Limited Systemic Sclerosis Research Articles

B-Lines in the Assessment of Interstitial Lung Disease Associated with Scleroderma: The Role of Handheld Devices

Background: Timely detection and aggressive management of interstitial lung disease (ILD) in systemic sclerosis (SSc) are essential to improving outcomes and reducing risks of irreversible lung injury. Objective: to explore the usefulness of an ultraportable ultrasound device for the management of SSc-related ILD and to compare it with clinical and instrumental data. Methods: A total of 19 consecutive SSc patients underwent a comprehensive pulmonary evaluation: clinical, pulmonary function tests (PFTs) (spirometry, DLCO), lung CT (1.5 mm slice thickness reconstruction; HRCT), and lung ultrasound (LUS). A total score was calculated based on the number of color-coded B-lines recorded for each lung sliding. B-lines were analyzed against dyspnea, cough, Velcro, CT imaging (Warrick’s score), and PFTs. Global and subgroup analysis were performed (diffuse versus limited cutaneous SSc, Warrick’s < 7 versus >7). Results: Symptomatic lung involvement with varying degrees of dyspnea was reported in about 74% of cases (functional NYHA > 2 in more than half), chronic dry cough in one-third, Velcro rales in 42%. A total of 84.24% were classified as SSc with ILD on CT imaging. Statistically significant mild-to-moderate correlations between B-lines and clinical manifestations were demonstrated, as well as PFTs and Warrick’s scores (more B-lines, lower pulmonary function, but higher extent and severity on CT) (p < 0.05); there were differences between SSc patients without and with ILD in terms of the number and distribution of B-lines (p < 0.05), as well as different B-lines patterns and numbers in diffuse versus limited SSc (p < 0.05). Conclusions: Ultraportable handheld LUS is a promising method suitable for the management (screening, early detection, and evaluation) of SSc patients.

Doppler ultrasound, a noninvasive tool for the study of mesenteric arterial flow in systemic sclerosis: a cross-sectional study of a patient cohort with review and meta-analysis of the literature.

Gastrointestinal involvement (GI) is a frequent and troublesome complication of systemic sclerosis (SSc), whose etiology is poorly understood, though it is hypothesized that autoimmunity and progressive vasculopathy may play a role. Vasculopathy is considered one of the main pathogenetic pathways responsible for many of the clinical manifestations of SSc, and, therefore, studying the principal splanchnic vessels (i.e., superior mesenteric artery-SMA and inferior mesenteric artery-IMA) with Doppler Ultrasound (DUS) may provide further insights into measuring the progression of vasculopathy, evaluating its possible association with SSc GI symptoms, and determining whether it plays a role in the development or severity of SSc GI disease. A cohort of SSc patients consecutively recruited underwent DUS examination, and associations with GI (UCLA-GIT 2.0 questionnaire) and extraintestinal SSc characteristics were evaluated. Semiquantitative DUS parameters (resistive index-RI and pulsatility index-PI), were applied for splanchnic vessel assessment in SSc patients and healthy subjects (HS). Moreover, a review and meta-analysis of the literature to understand which the values of the main semiquantitative DUS parameters (RI and PI) are both in SSc patients and HS has been conducted. Seventy-eight patients completed DUS examinations and clinical assessments. 30 (39%) were classified as diffuse cutaneous SSc (dcSSC), 35 (45%) as limited cutaneous SSc (lcSSc) and 13 (17%) as sine scleroderma. A significant difference was found both for SMA RI (p for trend = 0.032) and SMA PI (p for trend = 0.004) between patients with sine scleroderma, lcSSc and dcSSc, with lower values observed in the sine scleroderma and lcSSc groups. IMA RI and PI were significantly correlated with GI symptoms such as fecal incontinence (ῥ -0.33, p = 0.008 and ῥ -0.30, p = 0.021, respectively). By multivariate analysis, significant associations were confirmed between SMA RI and SMA PI and mRSS (β 0.248, p = 0.030 and β 2.995, p = 0.004, respectively) and with bosentan (β 0.400, p = 0.003 and β 3.508, p = 0.001, respectively), but not with anticentromere antibody (ACA). No significant differences were found between the weighted median values of SMA RI and SMA PI of SSc patients compared to those of HS that were derived from the meta-analysis of the literature (p = 0.72 and p = 0.64, respectively). This cross-sectional study confirms that the splanchnic vasculature of SSc patients can noninvasively been studied with DUS. Vascular splanchnic involvement correlates with the presence and/or severity of specific clinical features in SSc, including GI. Larger and prospective studies are needed to confirm these preliminary observations and to examine the role of DUS in SSc-risk stratification and GI progression and to obtain definitive data regarding both HS and SSc patients splanchnic DUS parameters.

