Significant attenuation of macrovascular involvement by bosentan in a patient with diffuse cutaneous systemic sclerosis with multiple digital ulcers and gangrene

Systemic sclerosis (SSc) is characterized by vascular injuries, and bosentan has recently been proved to be efficacious for the prevention of new digital ulcers in SSc. We herein report a case of SSc in a patient with refractory digital ulcers and gangrene treated with bosentan. Stenosis of the ulnar artery, evaluated by magnetic resonance angiography, was attenuated by the bosentan treatment, suggesting that bosentan exerts a reverse remodeling effect against the pathological organic changes of arteries in SSc.     

Digital ulcers in systemic sclerosis: prevention by treatment with bosentan, an oral endothelin receptor antagonist

OBJECTIVE: Recurrent digital ulcers are a manifestation of vascular disease in patients with systemic sclerosis (SSc; scleroderma) and lead to pain, impaired function, and tissue loss. We investigated whether treatment with the endothelin receptor antagonist, bosentan, decreased the development of new digital ulcers in patients with SSc. METHODS: This was a randomized, prospective, placebo-controlled, double-blind study of 122 patients at 17 centers in Europe and North America, evaluating the effect of treatment on prevention of digital ulcers. The primary outcome variable was the number of new digital ulcers developing during the 16-week study period. Secondary assessments included healing of existing digital ulcers and evaluation of hand function using the Scleroderma Health Assessment Questionnaire. RESULTS: Patients receiving bosentan had a 48% reduction in the mean number of new ulcers during the treatment period (1.4 versus 2.7 new ulcers; P = 0.0083). Patients who had digital ulcers at the time of entry in the study were at higher risk for the development of new ulcers; in this subgroup the mean number of new ulcers was reduced from 3.6 to 1.8 (P = 0.0075). In patients receiving bosentan, a statistically significant improvement in hand function was observed. There was no difference between treatment groups in the healing of existing ulcers. Serum transaminase levels were elevated to >3-fold the upper limit of normal in bosentan-treated patients; this elevation is comparable with that observed in previous studies of this agent. Other side effects were similar in the 2 treatment groups. CONCLUSION: Endothelins may play an important role in the pathogenesis of vascular disease in patients with SSc. Treatment with the endothelin receptor antagonist bosentan may be effective in preventing new digital ulcers and improving hand function in patients with SSc.     

Successful treatment of patients with severe secondary Raynaud's phenomenon with the endothelin receptor antagonist bosentan

Secondary Raynaud's phenomenon (RP) in patients with systemic sclerosis (SSc) and other collagen vascular diseases is a serious manifestation of microvascular damage that may precede the onset of visceral and/or cutaneous sclerosis for years. Recent studies have demonstrated that the endothelin receptor antagonist bosentan prevents the development of new digital ulcers in SSc. We investigated the potential benefits of bosentan in patients with secondary RP associated with pre-scleroderma and with SSc, independent of digital ulcers. Three patients with secondary RP received bosentan 62.5 mg twice daily for 4 weeks followed by 125 mg twice daily for 12 weeks during the winter season. Pain (visual analogue scale), Raynaud's disease activity (Scleroderma Health Assessment Questionnaire), number and severity of daily Raynaud's attacks (diary) and peripheral thermoregulation (thermography) were assessed during treatment periods. Pain, Raynaud's disease activity, number and severity of Raynaud's attacks significantly decreased during treatment periods. Thermography after 16-week treatment demonstrated improved peripheral thermoregulation. Although this is a small observational study, treatment with bosentan appears to measurably reduce the daily impact of Raynaud's disease and improve peripheral thermoregulation in patients with secondary RP, independent of digital ulcers.     

Effect of treatment with iloprost with or without bosentan on nailfold videocapillaroscopic alterations in patients with systemic sclerosis

Introduction: Vascular involvement plays a decisive role in systemic sclerosis (SSc) pathogenesis; it is responsible for some important clinical manifestations of the disease such as Raynaud’s phenomenon and digital ulcers (DU). Bosentan, a dual receptor endothelin antagonist, and iloprost, often in combination therapy, seems to be able to interfere with the scleroderma microangiopathy.

