Scleroderma Research Articles

The expression of the renin-angiotensin-aldosterone system in the skin and its effects on skin physiology and pathophysiology.

The local renin-angiotensin-aldosterone system (RAAS) is fully expressed in the human skin at the mRNA and protein level. Local RAAS is known to play a regulatory function in epidermal proliferation, wound healing, scarring, cutaneous heating adaptation, and aging. There are also some indications of its role in the regulation of hair growth and sebum secretion. Impaired wound healing, skin diseases associated with diabetes, cancer development, psoriasis, and scleroderma may be related to changes in skin RAAS activity. Extensive research has shown that RAAS-modulating drugs can affect the skin when applied orally or topically, creating new therapeutic approaches against dermatological diseases.

Unique clinical and autoantibody profile of a large Asian Indian cohort of scleroderma-do South Asians have a more aggressive disease?

A single-centre retrospective study was conducted using electronic medical records (EMR) of inpatients and outpatients with the diagnosis of "scleroderma" or "systemic sclerosis" visiting our clinic over the preceding 5years. A total of 327 patients' charts met our selection criteria; 301 were females. The median (IQR (inter quartile range)) age at onset of first non-Raynaud's symptom was 34.67 (27-43) years and median (IQR) disease duration prior to presentation to our department was 2.5 (1-5) years. Of these, 310 (94.8%) belonged to diffuse systemic sclerosis variety, 13 (4%) had limited systemic sclerosis, and 4 (1.2%) were of sine scleroderma type. A total of 289/302 (95.7%) patients were positive for ANA; of them, 245/327 (74.9%) were Scl-70 antibody-positive and 4% were CENP antibody-positive. Interstitial lung disease (ILD) was present in 288/327 (88.1%) patients. Among patients with available baseline forced vital capacity (FVC) data, 20% had a normal lung function and 28.4% had severe restriction. Pulmonary hypertension as assessed by echocardiography was present in 8.1% of patients. A significant association of Scl-70 antibody positivity with the presence of interstitial lung disease (ILD) (p = 0.000) and pulmonary hypertension (p = 0.035) was seen. On the other hand, presence of CENP antibody showed a protective trend against muscle weakness and/or muscle enzyme elevation (p = 0.052). Presence of arthritis was protective against development of digital ulceration (p = 0.021) and PAH (0.004). Patients younger than 40years of age had significantly higher frequency of Scl-70 positivity (p = 0.038), whereas CENP antibody positivity was more likely in those aged > 40years (p = 0.002). Younger age of onset and high prevalence of Scl-70 antibody are unique South Asian features common with large Indian, Thai, and Chinese series. High prevalence of ILD is a feature common to Indian and Chinese series. Strong correlation of Scl-70 antibody with younger age and pulmonary hypertension were unique features of our cohort. • Asian Indian scleroderma patients are younger by 2 decades compared to Caucasian series. • Higher prevalence of Scl-70 antibody, its association with young age, interstitial lung disease and pulmonary hypertension are features of our cohort. • High prevalence of interstitial lung disease (88.1%) was noted ; among those with baseline spirometry data (141/327), two thirds(66%) had moderate to severe restriction. • Younger age at onset, higher prevalence of Scl-70 antibody are features common to other Indian, Thai and Chinese series.

Scleroderma renal crisis: a review for emergency physicians.

Scleroderma renal crisis (SRC) remains a high-risk clinical presentation, and many patients require emergency department (ED) management for complications and stabilization. This narrative review provides an evidence-based summary of the current data for the emergency medicine evaluation and management of SRC. While SRC remains a rare clinical presentation, surveillance data suggest an overall incidence between 4 and 6% of patients with scleroderma. The diagnostic criteria for SRC include a new onset blood pressure > 150/85mm Hg OR increase ≥ 20mm Hg from baseline systolic blood pressure, along with a decline in renal function, defined as an increase serum creatinine of ≥ 10% and supportive features. There are many risk factors for SRC, including diffuse and rapidly progressive skin thickening, palpable tendon friction rubs, and new anemia or cardiac events. Critical patients should be evaluated in the resuscitation bay, and consultation with the nephrology team for appropriate patients improves patient outcomes.

