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Biomedical subjects

Richard M Silver

Publications and source records attributed to Richard M Silver.

At least 19 recordsLinked to original sources
PubMed2006

Racial variation in clinical and immunological manifestations of systemic sclerosis.

OBJECTIVE: To clarify which racial differences in disease manifestations can be attributed to differences in other factors such as gender, education, disease classification, and disease duration. METHODS: The study included white and black patients with systemic sclerosis (SSc) treated at a university hospital rheumatology clinic between November 1997 and April 2003. Demographic, clinical, and immunological measurements were obtained on each subject. Using multivariable statistical techniques we assessed differences in disease manifestations between white and black patients after adjusting for gender and classification and duration of disease. RESULTS: Two hundred sixty-three patients (199 whites, 64 blacks) were enrolled in the study. Blacks experienced an earlier age at disease onset than whites and were significantly more likely to have diffuse disease, digital ulcers, digital pitting, impaired lung function, and anti-RNP, and anti-Ro antibodies. Whites were significantly more likely to have anti-centromere antibodies. CONCLUSION: After adjusting for gender, disease classification, and disease duration, whites and blacks with SSc differ in some clinical and immunological manifestations of disease. Whether these differences can be attributed to genetic or environmental factors remains unknown.

Adult↗
PubMed2005

The influence of defects on the morphology of Si (111) etched in NH4F.

We have implemented a kinetic Monte Carlo (KMC) simulation to study the effects of wafer miscut and wafer defects on the morphologies of Si (111) surfaces etched in NH4F. Although a conventional KMC simulation reproduced previously published results, it failed to produce the morphologies observed in our experiments. By introducing both dopant sites and lattice defect sites into the model, we are able to simulate samples having different dopant elements and densities as well as different defect concentrations. Using the modified KMC simulation, the simulated surface morphologies agree well with the morphologies observed in our experiments. The enhanced model also gives insights to the formation mechanism for multiple level stacking pits, a notable morphology on the etched surfaces of samples with very small miscut angles.

Journal Article↗
PubMed2005

Opposing effects of protein kinase Calpha and protein kinase Cepsilon on collagen expression by human lung fibroblasts are mediated via MEK/ERK and caveolin-1 signaling.

The roles of MEK, ERK, the epsilon and alpha isoforms of protein kinase C (PKC), and caveolin-1 in regulating collagen expression were studied in normal lung fibroblasts. Knocking down caveolin-1 gave particularly striking results. A 70% decrease caused a 5-fold increase in MEK/ERK activation and collagen expression. The combined data reveal a branched signaling pathway. In its central portion MEK activates ERK, leading to increased collagen expression. Two branches converge on MEK/ERK. In one, increased PKCepsilon leads to MEK/ERK activation. In another, increased PKCalpha induces caveolin-1 expression, which in turn inhibits MEK/ERK activation and collagen expression. Lung fibroblasts from scleroderma patients with pulmonary fibrosis showed altered signaling. Consistent with their overexpression of collagen, scleroderma lung fibroblasts contain more activated MEK/ERK and less caveolin-1 than normal lung fibroblasts. Because cutaneous fibrosis is the hallmark of scleroderma, we also studied dermal fibroblasts. As in lung, there was more activated MEK/ERK in cells from scleroderma patients than in control cells, and MEK inhibition decreased collagen expression. However, the distinctive levels of PKCepsilon, PKCalpha, and caveolin-1 in lung and dermal fibroblasts from scleroderma patients and control subjects indicate that the links between these signaling proteins and MEK/ERK must function differently in the four cell types. Finally, we confirmed the relevance of these signaling cascades in vivo. The combined results demonstrate that a branched signaling pathway involving MEK, ERK, PKCepsilon, PKCalpha, and caveolin-1 regulates collagen expression in normal lung tissue and is perturbed during fibrosis.

