Tapani Helve

Prevalence and Mortality Rates of Systemic Lupus Erythematosus and Causes of Death in SLE Patients in Finland

Nationwide prevalence and mortality rates in systemic lupus erythematosus (SLE) were estimated using a computer file of all hospital discharge records and cause of death statistics from 1972 to 1978. Age-specific and sex-specific prevalence rates obtained from 1976 to 1978 and mortality rates from 1972 to 1978. In December 1978 the prevalence of SLE was 28:100 000. The overall mortality rate was 4.7 per million person-years in 1972-78. Active lupus nephritis, vascular events and infections were the most frequent causes of death in SLE patients.

Increased level of YKL-40 in sera from patients with early rheumatoid arthritis: a new marker for disease activity

Abstract. YKL-40 is a newly discovered major secretory protein of human chondrocytes and synoviocytes. We measured serum levels of YKL-40 in 52 patients with early onset rheumatoid arthritis (RA) by enzyme-linked immunosorbent assay (ELISA) during a 2-year prospective follow-up, correlating values with laboratory and clinical variables and radiographic progression. Levels at baseline before antirheumatic therapy were significantly higher in patients than in healthy controls. The levels of YKL-40 correlated with laboratory and clinical markers of disease activity both at baseline and during follow-up. Baseline YKL-40 values correlated with baseline Larsen scores but did not predict radiographic progression. Baseline and mean YKL-40 values did not differ between fast and slow radiological progressions. Mean YKL-40 levels correlated with the number of swollen joints but were not predictors of radiographic progression. These results suggest that in early RA, serum YKL-40 is an inflammatory marker correlating with disease activity. However, its levels do not predict clinical course or radiographic progression.

Transformation of Membranous Glomerulonephritis into Crescentic Glomerulonephritis with Glomerular Basement Membrane Antibodies

This case report describes a patient who initially had a pleuritis and arthalgias. During the follow-up he developed first a membranous glomerulonephritis with nephrotic syndrome and subsequently a crescentic, rapidly progressive glomerulonephritis with glomerular basement membrane antibodies (anti-GBM). An analysis of the serum samples obtained during the follow-up revealed no infections at the onset of renal failure. However, anti-GBM could be demonstrated in the serum samples obtained 2 months before the deterioration of the renal function. The anti-GBM did not react with alveolar BM and the patient had no signs of pulmonary hemorrhage. The etiology and the sequence of the pathological events of rapidly progressive glomerulonephritis is discussed in the light of these observations.

The prognostic value of HLA DR4 and B27 antigens in early rheumatoid arthritis.

The prognostic significance of HLA DR4 and B27 antigens was investigated in a 3-year follow-up of 87 patients with early rheumatoid arthritis (RA). The frequencies of DR1, DR4 and also of B27 were increased and the frequencies of DR2, DR3 and DR7 decreased compared with the normal Finnish population. During the follow-up with antirheumatic treatment, a similar improvement in clinical variables and laboratory measure assessing disease activity was found in both DR4-positive and DR4-negative RA patients. Despite clinical improvement a fast radiological progression in peripheral joints was observed but the presence of DR4 or B27 had no impact on the progression of joint damage. In some patients cervical changes developed early in the course of RA but were not related to DR4 or B27 positivity. The earlier observation of increased prevalence of HLA B27 in the Finnish RA patients was confirmed but the presence of B27 did not modify the clinical picture of RA.

Strawberry like gingivitis being the first sign of Wegener's granulomatosis.

Wegeners granulomatosis (WG) is a rare granulomatous necrotizing vasculitis of small vessels, affecting vascular structures having predilection for upper airways. If untreated WG can be lethal. WG is also known to cause oral mucosal lesions. We report a case of WG that was first diagnosed on oral gingival mucosa. A 51-year old woman was referred to a specialized dentist because of consistent irritative buccal gingival hyperplasia that did not react to conservative and microbial treatment. The lesion was biopsied and the diagnosis was suggestive for WG. Patient was further referred to the Department of Rheumatology and the diagnose of WG was confirmed and treated. The oral lesions cured totally. This case emphasizes the importance to recognize the oral manifestation of WG to get proper medication as soon as possible and avoid serious systemic tissue damage.

Arthritis and arthralgia three years after Sindbis virus infection: Clinical follow-up of a cohort of 49 patients

Sindbis virus (SINV) emerges as large human outbreaks in northern Europe every 7 years. Similar to many other alphaviruses, SINV is a mosquito-borne causative agent of a rash-arthritis. Previous reports suggest that in many alphavirus infections joint symptoms might persist for years. A prospective cohort of 49 patients was physically examined 3 y after verified acute SINV infection to reveal persistent joint symptoms. We carefully searched for a temporal association between the infection and current symptoms, and took into account other medical conditions. Sera were collected and analysed with enzyme immunoassays. Arthritis (swelling and tenderness on physical examination) was diagnosed in 4.1% (2/49) of the patients. Tenderness on palpation or in movement of a joint was found in 14.3% of the patients in the rheumatological examination, and an additional 10.2% complained of persisting arthralgia at the interview. Thus, 24.5% of the patients had joint manifestations attributable to the infection 3 y earlier. A positive IgM antibody response persisted in 3/49 of the patients; both patients with arthritis were in this group. As one-quarter of the patients were symptomatic 3 y after infection, it seems that persistent symptoms of SINV infection have considerable public health implications in areas with high seroprevalence.

