Lack of clinical benefit after treatment of systemic sclerosis with total lymphoid irradiation.

Six patients with systemic sclerosis and internal organ involvement were randomized to receive total lymphoid irradiation (TLI) or to serve as untreated controls. Despite evidence of profound immunosuppression, we were unable to detect any longlasting clinical benefit in the treated patients, with follow-ups ranging from 1-4 years after TLI. Moreover, the results suggest that this therapy may accelerate pulmonary and gastrointestinal deterioration in scleroderma.

Immunologic dysfunction in scleroderma: evidence for increased mast cell releasability and HLA-DR positivity in the dermis.

To investigate the role of mast cells and cell-mediated immunity in the pathogenesis of scleroderma, we studied wheal size after skin testing with compound 48/80, a liberator of mast cell histamine, and demonstrated increased mast cell releasability in skin that appeared normal, adjacent to involved skin. Immunofluorescent staining for HLA-DR showed dermal positivity in 12 of 13 involved- and 9 of 13 uninvolved-skin biopsy specimens from scleroderma patients, compared with only 1 of 10 controls. By immunoperoxidase staining, most of the DR positivity was found in fibroblast-like cells. These findings further support the notion of immunologic dysfunction in scleroderma.

Rheumatoid nodules of the spine: case report and review of the literature.

We present the case of a patient who had rheumatoid nodules of the vertebrae, which had resulted in bony destruction of the spine at 3 levels. Although there have been only 3 previous reports of such findings with confirmation by histologic analysis, we believe the condition is more common than has been thought. From a review of the literature, we found that similar clinical and radiographic features, as well as descriptions of rheumatoid granulation tissue invading the disc spaces, have been described in several subjects.

Tubulointerstitial renal disease in systemic lupus erythematosus.

Tubulointerstitial renal disease is found frequently in patients with systemic lupus erythematosus. Despite the frequency of this entity, little is known about the prognostic significance of this biopsy finding. We reviewed 46 consecutive renal biopsy specimens from patients with systemic lupus erythematosus who were followed up for a mean of 5.4 years. Tubulointerstitial abnormalities were present in 39% of the entire group of patients and in 51% of the patients who had clinical evidence of renal abnormalities. Tubulointerstitial inflammation was closely associated with diffuse proliferative glomerulonephritis, with elevation of serum creatinine (SCr) concentration at biopsy, and with increased frequency of proteinuria both at biopsy and at follow-up. Additionally, active interstitial inflammation was associated with an increased risk of doubling the entry SCr concentration. The presence or absence of tubulointerstitial disease, however, did not add additional prognostic information to the predictive power of the entry SCr concentration or the glomerular histologic features.

Systemic lupus erythematosus without clinical renal abnormalities: renal biopsy findings and clinical course.

The extent and significance of renal biopsy abnormalities in patients with systemic lupus erythematosus (SLE) without clinical renal abnormalities is controversial. We report 11 consecutive SLE patients who were biopsied without clinical renal abnormalities. All 11 patients had mesangial changes either by light microscopy or by immunofluorescent staining, and none had changes of focal or diffuse proliferative glomerulonephritis. Additionally none had deterioration of renal function during the mean follow-up period of 6.3 years.

Relationship between nailfold capillary abnormalities and organ involvement in systemic sclerosis.

Nailfold capillary abnormalities in 42 consecutive patients with systemic sclerosis were studied by wide field capillary microscopy, and capillary abnormalities were correlated with organ involvement. Twenty-eight patients hd diffuse skin disease, and 14 had the CREST variant of systemic sclerosis (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasis) with anticentromere antibodies. Nailfold capillary enlargement and loss were graded from photographs. There was no correlation between the severity of either nailfold capillary loss or enlargement and duration of disease, number of organ systems involved, or acroosteolysis. The presence of telangiectasis correlated with extreme capillary enlargement (P less than 0.025). Based on these findings it can be concluded that nailfold capillary changes in individual patients with systemic sclerosis are not useful in predicting organ involvement.

Increased dermal mast cell populations in progressive systemic sclerosis: a link in chronic fibrosis?

Dermal collagen deposition is the hallmark of the early indurative phase of progressive systemic sclerosis (scleroderma). This process, however, tends to remit in late stages of the disease. Because mast cells are believed to participate in the development of fibrotic processes, we measured the density of the cutaneous mast cell population in clinically involved and uninvolved skin of a group of patients with scleroderma. Mast cell counts in clinically involved skin of patients with early stages of scleroderma (111 +/- 28 [SD] cells/mm2) were significantly greater than those in clinically uninvolved skin of the same patients (58 +/- 26 cells/mm2) and also greater than those of normal controls (50 +/- 14 cells/mm2). Mast cell counts in clinically involved and uninvolved skin of patients with late scleroderma were normal. When mast cell density was analyzed by depth of dermis, an 85% increase was noted in involved papillary dermis and a 152% increase in involved reticular dermis in patients with early scleroderma when compared with densities in controls. These results suggest that mast cells may be important in the pathogenesis of the early cutaneous lesions of progressive systemic sclerosis, perhaps by promoting fibrosis.