Animals↗
PubMed2005

Correlation of the degree of dyspnea with health-related quality of life, functional abilities, and diffusing capacity for carbon monoxide in patients with systemic sclerosis and active alveolitis: results from the Scleroderma Lung Study.

OBJECTIVE: To determine whether baseline self-assessment measures of health status and physiologic indices of disease severity in alveolitis-positive patients with systemic sclerosis (SSc) correlate with the severity of their dyspnea, and to quantify functional impairment in patients with scleroderma lung disease and compare it with that in patients with chronic obstructive pulmonary disease (COPD). METHODS: SSc patients (n = 138) with diffuse (n = 81) or limited (n = 57) cutaneous disease and active alveolitis (determined by bronchoalveolar lavage and/or high-resolution computed tomography) who participated in the National Heart, Lung, and Blood Institute-sponsored, multicenter, parallel-group, double-blind, randomized, placebo-controlled trial of oral cyclophosphamide for treatment of SSc-associated interstitial lung disease were evaluated. Pearson's univariate correlations were determined between the Short Form 36 (SF-36) physical component summary (PCS) and mental component summary (MCS) scales, functional questionnaires, and physiologic parameters of breathing (forced vital capacity [FVC] and single-breath diffusing capacity for carbon monoxide [DLCO]). Student's t-test was used to compare subgroups. Scores from 2 instruments for self-assessment of breathlessness, Mahler's baseline dyspnea index (BDI) and a visual analog scale (VAS) for breathing, were divided at the median. Values for the DLCO and FVC (% predicted) were divided based on the American Thoracic Society guidelines for mild (>70% of predicted), moderate (50-70% of predicted), and severe (<50% of predicted) physiologic impairment. RESULTS: Scores on the BDI and VAS for breathing were highly correlated (r = -0.61). The PCS and MCS were able to differentiate patients with more breathlessness (measured by BDI and VAS for breathing) and more abnormal physiologic measures (FVC and DLCO). In SSc patients with alveolitis, all 8 domains of the SF-36 were significantly impaired as compared with the healthy population and were similar to those reported by patients with COPD. CONCLUSION: The SF-36 was able to discriminate between scleroderma lung disease patients with more severe and less severe breathlessness, the primary symptom of active alveolitis. The SF-36 complements the BDI and VAS scores for breathing in scleroderma lung disease and is variably correlated with results of pulmonary function tests, suggesting that the SF-36 should be included as an outcome measure in intervention trials in this population.

Carbon Monoxide↗
PubMed2005

Enzyme-linked immunosorbent assay for detection of anti-RNA polymerase III antibody: analytical accuracy and clinical associations in systemic sclerosis.

OBJECTIVE: We have recently developed an enzyme-linked immunosorbent assay (ELISA) for detection of anti-RNA polymerase III (anti-RNAP III) antibody, using a recombinant fragment containing the immunodominant epitope as the antigen source. This study was conducted to assess the analytical accuracy and clinical associations of the anti-RNAP III ELISA in patients with systemic sclerosis (SSc). METHODS: To evaluate analytical sensitivity and specificity of the ELISA, both immunoprecipitation tests and ELISA were used to detect anti-RNAP III antibody in 534 SSc sera from patients at 3 medical centers. Sera from 522 SSc patients and 516 controls, including patients with other connective tissue diseases and blood bank donors, were also evaluated to assess the clinical sensitivity and specificity of the ELISA. Clinical findings in anti-RNAP III antibody-positive SSc patients were compared between patient groups stratified according to anti-RNAP III antibody levels determined by the ELISA. RESULTS: In SSc patients, our ELISA showed analytical sensitivity of 91% and analytical specificity of 99% compared with the immunoprecipitation assay (a gold standard for detection of anti-RNAP III antibody). The additional analysis using a large series of SSc and control sera showed that clinical sensitivity and specificity of the ELISA with respect to the diagnosis of SSc were 17% and 98%, respectively. A high level of anti-RNAP III antibody was associated with diffuse cutaneous SSc, higher maximum total skin score, and increased frequency of tendon friction rubs. CONCLUSION: The anti-RNAP III ELISA is analytically accurate and clinically specific. With this assay, testing for anti-RNAP III antibody can be made routinely available.

