Biomarker analysis from the phase 2b randomized placebo-controlled trial of riociguat in early diffuse cutaneous systemic sclerosis.

OBJECTIVE: To examine disease and target engagement biomarkers in the RISE-SSc trial of riociguat in early diffuse cutaneous systemic sclerosis and their potential to predict the response to treatment. METHODS: Patients were randomized to riociguat (n = 60) or placebo (n = 61) for 52 weeks. Skin biopsies and plasma/serum samples were obtained at baseline and week 14. Plasma cyclic guanosine monophosphate (cGMP) was assessed using radio-immunoassay. Alpha smooth muscle actin (αSMA) and skin thickness were determined by immunohistochemistry, mRNA markers of fibrosis by qRT-PCR in skin biopsies, and serum CXC motif chemokine ligand 4 (CXCL-4) and soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1) by enzyme-linked immunosorbent assay. RESULTS: By week 14, cGMP increased by 94 ± 78% with riociguat and 10 ± 39% with placebo (p < 0.001, riociguat vs placebo). Serum sPECAM-1 and CXCL-4 decreased with riociguat vs placebo (p = 0.004 and p = 0.008, respectively). There were no differences in skin collagen markers between the 2 groups. Higher baseline serum sPECAM-1 or the detection of αSMA-positive cells in baseline skin biopsies were associated with a larger reduction of modified Rodnan skin score from baseline at week 52 with riociguat vs placebo (interaction P-values 0.004 and 0.02, respectively). CONCLUSION: Plasma cGMP increased with riociguat, suggesting engagement with the nitric oxide-soluble guanylate cyclase-cGMP pathway. Riociguat was associated with a significant reduction in sPECAM-1 (an angiogenic biomarker) vs placebo. Elevated sPECAM-1 and the presence of αSMA-positive skin cells may help to identify patients who could benefit from riociguat in terms of skin fibrosis. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02283762.

Associations of Digital Ulcers in Patients with Systemic Sclerosis: An 8-Year Retrospective Study.

INTRODUCTION: This study aimed to investigate the associations of digital ulcers (DUs) in patients with systemic sclerosis (SSc). METHODS: This retrospective study investigated the demographic characteristics, specific autoantibodies, organ involvement, and laboratory tests in patients with SSc from our hospital. RESULTS: This study enrolled 144 patients with SSc. The DU+ group consisted of 15 (10.4%) patients. Patients with SSc having DUs have longer disease duration, higher fibrinogen, higher fibrin degradation product, and lower cholesterol. None of the patients used cholesterol-lowering drugs before onset of DUs. The study also demonstrated a higher prevalence of anti-dsDNA and anti-histone antibodies in patients with SSc with DUs. Anti-dsDNA antibody is a specific antibody for SLE with a specificity of 96-99%. A total of 86.1% (124/144) of patients suffered from diffuse cutaneous SSc, and 28.5% (41/144) of patients suffered from overlap syndrome. CONCLUSION: Our study indicated that patients with SSc with fibrinogen of >2.895 g/L (p = 0.043) and cholesterol of <3.340 mmol/L (p = 0.036), which is equal to 129.258 mg/dL, are at high risk of developing DUs.

Systemic Sclerosis and Pulmonary Disease.

Systemic sclerosis is a complex, often progressive, multisystem autoimmune disease. It is commonly categorized into limited cutaneous or diffuse cutaneous systemic sclerosis. There is near universal involvement of skin fibrosis and gastrointestinal dysfunction, but lung disease is not only common but also a most serious complication. Severe lung disease is the top cause of mortality, displacing scleroderma renal crisis as the leading cause of death. Whether there is limited cutaneous or diffuse cutaneous manifestations can be predictive of what type of lung disease that can present in the patient. Limited cutaneous systemic sclerosis patients tend to have pulmonary hypertension whereas diffuse cutaneous systemic sclerosis patients tend to have interstitial lung disease. There are more rare phenotypes associated with antibodies Th/To and U3RNP that can have both pulmonary hypertension and interstitial lung disease concomitantly. There are inherent challenges in the management for both pulmonary hypertension and interstitial lung disease but with the focus on early diagnosis for each of these lung complications, treatment may have a higher chance of efficacy.

