Anti-IgE autoantibodies in systemic sclerosis (scleroderma).

An enzyme immunoassay was used to determine the prevalence of anti-IgE auto-antibodies in 66 patients with systemic sclerosis (scleroderma) stratified according to extent and duration of disease. Serum IgG anti-IgE antibodies were detected in 14 (21%) patients and IgM anti-IgE antibodies in nine (14%) patients. The overall prevalence of IgG or IgM isotypes was 21/66, (32%). Anti-IgE autoantibodies were not found in six patients with undifferentiated connective tissue disease or two patients with eosinophilic fasciitis. Attempts to demonstrate histamine release from basophils in vitro by using serum samples containing high titre anti-IgE antibody were unsuccessful. By multivariate analysis the presence of anti-IgE antibody was not associated with duration of systemic sclerosis; extent of scleroderma; specific visceral features, including heart, lung, renal, and gastrointestinal involvement; or mortality.     

Pericardial tamponade in systemic sclerosis (scleroderma).

The frequency of pericardial disease in scleroderma found at necropsy in high. The clinical recognition of pericarditis with or without effusion is rare and tamponade with haemodynamic impairment is exceptional. Three patients with scleroderma presented with an acute syndrome of dyspnoea, chest pain, and cardiomegaly requiring pericardiocentesis for relief of pericardial tamponade. One patient died. The mechanism of the pericardial effusion remains unknown. The haemodynamic data recorded from one patient suggested that pericardial fibrosis in scleroderma may predispose to pericardial tamponade.     

Telangiectasias in progressive systemic sclerosis (generalized scleroderma). Observation on 120 cases

120 patients with progressive systemic sclerosis (PSS) were studied and subdivided into five groups according to the PSS classification of Giordano et al. ("acute diffuse scleroderma", "intermediate syndrome", "acrosclerosis sensu stricto", "sclerodactylia" and "sclerosis sine scleroderma"). In all five subgroups telangiectasias incidence was high (from 75% to 100%). The "ramosus" and "telangiectatic mats" types occur more frequently than other forms of telangiectasias. The former particularly involves the face, neck and chest; whereas the latter more usually involves the upper extremities and is the only type which appears at the lips. Cuticular telangiectasia is a third type, as important as the others but less frequent. The incidence of telangiectasias is related to disease duration. Similar telangiectasias have been observed in rarer patients with other connective tissue diseases (SLE, RA, dermatomyositis and undifferentiated connective tissue diseases).     

The articular manifestations of progressive systemic sclerosis (scleroderma).

The articular manifestations of progressive systemic sclerosis (PSS) were studied in 38 patients. Of these, 66% experienced joint pain and 61% had signs of joint inflammation. Limitation of joint movement was seen in 45%. Radiological abnormalities included periarticular osteoporosis (42%), joint space narrowing (34%), and erosions (40%). Erosive disease did not correlate with disease duration, presence of rheumatoid factor, antinuclear antibodies, distal tuft resorption, or the extent of the scleroderma skin changes. Calcinosis was seen more frequently in those patients with articular erosions (67%). Erosive osteoarthritis of the distal interphalangeal joints (7 patients) was associated with impaired finger flexion. Joint involvement in PSS occurs frequently and may resemble rheumatoid arthritis in the early stages but is less destructive. The occurrence of unrelated arthropathy, such as primary osteoarthritis, is not uncommon, and its differentiation from true PSS joint disease can be difficult.     

Polyneuropathy as initial manifestation of systemic sclerosis (scleroderma).

We report the first case of a young female patient who developed a sensory-motor polyneuropathy, without any skin or internal involvement characteristic of SSc, but with a serological positivity of antitopoisomerase I antibodies. After 4 years she developed a rapid skin tightening with lung involvement, in a full blown picture of the diffuse subset of SSc. The case suggests that the peripheral nervous system deserves more attention, in particular in the earliest phase of SSc.     

A controlled trial of antihypertensive therapy in systemic sclerosis (scleroderma).

Antihypertensive treatment may be life saving in scleroderma renal crisis. Patients surviving such crises frequently have had dramatic improvement in the dermal manifestations of their scleroderma. To investigate the potential role of antihypertensive treatment in nonhypertensive patients we randomly assigned 28 patients with systemic sclerosis into drug (14) and placebo (14) groups, using blocked randomisation , and followed them up in a prospective, double-blind clinical trial for 24 months. Overall, both groups improved slightly, with both subjective and objective markers. There were no statistically significant differences and no clinically meaningful trends between the 2 groups, except that the blood pressure was reduced in the group on the active drug.     

Serum amyloid A protein concentration in progressive systemic sclerosis (scleroderma).

Serum amyloid A protein (SAA) concentrations were determined in 62 patients with progressive systemic sclerosis (PSS). Forty-seven patients had normal or slightly elevated SAA levels (less than 1000 ng/ml = micrograms/l), while 15 patients had moderately to markedly elevated SAA levels, similar to those observed in active rheumatoid arthritis (RA) (greater than or equal to 1000 ng/ml = micrograms/l). Five patients with PSS had SAA levels corresponding to those observed in amyloidosis secondary to RA. High SAA was associated with more severe skin thickening and diminished cumulative survival at five years. The rarity of amyloidosis secondary to PSS is unlikely to be related to an intrinsic defect in SAA production.     

