0.47+/-0.009 in normal bone). When bone resorption was decreased sufficiently with calcitonin or disodium etidronate in these patients, both the urinary ratios of Hy1/Hyp and Hy1(G1cGa1)/Hyl(Gal) rose. In normal subjects treated with calcitonin and excreting relatively little Hyp, the ratio of Hy1/H)P approached 0.7 and Hy1(G1ycGa1)/Hy1(Ga1) approached 3.5. There increased ratios reveal the existence of a source of collagen breakdown other than skin or bone. The first subcompoent of complement, Clq, which has collagen-like sequences, relatively high amounts of Hy1, and most of the glycosylated Hy1 as Hy1(G1cGa1), could be the source of these metabolites.

Medical management of rheumatoid arthritis.

The overall management of RA is multifaceted. It includes rest, both systemic and articular; physical therapy; utilization of the techniques and appliances of occupational therapy; drugs, both those that suppress inflammation and those that are capable of altering the disease course itself; a knowledge of specific articular and nonarticular complications; and the ability to refer for appropriate surgical management. Judicious, energetic application of these principles can favorably affect the outcome of rheumatoid disease in most patients.