The role of innate immune cells in systemic sclerosis in the context of autologous hematopoietic stem cell transplantation.

Systemic sclerosis (SSc) is a complex, heterogeneous autoimmune connective tissue disease. Autologous hematopoietic stem-cell transplantation (AHSCT) has emerged as a valuable treatment option for rapidly progressive diffuse cutaneous SSc (dcSSc) patients, and thus far is the only treatment that has been shown to have a long-term clinical benefit. AHSCT is thought to reintroduce immune homeostasis through elimination of pathogenic self-reactive immune cells and reconstitution of a new, tolerant immune system. However, the mechanism of action underlying this reset to tolerance remains largely unknown. In this study we review the immune mechanisms underlying AHSCT for SSc, with a focus on the role of the innate immune cells, including monocytes and natural killer (NK) cells, in restoring immune balance after AHSCT.

Skin improvement is a surrogate for favourable changes in other organ systems in early diffuse cutaneous systemic sclerosis.

OBJECTIVES: Skin improvement in diffuse cutaneous SSc (dcSSc), measured with modified Rodnan skin score (mRSS), is frequently used as a primary outcome in clinical trials, but it is uncertain whether mRSS changes reflect changes in other organ systems. This aim of this study was to explore if skin changes in early dcSSc over 1 and 2 years are associated with changes in severity of other organ involvement. METHODS: Canadian Scleroderma Research Group database patients with dcSSc, disease duration of ≤5 years, no evidence of initial end-stage organ damage and/or significant comorbidity who had 1 year (n = 154) and 2 years (n = 128) of follow-up data were included. mRSS changes of 25% and/or ≥5 points were considered significant. Organ involvement was assessed by Medsger Disease Severity Score and Canadian Scleroderma Research Group definitions using bivariate, chi-square, ANOVA, adjusted regression and longitudinal mixed effect model analyses. RESULTS: Improvement in mRSS was found in 41% of patients at 1 year and in 50% at 2 years. Improved patients showed less forced vital capacity decline (P = 0.012) and less frequent new cardiac involvement (P = 0.02) over 1 year, as well as better lung (by both Disease Severity Score, P = 0.006, and Δforced vital capacity%, P = 0.026), peripheral vascular (P = 0.006) and joint/tendon (P = 0.002) involvement over 2 years. mRSS worsening was consistently linked to less favourable lung outcomes at both 1- and 2-year follow-up visits, and more severe gastrointestinal disease at 2 years. CONCLUSION: Changes in lung function in early dcSSc closely parallel skin changes. mRSS improvement reflects better prognosis for visceral disease and may be a reliable outcome measure in clinical trials.

Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort.

OBJECTIVES: To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). METHODS: We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, valid mRSS at 12±3 months after baseline and ≥1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS >5 and ≥25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. RESULTS: Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ≥10% (53.6% vs 34.4%; p<0.001) and all-cause death (15.4% vs 7.3%; p=0.003) than non-progressors. These significant associations were also found in subgroup analyses of patients with either low baseline mRSS (≤22/51) or short disease duration (≤15 months). In multivariable analyses, skin progression within 1 year was independently associated with FVC decline ≥10% (HR 1.79, 95% CI 1.20 to 2.65) and all-cause death (HR 2.58, 95% CI 1.31 to 5.09). CONCLUSIONS: Progressive skin fibrosis within 1 year is associated with decline in lung function and worse survival in dcSSc during follow-up. These results confirm mRSS as a surrogate marker in dcSSc, which will be helpful for cohort enrichment in future trials and risk stratification in clinical practice.

Characteristics of patients with systemic sclerosis living in Qatar.