Antibodies, Antinuclear↗
PubMed2005

Clinical aspects of lung involvement: lessons from idiopathic pulmonary fibrosis and the scleroderma lung study.

Interstitial lung disease (ILD) occurs frequently among patients with systemic slcerosis (SSc) and accounts for significant morbidity and mortality. SSc-ILD resembles idiopathic pulmonary fibrosis (IPF) in many respects; each is characterized by a restrictive ventilatory defect that results from an active fibrosing process in the lung interstitium, and each is characterized by ground glass opacification on high resolution computed tomography (HRCT) and inflammatory cells in bronchoalveolar lavage fluid (BALF). Differences in the classification of lung histo-pathology are noted frequently and may account for some of the difference in outcome for patients with SSc-ILD and IPF. Optimal treatment of SSc-ILD remains to be determined, but cyclophosphamide has been reported to be effective in a number of case series. A randomized controlled trial, the Scleroderma Lung Study (SLS), will be completed in 2005; the outcome of the SLS should define the efficacy of daily oral cyclophosphamide for SSc-ILD patients with alveolitis defined by BALF and HRCT.

Comorbidity↗
PubMed2005

New developments in scleroderma interstitial lung disease.

PURPOSE OF REVIEW: To review the recent medical literature pertaining to interstitial lung disease found in association with systemic sclerosis remains a major contributor to morbidity and mortality. Significant progress is being made in terms of understanding the pathogenesis, the best approaches to clinical evaluation, and various options for therapy of systemic sclerosis patients whose disease course is complicated by interstitial lung disease. RECENT FINDINGS: Recent studies highlight the importance of microvascular disease, autoimmunity, and fibroblast differentiation/activation in the pathogenesis of systemic sclerosis-interstitial lung disease, particularly in the early phase of disease. It appears as if the balance between various pro-fibrotic/pro-inflammatory and anti-fibrotic/anti-inflammatory mediators may be central to interstitial lung disease pathogenesis, which presents potential opportunities for therapeutic intervention. The clinical approach to staging of disease activity remains controversial. High resolution computed tomography scans, bronchoalveolar lavage and various serum markers (e.g., surfactant protein D and KL-6) each may provide useful information about the degree of activity of the systemic sclerosis-interstitial lung disease. Currently, treatment recommendations are limited by a scarcity of well designed clinical trials, but the recently completed Scleroderma Lung Study is a model for future studies and is providing useful information about this important complication of systemic sclerosis. SUMMARY: Basic and clinical studies of systemic sclerosis patients with interstitial lung disease are yielding promising data that ultimately will be translated in to more effective diagnostic and therapeutic strategies.

Biopsy↗
PubMed2005

Correlates of depression, including overall and gastrointestinal functional status, among patients with systemic sclerosis.

OBJECTIVE: Patients with systemic sclerosis (SSc) may develop psychological problems in addition to physiologic symptoms. We investigated whether demographic and clinical factors are associated with comorbid depression. METHODS: From a university hospital's rheumatology clinic, 72 SSc patients who completed 3 questionnaires [Center for Epidemiologic Studies Depression (CES-D) scale, an abbreviated version of a functional status instrument, the Scleroderma Health Assessment Questionnaire (SHAQ), and the Gastrointestinal Quality of Life Index (GIQLI)] during an examination were recruited into the study. Correlations among scores on the 3 questionnaires [including upper and lower gastrointestinal (GI) tract subscales of the GIQLI] were calculated, and associations between CES-D scores and a variety of demographic and clinical characteristics were examined using stepwise linear regression. RESULTS: Higher CES-D scores (i.e., more depression symptoms) were significantly correlated with upper (r = -0.48, p < 0.0001) and lower (r = -0.41, p < 0.001) GI tract dysfunction and worse overall functional status (r = 0.51, p < 0.0001). Stepwise regression indicated that higher levels of depression were independently associated with lower levels of education (p < 0.01), worse upper GI tract functioning (p = 0.019), worse functional status (p = 0.34), current corticosteroid use (p = 0.061), and cardiac involvement (p = 0.086). CONCLUSION: Decreased functional status and abnormal GI functioning are significantly correlated with depression among patients with SSc. Other demographic and clinical indicators are also associated with depression.

