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Stiff skin syndrome is a rare disorder characterized by pronounced skin induration, mild hypertrichosis and limited joint mobility, predominantly on the buttocks and thighs. Many heterogeneous cases have been reported under the name of stiff skin syndrome. We present a case of stiff skin syndrome from China, the diagnosis based on the patient's typical clinical and histopathological features.
The presence of antinuclear antibodies (ANA) in the serum is a common finding in various connective tissue disorders, but usefulness of these antibodies in making diagnoses or prognoses is not known. We report the results of a panel of ANA determinations including ANA, anti-dsDNA, Sm, RNP, SSA, SSB, Jo-1, Scl-70 and PM-1 in 410 patients in a 5-year descriptive study of 410 patients with rheumatic disease symptoms of less than one year's duration. While some patients met diagnostic criteria for a specific rheumatologic diagnosis, others were classified as undifferentiated connective tissue disease (UCTD) and were subclassified by a constellation of symptoms. Our results show that ANA is sensitive in systemic lupus erythematosus (SLE) and progressive systemic sclerosis even in early disease but is not specific. Other "specific" autoantibodies were seen most frequently in SLE but were relatively insensitive and were seen in low frequency in UCTD. ANA have limited diagnostic value in patients with early disease. The prognostic value of these tests will be assessed as the prospective study of these cohorts progresses.
The modified Scleroderma Health Assessment Questionnaire (SSc HAQ) is a functional score to assess systemic sclerosis (SSc) comprising the HAQ disease index (HAQ-DI) plus five specific visual analogue scales (VAS). Since it was validated in English-speaking patients only, its general use in any other language necessitates prior cross-cultural adaptation and validation. We designed this study to assess its value in French-speaking patients and to validate the French version according to international recommendations. We elaborated a French version using the "forward-backward" method. We then validated its psychometric properties with 100 consecutive SSc French-speaking patients who had undergone simultaneous clinical and paraclinical examination. In addition, we calculated the SSc HAQ score, a new outcome measure, which is obtained by pooling the eight domains from the HAQ-DI with the five organ VAS. Our study confirmed the psychometric properties of the SSc HAQ in non-English-speaking patients with (a) structural validity: the major component analysis, performed on the HAQ-DI and the five VAS, yielding a two-factor structure; (b) convergent validity: with high correlation coefficients between the SSc HAQ score and the physical component score of the SF-36 (r=-0.74, p<0.0001); (c) discriminant validity: the SSc HAQ score was better in patients with limited than with diffuse SSc (0.5+/-0.5 vs 1.1+/-0.7, respectively, p<0.0001) in relation to the number of clinical involvements; (d) reproducibility was high using the test-retest procedure (r=0.98). This study showed the value of the SSc HAQ, which is a simple, discriminant, reproducible self-administered questionnaire to evaluate French-speaking SSc patients. In addition, we suggest the use of a new outcome measure, the SSc HAQ score, to assess this systemic disease more accurately.
Overall, the results of the analysis of 12 studies of VC production and polymerization workers demonstrate an enormously elevated risk of liver malignancies, the possibility of a twofold increased risk of brain and central nervous system tumors and perhaps, also, of malignancies of the lymphatic and hematopoietic system. However, the role of other agents cannot be excluded in the etiology of nonhepatic malignancies. Bronchogenic carcinoma does not appear to be increased from exposures to VC monomer, although a relationship to PVC dust was suggested in one study. These conclusions must be considered in light of limited data on workers followed more than 25 years from onset of exposure. Considering the numbers of observed and expected deaths in all studies, it would appear that the excess of malignancies at nonhepatic sites is less than the excess of liver tumors. Data presented elsewhere in this volume (Nicholson and Henneberger, 1983) suggest that exposure reductions in 1974 may have virtually eliminated the VC-associated risk of liver cancer if the current U.S. standard is met. To the extent that VC exposure is associated with other cancers, a similar risk reduction would be expected. Raynaud's phenomenon, acroosteolysis, scleroderma-like skin lesions, hepato- and splenomegaly with noncirrhotic hepatic fibrosis, and severe portal hypertension have been associated with past heavy exposures to VC. Evidence exists that the liver disease and portal hypertension may progress following cessation of exposure. However, all of the above syndromes were found largely in heavily exposed individuals. Their occurrence would be much less likely in workers exposed only to concentrations currently allowed. Pulmonary deficits, X-ray abnormalities, and, perhaps, lung cancer have been associated with VC/PVC exposure. Because of the possible contribution of PVC dust to these findings, engineering controls during polymer drying, bagging and usage are warranted.