Objective: The aim of this study was to determine the demographic, clinical, and immunological characteristics of patients with systemic sclerosis living in Qatar. Method: This retrospective study included 42 patients with systemic sclerosis who attended Rheumatology Clinics at Hamad General Hospital in Doha, Qatar, between January 2000 and December 2014. All patients fulfilled the 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis. Results: The 42 consecutively recruited patients of mixed ethnicities consisted of 37 (88.1%) females and 5 (11.9%) males. Of the total 42 patients, 22 (52.4%) had diffuse cutaneous systemic sclerosis (dcSSc) and 20 (47.6%) had limited cutaneous systemic sclerosis (lcSSc). Mean age at onset of first symptoms was 34.5 ± 12 years, and mean age at diagnosis was 36.1 ± 11.5 years. During follow-up, Raynaud's phenomenon occurred in 36 (85.7%) patients, sclerodactyly in 39 (92.9%) patients, digital ulcers in 16 (38.1%) patients, calcinosis in 6 (14.3%) patients, telangiectasia in 16 (38.1%) patients, and arthritis in 13 (31%) patients. The gastrointestinal and respiratory systems were the most frequently affected internal organs. Gastrointestinal involvement was present in 36 (85.7%) patients, and respiratory involvement was found in 30 (71.4%) patients. The majority of patients had positive antinuclear antibodies (ANA; 97.6%). Anti-Scl-70 antibody was found in 66.7% and anti-centromere antibody (ACA) was detected in 14.3% of the patients. Conclusion: To our knowledge, this is the first study that describes the clinical and immunological profile of patients with systemic sclerosis living in Qatar. This study cohort showed an earlier age of disease onset and diagnosis than that reported in other international studies. Furthermore, in contrast to several other studies, the diffuse type of scleroderma was more commonly observed than the limited type, which resulted in a high frequency of anti-Scl-70 antibody and interstitial lung disease.

Disability, fatigue, pain and their associates in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study.

Objectives: Our aim was to describe the burden of early dcSSc in terms of disability, fatigue and pain in the European Scleroderma Observational Study cohort, and to explore associated clinical features. Methods: Patients completed questionnaires at study entry, 12 and 24 months, including the HAQ disability index (HAQ-DI), the Cochin Hand Function Scale (CHFS), the Functional Assessment of Chronic Illness Therapy-fatigue and the Short Form 36 (SF36). Associates examined included the modified Rodnan skin score (mRSS), current digital ulcers and internal organ involvement. Correlations between 12-month changes were also examined. Results: The 326 patients recruited (median disease duration 11.9 months) displayed high levels of disability [mean (s.d.) HAQ-DI 1.1 (0.83)], with 'grip' and 'activity' being most affected. Of the 18 activities assessed in the CHFS, those involving fine finger movements were most affected. High HAQ-DI and CHFS scores were both associated with high mRSS (ρ = 0.34, P < 0.0001 and ρ = 0.35, P < 0.0001, respectively). HAQ-DI was higher in patients with digital ulcers (P = 0.004), pulmonary fibrosis (P = 0.005), cardiac (P = 0.005) and muscle involvement (P = 0.002). As anticipated, HAQ-DI, CHFS, the Functional Assessment of Chronic Illness Therapy and SF36 scores were all highly correlated, in particular the HAQ-DI with the CHFS (ρ = 0.84, P < 0.0001). Worsening HAQ-DI over 12 months was strongly associated with increasing mRSS (ρ = 0.40, P < 0.0001), decreasing hand function (ρ = 0.57, P < 0.0001) and increasing fatigue (ρ = -0.53, P < 0.0001). Conclusion: The European Scleroderma Observational Study highlights the burden of disability in early dcSSc, with high levels of disability and fatigue, associating with the degree of skin thickening (mRSS). Impaired hand function is a major contributor to overall disability.

Anti-RNA polymerase III antibody-associated scleroderma renal crisis in a patient with limited cutaneous systemic sclerosis: A case report.

A 69-year-old Japanese man was presented with hypertensive crisis. Renal histology revealed malignant nephrosclerosis, including an onion skin pattern with fibrinoid necrosis of the small arteries from arterioles up to interlobular arteries. Immunological investigation clarified positive anti-RNA polymerase (RNAP) III antibody, and limited cutaneous systemic sclerosis (Lc SSc) was diagnosed by skin biopsy as the underlying disease causing scleroderma renal crisis (SRC). Angiotensin covering enzyme (ACE) inhibitor therapy and calcium antagonist were effective for his renal condition. Although an association between SRC and anti-RNAP III antibody has already been reported in patients with diffuse cutaneous SSc (Dc SSc), this case indicates that SRC with hypetensive emergency with malignant nephrosclerosis can also be diagnosed on patients with Lc SSc patients by the examination of anti-RNAP III antibody.