Precipitating autoantibodies to mitochondrial proteins in progressive systemic sclerosis.

Sera from 88 patients with progressive systemic sclerosis were examined for precipitating mitochondrial antibodies using sonicated rat liver mitochondrial fraction as an antigen source in immunodiffusion. Precipitin lines indicating the presence of anti-mitochondrial antibodies (AMA) in 22 patients were detected. Only six of 22 sera had, additionally, precipitating antibodies to nuclear antigens. Standardized reference sera containing antibodies to mitochondrial antigens (M-A, M-B and M-C systems) were used to further characterize the type of mitochondrial antibodies. M-B antibody was most commonly detected (72.7%) either alone (eight patients) or in combination (eight patients) with M-A and M-C antibodies. M-A antibody was found in 12 patients (54.5%) and M-C antibody was present in three. The antigen related to M-B is DNAase and trypsin sensitive, in contrast to the resistant M-A antigen. AMA were detected in 21 of 22 patients by indirect immunofluorescence. When solid phase ELISA was used to detect AMA using mitochondrial fraction as antigen, a significant difference (P less than 0.005) was noted between sera with and without precipitating mitochondrial antibody. The antibody was frequently present in patients with progressive systemic sclerosis detected 2 or more years earlier (P less than 0.01). Three patients were found to have primary biliary cirrhosis and others had pruritus, hepatomegaly or abnormal liver function tests. The implication of the findings is discussed.

Identification of the SS-A/Ro intracellular antigen with autoimmune sera.

Autoantibodies to SS-A/Ro antigen have been described in the sera of certain patients with Sjögren's syndrome, systemic lupus erythematosus and in neonates with lupus and/or congenital heart block. SS-A/Ro is a trypsin-sensitive intracellular antigen which appears to be associated with another intracellular antigen SS-B/La in tissue extracts. This study describes a simple method of separation of SS-A/Ro and SS-B/La antigenic activity by differential salt elution in polybuffer ion exchange chromatography. The partially purified SS-A/Ro antigen was separated by polyacrylamide gel electrophoresis under non-denaturing conditions and identified by Western blot analysis as a single polypeptide of 61,000 Da. The pI of SS-A/Ro antigen was 4.67. The partially purified SS-A/Ro antigen derived from gel electrophoresis could be adapted to an enzyme linked immunosorbent assay (ELISA) for the detection of antibody.

Lower esophageal rings as a cause of dysphagia in progressive systemic sclerosis--coincidence or consequence?

Lower esophageal rings were found in five of 40 consecutive patients seen with progressive systemic sclerosis. Three of these five patients had diffuse skin involvement and two had the CREST variant of progressive systemic sclerosis. All of the patients with lower esophageal rings had intermittent esophageal obstruction (initially attributed to esophageal dysmotility), but so did five of seven patients with esophageal strictures without lower esophageal rings. Esophageal bougienage relieved this symptom in four of the five patients with rings in which it was performed. Persistent relief of these obstructive symptoms (6-36 months) in the patients with rings was in contrast to the recurrent dilatations that have been needed in the group of patients with peptic strictures. In contrast to esophageal aperistalsis and/or stricture formation, the lower esophageal ring, perhaps as a consequence of chronic gastroesophageal reflux, may be a more treatable cause of dysphagia in patients with progressive systemic sclerosis.

Association of antinuclear and antinucleolar antibodies in progressive systemic sclerosis.

Antinuclear and/or antinucleolar antibodies were demonstrated in the sera of 74 of 76 patients (97%) with progressive systemic sclerosis, using tissue culture cells (HEp-2) as substrate in the indirect immunofluorescent method. Six patterns of nuclear staining and three nucleolar patterns were recognized. The nuclear patterns were centromere, fine speckles, coarse speckles, diffusely grainy, homogeneous and nuclear dots. The nucleolar patterns were speckled, homogeneous and clumpy. The results of digestion studies with ribonuclease, deoxyribonuclease and trypsin suggested that the nuclear antigens are proteins, some of which may be associated with chromatin. The nucleolar antigens appeared to be nucleic acid in nature. Certain characteristic serologic and clinical features associated with staining patterns were observed. The diffusely grainy pattern was seen only in sera containing antibody to Scl-70 antigen. Centromere staining was confirmed to be highly selective for the CREST (Calcinosis, Raynaud's phenomenon, esophageal involvement, sclerodactyly and telangiectasis) variant of progressive systemic sclerosis with rheumatoid factor titres higher in these patients with anti-centromere antibodies.

The kidney in progressive systemic sclerosis: a prospective study.