6625 Adrenocortical Oncocytoma: Illuminating The Clinical And Biological Behavior Of An Extremely Rare Tumor Of The Adrenal Gland

Abstract Disclosure: H. Usmani: None. M. Arguello, MD: None. Background: Only 120 cases of adrenocortical oncocytoma have been reported in English literature (1). Standardized diagnostic criteria, or a typical clinical or biological course, have yet to be established. 58 yo woman with PMH HTN, COPD, CREST syndrome on chronic prednisone, previous 38-pk yr smoker, pulmonary nodule, current vaper, was incidentally found to have a left adrenal mass when she went for CT abd pelvis with IV and oral contrast to evaluate for suspected diverticulosis and anemia. CT showed a mass in the left adrenal gland measuring 5.6 x 4.4 cm in size, heterogeneous in density, with possible areas of necrosis. It is unclear how long the adrenal mass was there since the patient never had a CT scan before. Patient was asymptomatic except 50 lb wt loss in the last couple of years with a feeble appetite, self-reported abnormal hair growth (no hirsutism on exam), voice deepening attributed to smoking, and HTN- well controlled with nifedipine. Patient has no FHx of endocrinopathy. Adrenal function tests wnl except for plasma free normetanephrines slightly high at 1.64 nmol/L, which was unlikely from tumor considering tumor size. Normal adrenal function tests included 11-deoxycortisol, DHEA-S, plasma-free metanephrine, aldosterone, renin, aldosterone: renin ratio, androstenedione, ACTH, 1 mg overnight dexamethasone suppression test.She underwent left-sided lap adrenalectomy 4 mos after discovery of adrenal mass, with no complications. 6 days after surgery, a left in JP drain caught on a door at patient’s home, causing splenic subcapsular tear requiring emergent splenectomy. The path report shows an encapsulated neoplasm consisting of sheet-like proliferation of eosinophilia polygonal cells with nuclear atypia, low mitotic activity, and no capsular or vascular invasion. Immunohistochemical markers show neoplastic cells positive for SF1, Mart1, inhibin (focal), and synaptophysin (focal); negative for CK-OSCAR, CK7, CK20, chromogranin, HMB45, and TTF-1, Ki67 and pHH3 show low proliferative index. The pathology slides were sent to U of M, where the diagnosis of adrenal cortical oncocytoma was made. Removal of oncocytoma has not affected patient’s weight, blood pressure, deep voice, or hair growth on 4 month follow up. Lin-Wiess-bisceglia system (2) suggests a benign lesion. But, as mutation rate for this rare tumor is unclear, plan for CT abd pelvis in 1 yr. Conclusion: This case elucidates the clinical and biological course and pathologic diagnosis of an exceedingly rare adrenal tumor.

Early Systemic Sclerosis Presenting as Digital Tip Gangrene

Systemic sclerosis (SSc) is a chronic connective tissue disease characterized by vasculitis, fibrosis, and autoimmunity. Based on the skin involvement, it is classified into diffuse cutaneous SSc and limited cutaneous SSc. We describe a patient presenting with bilateral digital tip gangrene after lifting heavy weights intermittently as the first symptom. On further investigation, he was diagnosed with SSc, making it a rare presenting complaint.

Cross-sectional study using the University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Tract Instrument 2.0 (UCLA SCTC GIT 2.0) for gastrointestinal disorders of systemic sclerosis.