Cross-Sectional Studies↗
PubMed2005

Demographic and clinical factors associated with in-hospital death among patients with systemic sclerosis.

OBJECTIVE: To examine demographic and clinical predictors of in-hospital death of patients with systemic sclerosis (SSc) and determine to what extent apparent racial differences may be attributed to socioeconomic factors. METHODS: Data were obtained on all hospitalizations in South Carolina for patients who were ever hospitalized between 1996 and 2000 with a diagnosis of SSc. Multiple logistic regression was used to examine predictors of in-hospital death among whites, blacks, and other patients. RESULTS: Proportions of in-hospital deaths among blacks (23.0%) and others (27.7%) were higher than among whites (15.6%), a finding that remained after adjustment for other sociodemographic and clinical factors (black/white odds ratio: 1.70, 95% confidence interval: 1.01-2.86; other/white OR 2.06, 95% CI 1.04-4.09). Other factors associated with in-hospital death included transfer status, emergency admission, length of stay, number of hospitalizations during the time period, and presence of congestive heart failure (OR 1.79; 95% CI 1.06-3.03) or hypertension (OR 0.41; 95% CI 0.23-0.71). CONCLUSION: Black and other non-white patients with SSc appear to experience an elevated risk of death during their hospital stays. Further research is necessary to understand the reasons for these disparities.

Adult↗
PubMed2004

Distinct PKC isoforms mediate cell survival and DNA synthesis in thrombin-induced myofibroblasts.

Thrombin activates protease-activated receptor (PAR)-1 and induces a myofibroblast phenotype in normal lung fibroblasts that resembles the phenotype of scleroderma lung fibroblasts. We now demonstrate that PAR-1 expression is dramatically increased in lung tissue from scleroderma patients, where it is associated with inflammatory and fibroproliferative foci. We also observe that thrombin induces resistance to apoptosis in normal lung fibroblasts, and this process is regulated by protein kinase C (PKC)-epsilon but not by PKC-alpha. Overexpression of a constitutively active (c-a) form of PAR-1 or PKC-epsilon significantly inhibits Fas ligand-induced apoptosis in lung fibroblasts, whereas scleroderma lung fibroblasts are resistant to apoptosis de novo. Thrombin translocates p21Cip1/WAF1, a signaling molecule downstream of PKC, from the nucleus to cytoplasm in normal lung fibroblasts mimicking the localization of p21Cip1/WAF1 in scleroderma lung fibroblasts. Overexpression of c-a PKC-alpha or PKC-epsilon results in accumulation of p21Cip1/WAF1 in the cytoplasm. Depletion of PKC-alpha or inhibition of mitogen-activated protein kinase (MAPK) blocks thrombin-induced DNA synthesis in lung fibroblasts. Inhibition of PKC by calphostin or PKC-alpha, but not PKC-epsilon, by antisense oligonucleotides prevents thrombin-induced MAPK phosphorylation and accumulation of G(1) phase regulatory protein cyclin D1, suggesting that PKC-alpha, MAPK, and cyclin D1 mediate lung fibroblast proliferation. These data demonstrate that two distinct PKC isoforms mediate thrombin-induced resistance to apoptosis and proliferation and suggest that p21Cip1/WAF1 promotes both phenomena.