Long-term manometry of the tubular esophagus was performed in 20 consecutive patients (18 females, 2 males; median age 56.5 years) with progressive systemic sclerosis (PSS) and a control group of 20 healthy subjects (18 females, 2 males; median age 56.5 years). The measurements were performed via a data logger of 1 MByte memory capacity with the help of two pressure sensors placed 8 and 18 cm above the lower esophageal sphincter. Esophageal contractions were analyzed with respect to pressure amplitudes in the esophagus distal and proximal, quotient of pressure amplitudes distal/proximal, number of contraction waves in a 24-h period, and kind of spreading (propulsive, simultaneous). In the PSS group there was a significant decrease in pressure amplitudes in the distal sensor (median 31.5 versus 39.5 mbar in controls, P < 0.02), in the quotient of pressure amplitudes distal/proximal (median 0.885 versus 1.25 in controls, P < 0.001), in the number of waves in 24 h (median 939.5 versus 1656 in controls, P < 0.01), and in the occurrence of propulsive waves (median 34% versus 57% in controls, P < 0.01). Fifteen patients (75%) had hypomotility disorders as compared to the control group, in which the lower limit of normal values was defined by the 5th percentile of descriptive analysis. These first data of long-term manometry in patients with PSS indicate that long-term manometry may be an effective method for identifying esophageal involvement in PSS.
We report a case of systemic sclerosis, limited type, in a 5 year old boy in Taiwan. He presented with erythema, tight skin over his face and digits, subcutaneous calcification, telangiectasis, as well as Raynaud's phenomenon. The laboratory data showed weakly positive antinuclear antibody (ANA), and Topoisomerase 1 antibody (anti-Scl-70) titers. However his esophagogram, CO diffusion capacity, as well as cardiac and renal function were all normal. He suffered from the skin change for 2 to 3 years before visiting our pediatric clinic when he was 7 years old. We gave him Dipyridamole, D-penicillamine, Colchicine, and Nifedipine. There was some remission of the scleroderma and Raynaud's phenomenon after our treatment.
A 63 year old woman developed painful, up to 15 x 7 cm large ulcers on both lower limbs and an acral necrosis on the right big toe. The patient had no symptoms of intermittent claudication, but a history of 40 package years of cigarette smoking. Angiography showed circumscript stenosis of medium-sized vessels, deformed vessel segments, and rarification and obstruction of peripheral vessels. Arterial occlusive disease was diagnosed, and percutaneous transluminal angioplasty (PTA) of the right common iliac artery and both femoral arteries performed. However, despite documented patency of these vessels clinical symptoms worsened. The consulting rheumatologist found a history of Raynaud's syndrome, acral necrosis of the fourth finger of the right hand, sclerodactylia, and microstomia. Capillaroscopy revealed megacapillaries and vessel rarification. High titers of antinuclear antibodies with specificity for centrosomes (1:10240), which have not been described in this context to date, were detected and limited systemic sclerosis of the CREST type was diagnosed. Treatment with iloprost (50 micrograms/day i.v.) and pulsed cyclophosphamide (800 mg i.v./month) resulted in almost complete healing of the crural and digital ulcers and a significant reduction of the analgetic medication.
