Diffuse Skin Involvement Research Articles

Mortality and Associated Factors in Patients with Systemic Sclerosis Associated Pulmonary Hypertension with and without Interstitial Lung Disease: A Long-Term Follow-up Study.

We aimed to analyze the prevalence, mortality, and prognostic factors in systemic sclerosis (SSc) patients with pulmonary hypertension (PH) with or without interstitial lung disease (ILD). The associations between mortality and demographics, transthoracic echocardiography, right heart catheterization (RHC), pulmonary functional parameters at baseline, and treatment modalities in two groups; patients with pulmonary arterial hypertension (PAH, PH without significant ILD) and PH + ILD were evaluated. The mean age of the patients was 56.6±13.5 (range: 34-82, 44 women/ 2 men), and 23 (52.3%) were deceased during a median follow-up of 45 months. The survival rates of PH-SSc patients were 91% for the first year, 75% for 2 years, 68% for 3 years, and 43.1% for 5 years. The majority of deceased patients were in the PH + ILD group (p=0.007). The PH + ILD group had more diffuse skin involvement, anti-Scl-70 positivity, high C-reactive protein, low FVC, and lower DLCO values. The deceased patients had higher ePASP, low CO, and FVC values compared to surviving patients. Median survival time was significantly better in patients on combined therapy (44 vs. 61 months, p=0.01). The mortality-related factors in the PH + ILD group were decreased initial FVC, high ePASP on echocardiography, low cardiac output on RHC, deteriorated functional class, and monotherapy. This is the first reported SSc-PH cohort from Turkey by a multidisciplinary team after the implementation of PAH-specific drugs. SSc-PH is a severe complication of SSc with high mortality especially in patients with accompanying severe ILD.

Increased prevalence of osteopenia and osteoporosis in systemic sclerosis patients, including in men and young women- a case-control study.

To investigate bone mineral density (BMD), osteoporosis prevalence and systemic sclerosis (SSc) specific associations of BMD in SSc patients compared with background population. In total, 211 SSc patients (182 women, 29 men; mean age 61.3 and 62.2 respectively) and 505 age and sex matched controls from the same geographic area participated. BMD and T-score at total hip and lumbar spine was measured by Dual-energy X-ray absorptiometry. Osteopenia was defined as T-score -1.0 to -2.5; osteoporosis as T-score ≤-2.5. Associates of low BMD were identified by multiple regression analysis. Women with SSc had lower BMD for total hip (p< 0.001) and spine (p= 0.011), equivalent to ΔT-score -0.56 and -0.35 compared with controls. Osteopenia was present in 51.6% and 16.5% had osteoporosis (p= 0.001, compared with controls). Already in women below age 45, differences in hip BMD were apparent (ΔT-score -0.93, p= 0.005). In addition to expected risk factors for osteoporosis (older age, lower BMI and menopause), finger ulcers (p= 0.009) and diffuse skin involvement (p= 0.027) were associated with lower hip BMD in women. In men with SSc, more than half displayed osteopenia or osteoporosis and had numerically lower hip BMD than their age matched counterparts. SSc patients, including men and younger women, have lower BMD than the background population. Finger ulcers and diffuse skin involvement, in addition to older age, lower BMI and being post-menopausal, are associated with lower BMD in women. The data emphasizes the importance of performing bone health assessment of all SSc patients, including men and young subjects.

E029 Intracranial haemorrhage in scleroderma renal crisis; an unusual presentation

