Expert Perspectives On Clinical Challenges: Expert Perspectives: Challenges in Scleroderma.

You are consulted to evaluate a 56-year-old woman with known Raynaud's phenomenon, finger swelling of several; months' duration, and new hypertension with a blood pressure of 160/100 mm/Hg. She also reports progressive shortness of breath. Physical examination reveals telangiectasias, sclerodactyly, and proximal skin sclerosis (thick shiny skin on the chest and upper arms), and bibasilar crackles are found on chest examination. Laboratory tests reveal evidence of microangiopathic hemolytic anemia, thrombocytopenia, and elevation of the serum creatinine level (previously normal), and chest computed tomography shows evidence of ground-glass opacification in both lower lung fields.

Exploring the feasibility of an exercise programme including aerobic and resistance training in people with limited cutaneous systemic sclerosis.

OBJECTIVES: It is suggested that exercise can improve the vascular function and quality of life (QoL) in people with systemic sclerosis (SSc), potentially offering clinical benefits to this population. Yet the feasibility of such an intervention remains untested. Therefore, the purpose of this study is to examine the feasibility of a combined exercise protocol (aerobic and resistance training) in people with limited cutaneous SSc (lcSSc). METHODS: Thirty-two lcSSc patients (66.5 ± 12 years old) were randomly allocated in two groups (exercise and control group). The exercise group underwent a 12-week exercise programme, twice per week. All patients performed the baseline, three- and six-month follow-up measurements where functional ability, body composition and QoL were assessed. Participants' experiences were explored through interviews. RESULTS: Compliance was 92.6% with no dropouts. The individuals' confidence to participate in the study's exercise protocol for twice per week was 95%. The average value for the physical activity enjoyment scale was 103 ± 10 out of 119 (highest score). The mean values for the intention to engage in exercise twice per week were 6.4 ± 1 (likely) out of 7 (very likely). QoL for the exercise group showed to have a better life satisfaction, less anxiety and Raynaud's phenomenon-accompanied pain. CONCLUSIONS: Our results suggest that a combined exercise protocol was feasible for people with lcSSc, with no adverse events, resulting in high adherence and low attrition rates, high enjoyment levels and intentions for future engagement to this exercise. Thus, the specific protocol is a safe adjunct therapy for people with lcSSc. TRIAL REGISTRATION: ClinicalTrials.gov (NCT number): NCT03058887, February 23, 2017, https://clinicaltrials.gov/ct2/show/NCT03058887?term=NCT03058887&rank=1Key Points• High-intensity interval training in combination with resistance training constitutes a feasible exercise protocol for people with lcSSc.• Overall, the exercise programme demonstrated high adherence and enjoyment levels and low attrition rates.• The exercise protocol was proved to be safe with no adverse events for people with lcSSc.

Exploring the microcirculatory effects of an exercise programme including aerobic and resistance training in people with limited cutaneous systemic sclerosis.

PURPOSE OF THE STUDY: High intensity interval training (HIIT) is able to improve the endothelial-dependent microvascular function is people with limited cutaneous systemic sclerosis (lcSSc). Resistance training (RT) alone has shown significant improvements in the function of the vasculature; moreover, a combination of aerobic and RT have shown both in the past and recently to significantly improve the vascular function and the microcirculation. Therefore, the purpose of this study is to explore the effectiveness of a combined exercise protocol (aerobic and resistance training) on microvascular function in people with lcSSc. METHODS: Thirty-two lcSSc patients (66.5 ±â€¯12 years old) were randomly allocated in two groups (exercise and control group). The exercise group underwent a 12-week exercise programme twice per week. All patients performed the baseline, three- and six-month follow up measurements where microvascular function, transcutaneous oxygen tension (ΔTcpO2) and body composition were assessed. RESULTS: The time to peak endothelial-dependent reactivity was significantly improved (91 ±â€¯42 s, d = 1.06, p = 0.007) when compared to control group after the exercise intervention. Endothelial-independent function was also significantly improved (3.16 ±â€¯2, d = 1.17, p = 0.005) when compared to the control group. Baseline (5.71 ±â€¯4.4, p < 0.05)) and peak (15.4 ±â€¯7.5, p < 0.05) transcutaneous oxygen pressure were also significantly improved compared to the control group. CONCLUSIONS: Our results suggest that a combined exercise protocol (aerobic and RT) was effective in improving endothelial-dependent reactivity in people with lcSSc. The next step would be to explore its clinical- and cost- effectiveness. Therefore, we recommend a large, community-based intervention against standard pharmacotherapy only, which would assess these important factors and support a change in therapeutic protocols and guidelines for this clinical population. Trial registration ClinicalTrials.gov (NCT number): NCT03058887, February 23, 2017, https://clinicaltrials.gov/ct2/show/NCT03058887?term=NCT03058887&rank=1.

