Limited Cutaneous Scleroderma Research Articles

Pulmonary and extra-pulmonary effects of lung transplantation in an Italian cohort of patients with systemic sclerosis

Abstract Objectives Lung transplantation (LuTx) is a life-saving intervention for SSc patients with end-stage lung disease. The aim of this study was to evaluate patients’ survival and LuTx outcomes on systemic disease manifestations. Methods A retrospective evaluation was conducted on SSc patients who underwent LuTx between 2010 and 2021. Outcomes assessed at baseline, 6, 12 and 24 months post-LuTx included skin involvement by modified Rodnan skin score (mRSS), and global disease activity using a modified EUSTAR index (0–9 scale). Lung function rescue was evaluated by forced vital capacity (FVC). Patient survival was assessed by Kaplan–Meier analysis. Results Thirteen SSc patients were included, with a male/female ratio 9/4 and a median age of 48.7 years. Nine patients were affected by diffuse cutaneous scleroderma (dcSSc) and four by limited cutaneous scleroderma (lcSSc). FVC significantly increased from 56% of the predicted value at baseline to 78% at 2 years (P = 0.003). mRSS decreased from 7.4 ± 3.8 to 3.3 ± 2.5 in patients with dcSSc (P = 0.02). The modified EUSTAR index score decreased from 2.54 ± 1.8 at baseline to 0.49 ± 0.5 at 2 years (P = 0.02). Survival rate was 92.3% at 2 years, and 76.9% at 5 years. No unexpected adverse events were observed. Conclusions In SSc patients undergoing LuTx, an excellent 2-year survival was observed, without any disease-related adverse events. Our study supports LuTx as a viable option in SSc patients with end-stage lung disease. Apart from expected recovery of lung function, LuTx was associated with improvement of mRSS and global systemic disease activity.

LIMITED CUTANEOUS SYSTEMIC SCLEROSIS MIMICKING HEREDITARY ANGIOEDEMA WITH NORMAL C1 INHIBITOR

<h3>Introduction</h3> Hereditary angioedema with normal C1 inhibitor (HAE-nl-C1INH) is often diagnosed when patients with antihistamine-resistant angioedema respond to bradykinin-targeted therapies. We present a patient with limited cutaneous scleroderma initially diagnosed as HAE-nl-C1INH, with variable response to HAE therapy. <h3>Case Description</h3> 56-year-old woman with hypertension presented with recurrent periorbital swelling while on ACE inhibitor therapy. After discontinuation, she continued to have episodes of angioedema for two months, responsive to recombinant C1 inhibitor therapy. Initial workup included normal C1 esterase inhibitor antigen and function, C4, C1q, SPEP, tryptase, and thyroid studies. After a six-month symptom-free period, angioedema recurred in the setting of stressful life events, viral infection, and antihypertensive medication changes. When on-demand therapy with recombinant C1 esterase inhibitor was observed to provide insufficient control, she started lanadelumab prophylaxis which stabilized her symptoms. She then developed episodic fluid retention with daily joint and subcutaneous swelling involving the hands, abdomen, and lower extremities coincident with additional changes to her antihypertensive regimen. Discontinuation of suspected culprit medications did not resolve the progression of her symptoms. Evaluation by rheumatology for joint symptoms and persistent hand swelling led to the diagnosis of limited cutaneous systemic sclerosis (scleroderma). Angioedema symptoms resolved after starting mycophenolate mofetil and she no longer required HAE therapy. <h3>Discussion</h3> Our case highlights the complicated and nuanced nature of diagnosing HAE-nl-C1INH, particularly in patients with partial response to HAE therapy. Limited cutaneous scleroderma either mimicked or triggered angioedema in our patient. Her partial response to C1 inhibitor infusions and lanadelumab may have represented off-target effects of HAE therapy.