This study aimed to identify severe gastrointestinal ailments in patients with systemic sclerosis (SSc), investigate the role of antibodies in gastrointestinal disorders, and explore the relationship between limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) in terms of gastrointestinal involvement and its association with skin stiffness. We used the University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Tract Instrument 2.0 (UCLA SCTC GIT 2.0) questionnaire to assess gastrointestinal disturbances in 100 patients with SSc. Gastrointestinal impairment was categorized into three levels: absence of or minor symptoms, moderate symptoms, and severe symptoms, as indicated by the total gastrointestinal tract (GIT) score. Comparing 27 patients with dcSSc and 73 patients with lcSSc, severe gastrointestinal disturbances were found in 7.4% of patients with dcSSc and 4.1% of patients with lcSSc. A total of 18.0% of anticentromere antibody (ACA)-positive patients exhibited moderate to severe symptoms, while 9.1% of antitopoisomerase 1 antibody-positive patients displayed similar symptoms. The average disease duration in patients with severe symptoms was 15.0 years, in those with moderate symptoms was 10.3 years, and in those who were symptom-free or mildly affected was 8.5 years. Among 16 patients with moderate to severe gastrointestinal disorders, a positive correlation was observed between the modified Rodnan skin thickness score (mRSS) and total GIT score. In addition, a positive correlation was identified between fecal incontinence and mRSS, with weaker correlations for reflux and bloating symptoms. Patients with gastrointestinal disorders showed a tendency to worsen over time, particularly in ACA-positive patients with dcSSc. Furthermore, a correlation was observed between mRSS and fecal incontinence, reflux, and abdominal bloating in patients with moderate to severe gastrointestinal disturbances.

Systemic sclerosis associated with pulmonary arterial hypertension: Focus on the visceral form of the disease

Introduction. Systemic sclerosis is a connective tissue disease with the development of obliterating arteriolopathy and active fibrosis formation both in internal organs and in the skin. Pulmonary arterial hypertension is a life-threatening manifestation of systemic sclerosis, leading to death if diagnosed late. The search for predictors, as well as associated disease phenotypes, can facilitate early diagnosis and improve prognosis.Aim. To characterize the features of the visceral form in comparison with the limited variant in patients with pulmonary arterial hypertension associated with systemic sclerosis.Materials and methods. 14 patients with visceral and 63 with a limited variant of systemic sclerosis associated with pulmonary arterial hypertension were studied. The diagnosis of systemic sclerosis was established based on the 2013 ACR-EULAR criteria; pulmonary arterial hypertension was verified by right heart catheterization. In all patients, other causes of pulmonary hypertension – heart disease, lung disease, thrombophilia were excluded.Results. At the time of inclusion in the study, patients with visceral systemic sclerosis were younger (48 (35; 56) years) than those with limited systemic sclerosis (54 (49; 63) years, but the differences only approached significant (p = 0.057). All patients had the Raynaud’s syndrome, with limited systemic sclerosis, digital ischemic disorders were more often observed (41% compared to 14%, p = 0.11). Anticentromere antibodies caused by pulmonary arterial hypertension predominated; antibodies to topoisomerase-I were detected only in two patients with limited systemic sclerosis. The severity index was significantly higher in patients with limited systemic sclerosis (p < 0.05). The clinical manifestations of pulmonary arterial hypertension in both groups were also the same. When studying central hemodynamics, no significant differences were found. The median follow-up of patients was 68 (39; 111) months. Survival also did not differ: with visceral systemic sclerosis it was 63 (40; 99) months, with limited systemic sclerosis – 69 (36; 116) months.Conclusion. A comparative analysis demonstrated the similarity of the two systemic sclerosis phenotypes, which suggests the universality of approaches to the early diagnosis of pulmonary arterial hypertension.

Dacryoadenitis as a Rare Initial Presentation in a Patient with Suspected Crest Syndrome.