Systemic Sclerosis at an Intensive Care Unit: A Case Series and Literature Review.

INTRODUCTION: Systemic sclerosis (SSc) is a multisystemic autoimmune disease. Few studies have focused on the outcomes of SSC patients who require intensive care unit (ICU) admission, largely due to the absence of protocols for the optimal management of this disease during an ICU stay. OBJECTIVES: This study aimed to describe the outcomes of a series of SSc patients admitted to the ICU at a single center in Cali, Colombia. METHODS: Case series of SSc patients admitted to the ICU were reviewed. The main outcome was ICU mortality. Statistical analysis was performed with measures of central tendency and proportions. RESULTS: All the patients (n = 14) were female and either middle-aged or elderly; 9 (64%) were diagnosed with diffuse cutaneous sclerosis, and the remaining 5 patients with limited cutaneous sclerosis. Some were readmitted; therefore, the total number of ICU admissions was 21. The principal causes of ICU admissions were non-SSc-related causes (n = 15 [71.4%]). The respiratory system was the most involved on ICU admissions. The ICU mortality rate was 43% (n = 6). CONCLUSIONS: The severity of the disease at ICU admission and comorbidity are independently associated with ICU-related mortality. Furthermore, the optimal management of SSc patients includes accurate detection of SSc-associated organ involvement. More studies involving this category of patients are needed to establish the best effective protocols.

The effects of upper and lower limb exercise on the microvascular reactivity in limited cutaneous systemic sclerosis patients.

BACKGROUND: Aerobic exercise in general and high-intensity interval training (HIIT) specifically is known to improve vascular function in a range of clinical conditions. HIIT in particular has demonstrated improvements in clinical outcomes, in conditions that have a strong macroangiopathic component. Nevertheless, the effect of HIIT on microcirculation in systemic sclerosis (SSc) patients is yet to be investigated. Therefore, the purpose of the study was to compare the effects of two HIIT protocols (cycle and arm cranking) on the microcirculation of the digital area in SSc patients. METHODS: Thirty-four limited cutaneous SSc patients (65.3 ± 11.6 years old) were randomly allocated in three groups (cycling, arm cranking and control group). The exercise groups underwent a 12- week exercise program twice per week. All patients performed the baseline and post-exercise intervention measurements where physical fitness, functional ability, transcutaneous oxygen tension (ΔTcpO2), body composition and quality of life were assessed. Endothelial-dependent as well as -independent vasodilation were assessed in the middle and index fingers using LDF and incremental doses of acetylcholine (ACh) and sodium nitroprusside (SNP). Cutaneous flux data were expressed as cutaneous vascular conductance (CVC). RESULTS: Peak oxygen uptake increased in both exercise groups (p < 0.01, d = 1.36). ΔTcpO2 demonstrated an increase in the arm-cranking group only, with a large effect, but not found statistically significant,(p = 0.59, d = 0.93). Endothelial-dependent vasodilation improvement was greater in the arm-cranking (p < 0.05, d = 1.07) in comparison to other groups. Both exercise groups improved life satisfaction (p < 0.001) as well as reduced discomfort and pain due to Raynaud's phenomenon (p < 0.05). Arm cranking seems to be the preferred mode of exercise for study participants as compared to cycling (p < 0.05). No changes were observed in the body composition or the functional ability in both exercise groups. CONCLUSIONS: Our results suggest that arm cranking has the potential to improve the microvascular endothelial function in SSc patients. Also notably, our recommended training dose (e.g., a 12-week HIIT program, twice per week), appeared to be sufficient and tolerable for this population. Future research should focus on exploring the feasibility of a combined exercise such as aerobic and resistance training by assessing individual's experience and the quality of life in SSc patients. TRIAL REGISTRATION: ClinicalTrials.gov (NCT number): NCT03058887 , February 23, 2017.

Interstitial lung disease in systemic sclerosis: data from the spanish scleroderma study group.