Abstract Background/Aims Scleroderma renal crisis is a life-threatening complication of systemic sclerosis (SSc), which typically occurs in the first 5 years after disease onset. Several risk factors for development of renal crisis are well recognised, including diffuse skin involvement, presence of RNA polymerase 3 antibodies and preceding use of corticosteroids. Methods A 66 year old female 6 years post diagnosis of stable diffuse systemic sclerosis/ polymyositis overlap (PM Scl 100 positive) presented to her GP with a 1 week history of fatigue. She had been seen 2 months earlier by her rheumatologist with stable, mild skin involvement. She had no preceding history of hypertension or other significant co-morbidity. A month earlier she received antibiotics for a chest infection from which she made a slow but complete recovery. She was found to have shingles and started a course of oral acyclovir. Blood tests revealed acute kidney injury stage 3 (eGFR 10 from baseline 70). However, she deteriorated overnight, waking with headache and disturbed colour vision. This quickly deteriorated to bilateral blindness precipitating admission to the emergency department (ED). On arrival she was conscious but severely hypertensive with a BP of 240/105. She received ramipril, amlodipine and a GTN infusion with limited efficacy. CT head (CTH) showed a left occipitoparietal bleed. She then experienced a seizure in ED, which was terminated with lorazepam. She was intubated in the post ictal phase. Repeat CTH following the seizure showed a right frontal bleed extending into the subarachnoid space. Repeat CTH at 48 hours showed progression of the right frontal and left parieto-occipital intracerebral haemorrhages, with evidence of posterior reversible encephalopathy syndrome. Lumbar puncture was normal (VZV negative). Treatment was commenced with intravenous hydralazine. On day 2 of admission she required haemofiltration and subsequently regular renal dialysis. Results SSc was diagnosed in 2016, since when her main issue had been severe Raynaud’s phenomenon for which she took sildenafil. Her muscle disease had only ever manifested as a modestly raised CPK, which settled with a brief course of low dose prednisolone at diagnosis. She has never required DMARDs. She had mild reflux symptoms. Skin tightening was noted distally over her fingers, forearms, lower legs and feet. Annual echocardiography showed nothing to suggest developing pulmonary arterial hypertension. With supportive management she has made a remarkable neurological recovery and has returned to her pre-morbid level of function. She remains dialysis dependent at 4 months. Conclusion This lady lacked a single recognised risk factor for developing a renal crisis, and this occurred quite unexpectedly following a reassuring clinic visit just 2 months prior to presentation. As rheumatologists we must remain vigilant for features of a renal crisis and avoid being falsely reassured by a low risk profile. Disclosure L. Parker: None. N. Buchanan: None. E.L. Williams: None.

A case of non-Langerhans histiocytosis effectively treated with Cobimetinib: A rare case report

non-Langerhans histiocytosis is a group of very rare, clinically heterogeneous diseases, characterized by the proliferation of histiocytes in the connective tissue, it preferentially affects middle-aged men, their classification is difficult, it is based on clinical, histological, immune criteria histochemical and evolutionary. We report the case of a 58-year-old man with an HIV infection under treatment. The patient initially presented with skin lesions, the skin biopsy was in favor of xanthoma disseminatum, and then the patient presented with bone pain and respiratory symptoms. , the extension assessment and the biopsies confirm the diagnosis of Erdheim-Chester disease with bone, cardiac, aortic and pulmonary involvement and diffuse skin involvement « disseminated xanthoma », the patient was put on Cobimetinib 20 mg / day which resulted in an excellent clinical and radiological response with no reported toxicity. Cobimetinib is effective and well tolerated in cases of Erdheim-Chester disease; therefore, it could be considered as a good therapeutic option as a monotherapy for patients without BRAF mutation.

Het syndroom van Erasmus: een gevalsbespreking van silicageïnduceerde systeemsclerose

Silica-induced systemic sclerosis: a case report of Erasmus syndrome Erasmus syndrome is the association of silica exposure and the subsequent development of systemic sclerosis. It is a rare condition and the information available in medical literature is scarce, resulting in insufficient knowledge and awareness, which leads to underdiagnosis. The authors report a case of a 71-year-old man who developed systemic sclerosis following occupational exposure to silica. The patient presented with progressive dyspnoea due to interstitial lung disease. Further diagnostic assessment revealed the presence of a new-onset Raynaud phenomenon, initially without other skin involvement, an aberrant capillaroscopy and autoimmune serology positive for anti-Scl-70 antibodies. Despite adequate treatment, cutaneous involvement occurred with a rapid progression to diffuse skin involvement over the following 6 months. Careful screening of patients with interstitial lung disease and a positive autoimmune serology is important in order to facilitate an early diagnosis, resulting in a multidisciplinary approach that can lead to a better outcome for the patient.