Objectives: Aim of the study was to evaluate the effect of bosentan and iloprost on scleroderma microangiopathy, analyzed by means of capillaroscopic skin ulcer risk index (CSURI), in SSc patients treated for the prevention of DU.

Methods: Nailfold videocapillaroscopy (NVC) was performed in 95 SSc patients, treated with iloprost alone (group 1) or combination therapy with iloprost and bosentan (group 2), at baseline and after one year. In all patients CSURI was calculated according to the formula “diameter?×?number of megacapillaries/(total number of capillaries)²”: in addition, total number of capillaries, giant capillaries, micro-hemorrhages, disorganization of the vascular array, and ramified capillaries were evaluated by means of a semiquantitative score.

Results: After 12 months, we observed a reduction of the number of giant capillaries in both groups, while an increase of ramified capillaries was recorded only in group 2. CSURI improved slightly in group 2 without statistical significance; on the contrary, in group 1 a significant worsening was recorded (p?≤?0.001).

Conclusions: Our study confirms the effectiveness of bosentan, in combination with iloprost, in SSc microangiopathy observed to NVC. Moreover, the observed findings further support the role of CSURI in the evaluation and monitoring of SSc microangiopathy.     

Controlling the digital ulcerative disease in systemic sclerosis is associated with improved hand function

ObjectivesIschemic digital ulcers (DU) represent a major complication of systemic sclerosis (SSc). We investigated the impact of controlling the ulcerative disease on disability, pain, and quality of life in SSc patients receiving bosentan.MethodsECLIPSE (Study AC-052-517) is a 2-year prospective, multicenter, and observational study. Patients with SSc who experienced at least 1 DU in the previous year and received bosentan were included between October 2009 and March 2011. Disability scores [Cochin Hand Function Scale (CHFS) and Health Assessment Questionnaire Disability Index (HAQ-DI)], pain scores (visual analog scale), and quality-of-life scores (SF-36) were collected at inclusion and 1 year later (primary endpoint). A controlled ulcerative disease was defined by the absence of ongoing/new DU episode between inclusion and 1-year follow-up.ResultsData were available at 1 year for 120 patients out of 190 included. During follow-up, 46 (38.3%) patients experienced a new DU episode. The number of DU per patient decreased from 1.4 ± 1.8 at inclusion to 0.6 ± 1.6 (p < 0.0001) at 1 year. Disability scores decreased from 1.0 ± 0.7 to 0.9 ± 0.7 (p = 0.04) for the HAQ-DI and from 29 ± 20 to 25 ± 20 (p = 0.005) for the CHFS; the pain score decreased from 4.3 ± 3.1 to 2.9 ± 2.8 (p < 0.0001).This improvement was attributed to patients with a controlled ulcerative disease (48.3%), who significantly improved HAQ-DI (p = 0.04), CHFS (p = 0.04), and pain score (p = 0.046).ConclusionsIn patients with SSc, control of the ulcerative disease for 1 year was associated with significant attenuation of hand disability.     

High incidence of pulmonary arterial hypertension in systemic sclerosis patients with anti-centriole autoantibodies

Abstract

Systemic sclerosis (SSc)-related autoantibodies are useful tools in identifying clinically homogenous subsets of patients and predicting their prognosis. In this report, we described five SSc patients with anti-centriole antibodies. All five patients were females and had digital ulcers/gangrene. Four of five (80%) patients had pulmonary arterial hypertension (PAH). None of the five patients had active pulmonary fibrosis or developed renal crisis. Anti-centriole antibodies may be a marker for PAH and digital ulcers/gangrene.     