OBJECTIVES: To evaluate the clinical characteristics of patients with interstitial lung disease (ILD) in the setting of a large cohort of systemic sclerosis (SSc) patients, and to analyse the differences according to the SSc subtype (following the modification of classification criteria of the American College of Rheumatology for SSc proposed by LeRoy and Medsger), factors are associated with moderate-to-severe impairment of lung function, as well as mortality and causes of death. METHODS: A descriptive study was performed, using the available data from the Spanish Scleroderma Study Group. RESULTS: Twenty-one referral centers participated in the registry. By April 2014, 1374 patients with SSc had been enrolled, and 595 of whom (43%) had ILD: 316 (53%) with limited cutaneous SSc (lcSSc), 240 (40%) with diffuse cutaneous SSc (dcSSc), and 39 (7%) with SSc sine scleroderma (ssSSc). ILD in the lcSSc and the ssSSc subsets tended to develop later, and showed a less impaired forced vital capacity (FVC) and a ground glass pattern on high-resolution computed tomography (HRCT) less frequently, compared with the dcSSc subset. Factors related to an FVC < 70% of predicted in the multivariate analysis were: dcSSc, positivity to anti-topoisomerase I antibodies, a ground glass pattern on HCRT, an active nailfold capillaroscopy pattern, lower DLco, older age at symptoms onset, and longer time between symptoms onset and ILD diagnosis. Finally, SSc-associated mortality and ILD-related mortality were highest in dcSSc patients, whereas that related to pulmonary arterial hypertension was highest in those with lcSSc-associated ILD. CONCLUSIONS: Our study indicates that ILD constitutes a remarkable complication of SSc with significant morbidity and mortality, which should be borne in mind in all three subgroups (lcSSc, dcSSc, and ssSSc).

Successful long-term (22 year) treatment of limited scleroderma using therapeutic plasma exchange: Is blood rheology the key?

While a number of studies have shown short-term beneficial effects of therapeutic plasma exchange (TPE) for treating systemic scleroderma (SSc), there have been no reports on the very long-term usage of TPE as the sole systemic treatment intervention. We report the case of a male patient, originally diagnosed with limited systemic scleroderma (lcSSc) in early 1990, who has been undergoing regular plasmapheresis treatments for more than 22 years, beginning in late 1993. Prior to commencing treatment, the patient exhibited symptoms including severe gastro esophageal reflux disease (GERD) with esophagitis, frequent Raynaud's attacks, reduced lung function, and chronic chilling. With the exception of mild residual Raynaud's, all of the patient's symptoms reversed after three years of regular TPE treatments and he remains in complete remission. While the typical explanation for the therapeutic benefits seen with TPE focuses on temporary reduction of circulating antibodies or other pathogenic factors, we propose instead an explanation based on abnormal blood rheology as a novel disease pathogenesis model for SSc.

Systemic sclerosis sine scleroderma: a multicenter study of 1417 subjects.

OBJECTIVE: To describe the clinical and serological features of systemic sclerosis sine scleroderma (ssSSc) in a multicentered SSc cohort. METHODS: Data from 1417 subjects in the Canadian Scleroderma Research Group registry were extracted to identify subjects with ssSSc, defined as SSc diagnosed by an expert rheumatologist, but without any sclerodactyly or skin involvement prior to baseline study visit or during followup. Clinical and serological features of ssSSc subjects were compared to limited (lcSSc) and diffuse cutaneous SSc (dcSSc) subjects. RESULTS: At the first registry visit, only 57 subjects (4.0%) were identified as having ssSSc. Of these, 30 (2.1%) were reclassified as lcSSc within 1.9 years. Thus, only 27 ssSSc subjects (1.9%) remained, with mean followup of 2.4 years. Clinical profiles of ssSSc were generally similar or milder compared to lcSSc, and milder than dcSSc, including rates of interstitial lung disease (25.9% ssSSc, 25.4% lcSSc, 40.3% dcSSc). Patients with ssSSc had serological profiles similar to those with lcSSc, including high rates of anticentromere antibodies (50.0% ssSSc, 47.5% lcSSc, 12.1% dcSSc), and low rates of antitopoisomerase I (16.7% ssSSc, 7.0% lcSSc, 21.8% dcSSc) and anti-RNA polymerase III (0 ssSSc, 11.1% lcSSc, 34.9% dcSSc). CONCLUSION: The condition ssSSc is rare and resembles lcSSc. These observations suggest that ssSSc is most likely a forme fruste of lcSSc, and that the absence of skin involvement may in part be related to misclassification arising from early or subtle skin involvement. There is little evidence to consider ssSSc as a distinct clinical or serological subset of SSc.