Esophageal symptoms and their lack of association with high-resolution manometry in systemic sclerosis patients

The esophageal involvement in systemic sclerosis (SSc) causes impact in the morbidity and mortality. High resolution manometry assesses esophageal involvement. Our aim was to categorize esophageal motor disorder in patients with SSc by HRM. We carried out an observational, descriptive and cross-sectional study. All patients underwent HRM as well as semi-structured interviews to assess frequency and severity of upper GI symptoms. Patients also completed the gastroesophageal reflux questionnaire (Carlsson-Dent). We included 19 patients with SSc, 1 with morphea, and 1 with scleroderma sine scleroderma. Dysphagia and heartburn were the most frequent symptoms (61% each). We found an abnormal HRM in 15 (71.4%) patients. We found no statistically significant association between clinical or demographic variables and an abnormal HRM, or between any upper GI symptom and HRM findings. We observed a high prevalence of esophageal symptoms and of HRM abnormalities. However, there was no clear association between symptomatology and HRM findings. HRM does not seem to accurately predict upper GI symptomatology.

I072 Genetic mimics of scleroderma

I072 Genetic mimics of scleroderma

I073 Scleroderma in adulthood: survivors from childhood

I073 Scleroderma in adulthood: survivors from childhood

I071 Paediatric and adolescent scleroderma

I071 Paediatric and adolescent scleroderma

Aspergillosis, nocardiosis and scleroderma, a fatal and infrequent association

Aspergillosis, nocardiosis and scleroderma, a fatal and infrequent association

Nailfold capillaroscopy as a risk factor for pulmonary arterial hypertension in systemic lupus erythematosus patients

BackgroundPulmonary arterial hypertension (PAH) is a rare and severe complication of systemic lupus erythematosus (SLE). This study aimed to evaluate clinical and laboratory risk factors associated with PAH in SLE patients.MethodsThis was a retrospective case-control study in which patients with SLE with PAH (SLE-PAH) confirmed by right heart catheterization (RHC) were compared with SLE patients without PAH. Clinical and demographic variables related to SLE and PAH and nailfold capillaroscopy were evaluated by reviewing the medical records of the patients.ResultsTwenty-one patients with SLE-PAH and 44 patients with SLE without PAH matched for sex and disease duration were included. The scleroderma (SD) pattern on nailfold capillaroscopy was more frequently found in patients with SLE-PAH than in those without PAH (56.3% versus 15.9%, respectively, p = 0.002). By univariate analysis, Raynaud’s phenomenon, history of abortion, and SD pattern on capillaroscopy were associated with PAH. Arthritis was a protective factor for PAH development. Multivariate analysis showed that the SD pattern on capillaroscopy was the only variable associated with a significantly higher risk of PAH, with an odds ratio of 6.393 (95% confidence interval, 1.530–26.716; p = 0.011).ConclusionIn this study, SD pattern was associated with a 6.3-fold increased risk for PAH development in SLE patients, suggesting that nailfold capillaroscopy might be useful as a screening method to identify SLE patients with a high risk of developing this severe complication.

Drug-induced fibrosing syndromes: A scoping review

There are numerous case reports implicating drugs in the pathogenesis of scleroderma-like fibrotic syndromes. A MEDLINE and SCOPUS search was made in an attempt to review these drugs. The entire spectrum of sclerodermatous disorders ranging from localized morphea, fasciitis, and linear scleroderma to the classical diffuse systemic sclerosis with typical autoantibody formation have been reported in association with drugs. Some drugs such as bleomycin and pentazocine have been established to cause fibrosis and are used to create animal models of systemic sclerosis. There are controversies regarding the role of others such as beta-blockers. Certain chemotherapeutic agents and ergot derivatives can also lead to fibrosing disorders. The new checkpoint inhibitors have been shown to develop systemic sclerosis like disease among other “immune related adverse effects.” The mechanisms leading to fibrosis are poorly understood in case of most drugs due to paucity of data. This limits therapeutic strategies. However, many of these syndromes regress if the causative drug is withdrawn early. Thus, it is imperative for clinicians to have knowledge about these syndromes and identify them early.