Clinical characteristics and survival of pulmonary arterial hypertension with or without interstitial lung disease in systemic sclerosis

ObjectivesTo describe the clinical phenotype and prognosis of people in the Australian Scleroderma (SSc) Cohort Study with pulmonary arterial hypertension (PAH) with or without interstitial lung disease (ILD).MethodsParticipants meeting ACR/EULAR criteria for SSc were divided into four mutually exclusive groups: those meeting criteria for PAH (PAH-only), ILD (ILD-only), concurrent PAH and ILD (PAH-ILD) or neither PAH nor ILD (SSc-only). Logistic or linear regression analyses were used for associations between clinical features, health-related quality of life (HRQoL) and physical function. Survival analysis was performed using Kaplan–Meier estimates and Cox-regression modelling.ResultsOf 1561 participants, 7% fulfilled criteria for PAH-only, 24% ILD-only, 7% PAH-ILD and 62% SSc-only. People with PAH-ILD were more frequently male, with diffuse skin involvement, higher inflammatory markers, older age of SSc onset and higher frequency of extensive ILD than the cohort overall (p < 0.001). People of Asian race more frequently developed PAH-ILD (p < 0.001). People with PAH-ILD or PAH-only had worse WHO functional class and 6-min-walk-distance than ILD-only (p < 0.001). HRQoL scores were worst in those with PAH-ILD (p < 0.001).Survival was reduced in the PAH-only and PAH-ILD groups (p < 0.01). Multivariable hazard modelling demonstrated the worst prognosis in extensive ILD and PAH (HR = 5.65 95% CI 3.50–9.12 p < 0.01), followed by PAH-only (HR = 4.21 95% CI 2.89–6.13 p < 0.01) and PAH with limited ILD (HR = 2.46 95% CI 1.52–3.99 p < 0.01).ConclusionsThe prevalence of concurrent PAH-ILD in the ASCS is 7%, with poorer survival in those patients with PAH-ILD compared to ILD or SSc alone. The presence of PAH confers a poorer overall prognosis than even extensive ILD; however, further data are required to better understand the clinical outcomes of this high-risk patient group.

Psychological Morbidity, Fatigue and Burden of Disease in Patients With Connective Tissue Diseases

Objective: Depression and anxiety disorders are significant health problems that can coexist with other diseases and exert adverse effects on these diseases’ course and treatment response. Fatigue is a common and disabling symptom in chronic inflammatory diseases. The present study aimed to evaluate the fatigue, anxiety, depression and burden of disease (eg, disease activity, function, quality of life) in autoimmune connective tissue disease (CTD) patients.&#x0D; Methods: 160 patients diagnosed with CTD and 50 healthy control patients were included in the present study. Disease activity scores were recorded. All patients were asked to fill the Short Form-36, Fatigue Severity Scale, Hospital Depression and Anxiety Scale (HADS).&#x0D; Results: In all patients groups, anxiety, depression, and fatigue scores were significantly higher, and quality of life scores significantly lower than those of healthy controls. A significant positive correlation was found between rheumatoid arthritis activity, HADS anxiety and depression scores. It was also established that in scleroderma patients with diffuse skin involvement and pulmonary involvement, depression and anxiety scores were high.&#x0D; Conclusion: It is clear that psychiatric comorbidity and fatigue may be present in CTD and adversely affects quality of life. It is important to assess them and they should be an important treatment target.

Systemic sclerosis in Asians: Are there racial differences?

Systemic sclerosis is a multisystemic autoimmune disease characterized by vasculopathy and fibrosis. Racial factors exert a significant influence on the epidemiology, clinical manifestations, antibody profile, mortality and genetic factors in systemic sclerosis. In this review, we examined Asian systemic sclerosis cohorts reported in Asia and multi-racial cohort studies to evaluate the disease characteristics and outcomes of systemic sclerosis in Asians. Asian patients have distinct genetic susceptibility to systemic sclerosis, younger age of systemic sclerosis onset, higher frequency of diffuse skin involvement, different autoantibody profiles such as higher frequency of anti-Scl70 and anti-U1-RNP antibodies, and more severe clinical phenotype. There was a suggestion of poorer survival among Asians that may be contributed by more severe disease, socioeconomic factors and differences in healthcare systems. Recognizing the influence of racial differences in systemic sclerosis disease course is important as it has implications for appropriate treatment, monitoring and prognostication.

