Michael H. Ellman

Oral iloprost treatment in patients with Raynaud's phenomenon secondary to systemic sclerosis: A multicenter, placebo-controlled, double-blind study

OBJECTIVE To evaluate the efficacy and tolerability of an oral preparation of iloprost, a prostacyclin analog, in patients with Raynauds phenomenon (RP) secondary to systemic sclerosis (scleroderma). METHODS A multicenter, randomized, parallel-group, placebo-controlled double-blind study was performed at university and community-based medical centers. Patients were randomly assigned to receive either 50 microg of iloprost orally twice daily or an identical gelatin-coated capsule containing placebo for 6 weeks. Outcome measures included average total daily duration of RP attacks, average number of RP attacks, and RP condition scored via a standardized daily diary. RESULTS Three hundred eight patients with scleroderma (272 women, 36 men, mean age 49 years [range 18-80]) were enrolled. One hundred fifty seven were assigned to receive iloprost and 151 to receive placebo. One hundred forty-three patients in the iloprost group (91.1%) and 144 in the placebo group (95.4%) completed the 6-week treatment phase. Fifteen of these treated patients (8 iloprost, 7 placebo) failed to complete all of the followup visits. The mean reduction in the average duration of attacks from baseline to week 5-6 was 24.32 minutes in the iloprost group and 34.34 minutes in the placebo group (P = 0.569). Likewise, the mean reduction from baseline to week 5-6 in the daily frequency of attacks was 1.02 in the iloprost group and 0.83 in the placebo group (P = 0.459). The Raynauds condition score, a patient-completed assessment of the severity of RP attacks, was reduced by 1.32 in the iloprost group and 1.00 in the placebo group (P = 0.323). The lack of significant difference between treatment groups did not change when a variety of factors, including use of other vasodilators, duration of disease, classification of scleroderma (limited versus diffuse), or number of baseline digital ulcers were taken into account. Premature withdrawal from the study due to adverse events occurred in 10 patients (6.4%) in the iloprost group and 3 (2.0%) in the placebo group (P = 0.058). CONCLUSION Oral iloprost at a dosage of 50 microg twice daily is no better than placebo for management of RP secondary to scleroderma, either during 6 weeks of treatment or during 6 weeks of posttreatment followup.

Recombinant Human Relaxin in the Treatment of Systemic Sclerosis With Diffuse Cutaneous Involvement : A Randomized, Double-Blind, Placebo-Controlled Trial

OBJECTIVE A phase II randomized controlled trial of recombinant human relaxin suggested that a dosage of 25 microg/kg/day was safe and clinically effective in improving skin disease and reducing functional disability in scleroderma (systemic sclerosis; SSc). We undertook a large randomized, double-blind, placebo-controlled clinical trial to compare placebo with 10 microg/kg/day and 25 microg/kg/day recombinant human relaxin, given for 24 weeks in patients with stable, diffuse, moderate-to-severe SSc. METHODS Men and women ages 18-70 years with diffuse cutaneous SSc (dcSSc) were administered recombinant human relaxin (10 microg/kg/day or 25 microg/kg/day) or placebo for 24 weeks as a continuous subcutaneous infusion. There was a followup safety visit at week 28. RESULTS The primary outcome measure, the modified Rodnan skin thickness score, was similar among the 3 groups at baseline and at weeks 4, 12, and 24. Secondary outcomes such as functional disability were similar in all 3 groups, while the forced vital capacity decreased significantly in the relaxin groups. The discontinuation of both doses of relaxin at week 24 led to statistically significant declines in creatinine clearance and serious renal adverse events (defined as doubling of serum creatinine, renal crisis, or grade 3 or 4 essential hypertension) in 7 patients who had received relaxin therapy but in none who had received placebo. CONCLUSION Recombinant relaxin was not significantly better than placebo in improving the total skin score or pulmonary function or in reducing functional disability in patients with dcSSc. In addition, relaxin was associated with serious renal adverse events, the majority of which occurred after stopping the infusion. If relaxin is used therapeutically for any conditions other than scleroderma, close monitoring of blood pressure and renal function must be performed.

Therapeutic plasma exchange for the acute management of the catastrophic antiphospholipid syndrome: β2-glycoprotein I antibodies as a marker of response to therapy

We describe two patients with the catastrophic antiphospholipid syndrome associated with elevation of β2‐glycoprotein I antibodies and fulminant thrombotic diatheses. Both patients were treated with therapeutic plasma exchange (TPE), which resulted in a marked decrease in antibody titer accompanied by an improved clinical outcome in one patient (IgG antibody). In the second patient, the outcome was poor despite TPE (IgA antibody). There were no significant complications of TPE in either case. Because of the fulminant nature of the catastrophic antiphospholipid syndrome, we conclude that a trial of TPE is warranted for the acute management. Further studies are needed to clarify which patients may benefit from this treatment. J. Clin. Apheresis 14:171–176, 1999.

Prevalence of Knee Chondrocalcinosis in Hospital and Clinic Patients Aged 50 or Older

ABSTRACT: The prevalence of chondrocalcinosis was studied in 574 hospital and clinic patients aged 50 or older who had undergone x‐ray examination of the knee. Chondrocalcinosis was found in 9.6 percent of all these patients, in 5 percent of the 50–64 age group, and in 14.6 percent of the 65–94 age group. The prevalence of knee chondrocalcinosis increased in stepwise fashion between the ages of 65 and 80. A review of the literature and of the data on our few patients over the age of 80 suggests the existence of an even higher prevalence among persons of this advanced age group.

Crohn's disease arthritis treated with infliximab: an open trial in four patients.

Four patients with Crohns disease arthritis, who were unresponsive to conventional treatment, improved very rapidly and safely with the use of infliximab, the chimeric antibody directed against tumor necrosis factor alpha. The patients were able to stop or significantly decrease other antirheumatic medications after the infliximab infusions. It is likely that tumor necrosis factor plays a major role in the arthritis as well as the bowel involvement that is seen in Crohns disease. Suppression of this cytokine may effectively ameliorate Crohns disease arthritis in some patients.

Rheumatologic aspects of painful conditions affecting the shoulder

Patients with shoulder arthritis present to the orthopedic surgeon due to joint pain and loss of shoulder motion. A differential diagnosis is established, based on the history and physical examination and selected laboratory tests and roentgenograms. Synovial fluid analysis is often very helpful in the diagnosis of shoulder arthritis and critical for differential diagnosis of inflammatory, degenerative, and septic arthritis. Shoulder involvement in primary osteoarthritis is uncommon. The shoulder is rarely the initial joint involved in rheumatoid arthritis. Several uncommon conditions, e.g., amyloid arthropathy and reflex sympathetic dystrophy syndrome, may present early and frequently in the form of shoulder pain. The results of treatment are determined by etiology of shoulder joint disease. Patients with shoulder involvement in rheumatoid arthritis generally respond to the basic management for rheumatoid arthritis. Physical therapy to improve the range of motion of the shoulder and anti-inflammatory medications, including intra-articular corticosteroids, are helpful in most cases.

Are isolated antinucleolar antibodies a marker of scleroderma

Isolated antinuclear antibodies were neither very sensitive or specific for scleroderma in this study. This study was designed to determine the prevalence and positive predictive value of isolated antinucleolar antibody (ANA) in scleroderma patients. We identified 73 rheumatology clinic patients with isolated ANAs. ANA titers greater than 1:160 were considered positive. The overall prevalence of isolated ANAs was 2.9%. The prevalence of isolated ANAs in scleroderma, systemic lupus erythematosus (SLE), and rheumatoid arthritis were 20.3%, 2.68%, and 3.3%, respectively. Scleroderma and SLE were present in 12 patients (16.4%) each. Other rheumatologic disorders identified in these patients were RA (12.3%), undifferentiated connective tissue disease (8.2%), mixed connective tissue disease (4.1%), vasculitis (6.8%), fibromyalgia (8.2%), osteoarthritis (5.4%), crystal-related arthropathy (6.8%), seronegative arthritis (2.7%), sarcoidosis (4.1%), and others (8.2%). There were no statistically significant differences in the median ANA titers in scleroderma versus systemic lupus (P = 0.16) or undifferentiated connective tissue disease (P = 0.18). The median titers were higher in scleroderma in comparison with rheumatoid arthritis (P = 0.01), osteoarthritis (P = 0.007), fibromyalgia (P = 0.001), and crystal-related arthropathy (P = 0.009). Isolated ANAs have poor sensitivity (20.3%) and the positive predictive value for this test is only 16.4% for scleroderma.

Shoulder arthritis: Distinguishing among the many causes of inflammation

Shoulder inflammation occurs in many rheumatic diseases. It is present in about half of the patients with rheumatoid arthritis but in a higher percentage of patients with less common diseases (eg, amyloid arthropathy, polymyalgia rheumatica). Shoulder arthritis, probably more than arthritis involving any other joint, requires prompt diagnosis and treatment to prevent loss of motion and function. For most patients, antiinflammatory medications, range of motion exercises, and instruction in joint protection constitute adequate treatment. A baseline shoulder roentgenogram is usually recommended. Intraarticular corticosteroid therapy may be a helpful adjunct, provided infection has been excluded.

A new case of xanthinuria.

Abstract A new case—the ninth—of documented xanthinuria is reported. The patient has no symptoms attributable to xanthine oxidase deficiency. Xanthinuria was detected after discovery of hypouricemia on chemical profile screening of serum. Twenty-four hour urine, with the patient on a low purine diet, showed mean values of 2.9 mg uric acid, 287 mg xanthine and 76 mg hypoxanthine. Urinary excretion of orotic acid and orotidine was normal.

Septic Arthritis in Sickle-Cell States: Pathophysiology of Impaired Response to Infection and Implications for Management.

Excerpt Two patients with septic arthritis and sickle-cell disorders responded poorly to therapy. Although prompt responses are reported in nonsicklers,Escherichia coliandSalmonella enteritidispers...