Circulating DNA-antibodies in systemic lupus erythematosus

SummarySera from 57 patients with systemic lupus erythematosus (SLE) were tested for DNA-antibodies by three different methods: a radioimmunological test using the Farr technique, the Crithidia luciliae immunofluorescence assay for anti-double-stranded (native) DNA (anti-ds-DNA), and a solid-phase immunoenzymatic assay for anti-single-stranded (denatured) DNA (anti-ss-DNA) of IgG and IgM classes. There was a positive correlation between the activity of the disease and the levels of ds-DNA-antibodies and IgG anti-ss-DNA. Patients with active nephritis had a higher amount of anti-ds-DNA and anti-ss-DNA of IgG class than patients with inactive nephritis (P<0.05 and 0.01, respectively). Patients with SLE nephritis had lower levels of ss-DNA-antibodies of IgM class than patients without nephritis (P<0.02). There was a positive correlation between the IgG-anti-ss-DNA/IgM-anti-ss-DNA ratio and the activity score of the disease. These results suggest that the anti-ss-DNA assay may be useful in the follow-up of SLE. Complement fixing anti-ds-DNA and the highest levels of anti-ds-DNA by Farr assay were usually associated with an active disease, especially nephritis and joint involvement.

Prolonged Myalgia in Sindbis Virus Infection: Case Description and In Vitro Infection of Myotubes and Myoblasts

BACKGROUND Sindbis virus (SINV) is a mosquito-borne alphavirus found in Eurasia, Africa, and Oceania. Clinical SINV infection is characterized by febrile rash and arthritis and sometimes prolonged arthralgia and myalgia. The pathophysiological mechanisms of musculoskeletal and rheumatic disease caused by SINV are inadequately understood. METHODS We studied the muscle pathology of SINV infection ex vivo by examining a unique muscle biopsy obtained from a patient with chronic myalgia and arthralgia 6 months after acute SINV infection and assessed potential genetic predisposing factors by determining the human leukocyte antigen (HLA) and complement factor C4 genes and proteins. In addition, we performed in vitro SINV infections of primary human myoblasts and myotubes. RESULTS In the muscle biopsy we found evidence of muscle regeneration due to previous necrotic lesions likely caused by earlier SINV infection. We showed that human myoblasts and myotubes were susceptible in vitro for SINV infection as the cells became immunoreactive for viral antigens and cytopathic effect was observed. The patient was homozygous for HLA-B*35 alleles and heterozygous for HLA-DRB1*01 and HLA-DRB1*03 alleles and had total deficiency of C4B protein. CONCLUSIONS This study provides new insights concerning pathological processes leading to chronic symptoms in SINV infection and demonstrates for the first time the susceptibility of human myogenic cells to SINV infection.

Comparison of Intramuscular Gold and Sulphasalazine in the Treatment of Early Rheumatoid Arthritis: A one year prospective study

We compared the effects of intramuscular gold and sulphasalazine on early, active rheumatoid arthritis in 128 consecutive patients. Intramuscular gold was started in the first 70 consecutive patients and sulphasalazine in the subsequent 58 patients. The patient groups were comparable with regard to clinical characteristics. In both groups clinical and laboratory parameters improved, but there was no significant difference between the two groups. The clinical improvement was most pronounced during the first three months. However, despite the clinical improvement a clear progression in radiological changes was observed in both groups, 40% of the patients taking gold and 48% of patients taking sulphasalazine discontinued the treatment because of adverse drug reactions or inefficacy during the one year follow-up. Adverse drug reactions were the main reason in both groups. These findings suggest that intramuscular gold and sulphasalazine seem to have an equal, positive effect on symptoms and clinical variables, but that radiological progression does occur in most patients none the less.

Clinical Sindbis Alphavirus Infection Is Associated With HLA-DRB1*01 Allele and Production of Autoantibodies

BACKGROUND Sindbis virus (SINV) is a mosquito-borne alphavirus found in Eurasia, Africa, and Oceania. Clinical SINV infection, characterized by arthropathic disease that may persist for years, is primarily reported in Northern Europe where the disease has considerable public health importance in endemic areas. The aim of this study was to investigate the role of genetic factors in the susceptibility and outcome of SINV infection and to elucidate the association between SINV infection and autoimmunity. METHODS The study included 49 patients with serologically confirmed symptomatic SINV infection who were followed for 3 years after acute infection. Human leukocyte antigen (HLA) genes known to be associated with rheumatic and infectious diseases and complement C4 genes were determined in 35 patients. Furthermore, a set of autoantibodies was measured at the acute phase and 3 years after infection in 44 patients. RESULTS The frequency of DRB1*01 was significantly higher among patients with SINV infection than in the reference population (odds ratio, 3.3; 95% confidence interval, 1.7-6.5; P = .003). The DRB1*01 allele was particularly frequent in patients who at 3 years postinfection experienced joint manifestations. The frequency of rheumatoid factor at 3 years postinfection was 29.5% and had increased significantly (P = .02) during the 3-year period. In addition, antinuclear and antimitochondrial antibodies were present in serum 3 years postinfection with frequencies of 15.9% and 6.8%, respectively. CONCLUSIONS Our data show that symptomatic SINV infection is associated with the HLA system and that autoantibody titers are elevated in patients 3 years postinfection. These findings indicate that SINV-induced arthritis shares features with autoimmune diseases.