Limited Cutaneous Scleroderma

Introduction: Scleroderma is a rare autoimmune disease of connective tissue characterized by extensive fibrosis, inflammation, and vasculopathy. It classified as limited cutaneous and diffuse based on the degree of skin involvement. The management is still a challenge since it has a high morbidity and mortality rate. This case report aims to understand scleroderma and provide appropriate treatment that can improve the patient's prognosis.Case report: A 55-year-old female came with complaints of stiff skin on the forearms, lower legs and face since approximately eight months ago, initially on the right and left forearms, then to face, right and left lower legs. On physical examination, there was sclerosis of the skin on the face, forearms and lower legs, and salt and pepper appearance with Rodnan score were 26. The result from histopathological examination were sceleroderma. The patient was diagnosed with limited cutaneous scleroderma. The management consisted of methotrexate, folic acid, sulpha ferrous, vitamins B1, B6, B12 intraorally and 10% urea cream topically. She also was informed to practice moving the hands and fingers slowly.Conclusion: The diagnosis of limited cutaneous scleroderma is based on history, physical examination and investigations. It is still a life-threatening disease, however multidisciplinary management with early detection and treatment of complications can improve the prognosis.

Adult onset Still\u2019s disease in a patient with scleroderma: case report

BackgroundScleroderma and adult onset Still’s disease (AOSD) are both uncommon autoimmune disorders. These two disorders have rarely been documented to occur simultaneously. In fact, after a thorough literature review, we discovered only one prior case report in a pregnant individual. Here, we describe the first documented case of scleroderma and AOSD in a postmenopausal patient.Case presentationThe patient is a 61-year-old Caucasian female with a past medical history significant for peptic ulcer disease, mitral valve prolapse, chronic idiopathic pancreatitis, and limited cutaneous scleroderma with sclerodactyly, Raynaud’s, and calcinosis. She was sent to the emergency room by her primary care physician due to one-week history of intermittent spiking fevers (Tmax 101°F), sore throat, myalgias, arthralgias, and non-pruritic bilateral lower extremity rash. Diagnostic evaluation in the hospital included complete blood count, comprehensive metabolic panel, respiratory viral panel, antinuclear antibody panel, bone marrow biopsy, and imaging with computerized tomography. Our patient fulfilled Yamaguchi Criteria for AOSD and all other possible etiologies were ruled out. She was treated with a steroid taper and methotrexate was initiated on post-discharge day number fourteen. Clinical and biochemical resolution was obtained at three months.ConclusionsIn this report, we describe the first ever documented case of scleroderma and AOSD in a postmenopausal patient. The clinical presentation, diagnostic work up, and management discussed herein may serve as a framework for which rheumatologists and other physicians may draw upon in similar future encounters.

Scleroderma renal crisis: observations from the South Australian Scleroderma Register.

Scleroderma renal crisis (SRC) is a rare but feared complication with high morbidity and mortality. Its aetiopathogenesis is unclear. To investigate epidemiological, serologic and clinical features of all patients with SRC listed on the population-based South Australian Scleroderma Register and to examine possible factors in aetiopathogenesis. A case note review was performed on all SRC patients with relevant data extracted to determine incidence, clinical phenotype, presence of autoantibodies and survival. Possible precipitating and aetiopathogenic factors were also examined. Data from the South Australian Scleroderma Register and Australia Bureau of Statistics was sourced for comparative purposes. Over the 34-year period (1985-2018), 30 patients (21 females, 9 males) presented with SRC giving a South Australian mean annual incidence of 0.58/million/year (95% CI 0.39-0.89). Twenty-eight of these patients had diffuse cutaneous scleroderma and two with limited cutaneous scleroderma. The mean age at first symptom of scleroderma was 51.2 ± 15.9 (mean ± SD) years with SRC occurring 4.6 years later (median = 3.0 years, range 0.1-20 years). Possible precipitating factors for SRC included high dose steroids in five patients. Twelve patients were anti- RNA polymerase3 (RNAPol3) positive and two were anti-topoisomerase 1 (Topo1) positive. Renal outcome was poor with 13 patients requiring renal replacement therapy and two proceeding to renal transplantation. The mean age at death was 61.2 ± 11.6 years with SRC patient survival being significantly shorter than patients with diffuse scleroderma without renal involvement (P = 0.002). There was no significant difference in survival between the 1985-2002 and the 2003-2018 SRC cohorts (P = 0.2). Nailfold capillaroscopy performed in 10 patients revealed extensive microvascular damage with prominent capillary drop out. SRC is a rare occurrence with an incidence of 0.58/million/year in South Australia. This frequency has not changed over time. It continues to have a severe adverse outcome with frequent requirement for renal replacement therapy and poor survival. Nailfold capillaroscopy revealed evidence of extensive capillary damage. No improvement in survival was observed over the 34-year study period.

