Connective Tissue Disease Syndrome Research Articles

Mixed connective tissue disease and overlap syndromes

Mixed connective tissue disease and overlap syndromes

Echocardiographic evaluation of pulmonary arterial hypertension in patients with progressive systemic sclerosis and related syndromes.

In order to evaluate the usefulness of echocardiography in detection and characterization of pulmonary arterial hypertension (PAH) in scleroderma patients, we performed M-mode, two-dimensional, and Doppler echocardiography in 71 patients with progressive systemic sclerosis (PSS) and related syndromes: mixed connective tissue disease (MCTD) and overlap syndromes. We estimated systolic pressure gradients across the tricuspid valve from the peak velocity of tricuspid regurgitation (TR) by color-flow guided continuous wave Doppler. TR velocities of analyzable quality for gradient estimation were obtained in 28 patients (39%), of whom 12 showed PAH (peak TR velocity > or = 2.5 m/sec). In comparison, analyzable TR was recorded in 19 (35%) of 55 patients with left-sided cardiac disease. None of the 12 with Doppler-estimated PAH showed left ventricular dilatation or decreased fractional shortening by M-mode and two-dimensional measurements. Nonsimultaneous cardiac catheterization confirmed PAH in 8 of 9 with Doppler-estimated PAH and in 3 of 12 without analyzable TR who had hemodynamic study. Doppler-estimated right ventricular systolic pressures (RVSP) correlated well with catheterization-measured pulmonary arterial systolic pressures (PASP) (< 0.01). Our results indicate that Doppler echocardiography is useful in detecting subclinical PAH and estimating PASP in patients with collagen vascular disease. The results of pulmonary function studies suggest that PAH in MCTD is mainly caused by pulmonary vasculopathy.

Evaluation and Differential Diagnosis of Fibromyalgia: Approach to Diagnosis and Management

SUMMARY The combination of widespread musculoskeletal pain, high tender point count, and nonrestorative sleep are sufficient criteria for the diagnosis of fibromyalgia. The condition is primary in the absence of underlying disease and is considered concomitant or secondary when closely associated with another organic disease. Despite more simplified diagnostic criteria, the work-up for fibromyalgia must always be directed toward excluding the underlying causes. In addition to general and rheumatic history and physical examination and selected laboratory studies, careful attention to defining any existing sleep and mood disturbances is important in designing a management program. Although 46 medical conditions have been associated with fibromyalgia, a practical differential diagnostic list includes polymyalgia rheumatica, myofascial pain, connective tissue disease, endocrine myopathies, psychoneuroses, and other chronic fatigue syndromes.

Connective tissue disease associated with sclerodermoid features, early abortion, and circulating anticoagulant

An 18-year-old white woman admitted for an incomplete septic abortion was found to have thrombocytopenia, anemia, and increased activated partial thromboplastin time (PTT). Additionally, results of nontreponemal serologic tests for syphilis were positive, and the fluorescent antinuclear antibody was weakly positive. A mixture of the patienťs plasma with normal control plasma showed that the elevation in activated PTT was the result of a circulating anticoagulant, not an inherent clotting defect. Sclerodermoid features were present and consisted of bound-down, hairless skin and scattered subcutaneous indurated plaques. A faint pattern consistent with livedo reticularis was recognized on all extremities. Biopsy specimens of sclerodermoid lesions showed increased and thickened dermal collagen consistent with morphea. We believe that this patienťs condition represents an unusual connective tissue disease syndrome consisting of abortion, livedo reticularis, thrombocytopenia, circulating “anticoagulant,” negative or slightly positive antinuclear antibodies, and false positive results on nontreponemal serologic tests for syphilis. Sclerodermoid lesions were also a unique feature in our patient.

Epidemiology of Systemic Lupus Erythematosus and Other Connective Tissue Diseases in Rochester, Minnesota, 1950 Through 1979

The incidence and prevalence rates of connective tissue disease syndromes in Rochester, Minnesota, from 1950 through 1979 are reported. The incidence of definite systemic lupus erythematosus (SLE) has not increased since 1960. The incidence of SLE in the elderly population was higher than that in previous reports. Rates of SLE and discoid lupus erythematosus were approximately equal. Other diagnoses (in decreasing order of frequency) were suspected lupus erythematosus, scleroderma, drug-induced lupus, and overlapping connective tissue disease syndromes. The 10-year survival of patients with definite SLE was decreased, and the survival of patients with suspected SLE was the same as that of the general population.

