Allan L. Metzger

Lupus erythematosus in the 1980s: A survey of 570 patients

Five hundred seventy lupus erythematosus patients observed in a private practice between 1980 and 1989 were surveyed. Fifty-five percent were diagnosed after 1980. Five hundred three fulfilled criteria for systemic lupus erythematosus ( [SLE]; 464 idiopathic, 23 overlap, 16 drug-induced) and 67 had biopsy-documented cutaneous (discoid) lupus. In the idiopathic SLE group, symptoms began at a mean age of 31 years and patients were observed for a mean of 6 years. Findings in idiopathic SLE patients were (1) 27% have a family history of autoimmune disease; (2) nephritis patients without nephrotic syndrome rarely develop renal failure (4%); (3) nephrotic syndrome patients are relatively cyclophosphamide-resistant; (4) organ-threatening disease is present in 54%; and (5) 13% of women who become pregnant are recurrent aborters and 26% never conceive. In an analysis of cohort data, 5- and 10-year survivals were 97% +/- 2% and 93% +/- 3%, respectively. Additionally, men and patients with renal disease or thrombocytopenia had a poorer prognosis. Blacks had similar clinical findings and survival to whites. Approximately 50% of deaths were from active disease and 50% from complications of therapy. Prolonged survival has resulted from new diagnostic procedures and serologic tests, and improved antibiotics and antihypertensive agents, as well as more efficacious treatment modalities.

Polymyositis and dermatomyositis: combined methotrexate and corticosteroid therapy.

Abstract Twenty-two patients with polymyositis and dermatomyositis were treated with combined prednisone and intravenous methotrexate when moderate to high-dose cortisone alone was ineffective in c...

Proteomic analysis of secreted proteins in early rheumatoid arthritis: anti-citrulline autoreactivity is associated with up regulation of proinflammatory cytokines

Objectives: To identify peripheral blood autoantibody and cytokine profiles that characterise clinically relevant subgroups of patients with early rheumatoid arthritis using arthritis antigen microarrays and a multiplex cytokine assay. Methods: Serum samples from 56 patients with a diagnosis of rheumatoid arthritis of <6 months’ duration were tested. Cytokine profiles were also determined in samples from patients with psoriatic arthritis (PsA) and ankylosing spondylitis (n = 21), and from healthy individuals (n = 19). Data were analysed using Kruskal–Wallis test with Dunn’s adjustment for multiple comparisons, linear correlation tests, significance analysis of microarrays (SAM) and hierarchical clustering software. Results: Distinct antibody profiles were associated with subgroups of patients who exhibited high serum levels of tumour necrosis factor (TNF)α, interleukin (IL)1β, IL6, IL13, IL15 and granulocyte macrophage colony-stimulating factor. Significantly increased autoantibody reactivity against citrullinated epitopes was observed in patients within the cytokine “high” subgroup. Increased levels of TNFα, IL1α, IL12p40 and IL13, and the chemokines eotaxin/CCL11, monocyte chemoattractant protein-1 and interferon-inducible protein 10, were present in early rheumatoid arthritis as compared with controls (p<0.001). Chemokines showed some of the most impressive differences. Only IL8/CXCL8 concentrations were higher in patients with PsA/ankylosing spondylitis (p = 0.02). Conclusions: Increased blood levels of proinflammatory cytokines are associated with autoantibody targeting of citrullinated antigens and surrogate markers of disease activity in patients with early rheumatoid arthritis. Proteomic analysis of serum autoantibodies, cytokines and chemokines enables stratification of patients with early rheumatoid arthritis into molecular subgroups.

HL-A W27 — A Clue to the Diagnosis and Pathogenesis of Reiter's Syndrome

RECENTLY, an extraordinary correlation between the second-segregant series histocompatibility antigen (HL-A), W27, and a well characterized rheumatic disease, ankylosing spondylitis was reported.1 ...

Randomized controlled trial of pulse/synchronization cyclophosphamide/apheresis for proliferative lupus nephritis

To assess the efficacy of pulse/synchronization cyclophosphamide/apheresis in patients with proliferative lupus nephritis.