Treatment of digital ulcers in systemtic sclerosis with endothelin-1 receptor antagonist (bosentan)

In systemic sclerosis (SSc) occurrence of recurrent digital ulcers (DU) is cause of pain and functional disability of hands. Treatment with vasodilator agents, such as calcium channel blockers, ACE inhibitors, prostanoids, has not shown to be an effective therapy. There is evidence that endotelin-1 (ET-1) is a key mediator in regulation of vascular tone and its enhanced production in SSc is believed to lead to vasoconstriction, vessel remodelling, local ischemia and ulcers of fingertips. Recently, an oral endothelin receptor antagonist, bosentan, has been proved to be effective in the treatment of SSc associated pulmonar arterial hypertension (PAH) and to decrease the development of new DU in patients with SSc. In this study, we assessed the occurrence of new DU in eight patients with SSc associated PAH and one SSc patient with recurrent DU refractory to standard vasodilatation therapy. All patients received bosentan at dosage of 62.5 mg bid for 4 weeks and 125 mg bid thereafter for one year. All patients had 3-4 DU of hands at baseline and one patients had also ulcers at lower limbs. In seven out of nine patients we did not record the occurrence of new DU and we also observed a 50% reduction of existing DU, whereas new DU occurred only in two patients. These data suggest that ET-1 plays a key role in DU induction in SSc patients and that ET-1 inhibition by bosentan can be an effective therapeutic strategy.     

Improvement of vascular endothelial function using the oral endothelin receptor antagonist bosentan in patients with systemic sclerosis

OBJECTIVE: Increased endothelin activity may play a role in the pathogenesis of vascular injury, a primary feature of systemic sclerosis (SSc; scleroderma). Our goal was to test the hypothesis that treatment with the oral endothelin receptor antagonist bosentan might improve vascular endothelial function in SSc patients. METHODS: A 4-week, prospective, parallel-group study compared 12 SSc patients who did not receive bosentan treatment with 12 patients who did receive treatment (125 mg/day) for pulmonary hypertension and/or digital ulcers. There were no differences in demographic and clinical characteristics or medications between the 2 groups. Baseline endothelial dysfunction was documented by decreased brachial artery ultrasound-derived flow-mediated dilation (FMD%; <5.5). Pulse wave analysis, venous occlusion plethysmography, and measurement of serum vascular markers were performed in parallel. RESULTS: FMD%, the main end point, increased significantly from a mean +/- SD of 3.1 +/- 1.3% to 8.4 +/- 2.6% after 4 weeks of bosentan treatment (P < 0.001, compared with a change from 2.4 +/- 1.6% to 2.4 +/- 2.2% in control patients). Arterial blood pressure, endothelium-independent vascular function, augmentation index, peripheral flow reserve, as well as circulating intercellular adhesion molecule 1, E-selectin, vascular endothelial growth factor, and endothelin 1 were not significantly affected by bosentan treatment. In patients continuously treated for 4 months, during which the dosage of bosentan remained at 125 mg/day (n = 5) or increased to 250 mg/day (n = 5), the 4-week results remained unchanged. CONCLUSION: Small doses of bosentan improve endothelial function without affecting hemodynamic parameters or endothelial activation-related processes, thus supporting a direct, reversible effect of endothelin in SSc-associated vascular injury. A long-term, controlled trial to examine the potentially global clinical benefit of endothelin receptor blockade in patients with early SSc may be warranted.     

Associations with digital ulcers in a large cohort of systemic sclerosis: Results from the Canadian Scleroderma Research Group registry

Objective

Digital ulcers are a common complication of systemic sclerosis (SSc; scleroderma). Approximately half of SSc patients have had a digital ulcer, but information is lacking on whether digital ulcers are associated with patient demographics and clinical outcomes. We wanted to determine the associations between digital ulcers and other SSc vascular complications and organ involvement.

Methods

Data from the Canadian Scleroderma Research Group are collected annually on SSc patients, including presence, location, and number of digital ulcers; complications from digital ulcers; internal organ involvement; skin score; and laboratory results. Correlation coefficients, chi‐square test, and logistic regression modeling were done to determine the associations of digital ulcers with other factors, including internal organ complications.

Results

A total of 938 patients were included; 86% were women, the mean age was 55 years, the mean disease duration was 13.6 years, and 50% had limited cutaneous SSc. Eight percent had a digital ulcer currently and 44% had a digital ulcer ever; 53.1% had digital pitting scars. Digital ulcers were associated with increased modified Rodnan skin score (P = 0.0001), hand and finger skin score (P = 0.0001), Health Assessment Questionnaire score (P = 0.0001) and disease duration (P = 0.001), younger age of SSc onset (P = 0.0001), interstitial lung disease (ILD; P = 0.0001), and topoisomerase I (Scl‐70) antibodies (P = 0.0001) in limited and diffuse cutaneous SSc subsets. Digital ulcers were not associated with sex (P = 0.95), smoking (P = 0.9), pulmonary arterial hypertension (PAH; P = 0.35), and scleroderma renal crisis (SRC; P = 0.569). Digital ulcers were further associated with reduced diffusing capacity for carbon monoxide (DLCO ; P = 0.0001) and esophageal involvement (P = 0.0001) in diffuse cutaneous SSc only.