Rituximab in diffuse cutaneous systemic sclerosis: should we be using it today?

There is new evidence that B-cell depletion could be an effective intervention in patients with SSc. Observational case-control study data from the European League Against Rheumatism Scleroderma Trials and Research group has suggested that rituximab therapy may reduce progression of skin thickening and lung fibrosis, especially in a subgroup with early dcSSc. These positive data remain preliminary and need to be viewed with caution, recognizing the spontaneous regression of skin thickening that may occur during early disease. In this review, we summarize the clinical evidence for the therapeutic use of rituximab in SSc as well as the basic science evidence suggesting that B cells and autoantibodies are the primary drivers of fibrosis in skin and lung tissue. We have also reviewed the parallels between SSc and the other CTDs where B-cell depletion therapy is efficacious.

Pharmacokinetics of Fipaxalparant, a Small-Molecule Selective Negative Allosteric Modulator of Lysophosphatidic Acid Receptor 1, and the Effect of Food in Healthy Volunteers.

Dysregulated lysophosphatidic acid receptor 1 (LPAR1) signaling is implicated in fibrotic diseases, including systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF). Fipaxalparant (HZN-825) is a small molecule acting as a negative allosteric modulator of LPAR1 and is in phase 2 clinical evaluations for treating diffuse cutaneous SSc and IPF. This open-label, phase 1 study examined the pharmacokinetics (PKs), food effect, and safety of fipaxalparant in healthy volunteers. Dose proportionality was evaluated for fipaxalparant single doses of 150, 300, and 450 mg under fasted conditions. Food effect was tested with a 450-mg single dose under fasted conditions or with a high-fat meal. Multiple-dose PKs for twice-daily dosing of either 300 or 450 mg with low- or high-fat meals was also assessed. Fipaxalparant was safe and well tolerated in healthy volunteers (n = 36) under all conditions. Fipaxalparant exposure increased in a less than dose-proportional manner from 150 to 450 mg. At 450 mg, a high-fat meal increased the maximum observed concentration and area under the curve by approximately 1.9- and 2.1-fold, respectively. These results, combined with prior preclinical and phase 2a data, informed dose selection of fipaxalparant 300 mg once and twice daily with a meal for phase 2b studies.

Acute Respiratory Distress Syndrome in a Patient With Systemic Sclerosis: A Case of a Life-Threatening Complication.

Numerous pulmonary conditions, such as aspiration pneumonia and acute respiratory distress syndrome (ARDS), may result from aspiration of gastric or oropharyngeal contents passing into the lower respiratory tract. ARDS is a type of diffuse lung injury that is distinguished by the abrupt onset of extensive pulmonary inflammation accompanied by the failure of multiple organ systems. Systemic sclerosis is an uncommon connective tissue disorder that presents with skin thickening, the etiology of which remains unknown. Esophageal luminal dilatation is observed in the distal third of the esophagus in most cases of systemic sclerosis. This dilatation is primarily attributed to the greater abundance of smooth muscle fibers in this area. Here, we present the case of a 70-year-old female patient who was diagnosed clinically with diffuse systemic sclerosis and fulfilled the 2013 European League Against Rheumatism/American College of Rheumatology classification criteria. She had esophageal dilatation, with an esophageal luminal diameter measured at the upper, middle, and lower thoracic esophagus of 2.5 cm, 2.5 cm, and 3.5 cm, respectively. The patient was admitted to the intensive care unit (ICU) due to ARDS from aspiration pneumonia. Our patient's complicated condition at the time of ICU admission with ARDS secondary to aspiration pneumonia was primarily due to esophageal dilatation and reflux. Aggressive anti-reflux pharmacotherapy and bed elevation may be beneficial in preventing pulmonary injury caused by aspiration. Esophageal complications are common in such patients and can have a substantial impact on the prognosis and quality of life. Regular medical attention is necessary to identify and manage any potential issues.