A rare cause of dysphagia: CREST syndrome

&lt;p class="abstract"&gt;Reporting a case of a 29-year-old female patient who came to the outpatient department with features of CREST syndrome. This case report illustrates the ENT presentation of CREST syndrome. A 29 year female with features of CREST syndrome (Calcinosis+, Raynaud’s phenomena +, oesophageal dysmotility+ sclerodactyly+ and Telangiectasias+, with no pulmonary hypertension) with ANA titres positive. Complete blood count, serum electrolytes, renal function tests, liver function tests, chest X-ray ,barium swallow ,ECG was done. Rigid oesophagoscope was used for the bougie dilatation of the stricture of oesophagus and was conservatively treated for her symptoms and being followed up at present. GI disturbances such as heartburn, dysphagia or respiratory complaints. Example: dyspnoea are occasionally the first manifestations of the disease. Dysphagia, manifested by various abnormal swallowing sensation, is intially caused by impaired oesphageal motility but later can result from gastroesophageal reflux disease and secondary stricture formation. Hereby concluding that any patient coming in OPD with similar features as mentioned above we should have a differential diagnosis of CREST syndrome and limited cutaneous scleroderma, yet it is a rare case.&lt;/p&gt;

Genetic Susceptibility to Systemic Sclerosis in the Greek-Cypriot Population: A Pilot Study.

Background: Systemic Sclerosis (SSc), also known as scleroderma, is an autoimmune rheumatic disease, which is clinically subdivided into two major subgroups; limited (lcSSc) and diffuse cutaneous scleroderma (dcSSc). Even though the SSc etiologies remains unclear, some HLA and non-HLA genetic variants have been associated with the disease.Aim: This study was designed to evaluate the associations between several HLA-related genetic variants and SSc in the Greek-Cypriot population.Methods: Forty-one SSc patients and 164 controls were genotyped at 18 selected single nucleotide polymorphisms (SNPs) using restriction fragment length polymorphism analyses, Sanger sequencing, and a multiplex SNaPshot minisequencing assay. Logistic regression analysis under the log-additive model was used to evaluate all possible associations between these SNPs and SSc; nominal statistical significance was assumed at p < 0.05.Results: Associations of SSc with SNPs rs3117230, rs3128930, and rs3128965 within the HLA-DPB1 and HLA-DPB2 regions were observed in the Greek-Cypriot population at the level of p < 0.05. However, none of these associations survived a Bonferroni correction. The direction of the effect is consistent with the direction reported in previous studies. In addition, allele frequencies of the majority of the selected SNPs in the Greek-Cypriot population are similar to those reported in the European population.Conclusion: This study initiates the genetic investigation of SSc in the Greek-Cypriot population, a relatively small newly investigated population. Further investigation with a larger sample size and/or additional SSc susceptibility loci may confirm the association of some of these variants with SSc in the Greek-Cypriot population that could potentially be used for predictive testing.

Clinical and serological profile of systemic sclerosis in Tunisia: A retrospective observational study

The Prevalence of systemic sclerosis (SSc) and different clinical subsets varies across the world. Few data have been published on SSc patients in North Africa. Our objective was to describe a SSc cohort in south of Tunisia and to compare clinical findings, disease subsets and antibodies with other international SSc populations. In this retrospective observational study, Folders of patients with SSc seen in the internal medicine section of the Hedi Chaker Hospital between 2000 and 2013 were retrospectively analyzed. The diagnosis of SSc was retained according to ACR/EULAR 2013 criteria. Patients were classified into diffuse cutaneous SSc and limited cutaneous SSc subsets. Comparison with other cohorts was made based on published information. A higher female: male ratio (8:1) and a higher diffuse subset prevalence (82%) was found in this Tunisian cohort comparing with others. We also found a lower prevalence of calcinosis and anticentromere antibodies. Within each subset, diffuse cutaneous and limited cutaneous scleroderma clinical findings were similar with other systemic sclerosis populations except for a very low prevalence in renal crisis and pulmonary hypertension. Our results indicate overlap syndrome defined as scleroderma associated with others connective tissue disorder's is a relatively common condition. With slight variations, perhaps due to genetic, environmental or referral factors, SSc in this cohort appears to be similar to that described in other part of the world.