Do We Have Good Activity Indices in Systemic Sclerosis?

No fully validated index is available for assessing overall disease activity in systemic sclerosis (SSc). To estimate the effect of disease activity as measured by different disease activity indices on the risk of subsequent organ damage. The European Systemic sclerosis study group activity index (EScSG AI), the European Scleroderma Trials and Research Group Activity Index (r-EUSTAR AI), 12 point activity index proposed by Minier (12point AI) were calculated for 91 patients; the CRISS (The Composite Response Index for Systemic Sclerosis) for patients included after 2016. Data were analysed by parametric and non-parametric tests and logistic regression. EscSG AI, r-EUSTAR AI and 12point AI correlated with lung involvement. EScSG AI and r-EUSTAR AI correlated with diffuse skin involvement. EscSG AI correlated with digital ulcers and diffuse cutaneous involvement and r-EUSTAR AI with a renal crisis. Bivariate analysis showed an inverse correlation between the three disease activity scores and forced vital capacity (FVC) (p<0.001) and diffusing capacity for carbon monoxide (DLCO) (p<0.001) and positive correlation with pulmonary fibrosis (p<0.001), modified Rodnan skin score (mRSS) (p<0.001), health assessment questionnaire (HAQ) (p<0.001), systolic pulmonary pressure (sPAP) (p<0.001), C-reactive protein (CRP) (p<0.001) and capillaroscopy scoring (p<0.001) at both baseline visit and the 3-year follow-up visit. Logistic regression revealed that baseline EScSG AI adjusted for gender and age and that baseline 12-point AI both adjusted and unadjusted predicted worse skin involvement at 3-year follow-up; while adjusted EScSG AI predicted decreasing DLCO. Also, 12-point AI predicted a decline of FVC and higher HAQ scores at 3-year follow up; while baseline r-EUSTAR AI was able to predict muscular deterioration, decline of FVC and the increase of HAQ score during 3 years of following. An active disease according to EScSG AI at first visit predicted progression of joint involvement while an active disease at baseline showed by r- EUSTAR AI predicted muscular deterioration, FVC and DLCO worsening, as well as an increase in HAQ score during the follow-up period. r-EUSTAR AI was the only score to predict the decrease of FVC in a multiple regression prediction model (OR= 1.306 (1.025, 1.665), p=0.31) while baseline EScSG AI best predicted worsening of DLCO (OR=1.749 (1.104, 2.772), p=0.017). Our study could not establish a gold standard to assess disease activity in SSc; especially EscSG AI and r-EUSTAR AI could quantify and predict major organ involvement in daily practice. CRISS can be useful as an outcome measure for patients with short disease duration included in clinical studies.

Diffuse Geometric Erosions on the Skin of a Premature Infant, Fraternal Twin Unaffected

Diffuse Geometric Erosions on the Skin of a Premature Infant, Fraternal Twin Unaffected

Evaluation of serum interleukin-6 (IL-6), IL-13, and IL-17 levels and computed tomography finding in interstitial lung disease associated with connective tissue disease patients.