Salivary Flow Rate and Oral Status in Patients with Primary Sjögren's Syndrome and Diffuse Cutaneous Systemic Sclerosis: A Cross-Sectional Study.

Determination of salivary flow rate and oral status in patients with primary Sjögren's Syndrome (pSS) and diffuse cutaneous systemic sclerosis (dcSSc) and comparison with control subjects. Thirty-one pSS patients, 28 dcSSc patients, and 28 control subjects participated in this single-center, cross-sectional study. Unstimulated whole salivary flow rate (UWSFR) and stimulated whole salivary flow rate (SWSFR), salivary pH, DMFT index (D-decayed, M-missing, F-filled tooth), periodontal pocket depth (PPD), clinical attachment level (CAL), interincisal distance, and OHRQoL (oral health-related quality of life) were analyzed in all three groups of subjects. Primary SS and dcSSc patients had statistically significant lower values of UWSFR (0.20; 0.38 vs. 0.91 mL/min) and SWSFR (0.56; 0.70 vs. 1.64 mL/min) compared with control subjects (p < 0.001, Kruskal-Wallis test). Salivary pH values were statistically significantly lower in pSS and dcSSc patients compared with control subjects (6.00; 6.25 vs. 7.00, respectively) (p < 0.001, Kruskal-Wallis test). The DMFT index of dcSSc patients was higher (28.50) and statistically significant compared to control subjects (20.00) (p = 0.01). The prevalence of periodontitis was the same in pSS and dcSSc patients and control subjects (p = 0.384). Primary SS and dcSSc patients had a statistically significant decreased interincisal distance compared to control subjects (43.80; 38.00 vs. 48.00) (p = 0.003 and p < 0.001, respectively). Primary SS and dcSSc patients show decreased UWSFR and SWSFR, salivary pH values closer to an acidic medium, higher DMFT index, higher prevalence of periodontitis, decreased interincisal distance, and poorer OHRQoL, i.e., poor oral and periodontal health.

Rapid Progression of Skin Sclerosis Following Surgery for Carpal Tunnel Syndrome: A Case of Diffuse Cutaneous Systemic Sclerosis.

Carpal tunnel syndrome (CTS) is a frequently encountered compressive neuropathy that is often treated surgically. Here, we present an unusual case of a 74-year-old female who developed a rapid emergence of skin sclerosis following CTS surgery. The condition was initially misdiagnosed as complex regional pain syndrome. However, since her skin condition progressed, she was referred to the rheumatology department. Subsequent evaluations confirmed the diagnosis of diffuse cutaneous systemic sclerosis, accompanied by interstitial lung disease. Treatment with mycophenolate mofetil did not notably alter the interstitial lung shadows but led to minor improvement in skin sclerosis. It is crucial to consider the possibility of rheumatic diseases in patients with unexpected postoperative symptoms.

Comprehensive description of the prevalence, serological and clinical characteristics, and visceral involvement of systemic sclerosis (scleroderma) in a large cohort from the United Arab Emirates Systemic Sclerosis Registry.