Scleroderma and Related Disorders

Scleroderma spectrum diseases are a heterogeneous group of disorders that are distinguished by abnormalities of the connective tissue in the skin and, in some cases, other organs. Each disorder may be characterized by the extent of cutaneous and internal involvement, as well as histopathologic features of skin biopsy. Scleroderma spectrum diseases include systemic scleroderma, localized scleroderma, and eosinophilic fasciitis. This chapter reviews the classification, epidemiology, etiology, pathophysiology and pathogenesis, diagnosis, differential diagnosis, treatment, outcome measures, management, and clinical course of scleroderma as well as the definition and classification, etiology/genetics, differential diagnosis, and treatment of localized scleroderma. Also discussed are the definition and classification, epidemiology, etiology/genetics/pathogenesis, diagnosis, differential diagnosis, and treatment of eosinophilic fasciitis. Tables review the classification of—and antinuclear antibodies in—scleroderma as well as the key assessments and interventions in scleroderma management. Figures illustrate the disease's presentation and clinical manifestations, including several images of scleroderma of the hands; face, palmar, and buccal telangiectasias in a patient with scleroderma; a radiograph demonstrating calcinosis of the elbow; Raynaud’s phenomenon; high-resolution computed tomographic images of diffuse cutaneous scleroderma, scleroderma and severe pulmonary hypertension, and limited cutaneous scleroderma; plus an esophagram demonstrating hypomotility. This review contains 11 highly rendered figures, 3 tables, and 72 references.

Relationship Between Ventricular Arrhythmias, Conduction Disorders, and Myocardial Fibrosis in Patients With Systemic Sclerosis.

Delayed-enhancement magnetic resonance imaging (DE-MRI) is a noninvasive diagnostic tool able to identify myocardial fibrosis. In patients with scleroderma, its relationship with arrhythmias and conduction disorders has not been fully explored. The aim of this study was to evaluate the possible correlations between ventricular arrhythmias, conduction disorders, and myocardial fibrosis in patients with systemic sclerosis. Thirty-six patients with diffuse or limited cutaneous scleroderma underwent 12-lead electrocardiogram (ECG), 24-hour Holter ECG monitoring, transthoracic echocardiography, and cardiac DE-MRI, with gadolinium administration in 33 patients. High-quality DE-MRI scans were obtained in 30 patients. Myocardial fibrosis was detected in 25 patients (83.3%). Eighteen patients (60%) had ventricular arrhythmias or conduction disorders. There was no significant difference in ventricular arrhythmia burden (the total number of premature ventricular contractions [PVCs]/24 hours) (48 ± 304 vs. 69 ± 236, P = 0.97), ventricular arrhythmia severity (couplets, triplets, runs) on Holter ECG, or in the presence of conduction disorders (36% vs. 40%, P = 0.86) between patients with and without myocardial fibrosis. In univariate analysis, diffuse fibrosis was weakly associated with the number of PVCs/24 hours (R = 0.157, P = 0.03). A number of at least 597 PVCs/24 hours had a sensitivity of 60% and a specificity of 92% in predicting the presence of diffuse fibrosis on DE-MRI (area under the curve = 0.640). Delayed-enhancement magnetic resonance imaging can identify myocardial fibrosis in a high percentage of scleroderma patients. Its presence does not seem to influence the ventricular arrhythmia burden and severity or the presence of conduction disorders, with the exception of diffuse myocardial fibrosis, which modestly influences the total number of PVCs/24 hours.