Interstitial lung disease (ILD) is one of the most severe complications which is associated with connective tissue disease (CTD) and causes to morbidity and mortality. So, we aimed to determine serum levels of interleukin-6 (IL-6), IL-13, and IL-17, to investigate whether these cytokines are related to CTD-ILD, and to find their possible contribution to determining the prognosis of the disease. A total of 150 participants, 80 patients diagnosed with CTD-ILD (mean age, 58.21 ± 12.36) and 70 healthy controls (mean age, 57.07 ± 9.60) were recruited from the rheumatology department between January 2016 and June 2019 in the study. High-resolution computed tomography (HRCT) findings were scored as similarly to previous studies. Serum IL-6, IL 13, and IL-17 levels were measured by ELISA test kits. The levels of IL-6, IL-13, and IL-17 in CTD patients were significantly higher than the healthy individuals (p < 001), but the HRCT score's relation were not determined. IL-6 was associated with disease duration and disease activity scores of DAS28, ESDAII, and dSSc. There was a significant relation between dSSc, HCRT fibrosis, and total score.CRP, hemoglobin, and platelets were associated with the HRCT inflammation pattern. At the study, it has been observed that serum IL-13, IL-6 and IL-17 levels are increased in patients with CTD-ILD. Besides, IL-6 was associated with disease activity scores of DAS28, ESDAII, and dSSc. Also, HRCT fibrosis score is associated with dSSc. Further and comprehensive studies are needed to understand better the complex intersection of lung disease with systemic autoimmunity. Key Points • Serum IL-13, IL-6, and IL-17 levels are increased in patients with CTD-ILD. • IL-6 was associated with disease activity scores of DAS28, ESDAII, and diffuse skin involvement. • HRCT fibrosis score is associated with diffuse skin involvement in patients with SSc-ILD. • HRCT inflammation score is associated with PAH.

Systemic sclerosis-associated myositis features minimal inflammation and characteristic capillary pathology

Systemic sclerosis represents a chronic connective tissue disease featuring fibrosis, vasculopathy and autoimmunity, affecting skin, multiple internal organs, and skeletal muscles. The vasculopathy is considered obliterative, but its pathogenesis is still poorly understood. This may partially be due to limitations of conventional transmission electron microscopy previously being conducted only in single patients. The aim of our study was therefore to precisely characterize immune inflammatory features and capillary morphology of systemic sclerosis patients suffering from muscle weakness. In this study, we identified 18 individuals who underwent muscle biopsy because of muscle weakness and myalgia in a cohort of 367 systemic sclerosis patients. We performed detailed conventional and immunohistochemical analysis and large-scale electron microscopy by digitizing entire sections for in-depth ultrastructural analysis. Muscle biopsies of 12 of these 18 patients (67%) presented minimal features of myositis but clear capillary alteration, which we termed minimal myositis with capillary pathology (MMCP). Our study provides novel findings in systemic sclerosis-associated myositis. First, we identified a characteristic and specific morphological pattern termed MMCP in 67% of the cases, while the other 33% feature alterations characteristic of other overlap syndromes. This is also reflected by a relatively homogeneous clinical picture among MMCP patients. They have milder disease with little muscle weakness and a low prevalence of interstitial lung disease (20%) and diffuse skin involvement (10%) and no cases of either pulmonary arterial hypertension or renal crisis. Second, large-scale electron microscopy, introducing a new level of precision in ultrastructural analysis, revealed a characteristic capillary morphology with basement membrane thickening and reduplications, endothelial activation and pericyte proliferation. We provide open-access pan-and-zoom analysis to our datasets, enabling critical discussion and data mining. We clearly highlight characteristic capillary pathology in skeletal muscles of systemic sclerosis patients.

Esclerosis sistémica

Systemic sclerosis, also known as scleroderma, is a systemic autoimmune disease characterised by fibrosing involvement of the skin and internal organs. It is a disease of unknown cause, and its aetiopathogenesis involves genetic and environmental factors and three fundamental processes: vascular involvement, immune system intervention and fibrosis. It predominates in females and peaks in middle age. Skin involvement is divided into two types according to extent: limited skin involvement and diffuse skin involvement. It is a very heterogeneous disease, with a wide spectrum of manifestations, which can present with mild and stable forms over time or rapidly progressive severe forms. Raynaud's phenomenon, digestive tract involvement, especially the oesophagus, pulmonary hypertension, interstitial pulmonary, musculoskeletal, and cardiac involvement are characteristic of the disease. Diagnosis of the disease is medical, based on symptoms, examination, and complementary tests. Some involvement may be asymptomatic on onset, and therefore early detection and treatment is important since many of its manifestations entail significant morbimortality.