Serum collagenase-like peptidase activity in rheumatoid arthritis and systemic lupus erythematosus

Collagenase-like(CL) peptidase activity in serum, which was measured using a newly synthesized substrate, (succinyl-Gly-Pro-Leu-Gly-Pro)-4-methylcoumaryl-7-amide, was significantly lower in patients with advanced rheumatoid arthritis or with systemic lupus erythematosus than that in normal controls. Decrease of the serum enzyme activity was more pronounced in systemic lupus erythematosus. No significant change in serum CL-peptidase activity was found in other connective tissue diseases such as mixed connective tissue disease and Sjogren's syndrome.

Clinical and prognostic significance of vasculitis as an early manifestation of connective tissue disease syndromes.

The courses of 18 patients with arthritis and vasculitis in the first 2 years after onset of disease (mean follow-up, 54 months) were studied. The patients were categorized as having rheumatoid vasculitis, systemic vasculitis, and undifferentiated connective tissue syndrome. These patients cannot be distinguished on basis of organ involvement by vasculitis or histopathologic findings on biopsy, but can be separated clinically by the extent of joint involvement and the presence or absence of rheumatoid factor and antinuclear antibody. Early onset of vasculitis is associated with a poor outcome, especially in patients with rheumatoid arthritis, with rapid progression to vasculitic involvement of the viscera, resulting in death. On the basis of the 54-month follow-up period involving this selected series, the prognosis of patients with systemic vasculitis and undifferentiated connective tissue syndrome appears more favorable than that of patients with rheumatoid vasculitis.

Antibodies to Sm and RNP. Prognosticators of disease involvement.

The charts of 150 consecutive patients found to have antibodies to Sm, ribonucleoprotein (RNP), or both were examined to determine these antibodies' possible associations with certain clinical conditions as well as their diagnostic specificities. Patients with anti-Sm were more likely to have renal disease and antibodies to double-stranded DNA, single-stranded DNA, and nuclear protein than were patients with anti-RNP. No clinical associations were found for anti-RNP. Although most of the patients with antibodies to Sm, RNP, or both had systemic lupus erythematosus, some had other diagnoses, including cutaneous lupus, drug-induced lupus, rheumatoid arthritis, juvenile arthritis, mixed connective tissue disease, Raynaud's disease, progressive systemic sclerosis, miscellaneous rheumatic and nonrheumatic diseases, and undifferentiated connective tissue disease syndromes. These findings suggest that these antibodies may be associated with some diseases, but are not disease-specific.

Renal Failure and Tubular Dysfunction due to Zomepirac Therapy

RENAL failure has been described due to the use of several nonsteroidal anti-inflammatory drugs that are also inhibitors of prostaglandin synthesis—phenylbutazone, 1 indomethacin, 2 aspirin, 3 fenoprofen, 4 tolmetin, 5 naproxen, 6 and ibuprofen. 6 This report describes acute reversible decline in glomerular filtration rate (GFR) associated with use of zomepirac sodium (Zomax), a new nonnarcotic analgesic that is also an in vitro inhibitor of prostaglandin synthesis. Report of Cases Case 1.— A 65-year-old woman was undergoing treatment for multiple medical problems, including late-onset multiple sclerosis, hypertension, hypothyroidism, and a mixed connective-tissue disease syndrome of nondeforming arthritis, esophageal dysfunction, intermittently present speckled antinuclear antibodies, and increased ESR. She had, in addition, undergone mastectomies in 1949 and 1962 for breast carcinoma, without subsequent recurrence. She came to the nephrology service in 1979 with subnephrotic-range proteinuria and a creatinine clearance of 65 mL/min. Renal biopsy was deferred because of her fragile medical

Trigeminal neuropathy in progressive systemic sclerosis

Trigeminal neuropathy was identified in 16 (4 percent) of 442 consecutive patients with progressive systemic sclerosis (PSS) who were first evaluated during the period between 1972 and 1980. These cases, together with 25 others that are adequately documented in the literature, were reviewed and compared with the 426 cases of PSS (96 percent) without trigeminal neuropathy, Trigeminal neuropathy occurred most frequently in young women with PSS in overlap with other disorders, particularly the mixed connective tissue disease syndrome with clinical evidence of myositis. Serum antibodies to ribonucleoprotein were identified in nine (45 percent) of 20 PSS patients with trigeminal neuropathy as compared to 25 (8 percent) of 329 PSS patients without trigeminal neuropathy. Leukopenia, hypothyroidism, and Sjogren's syndrome were also found to be associated with trigeminal neuropathy.

Circulating autoantibodies to IgD in rheumatic diseases.