Broad spectrum of clinical features: Recognize that although CREST syndrome is primarily characterized by its hallmark features - calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia - it can also present with additional clinical features that may indicate the onset or presence of the syndrome.Diagnostic challenges and differentiation: Diagnostic challenges and differentiation: Bilateral dacryoadenitis can be challenging to diagnose due to its overlapping symptoms with other orbital or systemic conditions. The case report may highlight the importance of differentiating it from conditions like orbital cellulitis, sarcoidosis, or lymphoproliferative disorders. Advanced imaging techniques (like magnetic resonance imaging or computed tomography scans) and careful assessment of clinical history (including systemic symptoms like fever or autoimmune conditions) are crucial for accurate diagnosis.Awareness of atypical presentations and follow-up: The case report underscores the need for tailored management strategies for bilateral dacryoadenitis, from conservative treatments in mild cases to more aggressive therapies in severe ones, while also highlighting the importance of monitoring for complications and being vigilant about atypical presentations, such as those seen in patients with CREST syndrome.

Long-term prognosis of penetrating keratoplasty in a patient with limited form of Scleroderma- a case report.

To explore the challenges of managing recurrent graft rejections in patients with Macular Corneal Dystrophy (MCD) undergoing Penetrating Keratoplasty (PKP) who also have an underlying diagnosis of Systemic Sclerosis, specifically the limited form known as CREST syndrome. The case of a 47-year-old female diagnosed with MCD who underwent multiple PKPs over a 13 year period was reviewed. The patients treatment included extensive surgical interventions (PKPs, amniotic membrane transplatation, tarsorrhaphy) and medical management involving systemic and topical steroids and immunosuppressive therapy (Tacrolimus ointment). Initial PKP surgeries improved the patients vision, but subsequently graft rejections,both acute and chronic, required further surgical and medical interventions. Despite aggressive management, the patient experienced multiple graft failures, with the final visual outcome being significantly compromised (vision 6/60). the presence of CREST syndrome complicated the management and prognosis of graft survival. This case illustrates the significant impact of systemic autoimmune disorders like CREST syndrome on the prognosis of PKP in patients with MCD. It highlights the necessity for diligent systemic evaluation and possibly more aggressive immunosuppresive strategies to manage graft rejections and prolong graft survival in such complex clinical scenarios.

Utility of factor D and other alternative complement factors as biomarkers in systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH)

BackgroundActivation of the complement cascade is thought to play a role in scleroderma vasculopathy. We previously showed that complement factor D was elevated in patients with limited cutaneous SSc and pulmonary arterial hypertension (PAH). In this study, we sought to assess multiple relevant components of the complement cascade to determine if they are altered in SSc-PAH, as well as their potential utility as biomarkers of disease severity and progression. MethodsComplement components (n = 14) were measured using multiplex assays in 156 patients with SSc-PAH from a multi-site repository and were compared to 33 patients with SSc without PAH, and 40 healthy controls. Data were evaluated for correlations between complement levels, right heart catheterization measures, and clinical endpoints including 6-minute walk distance. To assess complement longitudinally, serum complement levels were assayed at 0, 4, 12, 24, 36 and 48 weeks in 52 SSc-PAH patients who participated in a prior clinical trial. ResultsWe found that factor D was significantly elevated in SSc-PAH compared to SSc without PAH (p < 0.0001) and was highly sensitive and specific for SSc-PAH (AUC=0.82, p < 0.001). In SSc-PAH patients, alterations in factor H, C4, and factor D were associated with measures of PAH disease severity including right heart catheterization measurements (cardiac output, right atrial pressure, and VO2 max), survival, and 6-minute walk distance. No significant changes in complement levels or clinical associations were seen over time or associated with treatment in the longitudinal clinical trial study. ConclusionOur work confirms prior studies demonstrating a role for complement activation in SSc vascular disease and elevations of factor D in a large SSc-PAH population. Further, factor H and other complement factors are associated with severity of PAH including mortality. Taken together, these findings suggest that the alternative complement pathway plays a role in SSc-PAH pathogenesis and may serve as a biomarker to inform diagnosis and prognosis.