Hematopoietic stem cell transplantation for systemic sclerosis: Brazilian experience

BackgroundIn the past 20 years, hematopoietic stem cell transplantation (HSCT) has been investigated as treatment for systemic sclerosis (SSc). The goal of HSCT is to eradicate the autoreactive immune system, which is replaced by a new immune repertoire with long-lasting regulation and tolerance to autoantigens. Here, we describe the clinical outcomes of severe and refractory SSc patients that underwent HSCT at a single Brazilian center.Patients and methodsThis is a longitudinal and retrospective study, including 70 adult SSc patients, with an established diagnosis of SSc, and who underwent autologous HSCT from 2009 to 2016. The procedure included harvesting and cryopreservation of autologous hematopoietic progenitor cells, followed by administration of an immunoablative regimen and subsequent infusion of the previously collected cells. Patients were evaluated immediately before transplantation, at 6 months and then yearly until at least 5-years of post-transplantation follow-up. At each evaluation time point, patients underwent clinical examination, including modified Rodnan’s skin score (mRSS) assessment, echocardiography, high-resolution computed tomography of the lungs and pulmonary function.ResultsMedian (range) age was 35.9 (19–59), with 57 (81.4%) female and median (range) non-Raynaud’s disease duration of 2 (1–7) years. Before transplantation, 96% of the patients had diffuse skin involvement, 84.2%, interstitial lung disease and 67%, positive anti-topoisomerase I antibodies. Skin involvement significantly improved, with a decline in mRSS at all post-transplantation time points until at least 5-years of follow-up. When patients with pre-HSCT interstitial lung disease were analyzed, there was an improvement in pulmonary function (forced vital capacity and diffusing capacity of lung for carbon monoxide) over the 5-year follow-up. Overall survival was 81% and progression-free survival was 70.5% at 8-years after HSCT. Three patients died due to transplant-related toxicity, 9 patients died over follow-up due to disease reactivation and one patient died due to thrombotic thrombocytopenic purpura.ConclusionsAutologous hematopoietic progenitor cell transplantation improves skin and interstitial lung involvement. These results are in line with the international experience and support HSCT as a viable therapeutic alternative for patients with severe and progressive systemic sclerosis.

Association of Anti–Topoisomerase I Antibodies of the IgM Isotype With Disease Progression in Anti–Topoisomerase I–Positive Systemic Sclerosis

ObjectiveAnti–topoisomerase I (anti–topo I) autoantibodies in systemic sclerosis (SSc) are associated with diffuse skin involvement and interstitial lung fibrosis. Thus far, however, the relationship between anti–topo I antibody response and disease course has not yet been fully evaluated. This study was undertaken to gain insight into the association between characteristics of the anti–topo I antibody response and clinical disease course in SSc patients positive for anti–topo I antibodies.MethodsLevels of anti–topo I IgG, anti–topo I IgM, and anti–topo I IgA were assessed in consecutive serum samples obtained from patients at baseline who were positive for anti–topo I IgG in the Leiden Combined Care In Systemic Sclerosis (CCISS) cohort. One‐year disease progression was defined by a relevant increase in modified Rodnan skin thickness score (MRSS), decline in pulmonary function, development of digital ulcers, renal crisis, and pulmonary hypertension, and/or mortality. Validation was performed in SSc patients who were positive for anti–topo I from the Oslo University Hospital and University Hospital Zurich.ResultsOf the 103 patients with anti–topo I IgG in the CCISS cohort, clinical data were available to assess 1‐year disease progression in 81 patients. Of these 81 patients, 23 (28%) had disease progression. At baseline, patients with disease progression were significantly more often anti–topo I IgM–positive than those who did not experience disease progression (21 [91%] of 23 versus 33 [57%] of 58; P < 0.01). This finding was confirmed in the independent validation samples.ConclusionIn SSc patients who were anti–topo I IgG–positive, presence of anti–topo I IgM, which might be considered as a surrogate for an ongoing autoreactive B cell immune response, is associated with disease progression.

Ethnic influence on the phenotype of French patients with systemic sclerosis.