Scleroderma and Related Disorders

Scleroderma spectrum diseases are a heterogeneous group of disorders that are distinguished by abnormalities of the connective tissue in the skin and, in some cases, other organs. Each disorder may be characterized by the extent of cutaneous and internal involvement, as well as histopathologic features of skin biopsy. Scleroderma spectrum diseases include systemic scleroderma, localized scleroderma, and eosinophilic fasciitis. This chapter reviews the classification, epidemiology, etiology, pathophysiology and pathogenesis, diagnosis, differential diagnosis, treatment, outcome measures, management, and clinical course of scleroderma as well as the definition and classification, etiology/genetics, differential diagnosis, and treatment of localized scleroderma. Also discussed are the definition and classification, epidemiology, etiology/genetics/pathogenesis, diagnosis, differential diagnosis, and treatment of eosinophilic fasciitis. Tables review the classification of—and antinuclear antibodies in—scleroderma as well as the key assessments and interventions in scleroderma management. Figures illustrate the disease's presentation and clinical manifestations, including several images of scleroderma of the hands; face, palmar, and buccal telangiectasias in a patient with scleroderma; a radiograph demonstrating calcinosis of the elbow; Raynaud’s phenomenon; high-resolution computed tomographic images of diffuse cutaneous scleroderma, scleroderma and severe pulmonary hypertension, and limited cutaneous scleroderma; plus an esophagram demonstrating hypomotility. This review contains 11 highly rendered figures, 3 tables, and 72 references.

Scleroderma and Related Disorders

Scleroderma spectrum diseases are a heterogeneous group of disorders that are distinguished by abnormalities of the connective tissue in the skin and, in some cases, other organs. Each disorder may be characterized by the extent of cutaneous and internal involvement, as well as histopathologic features of skin biopsy. Scleroderma spectrum diseases include systemic scleroderma, localized scleroderma, and eosinophilic fasciitis. This chapter reviews the classification, epidemiology, etiology, pathophysiology and pathogenesis, diagnosis, differential diagnosis, treatment, outcome measures, management, and clinical course of scleroderma as well as the definition and classification, etiology/genetics, differential diagnosis, and treatment of localized scleroderma. Also discussed are the definition and classification, epidemiology, etiology/genetics/pathogenesis, diagnosis, differential diagnosis, and treatment of eosinophilic fasciitis. Tables review the classification of—and antinuclear antibodies in—scleroderma as well as the key assessments and interventions in scleroderma management. Figures illustrate the disease's presentation and clinical manifestations, including several images of scleroderma of the hands; face, palmar, and buccal telangiectasias in a patient with scleroderma; a radiograph demonstrating calcinosis of the elbow; Raynaud’s phenomenon; high-resolution computed tomographic images of diffuse cutaneous scleroderma, scleroderma and severe pulmonary hypertension, and limited cutaneous scleroderma; plus an esophagram demonstrating hypomotility. This review contains 11 highly rendered figures, 3 tables, and 72 references.

Adipose tissue-derived stem cells ameliorates dermal fibrosis in a mouse model of scleroderma.

To investigate the therapeutic potential of adipose-derived stem cells (ADSCs) for limited cutaneous scleroderma (LS) in mouse models. ADSCs were isolated from pathogen-free female C57BL/6 mice and LS was induced in wild type (WT) C57BL/6 mice via daily injection of bleomycin (0.1mL×300μg/mL) for 4 weeks; then the ADSCs were subcutaneously injected into the dorsal area in the model treatment group, and 100μL of phosphate-buffered saline (PBS) solution was injected into the same site in the model control group. Green fluorescent protein (GFP) was used to track the cells using an invivo imaging system on days 7, 14, 21, and 28 after transplantation. All mice were sacrificed and histologic analyses were performed after 4 weeks, and the skin thickness, collagen deposition and the total content of hydroxyproline were evaluated. Additionally, immunohistochemistry were performed to compare the tissue expression and distribution of TGF-β1 and VEGF between the ADSCs treatment group and the treatment control group. WT C57BL/6 LS mouse model were successfully established and GFP invivo fluorescence imaging showed that the translated ADSCs survived at the local for at least 4 weeks. Compared with the control group, the ADSCs treatment group significantly attenuated bleomycin-induced dermal fibrosis, reduced the skin thickness and the total content of hydroxyproline (P<0.05). The ADSCs treatment group displayed significantly lower levels of TGF-β1 and higher levels of VEGF than the control group (P<0.05). ADSCs may provide a feasible and practical treatment for autoimmune diseases such as LS and ameliorate dermal fibrosis.