Most mature B lymphocytes possess IgD on their cell surface. Antibodies to IgD produce an adjuvant-like effect in many experimental systems. Employing sensitive class-specific radioimmunoassays, elevated concentrations of autoantibodies to IgD of the IgA, IgM, and IgG classes were detected in the sera of 55% of patients with adult onset rheumatoid arthritis (RA), of 45% with systemic lupus erythematosus (SLE), of 67% with mixed connective tissue disease syndrome (MCTD), and of only 8% of juvenile RA. Marked differences in the class of anti-IgD were noted. An elevated IgA anti-IgD was detected in 45% (p less than 0.01) of RA sera, 27% of SLE sera, and 58% (p less than 0.01) of MCTD sera. IgG anti-IgD was increased in only 26% of RA, 32% of SLE, and 8% of MCTD sera. IgM anti-IgD was elevated in only one patient. IgA anti-IgD was inhibited greater than 90% by IgD but not at all by IgG. Correlations between the concentration of immunoglobulin G and IgA anti-IgD were noted in RA (rs = 0.37, p = 0.02), SLE (rs = 0.46, p = 0.015), and MCTD (rs = 0.4). These data suggest a potential role for autoantibodies to cell surface IgD as modulators of the immune system in some patients with autoimmune disorders.

Laboratory diagnosis of rheumatoid diseases.

The diagnosis of most collagen diseases requires particular clinical findings. Rheumatoid factor assays are tests commonly used to detect seropositive rheumatoid arthritis. Latex tests are highly sensitive for rheumatoid factors but relatively nonspecific for rheumatoid arthritis, while sheep cell agglutination tests are moderately insensitive for rheumatoid factors but highly specific for rheumatoid arthritis. These tests are not helpful in following the course of the disease, however, since titers remain stable. Serial observations of elevated C-reactive protein levels or ESR may be more helpful in this regard. Specific antibodies have been identified for some collagen diseases, notably the mixed connective tissue disease syndrome, aiding in differential diagnosis.

Rheumatology: An Annotated Bibliography of Recent Literature

Rheumatology: An Annotated Bibliography of Recent Literature

The hand in mixed connective tissue disease

The mixed connective tissue disease syndrome has been described in the medical literature. The clinical and serological characteristics of the syndrome are defined in this paper. The hands of these patients differ from the hands of patients with systemic lupus, rheumatoid arthritis, or systemic sclerosis. In 10 patients there were no erosive changes on radiological examination and all 10 patients had Raynaud's phenomenon. The most striking finding was tightness in the flexors. Mild cases of flexor tightness improved with systemic steroids. One patient with severe flexor tightness required surgical release of adhesions from a chronic inflammatory process of fascia, muscle, and tenosynovium. Biochemical studies showed an abnormal collagen pattern that may be distinct for mixed connective tissue disease.

Sjögren's syndrome in progressive systemic sclerosis.

Thirty-five consecutive patients with progressive systemic sclerosis were prospectively evaluated for evidence of Sjögren's syndrome. Six of the 35 (17%) were judged to have the disorder. This is a higher prevalence than in most reports, but much lower than that recently reportedly by Alarcón-Segovia and associates (7). An additional 17 of the 35 patients (48%) had significant fibrosis in the absence of sufficient mononuclear cell infiltrates to confirm the diagnosis of Sjögren's syndrome. This group had particularly aggressive scleroderma with serious visceral features, and five died after a short duration of illness. No significant abnormalities were found in biopsies from six patients with the mixed connective tissue disease syndrome, five with Raynaud's phenomenon alone, or in 29 autopsy control subjects who had no evidence of connective tissue disease. Fibrosis in the absence of mononuclear infiltration in minor salivary glands of patients with progressive systemic sclerosis indicates a poor prognosis.