Autoantibodies directed against cytoplasmic antigens of neutrophils (ANCA), especially proteinase 3 (C-ANCA), have proved to be a useful clinical tool to support the diagnosis or to monitor disease activity in Wegener's granulomatosis (WG). Till now, human neutrophil granulocytes have represented the major antigen source used to detect antibodies in WG by the immunofluorescence technique (IFT). We have tested serum samples of 164 patients with different connective tissue diseases (50 suffering from clinically active WG) performing IFT on a human renal cancer line (SK-RC11) and have found antibodies against the nuclear and cytoplasmic antigens in 39 patients. C-ANCA+ sera displayed a characteristic diffuse cytoplasmic staining pattern. Antibody titers measured with human granulocytes were comparable to titers obtained using culture cells. Antibody binding could be inhibited by preabsorption with an extract of human granulocytes or purified proteinase 3. A protein of 29 kDa MW could be isolated by affinity purification using a SK-RC11 extract and a high-titer C-ANCA+ serum and antigenic identity was further confirmed by IFT using a monoclonal antibody to proteinase 3. Treatment of tumor cells with cytokines (interferon, tumor necrosis factor) led to a time dependent translocation of the antigen into the nucleus and back to the cytoplasm. The antigen was also expressed on the surface of live cells colocalized with MHC II. In addition, 21 WG patients had antibodies to cytoplasmic organelles identified by laser scanning microscopy as secretory vesicles of the Golgi complex, and five had antibodies to nuclear antigens. This is, to the best of our knowledge, the first report of proteinase 3 in human non-leukemic cells. Our data demonstrate, that the repertoire of antigens recognized by antibodies in WG sera is not limited to human neutrophils and monocytes and indicates a possible functional role of the antigenic proteins.
Gastric emptying studies, using an indigenously prepared radiolabeled solid food marker in the form of Indian bread called Chapati, were performed on 13 patients with systemic sclerosis. Six patients had limited cutaneous disease and seven had diffuse cutaneous disease. Earlier, the procedure was standardized in 30 healthy volunteers. Seven of the 13 (54%) patients (five with diffuse and two with limited cutaneous disease) had delayed gastric emptying. Most of these patients had gastric symptoms. This pattern of gastric emptying may be clinically significant, particularly in patients with diffuse cutaneous disease.
Evidence from multiple sources indicates that SSc does not occur randomly in the population; there are particular groups who are at greater risk. The overall incidence rate of SSc in the adult population of the United States is approximately 20 per million per year; this rate has increased from 1944 to 1973, but has been relatively stable since that time. The prevalence of SSc in the United States also seems to be stable over the past two decades with a prevalence estimate for adults of 240 per million. Recent population studies suggest that SSc occurs more frequently in the United States than in continental Europe, the United Kingdom, and in some areas in Asia. Overall survival has improved over the past few decades; mean survival is approximately 12 years from diagnosis. Renal disease accounts for some of the early mortality, but pulmonary disease has emerged as a major cause of death. Cardiac disease is also correlated with a poorer prognosis. Gastrointestinal involvement contributes to morbidity and, indirectly, to mortality, but the magnitude of this contribution is difficult to assess. Women are affected more frequently than men but the factors that are responsible for this are not apparent. Studies of reproductive history have provided conflicting data; some studies suggested that the number of pregnancies may influence later disease expression, whereas other studies found no correlation. Racial factors seem to play a role in disease susceptibility, as well as disease expression. Age-specific incidence rates are higher in black women than in white women; the greatest difference occurs in the young to middle adult age group (less than 54 years of age). Diffuse disease also seems to occur more commonly in the black population than in the white. Age at onset of diffuse disease is younger, on average, than the age at onset of limited disease; age-adjusted survival is worse in black women than in white women because of their predilection for diffuse disease. Reports of geographic clustering are intriguing; the reported clusters in London and Italy have not resulted in the identification of potential causal factors. The Choctaw Native American cluster suggests that genetic factors that have not been identified may play an important role. Familial clustering of SSc has been demonstrated in the United States and in Australia, which provides additional evidence of a genetic component. It is likely that there is a strong interplay among genetic factors, hormonal or reproductive-related events, and an external trigger that must interact to result in clinical disease.
BACKGROUND: Small intestinal manometry is a relatively simple technique. However, its use is usually limited to very few centers and mainly related to research studies. AIM: To report our experience with small intestinal motility studies in a group of normal controls and patients with symptoms suggesting a gastrointestinal motor disorder. PATIENTS AND METHODS: Seventy three studies were performed in 71 subjects: 18 asymptomatic controls and 55 patients presenting with symptoms characterized by abdominal pain, vomiting, bloating, constipation and diarrhea. In 33 patients the same symptoms remained without diagnosis, in spite of extensive laboratory studies. In 10 of these, dilated small intestinal loops were observed and intestinal pseudoobstruction was suspected. Twenty two additional patients with systemic disorders such as scleroderma, diabetes and previous vagotomies, were studied. Motility was assessed by means of perfused catheters connected to external transducers for a mean lapse of 280 min. RESULTS: An abnormal pattern of small intestinal motility suggesting neuropathic, myopathic or a mixed disorder was observed in 76% of all studied patients, with the exception of patients with scleroderma, in whom only myopathic and mixed alterations were observed. In 82% of patients, the results of manometry were useful for the management of the clinical condition. CONCLUSIONS: Small intestinal manometry is a relatively simple technique that, when used in selected groups of patients, provides useful information for clinical management.
Fetal cells in maternal blood are a potential source of fetal genetic material that can be obtained non-invasively. Efforts to isolate these cells from maternal peripheral blood are limited by their low circulating numbers (approximately 1 per ml of maternal blood in euploid pregnancies). Expansion of these cells by culture would provide more cells for diagnosis and give an opportunity to study fetal metaphase chromosomes. Despite extensive optimization of culture conditions, many groups have failed reproducibly to grow fetal cells from pre-procedural maternal samples. An unexpected benefit of this research has been the discovery of a novel population of fetal cells, the pregnancy-associated progenitor cell (PAPC), which remains in maternal blood and tissue for decades following delivery. These cells might play a role in some autoimmune diseases, such as scleroderma. PAPCs appear to have stem cell characteristics, such as the ability to proliferate and differentiate. Recently developed animal models will help to ascertain whether these cells cause disease, respond to disease, or have therapeutic applications.
We studied in vitro platelet aggregation response to serotonin in 19 patients with systemic sclerosis and 18 matched controls. Individuals with early systemic sclerosis had increased % platelet aggregation at 3 minutes over a wide range of serotonin concentrations when compared to individuals with late systemic sclerosis. Patients with generalized disease did not differ from those with limited disease. No significant differences in initial slope of platelet aggregation were detected in any patient subgroup. These data support previous studies suggesting platelet activation in systemic sclerosis and further suggest that future studies of platelet abnormalities in systemic sclerosis should consider the effects of disease duration.
In recent reports, researchers described an increased incidence of cancer in patients with systemic sclerosis (SScl). For this article, the authors investigated the frequencies of cancer in first-degree relatives of patients with SScl in a case-control family study. Information was obtained by personal interview of the probands. Fifty-three subjects with cancer were reported among 814 relatives of patients, compared with 17 subjects among 860 relatives of age- and sex-matched control subjects (age and sex adjusted odds ratio = 3.79, 95% confidence interval = 2.16-6.66, P < 0.001). Forty-six patients (27.7%) had one or more relatives with cancer, compared with 15 control subjects (9%). Within the limitations of the methods used, the researchers found an increased risk for cancer in first-degree relatives of patients with SScl. This suggests that a common genetic or environmental factor may be involved in the development of both cancer and SScl.
A variety of autoantibodies have been associated with vasculitis, including that to neutrophils or to endothelial cells. Anti-neutrophil cytoplasmic antibodies (ANCA) have been described as sensitive and specific markers for active Wegener's granulomatosis (WG). ANCA in WG produces a characteristic cytoplasmic staining pattern (cANCA) and are directed against proteinase 3 (PR3-ANCA). PR3-ANCA occur in more than 90% of patients with extended WG, in 75% of patients with limited WG without renal involvement and in some 40% to 50% of patients with vasculitic overlap syndrome such as microscopic polyarteritis. Change in levels of cANCA precede disease activity and may be used as guidelines for treatment. Antibodies producing a perinuclear staining of ethanol-fixed neutrophils (pANCA) occur in a wide range of disease. They are directed against different cytoplasmic constituents of neutrophils. Among these, antibodies to myeloperoxidase (MPO-ANCA) are found in patients with idiopathic crescentic glomerulonephritis, the Churg-Strauss syndrome, polyarteritis nodosa and vasculitic overlap syndromes. Anti-endothelial cell antibodies (AECA) have been described in various autoimmune (systemic lupus erythematosus, scleroderma, rheumatoid arthritis) and vasculitic disorders (WG, polyarteritis nodosa, Kawasaki syndrome). They have been implicated in the pathogenesis of vascular injury common to these disorders.
Werner syndrome, caused by the homologous mutation of RecQ3 RNA/DNA helicase (WRN), is often misdiagnosed as systemic sclerosis (SSc) because of apparent similar skin changes and its relatively high frequency in Japan. The present study was undertaken to determine whether anti-WRN antibodies assayed by specific enzyme-linked immunosorbent assay occur in 41 SSc patients (30 diffuse and 11 limited types) and, if so, to determine any clinical association, such as skin sclerosis. Serum level of IgG anti-WRN antibody in SSc was significantly higher than that from 30 age- and sex-matched normal volunteers (P < 0.001). The serum level of IgG anti-WRN antibody in diffuse type SSc was significantly higher than the limited type (P < 0.05). A significant correlation was observed between serum levels of IgG anti-topoisomerase I antibody and IgG anti-WRN antibody in the same samples from SSc (P < 0.05). Moreover, in 119 normal healthy individuals aged from 0 to 99 years, a statistically significant correlation (P < 0.001) existed between serum level of IgG anti-WRN antibody and advancing age. A significantly higher level of IgG autoantibody specific for WRN detected in diffuse than in limited type SSc and normal may contribute to the pathogenesis of skin sclerosis in SSc.
Mouth opening limitations following on soft tissue lesions are subdivided according to aetiology into collagen disease connectival lesions, cutaneous and mucosa lesions consequent on the action of physical agents and, finally, cicatricial lesions of the cheeks and lips as a result of surgery for cancer or trauma. The commonest forms of plastic surgery used to correct such lesions are reviewed.
This was a pilot study to investigate the new technique of laser Doppler imaging (scanning laser Doppler) as a tool to quantify microvascular blood flow in the digits of patients with primary Raynaud's phenomenon (PRP) and systemic sclerosis (SSc), and to determine in the first instance whether the flux patterns obtained differ between patients with SSc, patients with PRP, and healthy control subjects. Laser Doppler images of the dorsum of the hand and fingers were acquired at 23 and 30 degrees C in 17 healthy control subjects, 7 patients with PRP, 9 patients with the diffuse cutaneous variant of SSc, and 24 patients with the limited cutaneous variant of SSc. Different flux parameters were compared between groups. Analysis of variance found significant differences between groups in two tests: maximum difference in flux between fingertips of the same hand at 23 degrees C (P = 0.001) and maximum gradient in flux along a finger ("distal-dorsal" flux difference) at 30 degrees C (P = 0. 019). Post hoc tests highlighted the differences between controls and patients with limited cutaneous SSc. This pilot study suggests that laser Doppler imaging may allow objective measurement of microvascular flow in patients with PRP and SSc. This new technique may overcome many of the problems inherent in single-channel laser Doppler equipment.