Scleroderma overlap syndromes

Scleroderma overlap syndromes

Band-like Acral Osteolysis in Limited Cutaneous Scleroderma

Abstract: Acral osteolysis is a well-recognized manifestation of scleroderma. Scleroderma is characterized by abnormal deposition of collagen and other extra cellular matrix macromolecules leading to vascular damage, inflammation and tissue fibrosis. Acral osteolysis in scleroderma occurs due to digital ischemia resulting from the vasculopathy. Treatment is directed towards providing symptomatic relief and prevention of complications. Here we present a case of band-like acral osteolysis seen in a patient of limited cutaneous scleroderma. Keywords: Osteolysis; Acral osteolysis; Scleroderma; Systemic sclerosis Introduction:Scleroderma is a multisystem connective tissue disorder that is characterised by abnormal deposition of collagen and other connective tissue macromolecules in the skin and multiple internal organs leading to inflammation and fibrosis. The exact etiology is unknown. Various genetic, infectious, and environmental factors have been implicated in the pathogenesis of scleroderma leading to vascular injury, fibrosis, and immune activation. The pathological pathways include vasculopathy and abnormalities in both humoral and cellular immunity. Osteolysis is a well-recognized manifestation of scleroderma. Here we report a case of band-like acral osteolysis seen in a patient of scleroderma. Clinical Presentation: A 25 years old female presented with a history of progressive tightening of the skin over her fingers and face for 3 years associated with phasic changes in skin colour (white, blue and red) typical of Raynaud’s phenomenon. On physical examination, the skin over her face appear stretched out, tight and shiny. The skin over the distal part of most her fingers also appear tight and stretched out. The tips of most of her fingers appear shortened (Figure 1). A test for antinuclear antibodies was positive with a titre of 1: 1280. Her Anticentromere antibodies were positive. A radiograph of both hands showed symmetrical band-like osteolysis of the diaphysis of distal phalanges suggestive of acral osteolysis (Figure 2). Echocardiography revealed a normal study. Further test were done that ruled out other organ systems involvement. Discussion: Acral osteolysis in scleroderma is thought to result from impaired blood flow due to vasculopathy resulting in digital ischemia and subsequent damage to the terminal phalanges [1]. It may also be a result of pressure changes due to the induration and tightening of the skin. Acral osteolysis can also be seen in various other pathological conditions such as diabetes mellitus, tabes dorsalis, leprosy, psoriasis, rheumatoid arthritis, exposure to vinyl chloride, following trauma or in association with hyperparathyroidism [2]. Treatment options are limited and is focused on providing symptomatic relief and preventing complications. Patients should avoid prolonged cold exposure and avoid digital or skin trauma. Calcium channel blockers and alpha receptor blockers may reduce the ischemia by promoting vasodilatation. Phosphodiesterase-5 inhibitors such as sildenafil may also help provide symptomatic relieve. The disease is, however, progressive in nature and currently there are no approved therapy aimed at retarding the vascular damage, fibrosis and altered immunological response. Current experimental therapies are based on immune-suppression and immune-modulation and include drugs like methotrexate, mycophenolate mofetil, D-penicillamine and rituximab. Tocilizumab, an interleukin-6 (IL-6) receptor antagonist was recently granted breakthrough therapy designation status for systemic sclerosis by the United States Food and Drug Administration (USFDA) [3]. Various other possible immune-inflammatory therapies are currently under study, including modulators of the profibrotic pathways [4]. The safety and possible toxicity of these agents remain a cause for concern.

Polymorphisms in STAT4 and IRF5 increase the risk of systemic sclerosis: a meta-analysis.