Systemic sclerosis is an autoimmune condition characterized by a wide range of clinical presentations. Registries may serve to expand understanding about systemic sclerosis and aid in patient care and follow-up. The objective of this study was to analyze the prevalence of systemic sclerosis in a large cohort from the United Arab Emirates Systemic Sclerosis Registry and find the significant similarities and differences between the different subsets. All scleroderma patients in the United Arab Emirates were included in this multicenter national retrospective analysis. Data on demographics, comorbidities, serological characteristics, clinical aspects, and treatment were collected and analyzed, highlighting the most common traits identified. A total of 167 systemic scleroderma patients from diverse ethnic backgrounds were enrolled. Overall, 54.5% (91/167) of the patients were diagnosed with diffuse cutaneous systemic sclerosis, and 45.5% (76/167) with limited cutaneous systemic sclerosis. The prevalence of systemic sclerosis was 1.66 per 100,000 for the total registry and 7.78 per 100,000 for United Arab Emirates patients. Almost all patients in the diffuse cutaneous systemic sclerosis and limited cutaneous systemic sclerosis groups tested positive for the immunofluorescence antinuclear antibody. Antibodies against Scl-70 were significantly more associated with diffuse cutaneous systemic sclerosis, whereas anticentromere antibodies were significantly more associated with the limited cutaneous systemic sclerosis group (p < 0.001). Sclerodactyly, shortness of breath, and digital ulcers were more common in diffuse cutaneous systemic sclerosis patients compared with the limited cutaneous systemic sclerosis subtype in terms of clinical symptoms and organ involvement. Telangiectasia was much more common in the limited cutaneous systemic sclerosis group. Furthermore, diffuse cutaneous systemic sclerosis patients had more lung fibrosis (interstitial lung disease) than limited cutaneous systemic sclerosis patients (70.5% vs 45.7%), and pulmonary arterial hypertension was twice as common in limited cutaneous systemic sclerosis patients as it was in diffuse cutaneous systemic sclerosis patients. Local registries are paramount to understanding the clinical/serological characteristics of scleroderma. This study emphasizes the importance of raising disease awareness and distinguishing between the various systemic sclerosis subsets to implement patient-tailored strategies for early detection, better management, and higher quality of care.

Native T1 mapping in early diffuse and limited systemic sclerosis, and its association with diastolic function.

BACKGROUND: Systemic sclerosis (SSc) is divided into diffuse and limited cutaneous SSc (dcSSc and lcSSc). The dcSSc subtype has more severe internal organ damage. This study aimed to assess whether cardiovascular magnetic resonance (CMR) parametric mapping could detect early cardiac involvement and evaluate differences between these two subtypes. METHODS: Eighty SSc patients (37 dcSSc and 43 lcSSc) underwent CMR at 3.0 T (Philips Healthcare, Best, The Netherlands) in our hospital between July 2018 and July 2021. We analyzed myocardial damage by CMR parametric mapping and compared it with clinical data. RESULTS: The median duration of the disease was 10.2 months. The left ventricular ejection fraction was preserved in both groups. DcSSc had significantly higher native T1 (1333.4 ±â€¯71.2 ms vs. 1295.0 ±â€¯42.7 ms, p = 0.006) and extracellular volume fraction (32.6 ±â€¯4.1 % vs. 30.3 ±â€¯4.0 %, p = 0.018) in the mid-ventricular septum as compared to lcSSc, although there were no differences in T2 values. Native T1 values were positively correlated with the E/e' ratio and left atrial volume indices evaluated by transthoracic echocardiography in overall SSc and dcSSc, but not in lcSSc. Logistic regression analysis revealed that native T1 was an independent predictor of left ventricular diastolic dysfunction in SSc patients (odds ratio, 1.194; 95 % confidence interval, 1.021-1.396; p = 0.026). Native T1 was higher in SSc patients with progressive skin lesions. Additionally, there were positive correlations between brain natriuretic peptide, New York Heart Association functional classification, and native T1. CONCLUSIONS: CMR parametric mapping is a useful tool for detecting myocardial changes. Native T1 was the most sensitive parameter for identifying diffuse myocardial changes in the early stages of SSc and was associated with left ventricular diastolic function. DcSSc had more severe myocardial involvement than lcSSc; therefore, the use of CMR parametric mapping may aid in its prediction.

Efficacy of Fractional CO2 Laser for Improvement of Limited Mouth Opening in Systemic Sclerosis.