[Clinical and capillaroscopic regression of CD30 anaplastic lymphoma associated with limited cutaneous systemic sclerosis following autologous bone marrow transplantation]. / Régression clinique et capillaroscopique après autogreffe de moelle d'une sclérodermie systémique cutanée limitée associée à un lymphome anaplasique CD30.

BACKGROUND: In rare cases, tumors are associated with secondary Raynaud's phenomenon in systemic sclerosis (SSc). We report the case of a patient presenting cutaneous limited SSc associated with CD30 anaplastic lymphoma with cutaneous and lymph node involvement in whom the capillaroscopic scleroderma pattern regressed completely after autologous bone marrow transplantation, with complete remission of the lymphoma. CASE REPORT: A 37-year-old man presented bilateral Raynaud's phenomenon associated with digital ulcers contracted one year earlier but subsequently neglected. Right axillary lymph nodes and regional cutaneous tumors were present, leading to the diagnosis of CD30+ anaplastic lymphoma with cutaneous and lymph node involvement. Chemotherapy containing cyclophosphamide achieved only partial remission of the lymphoma. Clinical examination showed bilateral Raynaud's phenomenon, sclerodactyly, a right axillary subcutaneous nodule and a pathological Allen's test for the right hand. Antinuclear antibodies were positive without any other immunological abnormalities, and capillaroscopy showed an SSc pattern with numerous megacapillaries. Digital blood pressure was reduced in the right index and the left middle fingers, in which ulcers of the pulp were observed. Bone marrow transplantation was performed, resulting in complete remission of the lymphoma and disappearance of the sclerodactyly, with no recurrence of the pulp ulcers and complete normalization of capillaroscopic appearance and digital pressure. DISCUSSION: This case raises the question of authentic SSc and neoplasia and highlights the importance of capillaroscopy in the follow-up of SSc. The complete regression of SSc and of capillaroscopic abnormalities could be explained by the paraneoplastic nature of SSc or by the direct action of the chemotherapy and bone marrow transplantation.

Bath psoralen-UVA photochemotherapy for localized scleroderma: experience from a single institute.

BACKGROUND: Localized scleroderma (LS) comprises a spectrum of sclerotic autoimmune diseases primarily affecting the dermis. Various treatment modalities have been recommended for the management of LS, but only a few studies exist regarding the efficacy of bath PUVA photochemotherapy in the treatment of LS. OBJECTIVES: To evaluate the efficacy of bath PUVA photochemotherapy in the management of LS in a retrospective study. METHODS: Twenty-eight patients (23 women and five men) with a diagnosis of LS, confirmed by histology, were included in the study. Patients were treated with a thrice-weekly regimen of bath immersion in 0.2 mg/1 water solution of 8-methoxypsoralen, followed by irradiation with UVA. RESULTS: Eleven patients (39%) showed complete remission (complete softening of the sclerotic plaques with or without postinflammatory hyper- or hypopigmentation) after a mean of 71 treatments (range 33-170) and a mean cumulative dose of 115 J/cm(2) (range 11-232). Partial softening and regression of the sclerotic plaques was observed in 14 patients (50%). Three patients (10.7%) showed no effect, and in none of the patients was worsening noted during treatment. CONCLUSIONS: In our experience, bath PUVA photochemotherapy is an effective and well-tolerated treatment option for LS and should be considered as one of the first-line treatment modalities.

Cardiac involvement and treatment-related mortality after non-myeloablative haemopoietic stem-cell transplantation with unselected autologous peripheral blood for patients with systemic sclerosis: a retrospective analysis.