Systemic sclerosis (SSc) is a rare multisystem autoimmune disorder. It has a worldwide distribution but geographical and ethnic influences are poorly known. The aim of the study was to compare demographic characteristics and frequency of internal organ system involvement of Black SSc patients to those of White SSc patients in France. Patient population included 425 SSc patients recruited at Cochin Hospital in Internal medicine and Rheumatology departments. Data were collected at the baseline visit, each Black patient was matched with 2 to 3 White controls from the same department. One hundred and five Black patients and 320 White were included. Demographic comparison highlighted an older age for the White patients (48.66±14.87 vs 39.56±10.79, P<0.0001). Phenotypic comparison showed more severe skin involvement for Black patients: they had more often diffuse skin involvement than White patients (69.2% vs. 44.7%, P<0.0001) with a higher baseline modifiedRodnan skin score (15.8 vs. 11.3, P<0.001). Comparisons also showed more active ulcers (46.5% vs. 21.6%, P<0.001) and more common interstitial lung disease (73.7% vs. 43%, P<0.0001) for Black patients. Auto-antibody testing showed that White patients were more likely to harbor anti-centromere antibodies (ACA) (26.6% vs. 9%, P<0.001) whereas Black patients were more likely to have anti-U1RNP antibody (24.6% vs. 6.2%, P<0.0001). In this population recruited in a disease referral center, Black patients had more severe skin and lung involvements with lower prevalence of ACA as compared to White patients, supporting a more severe phenotype.

Mycophenolic acid drug monitoring in patients with systemic sclerosis associated with diffuse skin and/or pulmonary involvement: A monocentric and retrospective French study.

To explore pharmacokinetic/pharmacodynamic relationship between mycophenolic acid area under the curve and clinical response at 1 year on skin involvement or interstitial lung disease in patients with systemic sclerosis. Retrospective, monocentric study based on French Scleroderma Database in patients receiving mycophenolate mofetil who experienced a limited sampling strategy to estimate individual mycophenolic acid area under the curve plus two pulmonary function tests and skin evaluation after 1 month and 1 year. Efficacy criterions were variations of modified Rodnan skin score, forced vital capacity, and diffusing lung capacity for carbon monoxide at 1 year. We included 52 patients; mean age was 49 years (range 17-79), and 36 (69%) were females. Fifty patients (96%) had skin sclerosis, 39 (75%) had diffuse skin involvement with a median modified Rodnan skin score of 14 (0-38). Thirty-eight (76%) had interstitial lung disease, with median forced vital capacity and diffusing lung capacity for carbon monoxide of 81% (37-127) and 56% (28-103) from predicted values, respectively. Twenty-five (51%) patients had pulmonary fibrosis. Mycophenolate mofetil was given for 10 months (0-173) at a median dose of 2000 mg/day (500-3000). In the entire population, no relationship was found between area under the curve and modified Rodnan skin score (p = 0.085), forced vital capacity (p = 0.80), or diffusing lung capacity for carbon monoxide (p = 0.72) variations at 1 year. In this retrospective study, we failed to document any relationship between mycophenolic acid area under the curve and skin involvement or interstitial lung disease evolution. Routine monitoring of mycophenolic acid in systemic sclerosis patients treated with mycophenolate mofetil cannot be recommended based on our results.

Systemic sclerosis in sub-Saharan Africa: a systematic review.

Systematic studies on connective tissue disorders are scarce in sub-Saharan Africa. Our aim was to analyse the published clinical data on systemic sclerosis (SSc) in sub-Saharan Africa. A systematic review was carried out in accordance with the PRISMA guidelines. We screened the Embase, PubMed and African Health Sciences databases for literature published until March 2018. Searches produced 1210 publications. After abstract and full-text screenings, 91 publications were analysed, and epidemiological information and clinical features extracted. Publications were mostly publications case reports (36%), cross-sectional studies (26%) and case series (23%) and came predominantly from South Africa (45%), Nigeria (15%) and Senegal (14%). A total of 1884 patients were reported, 66% of patients came from South Africa. The patients were between 4 and 77 years old; 83% of patients were female. Overall, 72% had diffuse SSc. Raynaud´s phenomenon was reported in 78% and skin ulcerations in 42% of patients. Focal skin hypopigmentation was common and telangiectasia not frequent. Interstitial lung involvement was reported in 50%, pulmonary hypertension in 30%, heart involvement in 28% of patients. Oesophageal reflux was observed in 70% and dysphagia in 37% of patients. Antinuclear antibodies were positive in 65% of patients. Anti-centromere autoantibodies (9.2%) and RNA polymerase 3 antibodies (7.1%) were rare and anti-fibrillarin most frequent (16.5%). SSc presentations in sub-Saharan Africa differ from those reported in Europe and America by a frequent diffuse skin involvement, focal skin hypopigmentation and a high prevalence of anti-fibrillarin autoantibodies.