Background: Systemic sclerosis is a multisystem auto-inflammatory disease-causing fibrosis in the skin and internal organs. A frequent complication of systemic sclerosis is the limited mouth opening (LMO), a difficult-to-treat condition with only a few treatment options available. Aims and Objectives: The aim of this study was to evaluate the response of fractional carbon dioxide (CO2) laser resurfacing in LMO associated with systemic sclerosis. Materials and Methods: This was a hospital-based prospective study in which diagnosed cases of systemic sclerosis were taken. Patients who had significant LMO and who gave informed consent were included in the study. Fractional CO2 laser treatment was performed in the perioral area. Patients were assessed at baseline, after three and six sessions, and 3 months after the last session. Assessment was done by measurement of the interincisor distance (IID) using a ruler and calculation of the mouth handicap in systemic sclerosis (MHISS) scale. Results: Improvement in IID occurred 3 months after the first session with a mean gain of +5 mm (range 2-7). At 6 months, a mean gain of +8.5 mm (range 7-10) in IID was observed (P < 0.001). The MHISS score decreased by a mean of 14 (range 11-17) (P < 0.001). All patients showed improvement of mouth opening, which allowed the patients to have better phonation and the patients were able to have proper dental care posttreatment in the form of brushing of teeth and other dental procedures. The adverse effects noted in these patients included erythema that resolved spontaneously or after icing posttreatment. Other adverse effects noted were stinging and burning sensations that were mild and transient. Conclusion: Fractional CO2 laser forms a safe, effective, and well-tolerated treatment modality for improvement of LMO in systemic sclerosis. Limitations: The limitations of this study were less number of patients and no long-term follow-up.

Cannabinoids for the Treatment of Dermatologic Conditions.

In recent years, cannabinoid (CB) products have gained popularity among the public. The anti-inflammatory properties of CBs have piqued the interest of researchers and clinicians because they represent promising avenues for the treatment of autoimmune and inflammatory skin disorders that may be refractory to conventional therapy. The objective of this study was to review the existing literature regarding CBs for dermatologic conditions. A primary literature search was conducted in October 2020, using the PubMed and Embase databases, for all articles published from 1965 to October 2020. Review articles, studies using animal models, and nondermatologic and pharmacologic studies were excluded. From 248 nonduplicated studies, 26 articles were included. There were 13 articles on systemic CBs and 14 reports on topical CBs. Selective CB receptor type 2 agonists were found to be effective in treating diffuse cutaneous systemic sclerosis and dermatomyositis. Dronabinol showed efficacy for trichotillomania. Sublingual cannabidiol and Δ-9-tetrahydrocannabinol were successful in treating the pain associated with epidermolysis bullosa. Available evidence suggests that CBs may be effective for the treatment of various inflammatory skin disorders. Although promising, additional research is necessary to evaluate efficacy and to determine dosing, safety, and long-term treatment guidelines.

Clinical trial protocol: PRednisolone in early diffuse cutaneous Systemic Sclerosis (PRedSS).

BACKGROUND: Many of the painful, disabling features of early diffuse cutaneous systemic sclerosis have an inflammatory component and are potentially treatable with corticosteroid therapy. These features include painful and itchy skin, fatigue and musculoskeletal involvement. Yet many clinicians are understandably reluctant to prescribe corticosteroids because of the concern that these are a risk factor for scleroderma renal crisis. The aim of PRedSS (PRednisolone in early diffuse cutaneous Systemic Sclerosis) is to evaluate the efficacy and safety of moderate dose prednisolone in patients with early diffuse cutaneous systemic sclerosis, specifically whether moderate dose prednisolone is (a) effective in terms of reducing pain and disability, and improving skin score and (b) safe, with particular reference to renal function. METHODS: PRedSS is a Phase II, multicentre, double-blind randomised controlled trial which aims to recruit 72 patients with early diffuse cutaneous systemic sclerosis. Patients are randomised to receive either prednisolone (dosage approximately 0.3 mg/kg) or placebo therapy for 6 months. The two co-primary outcome measures are the difference in mean Health Assessment Questionnaire Disability Index at 3 months and the difference in modified Rodnan skin score at 3 months. Secondary outcome measures include patient reported outcome measures of itch, hand function, anxiety and depression, and helplessness. RESULTS: Recruitment commenced in December 2017 and after a slow start (due to delays in opening centres) 25 patients have now been recruited. CONCLUSION: PRedSS should help to answer the question as to whether clinicians should or should not prescribe prednisolone in early diffuse cutaneous systemic sclerosis.