Aged↗
PubMed2004

Curcumin-induced apoptosis in scleroderma lung fibroblasts: role of protein kinase cepsilon.

Scleroderma, a disease involving excessive collagen deposition, can be studied using fibroblasts cultured from affected tissues. We find that curcumin, the active component of the spice turmeric, causes apoptosis in scleroderma lung fibroblasts (SLF), but not in normal lung fibroblasts (NLF). This effect is likely to be linked to the fact that although curcumin induces the expression of the phase 2 detoxification enzymes heme oxygenase 1 and glutathione S-transferase P1 (GST P1) in NLF, SLF are deficient in these enzymes, particularly after curcumin treatment. The sensitivity of cells to curcumin-induced apoptosis and the expression of GST P1 (but not heme oxygenase 1) are regulated by the epsilon isoform of protein kinase C (PKCepsilon). SLF, which contain less PKCepsilon and less GST P1 than NLF, become less sensitive to curcumin-induced apoptosis and express higher levels of GST P1 when transfected with wild-type PKCepsilon, but not with dominant-negative PKCepsilon. Conversely, NLF become sensitive to curcumin-induced apoptosis and express lower levels of GST P1 when PKCepsilon expression or function is inhibited. The subcellular distribution of PKCepsilon also differs in NLF and SLF. PKCepsilon is predominantly nuclear or perinuclear in NLF but is associated with stress fibers in SLF. Just as PKCepsilon levels are lower in SLF than in NLF in vitro, PKCepsilon expression is decreased in fibrotic lung tissue in vivo. In summary, our results suggest that a signaling pathway involving PKCepsilon and phase 2 detoxification enzymes provides protection against curcumin-induced apoptosis in NLF and is defective in SLF. These observations suggest that curcumin may have therapeutic value in treating scleroderma, just as it has already been shown to protect rats from lung fibrosis induced by a variety of agents.

Animals↗
PubMed2004

Ethnic differences in cytotoxic T lymphocyte associated antigen 4 genotype associations with systemic sclerosis.

OBJECTIVE: To determine the role of cytotoxic T lymphocyte associated antigen 4 (CTLA-4) genetic polymorphisms in susceptibility to systemic sclerosis (SSc, scleroderma). METHODS: The study population consisted of 293 African American and Caucasian patients with SSc and matched controls. Subjects were genotyped for allelic determinants at 4 polymorphic sites: 3 in the promoter region (positions -318, -1661, -1722) and one in the first exon (position +49) of the CTLA-4 gene, using polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) methods. Genotype frequencies were compared using Pearson's chi-square or Fisher's exact test. RESULTS: In African American patients, the frequency of AG heterozygotes at position +49 was significantly higher than in controls (71% vs 36%, p = 0.003; OR = 4.37), while the frequency of AA homozygotes was significantly lower in patients than in controls (29% vs 61%, p = 0.007; OR = 0.26). The distribution of CTLA-4 alleles at other loci did not differ significantly between patients and controls. CTLA-4 genotypes were not associated with SSc in Caucasians. No differences in CTLA-4 genotype distributions were observed between patients with the limited and diffuse forms of the disease. CONCLUSION: Our data show that the exon 1 (+49) polymorphism of the CTLA-4 gene is associated with systemic sclerosis in African Americans.

Black or African American↗
PubMed2003

Contractile activity and smooth muscle alpha-actin organization in thrombin-induced human lung myofibroblasts.

