Objective. To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active psoriatic arthritis (PsA) resistant to nonsteroidal antiinflammatory drug therapy.Methods. Two hundred twenty-one patients with PsA were recruited from 15 clinics, randomized (doubleblind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on joint p a i d Address reprint request requests to Daniel 0. Clegg, MD, Division of Rheumatology, 4B200-SOM, 50 North Medical Drive, Salt Lake City, UT 84132.Submitted for publication March 19,1996; accepted in revised form July 19, 1996. tenderness and swelling scores and physician and patient global assessments.Resubs. Longitudinal analysis revealed a trend favoring SSZ treatment (P = 0.13). At the end of treatment, response rates were 57.8% for SSZ compared with 44.6% for placebo (P = 0.05). The Westergren erythrocyte sedimentation rate declined more in the PsA patients taking SSZ than in those taking placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints, including dyspepsia, nausea, vomiting, and diarrhea.Conclusion. SSZ at a dosage of 2,000 mg/day is well tolerated and may be more effective than placebo in the treatment of patients with PsA.

Deoxyadenosine at low concentrations and in the presence of an inhibitor of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) is markedly toxic to lymphoblast cell lines of T cell origin but does not impair growth of B cell lines. Deoxyguanosine is also more toxic for T lymphoblasts. In the presence of deoxyadenosine or deoxyguanosine, elevation of the corresponding deoxyribonucleoside triphosphate (dATP or dGTP) occurs in T cell, but not in B cell, lines. The addition of deoxycytidine or dipyridamole results in lower dATP and dGTP levels and prevents deoxyribonucleoside toxicity. These findings provide a molecular basis for the immunodeficiency observed in individuals with several inborn errors of purine metabolism.Deficiencies of two enzymes catalyzing sequential reactions in the purine catabolic pathway (Fig. 1) are associated with clinical immunodeficiency states. Adenosine deaminase (ADA; adenosine aminohydrolase, EC 3.5.4.4) catalyzes the deamination of adenosine and deoxyadenosine to inosine and deoxyinosine respectively; the deficiency of this enzyme is associated with severe T lymphocyte and more variable B lymphocyte dysfunction (1, 2). Purine-nucleoside phosphorylase (PNP; purine-nucleoside:orthophosphate ribosyltransferase, EC 2.4.2.1) catalyzes the conversion of the purine nucleosides, inosine, xanthosine, and guanosine, as well as their 2'-deoxy derivatives, to their respective purine bases. PNP deficiency in man is associated with disturbed T cell function and with little, if any, B cell dysfunction (3, 4). The molecular mechanism by which lymphocyte differentiation and function is impaired in these disorders remains obscure.Recent reports of markedly elevated dATP levels in erythrocytes from ADA-deficient children (5, 6) and of elevated levels of deoxyinosine and deoxyguanosine in the urine from patients with PNP deficiency (7) have focused attention on deoxyribonucleosides as potential mediators of lymphocyte dysfunction. Indeed, deoxyadenosine in the presence of an ADA inhibitor reduces the responsiveness of peripheral blood lymphocytes to phytohemagglutinin stimulation (8, 9), whereas deoxyguanosine and, to a lesser extent, deoxyinosine were found to inhibit growth of a lymphoblast cell line (8). In addition, deoxyribonucleoside kinases capable of phosphorylating deoxyguanosine and deoxyinosine are located predominantly in the lymphoid system (8). We now present evidence that deoxyribonucleosides at low concentrations are far more toxic to human lymphoblasts of T cell origin than they are to human lymphoblast lines of B cell origin. Deoxyribonucleosides that are cytotoxic cause a selective accumulation of the corresponding deoxyribonucleoside triphosphates in T lymphoblasts, whereas agents that reduce deoxyribonucleoside toxicity decrease these levels. Deoxyribonucleoside triphosphate accumulation may play an important role in the pathogenesis of observed T lymphocyte abnormalities. The MGL-8 B lymphoblast line was derived from a normal individual and was a gift from J. Epstei...

Objective. To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active ankylosing spondylitis (AS) that is not controlled with nonsteroidal antiinflammatory drug therapy.Methods. Two hundred sixty-four patients with AS were recruited from 15 clinics, randomized (doubleblind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on morning stiffness, back pain, and physician and patient global assessments.Results. While longitudinal analysis revealed a trend favoring SSZ in the middle of treatment, no difference was seen at the end of treatment. Response rates were 38.2% for SSZ and 36.1% for placebo (P = 0.73). The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P c 0.0001). AS patients with associated peripheral arthritis showed improvement that favored SSZ (P = 0.02). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints.Conclusion. SSZ at a dosage of 2,000 mg/day does not seem to be more effective than placebo in the treatment of AS patients with chronic, longstanding disease. SSZ is well tolerated and may be more effective than placebo in the treatment of AS patients with peripheral joint involvement. This effect is more pronounced in treatment of the peripheral arthritis in this subgroup of AS patients.Ankylosing spondylitis (AS) is a disease characterized by sacroiliitis and spondylitis commonly involving the lumbar spine and, less commonly, the thoracic and cervical spine. Despite a number of advances in the immunogenetics of AS, the etiology of this disease has not been elucidated. Thus, treatment remains empirical and unsatisfactory. Patient education about the natural history and course of AS is an important adjunct to treatment. Nonsteroidal antiinflammatory drugs (NSAIDs) have been the foundation of medical therapy,

Objective. To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mglday is effective in the treatment of reactive arthritis (ReA) that has been unresponsive to nonsteroidal antiinflammatory drug (NSAID) therapy.

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