Epigastric discomfort in a young woman: unveiling a case of CREST syndrome

Introduction and Importance: CREST syndrome is a clinical condition, seen in relation with systemic sclerosis, which meets at least three of its five clinical features: calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia. Three of these clinical features (Raynaud’s phenomenon, sclerodactyly and esophageal dysmotility) are often present in classical subsets of SSc: limited and diffuse, and their presence alone in association does not define CREST syndrome. The laboratory findings (autoimmunity) are the most crucial for diagnosis. Hence, a comprehensive clinical assessment, autoimmune investigations should be performed to make the final diagnosis of CREST Syndrome, as per the criteria states. We describe a case involving a 34-years-old female who was diagnosed with CREST Syndrome during medical evaluation of her epigastric discomfort. Case Presentation: We present the case of a 34-year-old female, presented with clinical cutaneous and gastrointestinal manifestations along with autoantibody production when investigated, which was compatible with the diagnosis of a limited form of systemic sclerosis (SSc), CREST Syndrome. Clinical Discussion: In the absence of a diagnostic test to prove the absence or presence of SSc, the diagnosis is based on a combination of clinical and laboratory findings. Thus, a detailed clinical history and careful physical examination are required. With regard to the diagnosis, an updated classification criteria for SSc as published by ACR/EULAR in 2013 is used and helped us to reach the final diagnosis. Conclusion: CREST syndrome, a rare clinical entity, warrants consideration by primary physicians while evaluating it. Despite its rarity, inclusion in differentials is essential to prevent worsening of the condition and having further complications. Heightened awareness among healthcare providers is pivotal for prompt recognition and appropriate management.

Changes of cerebral structure and perfusion in subtypes of systemic sclerosis: a brain magnetic resonance imaging study.

The characteristics of brain impairment in different subtypes of systemic sclerosis (SSc) (dcSSc, diffuse cutaneous SSc; lcSSc, limited cutaneous SSc) remain unclear. This study aimed to characterize cerebral structure and perfusion changes in different subtype of SSc patients using magnetic resonance (MR) imaging. Seventy SSc patients (46.0 ± 11.7 years, 62 females) and 30 healthy volunteers (44.8 ± 13.7 years, 24 females) were recruited and underwent brain MR imaging and Montreal Cognitive Assessment (MoCA) test. Gray matter (GM) volumes were measured using voxel-based morphometry analysis on T1-weighted images. Voxel-based and regional cerebral blood flow (CBF) was calculated on arterial spin labelling images. The cerebral structural and perfusion measurements by MR imaging were compared among dcSSc, lcSSc and healthy subjects using one-way ANOVA. The correlations between clinical characteristics and MR imaging measurements were also analyzed. The dcSSc patients exhibited a significant reduction in GM volume in the para-hippocampal region (cluster p < 0.01, FWE corrected) compared with healthy volunteers. Whereas, SSc patients, particularly lcSSc patients, showed elevated CBF in cerebellum, insula, cerebral cortex, and subcortical structures (regional analyses: all p < 0.05; voxel-based analyses: cluster p < 0.01, FWE corrected). Furthermore, clinical characteristics of modified Rodnan skin score (mRSS) (r value ranged from -0.29 to -0.45), MoCA scores (r = 0.40) and antinuclear antibody (ANA) positivity (r=-0.33) were significantly associated with CBF in some regions (all p < 0.05). The manifestations of brain involvement vary among different subtypes of SSc. In addition, severe skin sclerosis may indicate higher risk of brain involvement in SSc patients.

A randomised, parallel-group, double-blind, placebo-controlled phase 3 study to Determine the effectiveness of the type I interferon receptor antibody, Anifrolumab, In SYstemic sclerosis: DAISY study design and rationale.