Activated fibroblasts, or myofibroblasts, are crucial players in tissue remodeling, wound healing, and various fibrotic disorders, including interstitial lung fibrosis associated with scleroderma. Here we characterize the signaling pathways in normal lung fibroblasts exposed to thrombin as they acquire two of the main features of myofibroblasts: smooth muscle (SM) alpha-actin organization and collagen gel contraction. Our results show that the small G protein Rho is involved in lung myofibroblast differentiation. Thrombin induces Rho-35S-labeled guanosine 5'-O-(3-thiotriphosphate) binding in a dose-dependent manner. It potently stimulates Rho activity in vivo and initiates protein kinase C (PKC)-epsilon-Rho complex formation. Toxin B, which inactivates Rho by ADP ribosylation, inhibits thrombin-induced SM alpha-actin organization, collagen gel contraction, and PKC-epsilon-SM alpha-actin and PKC-epsilon-RhoA coimmunoprecipitation. However, it has no effect on PKC-epsilon activation or translocation of PKC-epsilon to the membrane. Overexpression of constitutively active PKC-epsilon and constitutively active RhoA induces collagen gel contraction or SM alpha-actin organization, whereas, individually, they do not perform these functions. We therefore conclude that the contractile activity of myofibroblasts induced by thrombin is mediated via PKC-epsilon- and RhoA-dependent pathways and that activation of both of these molecules is required. We postulate that PKC-epsilon-RhoA complex formation is an early event in thrombin activation of lung fibroblasts, followed by PKC-epsilon-SM alpha-actin coimmunoprecipitation, which leads to the PKC-epsilon-RhoA-SM alpha-actin ternary complex formation.

Actins↗
PubMed2003

Persistent down-regulation of Fli1, a suppressor of collagen transcription, in fibrotic scleroderma skin.

The molecular and cellular mechanisms that maintain proper collagen homeostasis in healthy human skin and are responsible for the dysregulated collagen synthesis in scleroderma remain primarily unknown. This study demonstrates that Fli1 is a physiological negative regulator of collagen gene expression in dermal fibroblasts in vitro and in human skin in vivo. This conclusion is supported by the analyses of mouse embryonic fibroblasts from Fli1(-/-), Fli1(+/-), and Fli1(+/+) mice. In cultured human and mouse fibroblasts Fli1 expression levels are inversely correlated with the collagen type I expression levels. These in vitro observations were validated in vivo. In healthy human skin Fli1 protein is expressed in fibroblasts and endothelial cells. Significantly, absence of Fli1 expression in individual fibroblasts correlates with elevated collagen synthesis. In contrast to healthy skin, Fli1 protein is consistently absent from fibroblasts and significantly reduced in endothelial cells in clinically involved scleroderma skin, which correlates with enhanced collagen synthesis in systemic sclerosis skin. This study supports the role of Fli1 as a suppressor of collagen transcription in human skin in vivo. Persistent down-regulation of Fli1 in scleroderma fibroblasts in vivo may directly contribute to uncontrolled matrix deposition in scleroderma skin.

Adult↗
PubMed2003

Patterns of hospital admissions and emergency room visits among patients with scleroderma in South Carolina, USA.

OBJECTIVE: Little research has examined patterns of hospitalization and use of emergency rooms (ER) among patients with systemic sclerosis (SSc). We compared the incidence of hospitalizations and ER visits across 3 race groups (non-Hispanic white, non-Hispanic black, other) and determined predictors of referral to the Medical University of South Carolina (MUSC), a major referral center for patients with SSc residing in the southeastern United States. METHODS: Data were obtained on all South Carolina hospitalizations (1996-2000) for patients who were ever hospitalized for a diagnosis of SSc during that time period. Hospitalization and ER incidence rates were determined in conjunction with corresponding population sizes obtained from the 2000 US Census, and rates were compared across race, sex, and age groups using Poisson regression models. Logistic regression was used to determine predictors of being treated at MUSC. RESULTS: The hospitalization incidence rate was significantly (p < 0.05) higher among blacks compared to whites (rate ratio 1.66; 95% confidence interval 1.41, 1.96), as was the ER incidence rate (rate ratio 1.78; 95% CI 1.50, 2.11). Even after adjusting for sex, age, median household income, primary insurance claim payor, county, and comorbidity, blacks were 60% less likely (p < 0.05) than whites to receive inpatient treatment at MUSC. Similar results were observed when comparing other non-whites to whites. CONCLUSION: The increased hospitalizations and ER visits among non-whites provide additional evidence of greater disease burden among these population groups. Despite this increased burden, non-whites are less likely to receive care at a major SSc referral center.