Conclusion

Digital ulcers are associated with worse disease, including skin and lung involvement, but are not associated with PAH and SRC. However, the low DLCO that is associated with SRC could represent ILD or microvasculopathy.     

Long-term experience of bosentan for treating ulcers and healed ulcers in systemic sclerosis patients

OBJECTIVES: Our objective was to evaluate the efficacy and tolerability of bosentan in patients with systemic sclerosis (SSc) who develop ulcers and healed ulcers. We also wanted to analyse the effect of bosentan on other skin and general outcome measurements. METHODS: In the present prospective, observational, non-controlled study, we followed all patients with SSc who started treatment with bosentan for ischaemic ulcers and healed ulcers from January 2003 to June 2006 in our centre. We recorded skin and general outcome measurements at baseline and at 6 months. RESULTS: Fifteen patients were included. After a median follow-up of 24.7 months (range: 4-36), there was a significant decrease in the number of ulcers. A trend towards efficacy was seen in the number of healed ulcers and in the severity of ulcers. No significant effect was seen in other skin and general outcome measurements. Toxicity related to bosentan included mild transitory events and one toxic hepatitis. CONCLUSION: Bosentan may be a safe long-term alternative for treating the recurrence of skin ulcers and healed ulcers in SSc patients.     

Low occurrence of digital ulcers in scleroderma patients treated with bosentan for pulmonary arterial hypertension: a retrospective case–control study

Digital ulcers (DU) are one of the most common and debilitating manifestations of vasculopathy in systemic sclerosis (SSc). Their prevention is important in order to improve patients’ outcome and as a result of the economic impact they have on society. Randomised controlled studies have demonstrated that bosentan, an endothelin receptor antagonist, reduces the appearance of new DU. The aim of this retrospective study was to evaluate the occurrence of DU in a group of patients receiving long-term bosentan treatment for pulmonary arterial hypertension associated with SSc (PAH-SSc). Patients with PAH-SSc and treated with bosentan for at least 6 months (n?=?30) were evaluated. Thirty patients with SSc not treated with bosentan, but matched for sex, age, disease duration and cutaneous form of SSc, were considered as a control group. The occurrence of DU, defined as loss of tissue of varying degrees in the epidermis, dermis and subcutaneous tissue, was determined in the bosentan-treated and untreated groups. Mean duration of bosentan treatment was 3.6 years. DU were detected in six patients in the bosentan-treated group (20.0 %) and 16 patients (53.3 %) in the untreated group (p?=?0.0015). There were no significant differences in demographic or clinical characteristics between patients with or without DU at study end. The occurrence of DU in patients with PAH-SSc receiving long-term bosentan treatment was significantly lower than in untreated patients. The results from this long-term observational study provide valuable information on management of patients with PAH-SSc.     

Clinical correlation of brachial artery flow-mediated dilation in patients with systemic sclerosis

Abstract

Objective To investigate the clinical significance of flow-mediated dilation (FMD) in systemic sclerosis (SSc).

Methods Thirty-three SSc patients and 12 healthy controls were studied. Ultrasound assessment of the brachial artery FMD was performed on all subjects. The results were expressed as the percentage of increase in brachial artery diameter following hyperemia.

Results Limited cutaneous SSc (lcSSc) patients had significantly lower FMD values than healthy controls (5.3 ± 2.7 versus 7.7 ± 2.0 %, p < 0.05), while the values in diffuse cutaneous SSc (dcSSc) patients (6.7 ± 4.0 %) were comparable to those in lcSSc patients and healthy controls. Although FMD values did not correlate with any clinical features in dcSSc patients, there was an inverse correlation between FMD values and disease duration in lcSSc patients (r = ?0.64, p < 0.05). Furthermore, lcSSc patients with decreased FMD values showed significantly higher prevalence of digital ulcers and elevated right ventricular systolic pressure than those with normal values (for each; 75 versus 10 %, p < 0.05).