Systemic sclerosis (SSc) is the most severe connective tissue disorder. Recent studies have demonstrated that genetic factors may play a role in the development of SSc. The aim of this study was to investigate the association of signal transducer and activator of transcription 4 (STAT4) rs7574865 and interferon regulatory factor 5 (IRF5) rs2004640 polymorphisms with risk of SSc. Case-control studies were obtained from the electronic database of PubMed, Medline, Embase, and CNKI (China National Knowledge Infrastructure) up to December 2013. The association between STAT4 and IRF5 polymorphisms and SSc susceptibility was assessed by pooled odds ratios (ORs) and 95% confidence intervals (CI). Six related studies, including 4746 SSc cases and 7399 healthy controls, were pooled in this meta-analysis. For STAT4 polymorphism, we observed a statistically significant positive association between risk factor T allele carriers and SSc susceptibility (OR = 1.37, 95% CI = 1.27-1.48, P < 0.00001) in the overall population. The presence of limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) scleroderma also showed a significant association with each of the genetic models (P < 0.00001). For IRF5 polymorphism, the T allele was shown to be strongly associated with increased SSc risk (OR = 1.27, 95% CI = 1.17-1.39, P < 0.00001). No significant heterogeneity between studies was found. The results demonstrated that STAT4 rs7574865 and IRF5 rs2004640G/T substitution are associated with a susceptibility to SSc, and they may serve as the SSc genetic susceptibility factor. These data confirmed that genetic polymorphisms may play a role in the development of SSc and have provided new insight into the pathogenesis of SSc.

Primary sclerosing cholangitis associated with CREST (calcinosis, Raynaud phenomenon, oesophageal dysmotility, sclerodactyly and telangiectasia) in an elderly woman: a case report

IntroductionCREST (calcinosis, Raynaud phenomenon, oesophageal dysmotility, sclerodactyly, and telangiectasia) syndrome comprising calcinosis cutis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia and primary sclerosing cholangitis are both chronic fibrotic diseases but the association between them is extremely rare. While primary sclerosing cholangitis has been associated with diffuse cutaneous scleroderma, the association with limited cutaneous scleroderma or CREST has not been previously reported in the literature. This case report illustrates the association between CREST and primary sclerosing cholangitis.Case presentationWe report the case of an 84-year-old Asian woman with a long history of CREST who was admitted with abdominal pain, fatigue and progressive derangement of her liver enzymes. This was initially thought to be secondary to her bosentan therapy for pulmonary hypertension but it persisted despite bosentan being ceased. Primary sclerosing cholangitis was subsequently diagnosed on magnetic resonance cholangiopancreatography and she was referred to a hepatologist for treatment.ConclusionsThis case highlights the need to consider primary sclerosing cholangitis in patients with CREST who present with abdominal symptoms and deranged liver enzymes when other causes have been excluded. Relevant differential diagnoses for this presentation, which can be difficult to exclude, include immunoglobulin G4-associated cholangitis and antimitochondrial antibody negative primary biliary cirrhosis. It is of particular significance to rheumatologists and gastroenterologists but has broader relevance to all medical specialists involved in the care of patients with CREST.

EVALUATION OF CARDIAC AUTONOMIC FUNCTION WITH HOLTER ECG MONITORING IN PATIENTS WITH SYSTEMIC SCLEROSIS

Purpose. Cardiac autonomic dysfunction is frequently encountered among patients with systemic sclerosis. Its presence correlates with potentially fatal ventricular arrhythmias, having a good positive predictive value for mortality. The aim of this paper was to identify cardiac autonomic dysfunction in patients with systemic sclerosis using Holter ECG monitoring and to assess the possible correlations between its presence and other disease characteristics. Material and methods. Forty nine patients with diffuse cutaneous and limited cutaneous scleroderma, diagnosed according to the American College of Rheumatology/EULAR 2013 criteria underwent ECG, transthoracic echocardiography, blood sample testing, chest X-ray and spirometry. Subsequently, all patients and a control group of 49 healthy subjects underwent Holter ECG monitoring with time and frequency domain heart rate variability (HRV) analysis. Results. Scleroderma patients had significantly lower HRV values compared to controls: SDNN (123 ± 39.4 vs. 143.2 ± 32, p =0.001), SDANN (137.2 ± 34.9 vs. 127.9 ± 25.7, p=0.001), TI (-) (30.6 ± 9.6 vs. 38.1 ± 8.9, p=0.01) and TINN (758.8 ± 208 vs. 815.1 ± 138, p=0.04). The LF/HF ratio was significantly higher among patients with diffuse scleroderma (1.18 ± 0.34 vs. 1.08 ± 0.43, p= 0.005). There was a positive correlation between the TI values, SDANN and the duration from the onset of Raynaud’s phenomenon (r=0.399, p=0.016) (r=0.419, p=0.011), between the SDANN values and systolic pulmonary arterial pressure (sPAP) values (0.032, p=0.034) and a negative correlation between the LF/HF values and the patients’ age (r=-0.442, p=0.001), the duration from the onset of non-Raynaud’s phenomenon (r=-0.395, p=0.034), echocardiographic value of sPAP(r=-0.330, p=0.035) and the total number of premature ventricular contractions (r=-0.0459, p=0.001). Conclusion. Patients with systemic sclerosis often have cardiac autonomic dysfunction, which can be diagnosed with Holter ECG monitoring.