The cardiovascular manifestations of systemic sclerosis (scleroderma)

In conclusion, systemic sclerosis is both a fascinating and frustrating affliction. It is a systemic disease of multiple stages. Prognosis is dependent on the site and extent of visceral involvement. There is evidence to implicate the vascular system as the primary target organ of the disease. The cardiovascular manifestations include myocardial fibrosis, pericarditis, and a variety of arrhythmias and conduction abnormalities. Intractable heart failure or sudden cardiac death can ensue. Cardiac involvement in systemic sclerosis portends an ominous prognosis, and is probably most directly related to the extent of myocardial fibrosis which is present. The pathogenesis of myocardial fibrosis has not been determined, but it appears to be a result of an impairment of myocardial perfusion at both the small artery and microvasculature level. Obstructive, vasospastic, and devascularization factors all may be playing a role.     

The 'CREST' syndrome. Comparison with systemic sclerosis (scleroderma)

The CREST syndrome refers to a disorder comprising the manifestations of calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia. Thirteen CREST patients (two with CRST) were compared with 26 patients with systemic sclerosis but without the full manifestations of the CRST syndrome. No significant difference was found between the groups in the age of onset of Raynaud's phenomenon, degree of multiphasic digital color changes, ulcerations of fingers, sclerodactyly, or in the frequency of abnormal esophageal peristalsis or dysphagia. Laboratory results were similar, including the frequency of an elevated ESR. However, the CREST patients had a significantly lower frequency of arthralgia (54%) and arthritis (15%) than did those with scleroderma (88% and 65%, respectively). All but one of the CREST patients were women, which was a greater proportion than found among scleroderma cases (69%), and all were white (P less than .05). Most patients with the CREST syndrome had rather severe acrosclerosis. At last evaluation, four patients were chronically ill and three had died. The CREST and CRST syndromes are closely related disorders that seem to be part of the spectrum of systemic sclerosis.     

HLA class II genes associated with anticentromere antibody in Japanese patients with systemic sclerosis (scleroderma).

OBJECTIVE--To define further HLA class II gene associations with anticentromere antibody (ACA), a major serum antinuclear antibody in patients with systemic sclerosis (SSc). METHODS--HLA class II genes were determined using polymerase chain reaction/restriction fragment length polymorphisms in 94 Japanese patients with SSc (22 ACA positive and 72 ACA negative) and 50 race matched normal control subjects. RESULTS--Frequency of DQB1*0501 was increased in ACA positive SSc patients compared with ACA negative SSc patients (36% versus 13%; p = 0.02, odds ratio = 4.0, 95% confidence interval 1.1 to 13.9), but the association of ACA with a polar amino acid at position 26 in the DQB1 beta 1 domain, which was demonstrated in white North Americans, was not observed in Japanese. The DRB1*0101, *0405, and *1302 alleles were associated with high ACA titres, whereas DRB1*1502 was associated with low ACA titres and a low frequency of centromere protein C (CENP-C) reactivity. CONCLUSIONS--These results suggest that the ACA response is associated with multiple HLA class II genes and that ACA positive SSc patients are heterogeneous in terms of immunogenetic background.     

Adhesion of peripheral blood mononuclear cells to vascular endothelium in patients with systemic sclerosis (scleroderma).

OBJECTIVE. Perivascular infiltrates in skin, subcutaneous tissue, and internal organs are a characteristic feature of early systemic sclerosis (SSc). We studied the first step of migration of peripheral blood mononuclear cells (PBMC) through the vessel wall to the extravascular space, i.e., adhesion of PBMC to endothelial cells (EC), in patients with various forms of SSc (limited scleroderma, diffuse scleroderma, and the transitional form). METHODS. Radioisotope-labeled patient PBMC were coincubated with umbilical cord EC in vitro, and the percentage adhesion was measured. RESULTS. Adhesion of PBMC to EC was markedly decreased, while adhesion of isolated active rosette-forming cells (ARFC) was significantly increased, in SSc patients compared with healthy controls. Decreased adhesion of PBMC to EC was found to correlate with a diminished percentage of ARFC in the peripheral blood. Preincubation of PBMC from healthy donors with interleukin-2 (IL-2) enhanced their adhesion to EC, while preincubation of PBMC from SSc patients with this cytokine resulted in a decrease in adhesion in 10 of 14 individuals. IL-1, interferon-gamma, and transforming growth factor beta had no significant effect on adhesion of SSc patient PBMC to EC. Differences in adhesion of PBMC to EC among the SSc subgroups were not significant. CONCLUSION. Our findings suggest that in SSc, activation of subpopulations of PBMC leads to their enhanced adhesion to vascular endothelium in vivo and to migration of these cells to the extravascular space, resulting in the elimination from the peripheral blood of those PBMC with high ability to adhere to EC.