POLYNEUROPATHY AND ANASARCA: A NEW CONNECTIVE TISSUE DISEASE SYNDROME WITH MICROVASCULAR ALTERATIONS

International Journal of DermatologyVolume 16, Issue 8 p. 670-674 POLYNEUROPATHY AND ANASARCA: A NEW CONNECTIVE TISSUE DISEASE SYNDROME WITH MICROVASCULAR ALTERATIONS A. T. MASI M.D., DR. P.H., Corresponding Author A. T. MASI M.D., DR. P.H. From the Section of Rheumatology, Division of Connective Tissue Diseases, Department of Medicine, University of Tennessee Center for the Health Sciences, Memphis, TennesseeAddress for reprints: A. T. Masi, M.D., Director, Division of Connective Tissue Diseases, University of Tennessee Center for the Health Sciences, 858 Madison Avenue, Memphis, TN 38163.Search for more papers by this author A. T. MASI M.D., DR. P.H., Corresponding Author A. T. MASI M.D., DR. P.H. From the Section of Rheumatology, Division of Connective Tissue Diseases, Department of Medicine, University of Tennessee Center for the Health Sciences, Memphis, TennesseeAddress for reprints: A. T. Masi, M.D., Director, Division of Connective Tissue Diseases, University of Tennessee Center for the Health Sciences, 858 Madison Avenue, Memphis, TN 38163.Search for more papers by this author First published: October 1977 https://doi.org/10.1111/j.1365-4362.1977.tb01879.x Supported in part by Grants AM-12049 and AM-05055 of the National Institute of Arthritis, Metabolism and Digestive Diseases, Bethesda, MD. The case referred here was studied in association with Drs. David E. Trentham and Howard W. Marker. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume16, Issue8October 1977Pages 670-674 RelatedInformation

Mixed connective tissue disease syndrome

Fifteen patients with epidermal nuclear staining on direct immunofluorescence of normal skin and high titer serum antibody to ribonuclease-sensitive extractable nuclear antigen (ENA) had diffuse nonscarring and focal alopecia, abnormal pigmentation, swollen hands with sclerodactyly, and chronic cutaneous lupus erythematosus (LE) as the most common dermatologic features. Direct immunofluorescence of normal, unexposed skin revealed a particulate ('speckled') epidermal nuclear staining pattern in all 15 patients and subepidermal immunoglobulin deposits in 5. Ribonucleoprotein antibodies in high titer are associated with this characteristic type of epidermal nuclear staining. These findings provide easily detectable markers for a less aggressive subset of LE characterized by distinctive clinical and laboratory features consistent with mixed connective tissue disease.

Mixed Connective Tissue Disease Syndrome

• Fifteen patients with epidermal nuclear staining on direct immunofluorescence of normal skin and high titer serum antibody to ribonuclease-sensitive extractable nuclear antigen (ENA) had diffuse nonscarring and focal alopecia, abnormal pigmentation, swollen hands with sclerodactyly, and chronic cutaneous lupus erythematosus (LE) as the most common dermatologie features. Direct immunofluorescence of normal, unexposed skin revealed a particulate ("speckled") epidermal nuclear staining pattern in all 15 patients and subepidermal immunoglobulin deposits in 5. Ribonucleoprotein antibodies in high titer are associated with this characteristic type of epidermal nuclear staining. These findings provide easily detectable markers for a less aggressive subset of LE characterized by distinctive clinical and laboratory features consistent with mixde connective tissue disease. (<i>Arch Dermatol</i>113:583-587, 1977)

Characteristics of patients with serum antibodies to extractable nuclear antigens.

A distinguishing feature of the mixed connective tissue disease (MCTD) syndrome is the presence in the serum of antibody in high titer to ribonucleoprotein (RNP). To determine whether this was an exclusive observation, a large rheumatic disease population was surveyed for the presence of antibody in high titer to extractable nuclear antigens (ENA) including RNP. Of 650 sera examined, 440 (from 240 patients) had antinuclear antibody. Only 39 patients had serum antibody to ENA in titers greater than or equal to 1:200 dilution. In 16 the anti-ENA was shown by RNAse digestion to be anti-RNP. Although many clinical and laboratory characteristics were similar in these two groups, the patients more closely resembled the previously described MCTD syndrome and, importantly, less often had severe renal and central nervous system disease manifestations. Thus the presence of serum antibodies to ENA that are predominantly RNAse-sensitive (anti-RNP) helps to identify a rheumatic disease syndrome and also appears to have prognostic value.

Profiles of antinuclear antibodies in systemic rheumatic diseases.

The prevalence of different antinuclear antibodies was examined in systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, progressive systemic sclerosis, dermatomyositis, discoid lupus erythematosus, and mixed connective tissue disease. Antibody to Sm antigen (a nuclear acidic protein) was found almost exclusively in serums of patients with systemic lupus erythematosus, suggesting that this antibody might be a "marker" antibody for this disease. However, antibodies to native DNA and to nuclear ribonucleoprotein were found in a variety of systemic rheumatic diseases. In systemic lupus erythematosus, antibody to native DNA was present in high titer but in other rheumatic diseases in low titer. Antibody to nuclear ribonucleoprotein occurred in certain other systemic rheumatic diseases besides the mixed connective tissue disease syndrome. These studies showed that there were distinct profiles of antinuclear antibodies in certain systemic rheumatic diseases, characterized by the presence or absence of certain antibodies and by differences in their mean titers.