L’HTA au cours de la sclérodermie systémique : une urgence vitale

PurposeIn systemic sclerosis, hypertension is feared because it is often heralding severe renal impairment. The objective of our study was to identify the frequency of arterial hypertension and clarify its etiologies in this condition. Patients/methodsOur study was prospective. From January 2008 to May 2012, we have included all patients over the age of 16 years which featured a systemic scleroderma meeting the criteria for classification of Leroy and Medsger modified. Blood pressure was systematic and hypertension was defined as a greater than 140/90mmHg PAS/PAD. ResultsWe have collected 60 patients. It was 50 women and 10 men with an average age of 41.1ans±13.03. Arterial hypertension was noted in sixteen patients (26.7%) with an average age of 48.8 years±13.21. It was nine diffuse cutaneous systemic scleroderma of six limited cutaneous scleroderma and one case of scleroderma sine scleroderma. Etiologic research hypertension had concluded to a renal cause in 12 patients. It was five scleroderma renal crisis (SRC), three vascular nephropathies, four chronic kidney failure (CKD) including three terminals and a moderate CKD. An ‘essential’ so-called HTA was observed in four patients. Hypertension was a major sign that reported five cases of SRC. These patients had received treatment anti hypertensive and renal extra cleansing. DiscussionHypertension is common in systemic scleroderma. Our data approximates of literature when its frequency and severity. ConclusionHypertension is a major warning sign that under no circumstances should overlook it or novo or secondary aggravation. Its support must be very early under penalty to put at stake the life-threatening in particular during the CRS.

Vitiligo and associated disorders including autoimmune diseases: A prospective study of 200 Indian patients

Background: Vitiligo is commonly associated with autoimmune and nonautoimmune disorders. However, there is a paucity of such data in the Indian context. Aims: We studied common disorders including autoimmune diseases associated with vitiligo. Methods: Clinical details and the results of serological studies comprising anti-TPO and anti-TG antibodies, antiparietal cell antibody, antinuclear antibodies, hepatitis B surface antibody, anti-hepatitis C virus immunoglobulin M antibody, rheumatoid factor, and immunoglobulin E (IgE) levels were analyzed in 200 consecutive vitiligo patients.Results: These 200 (male:female 96:104) patients were aged between 3 and 78 (median age 25) years having vitiligo for 15 days to 60 years. Nonsegmental vitiligo in 192 (96%) patients was the commonly reported pattern. Fifty-three (26.5%) patients had another affected a family member. Clinically, 37 (18.5%) patients had autoimmune disorders and 121 (60.5%) had serological evidence of autoimmunity. Autoimmune thyroid disorders in 85 (42.5%) patients were the most common. Others were rheumatoid arthritis 9 (4.5%), plaque psoriasis 5 (2.5%), alopecia areata 3 (1.5%), and limited cutaneous scleroderma 1 (0.5%). The presence of antithyroglobulin antibody in 53 (26.5%) and antithyroid peroxidase antibody in 44 (22%) patients, rheumatoid factor in 9 (4.5%) patients, and hyper IgE in 75 (37.5%) patients was significant observation. No patient had antiparietal cell antibodies or pernicious anemia. Conclusion: Clinical presentation of our patients conforms to established patterns of vitiligo. Subclinical autoimmune thyroiditis observed in the most cases is indicative of the potential benefit of screening these patients for concurrent thyroid disorders. The association of atopy remains poorly understood. Pernicious anemia and antiparietal cell antibodies do not appear a significant association in our patients.