Conclusion The FMD values represent the severity of vascular damages, which progress along with disease duration and lead to digital ulcers and pulmonary arterial hypertension, in lcSSc patients.     

Improvement of plasma endothelin-1 and nitric oxide in patients with systemic sclerosis by bosentan therapy

The aim of this study was to evaluate the effects of bosentan on plasma endothelin-1 (ET-1) and nitric oxide (NO) as pulmonary hypertension (PH)-associated biochemical markers in patients with systemic sclerosis (SSc). Twenty-four SSc patients receiving bosentan for 24 weeks were registered in this prospective observational study. Ten patients were complicated with clinically suspected PH. Plasma levels of ET-1 and NO were assessed at baseline and after 24 weeks of treatment in SSc patients and in 15 healthy controls. Plasma levels of ET-1 and NO at baseline were significantly higher in SSc patients than in healthy controls (p < 0.000), and they were also significantly higher in SSc patients with PH than in those without PH (p < 0.01). Plasma ET-1 levels were significantly decreased after 24 weeks of bosentan therapy (p < 0.0001), and ET-1 levels of SSc patients with PH decreased to a level comparable to that in patients without PH. In the 10 SSc patients with PH, changes in plasma ET-1 levels during the 24 weeks of the study were significantly larger in the 5 patients whose functional class (FC) improved than in the 5 patients whose FC was unchanged (p < 0.05). Plasma NO levels were also slightly decreased in SSc patients after 24 weeks of bosentan therapy. Plasma ET-1 levels could reflect the presence and severity of PH in SSc patients. Additionally, changes in plasma ET-1 levels may indicate the response to bosentan therapy in SSc patients with PH.     

Ultrasound evaluation of the hands and wrists in patients with systemic sclerosis: Osteophytosis is a major contributor to tender joints

ObjectiveTo evaluate the prevalence and clinical associations of ultrasound (US) findings of inflammatory arthritis and joint and soft tissue pathology in patients with systemic sclerosis (SSc).MethodsThe hands and wrists of 43 SSc patients and 35 age-balanced controls were evaluated by clinical exam and musculoskeletal US. Synovial and tenosynovial pathology were assessed using semi-quantitative Gray Scale (GS) and Power Doppler (PD) scoring. US evaluation for osteophytes, erosions, ulnar artery occlusion, and median nerve cross-sectional areas was performed. Tender joints (TJ), swollen joints (SJ), modified Rodnan skin score (mRSS), digital ulcers, contractures, and calcinosis were evaluated. Concordance between US and physical exam findings at each joint region were assessed, and associations between their severity were analyzed.ResultsTJs and SJs were present in 44.2% and 62.8% of SSc patients, respectively. Inflammatory arthritis, defined as having both GS>0 and PD>0, was observed in 18.6% of SSc patients and no controls. There was a high concordance by joint region between GS synovial hypertrophy and osteophytes (κ=0.88) as well as TJs (κ=0.72). SSc patients had more osteophytes compared to controls (48.8% vs 22.9%, p = 0.018) as well as higher osteophyte severity (p = 0.033).ConclusionsDespite a high percentage of tender and swollen joints, less than 20% of SSc patients met criteria for inflammatory arthritis on US. The high concordance of osteophytes with GS synovial hypertrophy and tender joints suggest that osteophytosis may be a significant contributor to joint pain in SSc patients.     

Scleroderma digital ulcers complicated by infection with fecal pathogens

Objective

Digital ulcers represent one of the most frequent complications of systemic sclerosis (SSc; scleroderma); they are very painful, scarcely responsive to treatment, and often responsible for marked limitations on daily activities, including patient self‐care. Infectious complications may severely compromise the outcome of skin lesions in a significant percentage of patients. Numerous pathogens of different origin may be involved, including bacteria from patient endogenous flora. Here we evaluated the possible involvement of fecal pathogens in scleroderma digital ulcers.