Total Skin Electron Beam Therapy in Patients with Advanced Cutaneous T Cell Lymphoma Undergoing Allogeneic Stem Cell Transplantation: A Single Centre Experience

Introduction: Total skin electron beam (TSEB) therapy represents a valid treatment option in the management of patients with cutaneous T-Cell lymphoma (CTCL) with diffuse skin involvement. While the efficacy of TSEB for palliative treatment is well established, its inclusion as a debulking strategy before reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been only recently reported. Due to the lack of hematopoietic toxicity, TSEB may also be effectively administered in patients relapsing after allo-HSCT. With this study we aimed to retrospectively investigate the use of TSEB among patients who underwent to allo-HSCT in our Center for advanced CTCL. Patients &amp; Methods: As of July 2019, 45 CTCL patients (26 M and 19 F, median age 54 years, range 19-66) all having stage IIB to IV refractory Mycosis Fungoides (MF, n=33) or Sézary Syndrome (SS, n=12) underwent allo-HSCT from HLA-identical sibling (n=18), unrelated donors (n=23) or haploidentical related donors (n=4). Median time from diagnosis to HSCT was 46 months and median number of previous treatment lines was 6. Source of stem cells was peripheral blood in 40 patients, bone marrow in 4 patients and cord blood in 1 patient. Conditioning regimens included FC/TBI200, pentostatin/TBI200, fludarabine/melphalan and TT/CTX/Fluda/TBI200. Outcomes at 5-years were: OS 51% (33%-66%), DFS 40% (20%-50%), NRM 15% (4%-27%) and relapse incidence 48% (32%-65%). Clinical charts of the whole series of patients were extensively reviewed to collect information on the use of TSEB from diagnosis to the last follow up date. Results: Overall 21 patients of the series received TSEB with dose fractionation of 2 Gy in 2 days administered with the Stanford Technique as part of their treatment strategy. In six cases it was included among the lines of treatment administered over the disease course preceding transplant referral, with a total dose of 36 Gy in all of them. In 13 patients TSEB was part of the debulking strategy for patients with chemorefractory disease just prior to allo-HSCT with a median total dose of 24 Gy (range 10.8- 36). In 4 patients TSEB was administered after transplantation: as a salvage treatment for skin relapse during early post tranplant intense immunosuppression phase in 3 cases (12, 36, 21.6 Gy respectively) and as palliative treatment for disease progression in one case (36 Gy). Among patients who received TSEB as a bridge to transplant strategy, CR was achieved in 5 cases: at the last follow up visit (median time from transplantation 23 months, range 6-80) 4 were alive with persistent CR, whereas 1 patient who experienced graft failure died from disease progression 31 months after transplantation. Partial remission (PR) was documented in 7 (very good in 2): at the last follow up visit (median time from transplantation 14 months, range 6-52) 2 patients were alive in CR and 5 died: 3 from disease progression, 1 from GVHD and 1 from myocardial infarction 42 months after transplantion. In 1 patient, who only showed minimal response to TSEB therapy, death from disease progression occurred 9 months after an autologous-allogeneic tandem transplant strategy. All the 3 patients receiving TSEB after allo-HSCT for early relapse achieved a new and durable CR maintained at the last follow up date (42, 21 and 10 months after transplant respectively), suggesting the occurrence of a durable graft-versus-lymphoma effect following TSEB. As far as safety is concerned, only grade 1 skin toxicity (erythematous reactions) was observed in a minority of patients, while no case of haematological toxicity was documented. Conclusions: Our experience confirmed TSEB as a particularly safe and potentially effective treatment strategy in CTCL patients, both to induce remission prior to allo-HSCT and to rescue early post transplant relapse occurring before immunosuppression withdrawal. Disclosures No relevant conflicts of interest to declare.

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study.

Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP. AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001]. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality.