Kenneth R. Wilske

Diffuse Pulmonary Injury Associated with Gold Treatment

Two patients had diffuse, reversible pulmonary injury possibly owing to gold sodium thiomalate treatment: a 32-year-old woman with chronic inflammatory arthritis compatible with seronegative rheumatoid arthritis and a 32-year-old man with shoulder arthralgia. The patients had received 420 mg and 325 mg of gold sodium thiomalate, respectively. Cough and dyspnea began in the seventh and fifth weeks of therapy, respectively. In both patients x-ray study showed bilateral pulmonary infiltrates, with no evidence of pleural disease. The woman had no other manifestations of hypersensitivity to gold. The man had exfoliative dermatitis fever and anemia. Lung biopsies from both patients revealed lymphocytes and plasma cells infiltrating the alveolar septa and interstitial fibrosis. The woman improved slowly during four months after discontinuation of therapy. Pulmonary symptoms recurred after additional gold therapy, and again resolved when gold was discontinued. The man, treated with prednisone, showed prompt remission and remains will without medication.

Small-Vessel Vasculitis and Methotrexate

Excerpt To the editor: The use of chemotherapeutic agents is clearly associated with hypersensitivity reactions, including anaphylaxis and urticarial reactions when these drugs are used in moderate...

Case Report: Thrombotic Thrombocytopenic Purpura in a Patient with Polymyositis: Therapeutic Importance of Early Recognition and Discussion of Pathogenic Mechanisms

Thrombotic thrombocytopenic purpura (TTP) is characterized by the pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia, fluctuating neurologic symptoms, and renal dysfunction. Thrombotic thrombocytopenic purpura has recently been reported in association with rheumatic diseases (RDs). The authors present a patient with TTP and polymyositis and speculate on the pathophysiology linking these two conditions. Thrombotic thrombocytopenic purpura and RDs may present with overlapping clinical and laboratory features. It is important to identify TTP as a cause of thrombocytopenia and hemolysis when occurring in patients with RDs since management, treatment, and prognosis differ. Early recognition and prompt institution of plasmapheresis may improve the outcome in patients with TTP.

Equivalent responses to disease-modifying antirheumatic drugs initiated at any time during the first 15 months after symptom onset in patients with seropositive rheumatoid arthritis

Objective. To evaluate responses by time to initiation of nonbiologic disease-modifying antirheumatic drugs (DMARD) in a DMARD-naive cohort of patients with early seropositive rheumatoid arthritis (RA). Methods. Subjects were categorized by the time from symptom onset to the first DMARD use (median 5.7 months, range 0.6–15.9). Subjects who started their first DMARD within 5 months of symptom onset were compared to subjects who started after 5 months. Disease Activity Scores (DAS-44) and total Sharp Score (TSS) progression rates were analyzed using Wilcoxon rank-sum and chi-square tests; multiple linear regression analysis adjusted for potential covariates. The slope of the least-squares regression line was calculated to estimate the annualized TSS progression rates. Results. Of 233 RA patients, 76% were female and mean age was 50 (SD 13) years. At DMARD start, DAS-44 was similar in all subsets within the 0.6 to 15 months’ duration between symptom onset and DMARD initiation. Erosion scores tended to be higher in those who started DMARD later, but Health Assessment Questionnaire-Disability Index (HAQ-DI) scores were higher in those who started DMARD earlier. During the 2 years after DMARD initiation, improvements in HAQ-DI and DAS-44 were similar in the various duration subsets, with about 25% ever achieving DAS remission (DAS < 1.6). Radiographic progression tended to be numerically but not statistically more rapid in the earlier subsets. Conclusion. Following initiation of nonbiologic DMARD therapy at various times within 15 months of symptom onset, improvements of DAS-44, HAQ-DI, remission rate, and radiographic progression rate were similar, although higher baseline erosion scores were present in those with later initiation of DMARD.

HLA-DR4-Associated Disease: Oligonucleotide Probes Identify Specific Class II Susceptibility Genes in Type I Diabetes and Rheumatoid Arthritis

Distinct patterns of linked DRβ (HLA-DRB1) and DQβ (HLA-DQB1) genes are found on at least seven different haplotypes that carry the HLA-DR4 specificity (1,2). We have constructed 20 and 21-base synthetic oligonucleotide DNA probes capable of distinguishing between different DRβ alleles and between different DQβ alleles expressed on these DR4-positive haplotypes. Hybridization analysis indicates striking differences in the distribution of individual DQβ and DRβ alleles in DR4-positive patients with rheumatoid arthritis (RA) and DR4-positive patients with insulin-dependent diabetes mellitus (IDDM, type I diabetes). Probes identifying Dw14 or Dw4 DRβ genes hybridized to greater than 93% of patients with seropositive rheumatoid arthritis, consistent with the concept that these two alleles account for the DR4 association with this disease. No difference was observed between the distribution of different DQβ alleles in rheumatoid arthritis as compared to normal individuals. In contrast, DQβ 3.2 specific oligonucleotide probes hybridized to greater than 96% of DR4-positive IDDM patients, regardless of the linked DR4-positive DRβ gene.

Remodeling the therapeutic pyramid: evolving therapeutic strategies for rheumatoid arthritis

The approach to treatment of rheumatoid arthritis (RA) is undergoing dramatic change, With a prevalence of 1% of the general population. RA is the most common cause of disability that is potentially reversible if correct management of the disease is begun in the early phases. While the traditional therapeutic pyramid model has been in place for the past 25 years, evolving therapeutic strategies suggest that it is appropriate primarily for patients with benign synovitis, and an inverted pyramid is necessary to treat aggressive synovitis, control inflammation early and to prevent rapid joint destruction, disability and early death. Important principals underlying the remodeling of the therapeutic pyramid and evolving therapeutic strategies include: identifying patients with benign and aggressive synovitis: early control of inflammation to stabilize functional status at near normality; need for combination therapy in aggressive synovitis until a major breakthrough or ‘magic’ bullet becomes available; awareness that drugs that control inflammation in a more fundamental manner, such as disease-modifying anti-rheumatic drugs, are more effective in pain control and disability than non-steroidal anti-inflammatory drugs; and, most importantly, education of patients, primary and managing care physicians, health maintenance organizations, insurance companies, and government officials that two-thirds of the cost of RA lies in the complications of the disease and that providing resources for early aggressive therapy is a good investment for all. Successful treatment of rheumatoid arthritis is best accomplished by a coordinated team of a consultant rheumatologist and a managing primary care physician. Much like an early consultation with an oncologist when cancer is suspected, an early consultation with a rheumatologist can help separate benign and aggressive synovitis. If the latter, the rheumatologist can help identify important co-morbid conditions and recommend appropriate therapy. Follow-up programs can then be outlined to maintain control of inflammation at all times, utilize appropriate pharmacologic and non-pharmacologic physical and occupational therapy modalities for mechanical pain, and highlight potential toxicities to be monitored. This program, initiated early, will help prevent administration of toxic drugs to patients with benign synovitis. And, just as important for patients with aggressive synovitis, this strategy is designed to reduce the high incidence of morbidity and mortality and the costly episodes of hospitalizations and salvage surgery that can be so devastating to patients and their families.

Anemia as a Primary Manifestation of Giant Cell Arteritis.

Excerpt This report describes seven older women whose primary problem was anemia. They sought medical attention because of fatigue and malaise; headache and muscle pains were either not present or ...