Methods

Among a series of 82 SSc patients with digital ulcers, we retrospectively analyzed 42 subjects with clinical signs of local bacterial infection. All digital ulcers with suspected infection have been investigated by microbiologic examinations.

Results

Bacterial infection was confirmed in all 42 patients investigated; in particular, Staphylococcus aureus were the most frequently found (50%). Interestingly, 11 (26%) of 42 patients showed digital ulcers infected with intestinal bacteria; specifically, 7 patients were positive for Escherichia coli and 4 for Enterococcus faecalis. Diffuse cutaneous SSc patients were more numerous in this subgroup versus the other 31 patients (Fisher's P = 0.011).

Conclusion

A number of effective measures involving health care personnel and hospital environment are essential in the management of digital ulcers and prevention of infectious complications. In addition, the prevalence of fecal pathogens in one‐quarter of cases, never reported previously, suggests an important role of a patient's self‐care limitations, mainly during intercurrent home medications. Consequently, methodical education on hand hygiene of both patients and relatives, frequently involved in ulcer medications, is mandatory to avoid such deleterious complications.     

Antinuclear antibody-negative systemic sclerosis

ObjectiveTo examine the demographic and clinical characteristics of systemic sclerosis (SSc) patients without antinuclear antibodies (ANA) compared to ANA-positive patients.MethodsSSc patients enrolled in the Scleroderma Family Registry and DNA Repository were included. Relevant demographic and clinical data were entered by participating sites or obtained by chart review. ANA and SSc-related antibodies were determined in all investigated patients using commercially available kits at our laboratories.ResultsThis study included 3249 patients, of whom 208 (6.4%) were ANA negative. The proportion of male patients was higher in the ANA-negative group (OR = 1.65; p = 0.008). ANA-negative patients experienced less vasculopathic manifestations of SSc. The percent predicted diffusing capacity of carbon monoxide (DLCO) was higher in ANA-negative patients (p = 0.03). Pulmonary arterial hypertension (PAH) per right heart catheterization was less common in the ANA-negative group (OR = 0.28; p = 0.03). Furthermore, patients with negative ANA had a lower prevalence of telangiectasias and digital ulcers/pits (OR = 0.59, p = 0.03 and OR = 0.38, p = 0.01, respectively). Although diffuse cutaneous involvement was more common, the modified Rodnan Skin Score (mRSS) was lower in the ANA-negative group (2.4 points lower, p = 0.05). Furthermore, they experienced more malabsorption (p = 0.05). There was no difference in the frequency of pulmonary fibrosis or scleroderma renal crisis. All-cause mortality was not different between the 2 groups (p = 0.28).ConclusionsIn conclusion, the results of this study suggest that SSc patients who are ANA negative constitute a distinct subset of SSc with less vasculopathy (less PAH, digital ulcers, and fewer telangiectasias), a greater proportion of males, and possibly, more frequent lower gastrointestinal involvement.     

Effects of bosentan on the skin lesions: an observational study from a single center in Japan

Effects of a dual endothelin receptor antagonist, bosentan on peripheral circulatioin and skin lesions as well as pulmonary arterial hypertension (PAH) were investigated in Japanese patients with connective tissue diseases (CTD). Fifteen patients with PAH associated with CTD [systemic sclerosis (SSc) 13, mixed connective tissue disease (MCTD) 2] were treated with bosentan for 40–96 weeks, and changes of exercise capacity (6-min walk distance and Borg’s dyspnea scale), cardio-pulmonary hemodynamics (right ventricular pressure, specific activity scale and cardiac index), Raynaud’s phenomenon, digital ulcers and dermal sclerosis were observed. Bosentan improved exercise capacity, had a positive effect on hemodynamic parameters, and was well tolerated as previously reported. After a median 8 weeks of treatment, 13 out of 15 patients had improved Raynaud’s phenomenon. Digital ulcers also improved after a median 12 weeks’ treatment in all of 8 patients. Modified Rodnan total skin score decreased from 21.0 ± 5.9 to 11.5 ± 3.9 in diffuse cutaneous SSc and from 17.0 ± 6.5 to 9.5 ± 4.5 in limited cutaneous SSc after 24 months’ treatment, reaching significance after 6 months in both groups. These data suggest that bosentan is effective for both PAH and peripheral vascular diseases in Japanese patients with CTD. The pathological background to the improvement in dermal sclerosis observed in this study should be further investigated.     