BACKGROUND: Autologous haemopoietic stem-cell transplantation (HSCT) benefits patients with systemic sclerosis but has been associated with significant treatment-related mortality and failure to improve diffusion capacity of carbon monoxide (DLCO). We aimed to assess efficacy of HSCT and use of rigorous cardiac screening in this group. METHODS: We assessed patients with diffuse systemic sclerosis or limited systemic sclerosis and interstitial lung disease who were treated with HSCT as part of a study or on a compassionate basis at Northwestern University (Chicago, IL, USA) or the University of São Paulo (Ribeirão Preto, Brazil). Unselected peripheral blood stem cells were harvested with cyclophosphamide (2 g/m(2)) and filgrastim. The transplant regimen was a non-myeloablative regimen of cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulin (rATG; 4·5-6·5 mg/kg). We followed patients up to 5 years for overall survival, relapse-free survival, modified Rodnan skin score, and pulmonary function tests. FINDINGS: Five (6%) of 90 patients died from treatment-related causes. Despite standard guidelines that recommend echocardiogram for screening before transplantation, four treatment-related deaths occurred because of cardiovascular complications (one constrictive pericarditis, two right heart failures without underlying infection, and one heart failure during mobilisation), and one death was secondary to sepsis without documented underlying heart disease. Kaplan-Meier analysis showed survival was 78% at 5 years (after eight relapse-related deaths) and relapse-free survival was 70% at 5 years. Compared with baseline, we noted improvements after HSCT in modified Rodnan skin scores at 1 year (58 patients; p<0·0001), 2 years (42 patients; p<0·0001), and 3 years (27 patients; p<0·0001) and forced vital capacity at 1 year (58 patients; p=0·009), 2 years (40 patients; p=0·02), and 3 years (28 patients; p=0·004), but total lung capacity and DLCO were not improved significantly after HSCT. Overall mean DLCO was significantly improved in patients with normal baseline echocardiograms (p=0·005) or electrocardiographs (p=0·05). INTERPRETATION: Autologous HSCT with a non-myeloablative regimen of cyclophosphamide and rATG with a non-selected autograft results in sustained improvement in skin thickness and forced vital capacity. DLCO is affected by baseline cardiac function. Guidelines for cardiac screening of patients with systemic sclerosis to assess treatment-related risk from pulmonary artery hypertension, primary cardiac involvement, or pericardial disease should be reconsidered and updated. FUNDING: None.

[Some aspects of systemic and localized (limited) sclerosis in children]. / Twardzina ukladowa i miejscowa (ograniczona) u dzieci--wybrane aspekty.

Sclerosis is a rare connective tissue disease. Uncontrolled process of fibrosis and collagen accumulation in the tissues leads to functional impairment and structural changes in the skin and internal organs. A leading role in the pathogenesis of sclerosis is played by the interrelated mechanism of vascular injury, immune changes, and fibroblast activation. Fibrosis of the connective tissue of the skin and internal organs determines two forms of the disease: systemic sclerosis and localized (often called limited) sclerosis. Despite similarities in the histopathology of the skin, these two types differ fundamentally as to course and prognosis. The prevalence of sclerosis among children has not been determined. 2% to 11.5% of adults with systemic sclerosis noted the onset of the disease before the age of 16 years. The onset was prior to 10 years of age in 1% to 2% of adult patients. According to some authors, localized sclerosis is found approximately 2.7 per 100,000 thousand of children, 3 to 4 times more often in girls especially in the preschool and early school age. Localized sclerosis is seen 9 to 10 times more often than systemic sclerosis. This work discussed diagnostic criteria, differential diagnosis, and prognosis of sclerosis in children were.

Profile of gastrointestinal involvement in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease. Of the numerous organ manifestations, involvement of the upper and lower gastrointestinal tract (GIT) appears to be the most frequent with regard to the clinical symptoms. However, as the frequency and clinical relevance of GI involvement in patients with SSc are not known in detail, the German network of the systemic sclerosis (DNSS) has developed a detailed questionnaire to evaluate the extent and profile of gastrointestinal involvement in SSc patients. The multi-symptom questionnaire was used at baseline and after 1 year in registered patients of the DNSS. In addition, the results were compared with gastrointestinal disorders in patients with SSc and other rheumatic diseases, as well as with the medical history of the patients. In total, 90 patients were included in the study. The results of the study show that in reality, a much higher (nearly all) percentage of (98,9%) patients than expected suffer from GI-symptoms, regardless of the stage of their disease. Of these, meteorism (87,8%) was the most common followed by coughing/sore voice (77,8%), heartburn (daytime 68,9%, nighttime 53,3%), diarrhea (67,8%), stomach ache (68,9%) and nausea (61,1%). Although SSc patients were treated according to the respective recommendations, only limited improvements with regard to GI-symptoms could be achieved after 1 year of follow-up. In addition, the study revealed that the multi-symptom questionnaire is a useful tool to contribute to identify the gastrointestinal sequelae in systemic sclerosis.