Lupus in the 1980s: III. Influence of clinical variables, biopsy,and treatment on the outcome in 150 patients with lupus nephritis seen at a single center

Of 500 patients with systemic lupus erythematosus observed at our center, 150 fulfilled criteria for lupus nephritis. Of these 150 patients, 91% were female, and 67% were white. The mean age of onset was 26.2 years, and the mean follow-up duration was 11.7 years. Biopsies (n = 142) performed on 107 patients showed the following World Health Organization (WHO) class distribution: class I, n = 1; class II, n = 13; class III, n = 19; class IV, n = 69; class V, n = 17; class VI, n = 8; and class not determinable, n = 15. Ninety-five patients were nephrotic. Therapeutic intervention courses given to all patients (n = 356) included parenteral (IV) cyclophosphamide (n = 58), high-dose oral steroids (n = 126), pulse steroids (n = 49), apheresis (n = 39), azathioprine (n = 43), oral cyclophosphamide (n = 5), nitrogen mustard (n = 27), and chlorambucil (n = 6). In addition to examining the course of disease for various subsets, various predictors for fatality and end-stage renal disease (ESRD) were analyzed. Descriptive data for the short-term response to five therapies are provided for the complete patient sample, proliferative disease, and nephrotic syndrome. Twenty patients died, primarily from cardiovascular complications and sepsis, with 97% and 92% 5- and 10-year survival rates, respectively. Twenty-nine were dialyzed, and 11 were transplanted. Risk of ESRD by WHO class at 5 years was as follows: class III, 0%; IV, 9%; V, 16% (P = .04 for class V v other patterns).(ABSTRACT TRUNCATED AT 250 WORDS)

Follow-up study of juvenile chronic polyarthritis with particular reference to histocompatibility antigen W. 27.

The HL-A antigen W.27 has been found in 88 to 96% of patients with ankylosing spondylitis (Brewerton, Caffrey, Hart, James, Nicholls, and Sturrock, 1973a; Caffrey and James, 1973; Schlosstein, Terasaki, Bluestone, and Pearson, 1973). More recently a high frequency of W.27 has been reported in Reiters syndrome (Brewerton, Caffrey, Nicholls, Walters, Oates, and James, 1973c), acute anterior uveitis (Brewerton, Caffrey, Nicholls, Walters, and James, 1973b), and Yersinia arthritis (Aho, Ahvonen, Lassus, Sievers, and Tiilikainen, 1973). In a control Caucasian population, the frequency ofW.27 is 4 to 8% (Brewerton and others, 1973a; Schlosstein and others, 1973). The long-term follow-up of juvenile chronic polyarthritis has shown that a small proportion of patients presenting with peripheral arthritis may ultimately develop definite ankylosing spondylitis (Ansell, 1969; Chalmers, 1971), and others may show radiological sacroiliitis of ankylosing spondylitis type (Bywaters and Ansell, 1965). Family studies of patients with juvenile chronic polyarthritis have shown an increased incidence of ankylosing spondylitis in male relatives and of seronegative chronic polyarthritis in female relatives (Ansell, Bywaters, and Lawrence, 1962), and of sacroiliitis in male relatives aged 15 and over and in female relatives aged 45 and over (Ansell, Bywaters, and Lawrence, 1968). We decided to tissue type a small group of patients with juvenile chronic polyarthritis, who had been followed up for many years so that their pattern of disease had become established.

Computer-Assisted Pattern Recognition of Autoantibody Results

ABSTRACT Immunoassay-based anti-nuclear antibody (ANA) screens are increasingly used in the initial evaluation of autoimmune disorders, but these tests offer no “pattern information” comparable to the information from indirect fluorescence assay-based screens. Thus, there is no indication of “next steps” when a positive result is obtained. To improve the utility of immunoassay-based ANA screening, we evaluated a new method that combines a multiplex immunoassay with a k nearest neighbor (kNN) algorithm for computer-assisted pattern recognition. We assembled a training set, consisting of 1,152 sera from patients with various rheumatic diseases and nondiseased patients. The clinical sensitivity and specificity of the multiplex method and algorithm were evaluated with a test set that consisted of 173 sera collected at a rheumatology clinic from patients diagnosed by using standard criteria, as well as 152 age- and sex-matched sera from presumably healthy individuals (sera collected at a blood bank). The test set was also evaluated with a HEp-2 cell-based enzyme-linked immunosorbent assay (ELISA). Both the ELISA and multiplex immunoassay results were positive for 94% of the systemic lupus erythematosus (SLE) patients. The kNN algorithm correctly proposed an SLE pattern for 84% of the antibody-positive SLE patients. For patients with no connective tissue disease, the multiplex method found fewer positive results than the ELISA screen, and no disease was proposed by the kNN algorithm for most of these patients. In conclusion, the automated algorithm could identify SLE patterns and may be useful in the identification of patients who would benefit from early referral to a specialist, as well as patients who do not require further evaluation.

Proceedings: HL-A antigen W27 in juvenile chronic polyarthritis.

DR. M. I. V. JAYSON (Bristol) With respect to the particular experiments in which you studied the effects of histamine after metiamide, in several of them the half-life of the xenon within the joint was considerably lower than normal before injection of the histamine. In these particular cases, may it not be a bit much to expect a further shortening of the half-life and increased clearance by the histamine so that the lack of histamine response at these concentration ratios of 500: 1 and 1,000: 1 may not indicate a specific blocking effect?