Nine normotensive progressive systemic sclerosis patients with normal renal function underwent renal biopsy. Four specimens had prominent vascular abnormalities, two mild vascular abnormalities, and three were normal. Vascular deposits of C3 were present in all specimens. Plasma renin activity was elevated in three of four patients with prominent vascular abnormalities, one of two patients with mild vascular lesions, and none of two patients with normal biopsies. Plasma renin activity elevation in response to cold pressor testing in the four patients with prominent vascular lesions was 5.6 ng/ml.h compared to 0.55 ng/ml.h in those with mild or no lesions and 0.26 ng/ml.h in six control subjects. These data indicate that renal vascular lesions may be present in normotensive patients. Elevation or a substantial rise in plasma renin activity (1.8 ng/ml.h or greater) in response to cold pressor testing suggests preclinical renal involvement.

Acute pseudogout in the absence of synovial fluid Leukocytes.

A case of acute pseudogout that occurred in the absence of synovial fluid leukocytes is described. This finding implies that there may be an alternative inflammatory mechanism for acute pseudogout that does not depend on polymorphonuclear leukocytes.

Carpal tunnel syndrome as the initial manifestation of tuberculosis.

Two patients presenting with carpal tunnel syndrome as the initial manifestations of tuberculosis were seen during a recent four month period at a larg city-county hospital. Although the clinical picture of the carpal tunnel syndrome was typical, a definite diagnosis could not be made until the time of surgery because of the many other causes of the carpal tunnel syndrome. A review of the experience with musculoskeletal tuberculosis and carpal tunnel syndrome at our hospital indicates that although this combination is not common, it is one of the treatable causes of the carpal tunnel syndrome. A review of the literature substantiates this impression.

Esophageal varices in Felty's syndrome: A case report and review of the literature.

A case of upper gastrointestinal tract hemorrhage secondary to esophageal varices in a patient with Felty's syndrome prompted a review of the pathogenesis and treatment of this condition. Six previously reported cases of this association were found. The clinical picture is that of long-standing rheumatoid arthritis with severe articular and extraarticular manifestations including splenomegaly, depression of the blood elements, mild liver function abnormalities, portal hypertension without cirrhosis or portal vein obstruction, an elevated splenic blood flow, and a reduction in portal hypertension by simple splenectomy. The presence of portal hypertension with varices may be another indication of splenectomy in patients with Felty's syndrome.

Pulmonary manifestations of systemic lupus erythematosus: review of twelve cases of acute lupus pneumonitis.

Acute lupus pneumonitis was the presenting manifestation of systemic lupus erythematosus in six of 12 cases in this series. The clinical picture was characterized by severe dyspnea, tachypnea, fever and arterial hypoxemia. Radiographic findings included an acinar filling pattern which was invariably found in the lower lobes and was bilateral in 10 of the cases. Studies failed to reveal evidence of infection as a cause of the acute pulmonary infiltrates. All patients were treated with oxygen and corticosteroids; seven received azathioprine. Six patients survived and are clinically well 14 months to four years following their acute illness. Three of these patients have residual interstitial infiltrates with persistent pulmonary function test abnormalities indicating progression to chronic interstitial pneumonitis. Histologic sections of the lungs available from four patients revealed hyaline membranes and interstitial edema (four cases), acute alveolitis (two cases), arteriolar thrombosis (one case) and a prominent lymphocytic interstitial pneumonitis with organizing bronchiolitis (one case).

Bone resorption of the mandible in progressive systemic sclerosis.

Five of 16 patients with progressive systemic sclerosis were found to have bone resorption at the angle of the mandible. This finding appears to be closely related to the tightness of the skin of the face, atrophy of the masseter and pterygoid muscles, small size of the oral orifice, and a significantly high frequency in blacks. The mandible must therefore be added to the list of those bones that can be resorbed in progressive systemic sclerosis.

Sialic acids. Enzymatic synthesis of Tay-Sachs ganglioside.

A particulate preparation from embryonic chicken brain catalyzed the transfer of N-acetylgalactosamine from uridine diphospho-N-acetylgalactosamine to the ganglioside GM3 (hematoside, sialyllactosylceramide). The kinetic properties of the transferase were determined. The product was isolated and on the basis of chemical analysis and chromatographic behavior was shown to be Tay-Sachs ganglioside (GM2). The particulate preparation also utilized N-acetyl-D-glucosamine and some of its derivatives as acceptors, but partial heat inactivation and substrate competition experiments indicated that the two classes of acceptors, hematoside and N-acetylglucosamine, were substrates for different N-acetylgalactosaminyltransferases. The enzyme that utilized hematoside showed low but detectable activity with analogues such as lactosylceramide and sialyllactose, but no activity with a wide range of other beta-galactosides and glycosphingolipids. These results are in accord with a proposed pathway for the biosynthesis of the gangliosides and for the patterns of these substances in different cell types and tissues.