The type I interferon pathway is a promising target for treatment of patients with systemic sclerosis (SSc). Here, we describe the design of a multinational, randomised phase 3 study to Determine the effectiveness of the type I interferon receptor antibody, Anifrolumab, In SYstemic sclerosis (DAISY). DAISY includes a 52-week double-blind, placebo-controlled treatment period, a 52-week open-label active treatment period, and a 12-week safety follow-up period. The patient population includes a planned 306 adults with limited or diffuse cutaneous active SSc who satisfied American College of Rheumatology/European Alliance of Associations for Rheumatology 2013 SSc criteria. Use of standard immunosuppressants, including mycophenolate mofetil, at a stable dose prior to randomisation is permitted in addition to weekly subcutaneous anifrolumab or placebo. Efficacy will be assessed at Week 52 via Revised-Composite Response Index in SSc (CRISS)-25 response (primary endpoint). Lung function and skin thickness will be assessed via change from baseline in forced vital capacity in patients with SSc-associated interstitial lung disease and modified Rodnan Skin Score, respectively (key secondary endpoints). The DAISY trial will evaluate the efficacy and safety of anifrolumab as a first-in-class treatment option for patients with both limited and diffuse cutaneous SSc and will provide insight into the contributions of type I interferon to SSc pathogenesis. Revised-CRISS-25 can account for improvement and worsening in a broad set of validated clinical measures beyond lung function and skin thickness, including clinician- and patient-reported outcomes, capturing the heterogeneity of SSc.

Elevated neutrophil extracellular traps in systemic sclerosis-associated vasculopathy and suppression by a synthetic prostacyclin analog

ObjectivesNeutrophils and neutrophil extracellular traps (NETs) contribute to the vascular complications of multiple diseases, but their role in systemic sclerosis (SSc) is understudied. We sought to test the hypothesis that NETs are implicated in SSc vasculopathy and that treatment with prostacyclin analogs may ameliorate SSc vasculopathy not only through vasodilation but also by inhibiting NET release.MethodsBlood from 125 patients with SSc (87 diffuse cutaneous SSc and 38 limited cutaneous SSc) was collected at a single academic medical center. Vascular complications such as digital ulcers, pulmonary artery hypertension, and scleroderma renal crisis were recorded. The association between circulating NETs and vascular complications was determined using in vitro and ex vivo assays. The impact of the synthetic prostacyclin analog epoprostenol on NET release was determined.ResultsNeutrophil activation and NET release were elevated in patients with SSc-associated vascular complications compared to matched patients without vascular complications. Neutrophil activation and NETs positively correlated with soluble E-selectin and VCAM-1, circulating markers of vascular injury. Treatment of patients with digital ischemia with a synthetic prostacyclin analog boosted neutrophil cyclic AMP, which was associated with the blunting of NET release and reduced NETs in circulation.ConclusionOur study demonstrates an association between NETs and vascular complications in SSc. We also identified the potential for an additional therapeutic benefit of synthetic prostacyclin analogs, namely to reduce neutrophil hyperactivity and NET release in SSc patients.

A pilot study of skin barrier function in patients with systemic sclerosis and primary Sjögren's syndrome.

Although the close interactions between the epidermis and dermis of the skin have been widely explored, the skin barrier functions of the stratum corneum (SC) in patients with systemic sclerosis (SSc) and primary Sjögren's syndrome (pSS) are not well known. We aimed to investigate the biophysical characteristics of the skin, including transepidermal water loss (TEWL), the SC water content, erythema, and the melanin index, in patients with SSc and pSS. This case-control study included 34 patients with SSc, 31 patients with pSS, and 25 healthy controls. All parameters were measured on the extensor surface of the forearm and compared between patients and healthy controls. In patients with SSc, we performed subgroup analyses by disease subtype (diffuse and limited cutaneous SSc), the modified Rodnan skin sclerosis score (>6 or ≤6), and comorbid secondary SS status. In patients with pSS, subgroup analyses were performed by anti-Ro/SSA antibody status and the findings of salivary gland ultrasound. No statistically significant differences were observed in TEWL or skin hydration between patients with SSc and pSS and healthy controls. In the pSS group, only the erythema index was significantly increased compared to the control group. In subgroup analyses, no significant differences were observed in the extent of TEWL or skin hydration by disease subtype, severity, autoantibody profile, or comorbidities. Patients with SSc or pSS did not exhibit specific impairments of skin barrier function or skin hydration. Further studies with larger sample sizes and age-matched controls are required.