Academic Medical Centers↗
PubMed2003

HLA class II alleles in systemic sclerosis patients with anti-RNA polymerase I/III antibody: associations with subunit reactivities.

OBJECTIVE: To examine HLA class II gene associations with anti-RNA polymerase (RNAP) I/III antibody responses in patients with systemic sclerosis (SSc). METHODS: HLA-DRB1, DRB3, DRB4, and DQB1 alleles were determined using polymerase chain reaction-based methods in 257 SSc patients (129 Japanese and 128 Caucasians) and 271 race-matched regional controls (138 Japanese and 133 Caucasians). Anti-RNAP I/III antibodies were identified by immunoprecipitation assay, and reactivities to individual RNAP subunits were determined by immunoblots using affinity-purified RNAP I, II, and III. RESULTS: Serum anti-RNAP I/III antibody was detected in 10 (8%) Japanese and 24 (19%) Caucasian patients with SSc. The presence of anti-RNAP I/III antibodies was associated with DRB1*0405, DRB4*01, and DQB1*0401 in Japanese, and with DRB3*02 in Caucasians, but these associations were weak and inconsistent between these 2 ethnic groups. When anti-RNAP I/III-positive SSc patients were divided into 2 groups based on the presence or absence of reactivities to individual RNAP subunit proteins, significant associations of anti-IIa/IIo reactivity with DRB3*02, anti-Ia reactivity with DRB1*04, anti-43-kDa subunit reactivity with DRB4*01, and anti-34-kDa subunit reactivity with DRB1*15 were detected. These HLA associations with subunit reactivities were generally shared by Japanese and Caucasian patients with SSc. CONCLUSION: Our results suggest that in patients with SSc, anti-RNAP I/III antibodies are composed of subsets defined by combinations of reactivities to individual RNAP subunits having specific HLA class II correlations.

Alleles↗
PubMed2002

Ulnar artery involvement in systemic sclerosis (scleroderma).

OBJECTIVE: Microvascular disease is one of the hallmarks of systemic sclerosis (SSc, scleroderma), but macrovascular involvement also exists in some patients. Patients with SSc may have severe Raynaud's phenomenon (RP) characterized by refractory digital ulcerations. We investigated if large artery involvement, that is, ulnar artery occlusion, has a role in the development of refractory digital ulcerations, and if both screening for this involvement and revascularization of the ulnar artery occlusive disease may improve digital ulcer healing. METHODS: A retrospective chart review was performed of 15 patients with SSc, all of whom had severe RP and digital ulceration, together with a positive Allen test and ulnar artery occlusive disease documented by angiography. RESULTS: Women outnumbered men 2:1, with limited disease predominating (7), 5 patients having diffuse cutaneous disease and 3 overlap syndromes. All patients had positive antinuclear antibody and capillary microscopy findings consistent with SSc. Antiphospholipid antibodies were present in 4 of 6 patients tested. Tobacco use was seen in 5 patients, only 2 of whom were current smokers. All patients failed conventional medical therapy (nitrates, calcium channel blockers, antiplatelet agents) for RP and digital ulceration. Only 1/8 patients improved with stellate ganglion block, and one patient had no improvement following digital sympathectomy. Eight patients underwent ulnar artery revascularization combined with digital sympathectomy, and 8 experienced dramatic improvement in RP and healing of digital ulcers. CONCLUSION: An Allen test should be performed routinely on all SSc patients with severe RP and refractory digital ulceration to investigate the possibility of ulnar artery occlusive disease. If suspected ulnar artery occlusion is confirmed by angiography or ultrasonography, ulnar artery revascularization with or without digital sympathectomy should be considered in patients who fail conventional medical therapy.

Antibodies, Antinuclear↗