Osteomyelitis complicating scleroderma digital ulcers

Skin ulcers are very frequent in scleroderma (SSc), often complicated by local infection; the latter may be responsible for osteomyelitis (OM) of underlying bone. We retrospectively investigate the prevalence of OM in our SSc patients. The study included 248 SSc patients (M/F 21/227, mean age 61?±?13.5 SD years) followed at our Rheumatology Unit for a mean time period of 60.8?±?20.9 SD months. Patients with infected skin ulcers were carefully evaluated for complicating OM, which was diagnosed on the basis of typical clinical symptoms, laboratory, and radiological alterations. Skin ulcers were observed in 119/248 (48 %) SSc patients, more frequently digital ulcers (110/119, 92 %). These patients presented a significantly lower mean age (59?±?14.5 SD vs. 64?±?12.2 SD years; p?=?0.005) and a lower percentage of anticentromere antibodies (40/119, 33.6 %, vs. 66/129, 51.2 %; p?=?0.007) compared with those without ulcers. The prevalence of OM in the entire SSc patients’ series was 7.7 % (19/248); it was invariably found in the setting of patients with infected digital ulcers, showing a surprisingly high percentage of underlying bone involvement (19/45, 42 %). The OM was localized at the hands in 14 patients and feet in 5; moreover, the most frequently isolated pathogens from infected digital ulcers were Staphylococcus aureus and Escherichia coli. Finally, patients with OM presented a significantly lower mean age (p?<?0.016) and higher percentage of anti-Scl70 autoantibodies (p?<?0.0128) compared to those without. We firstly demonstrated, in a large cohort of SSc patients, high prevalence of OM, invariably associated to infected digital ulcers, which represent the main predisposing condition for the development of such a harmful complication.     

Capillaroscopic skin ulcer risk index: A new prognostic tool for digital skin ulcer development in systemic sclerosis patients

Objective

Digital ulcerations are one of the most frequent manifestations of microangiopathy in patients with systemic sclerosis (SSc; scleroderma). The early detection of SSc patients who are at high risk to develop digital ulcers could allow a preventive treatment of these complications with reduction of morbidity and social costs. The aim of our study was to develop a capillaroscopic skin ulcer risk index (CSURI) that can predict the onset of new digital ulcers by using nailfold videocapillaroscopy (NVC) in patients with SSc.

Methods

We performed NVC in 120 consecutive unselected patients with SSc (13 men, 107 women, mean ± SD age 56.1 ± 13.4 years, mean ± SD SSc duration 44.7 ± 60.7 months) to assess the total number of capillaries in the distal row (N), maximum loop diameter (D), number of megacapillaries (M), and the M:N ratio.

Results

Within 3 months since NVC examination, 35 of 120 patients experienced digital ulcers. A significant association between ischemic lesions and the M:N ratio, N, and D was observed; the combination of these parameters allowed us to develop the CSURI, which is characterized by the formula D × M:N². A receiver operating characteristic curve analysis showed an area under the curve of 0.926 for ulcer appearance, with specificity and sensitivity of 85.9% and 94.3%, respectively, at the cutoff value of 2.94. Interestingly, 33 of 35 patients with new skin ulcers had a CSURI >2.94, but only 2 of 35 had a CSURI ≤2.94.

Conclusion

The proposed CSURI may represent a novel tool with the ability to predict the development of digital ulcers in patients with scleroderma.     

Systemic lupus erythematosus,complicated with refractory skin ulcers,treated successfully with bosentan

Abstract

A 20-year-old woman was admitted to our hospital because of bilateral pretibial edema. Administration of prednisolone was started after she was diagnosed with systemic lupus erythematosus (SLE). However, skin ulcers on her extremities developed; they subsequently worsened with tapering of prednisolone. She also developed pulmonary hypertension (PH). Her skin ulcers improved considerably after administration of bosentan, an endothelin receptor antagonist. Bosentan may be efficacious not only for PH but also for refractory skin ulcers.