Skin Ultrasound Assessment of Patients with Systemic Scleroderma-An Observational Study.

This study aims to analyze the changes in dermal thickness in patients with systemic scleroderma (SSc) in comparison with normal skin and also compare clinical forms with diffuse and limited cutaneous involvement. The study group consisted of female patients diagnosed with SSc with a disease history not exceeding 5 years. The areas of interest for ultrasound examination included the proximal phalanx of the third finger, the second intermetacarpal space, and the extension surface of the lower third of the forearm. The study included 20 patients diagnosed with SSc and 14 controls. SSc patients were subdivided into two subgroups based on the clinical form. Compared to the control group, patients with SSc had higher mean measurements in all three skin areas, with statistically significant differences in the hand and forearm areas. Patients with diffuse SSc displayed, on average, higher skin thickness compared to limited SSc in all skin areas examined, with a statistically significant difference only in the forearm area. Based on disease manifestations, significant differences were observed only with regard to the presence of pulmonary hypertension in the diffuse SSc group. In conclusion, skin ultrasound is a useful and accessible imaging method for diagnosing and quantifying dermal fibrosis in systemic scleroderma.

A case report on CREST syndrome with acrodermatitis

A case report on CREST syndrome with acrodermatitis

Late-age onset systemic sclerosis—clinical and serological characteristics

The clinical course and serological profile of the late-age onset systemic sclerosis (LAO SSc) and the early-age onset SSc (EAO SSc) was compared. The study enrolled 157 patients that fulfilled the American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) classification criteria for systemic sclerosis (SSc). Among them, 69 had diffuse cutaneous SSc (dcSSc) and 88 limited cutaneous SSc (lcSSc). Within this population, 39 patients developed the disease over the age of 60 years old (LAO SSc) and 118 prior to that age (EAO SSc). The subtype of SSc, the incidence of internal organ involvement, the prevalence of malignancy, mortality, and serological profile were compared between both groups. The LAO SSc was observed in 39 of total 157 patients with SSc and exhibited a notably higher prevalence of pulmonary arterial hypertension (p = 0.014), heart involvement (p = 0.0014), and renal involvement (p = 0.0002). The occurrence of arthralgias was less common in the LAO SSc group (p = 0.02) than in the EAO SSc group. Furthermore, in the LAO SSc group, the prevalence of anti –RNA polymerase III antibodies (p = 0.008) and antiPM/Scl antibodies (p = 0.048) were significantly lower than in the EAO SSc group. On the other hand, higher anti-Th/To antibody levels (p = 0.014) were recorded in the LAO SSc group. Approximately 25% of SSc patients experienced a delayed onset of the disease after the age of 60 years old. Some clinical and serological features of late-onset SSc were markedly different from that in early-onset disease. Particularly noteworthy is the fact that involvement of internal organs such as heart and kidneys, as well as pulmonary arterial hypertension were much more often observed among patients with LAO SSc which in our suggestion may be referred to age-related co-morbidities.Key Points• Significant differences in clinical and serological profile of the disease were found between late-age onset (LAO) and early-age onset (EAO) SSc.• Incidence of dcSSc as well as prevalence of anti–RNA polymerase III and anti-PM/Scl antibodies were found to be lower in patients over 60 years old compared to those before 60, but regardless of the age of the disease onset.• Internal organ morbidity, notably pulmonary arterial hypertension, renal impairment and heart disease were significantly more common in elder SSc patients as well as in those with late disease onset.• These findings may suggest an impact of age-related co-morbidities on the course of late-age onset SSc.

Long-term outcomes in patients with primary biliary cholangitis complicated with CREST syndrome

Primary biliary cholangitis (PBC) is frequently associated with autoimmune disease. Although PBC complicated with CREST syndrome (PBC-CREST) has been reported, the long-term outcomes of the affected patients have not been fully investigated. Herein, the long-term outcomes of PBC-CREST were evaluated. Next, the GLOBE and UK-PBC scores were validated and compared between the PBC alone and PBC-CREST groups. A total of 302 patients who were diagnosed with PBC between December 1990 and August 2021 at Fukushima Medical University Hospital were included. The liver transplantation (LT)-free survival rates were compared between patients with PBC alone (n = 245) and those with PBC-CREST (n = 57). Moreover, 173 patients, excluding those with liver-related death/LT within 1 year after ursodeoxycholic acid administration, were divided into two subgroups (PBC alone (n = 147) and PBC-CREST (n = 26)), and the GLOBE and UK-PBC scores were compared between the subgroups. The survival rates without LT (3/5/10 years) were 92/87/80% for the PBC-alone group and 98/96/96% for the PBC-CREST group, with a significantly better prognosis in the PBC-CREST group (log-rank P = 0.0172). Multivariate analysis revealed that the presence of CREST syndrome is an independent protective factor for the presence of cirrhosis. The predicted 5/10/15-year risks of liver-related death or LT based on the UK-PBC score were significantly lower in the PBC-CREST group (2.4/7.6/13.2%) than in the PBC-alone group (4.8/11.8/18.8%) (P < 0.05). The predicted 3/5-year LT-free survival rates based on the GLOBE score were significantly higher in the PBC-CREST group (93/88%) than in the PBC-alone group (88/81%) (P < 0.05). Patients with PBC-CREST may have better long-term outcomes than those with PBC alone.

Heart rate variability helps classify phenotype in systemic sclerosis

We aimed to develop a systemic sclerosis (SSc) subtypes classifier tool to be used at the patient’s bedside. We compared the heart rate variability (HRV) at rest (5-min) and in response to orthostatism (5-min) of patients (n = 58) having diffuse (n = 16, dcSSc) and limited (n = 38, lcSSc) cutaneous forms. The HRV was evaluated from the beat-to-beat RR intervals in time-, frequency-, and nonlinear-domains. The dcSSc group differed from the lcSSc group mainly by a higher heart rate (HR) and a lower HRV, in decubitus and orthostatism conditions. Stand-up maneuver lowered HR standard deviation (sd_HR), the major axis length of the fitted ellipse of Poincaré plot of RR intervals (SD2), and the correlation dimension (CorDim) in the dcSSc group while increased these HRV indexes in the lcSSc group (p = 0.004, p = 0.002, and p = 0.004, respectively). We identified the 5 most informative and discriminant HRV variables. We then compared 341 classifying models (1 to 5 variables combinations × 11 classifier algorithms) according to mean squared error, logloss, sensitivity, specificity, precision, accuracy, area under curve of the ROC-curves and F1-score. F1-score ranged from 0.823 for the best 1-variable model to a maximum of 0.947 for the 4-variables best model. Most specific and precise models included sd_HR, SD2, and CorDim. In conclusion, we provided high performance classifying models able to distinguish diffuse from limited cutaneous SSc subtypes easy to perform at the bedside from ECG recording. Models were based on 1 to 5 HRV indexes used as nonlinear markers of autonomic integrated influences on cardiac activity.

Ocular Manifestation in Systemic Sclerosis-A Literature Review.

Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease that affects more than 2 million people worldwide. It manifests through vasculopathy, an abnormal immunological response, and fibrosis leading to dysfunction of the multiple organs. The disease is categorized into two subtypes: limited cutaneous SSc and diffuse cutaneous SSc. Scleroderma can affect vital organs with respiratory, cardiac, renal, ocular, and dermatological complications. The ocular manifestations of the disease can occur in the anterior and posterior segments of the eye. Changes in the anterior segment related to the disease include eyelid skin remodeling, dry eye syndrome, and conjunctival abnormalities. The disease's impact on the posterior segment of the eye mostly causes pathologies in the retinal microcirculatory system and abnormalities in the optic nerve. This review provides detailed insights into ocular complications associated with scleroderma.