Twardzina ograniczona (morphea). Rekomendacje diagnostyczno-terapeutyczne Polskiego Towarzystwa Dermatologicznego

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Krasowska D, Rudnicka L, Dańczak-Pazdrowska A, et al. Localized scleroderma (morphea). Diagnostic and therapeutic recommendations of the Polish Dermatological Society. Dermatology Review/Przegląd Dermatologiczny. 2019;106(4):333-353. doi:10.5114/dr.2019.88252. APA Krasowska, D., Rudnicka, L., Dańczak-Pazdrowska, A., Chodorowska, G., Woźniacka, A., & Lis-Święty, A. et al. (2019). Localized scleroderma (morphea). Diagnostic and therapeutic recommendations of the Polish Dermatological Society. Dermatology Review/Przegląd Dermatologiczny, 106(4), 333-353. https://doi.org/10.5114/dr.2019.88252 Chicago Krasowska, Dorota, Lidia Rudnicka, Aleksandra Dańczak-Pazdrowska, Grażyna Chodorowska, Anna Woźniacka, Anna Lis-Święty, and Joanna Czuwara et al. 2019. "Localized scleroderma (morphea). Diagnostic and therapeutic recommendations of the Polish Dermatological Society". Dermatology Review/Przegląd Dermatologiczny 106 (4): 333-353. doi:10.5114/dr.2019.88252. Harvard Krasowska, D., Rudnicka, L., Dańczak-Pazdrowska, A., Chodorowska, G., Woźniacka, A., Lis-Święty, A., Czuwara, J., Maj, J., Majewski, S., Sysa-Jędrzejowska, A., and Wojas-Pelc, A. (2019). Localized scleroderma (morphea). Diagnostic and therapeutic recommendations of the Polish Dermatological Society. Dermatology Review/Przegląd Dermatologiczny, 106(4), pp.333-353. https://doi.org/10.5114/dr.2019.88252 MLA Krasowska, Dorota et al. "Localized scleroderma (morphea). Diagnostic and therapeutic recommendations of the Polish Dermatological Society." Dermatology Review/Przegląd Dermatologiczny, vol. 106, no. 4, 2019, pp. 333-353. doi:10.5114/dr.2019.88252. Vancouver Krasowska D, Rudnicka L, Dańczak-Pazdrowska A, Chodorowska G, Woźniacka A, Lis-Święty A et al. Localized scleroderma (morphea). Diagnostic and therapeutic recommendations of the Polish Dermatological Society. Dermatology Review/Przegląd Dermatologiczny. 2019;106(4):333-353. doi:10.5114/dr.2019.88252.

Диабетическая склеродермия (клинический случай).

Диабетическая склеродермия (клинический случай).

Sklerodermalı Hastalarımızın Klinik ve Laboratuvar Sonuçları ve Prognozu: Tek Merkez Deneyimi

Systemic scleroderma (SSc) is a rare connective tissue disease accompanied by progressive fibrosis. Especially pulmonary, cardiac and renal involvement is a major cause of morbidity and mortality in the disease while skin involvement and Raynaud's phenomenon (RP) can also decrease the quality of life by increasing morbidity. In this study, our aim was to determine the demographics, organ involvement and prognosis of our SSc patients followed up in Rheumatology department and compare the data with the literature. For this purpose, the data of 79 patients who were followed up in our department were evaluated retrospectively. 74 (93.7%) of the 79 patients were female, the mean age of the patients was 54.3 ± 12.7 (22-76) years and the mean duration of disease was 7.29 ± 7.02 years. 71 (89.8%) had limited cutaneous SSc (lcSSc), 6 (7.6%) had diffuse cutaneous SSc (dcSSc) and 2 (2.5%) had sine scleroderma. When the cumulative organ involvement of the patients was evaluated, it was seen that 73 (92.4%) had RP, 63 (79.7%) sclerodactyly, 14 (17.7%) digital ulcer and 22 (27.8%) telangiectasia. Eight (10.1%) patients had articular complaints. Antinuclear antibody (ANA) was (+) in 49 (62%) of the patients and anti-Scl-70 was (+) in 31 (39.2%). 74 patients (93.7%) were still alive and 5 (6.3%) died. No disease-related factor was found to be effective on mortality (p> 0.05). Malignancy was developed in 4 (5.1%) patients. Only high resolution computed chest tomography (HRCT) shot count were found to be an effective factor for cancer development (OR 1.74, p = 0.023 (CI 1.081-2.829). In conclusion, causes of mortality and malignancy were similar with the literature in patients we followed up with SSc. We found a correlation between the incidence of chest CT and the malignancy development unlike the literature. This result should be supported by studies involving larger patient numbers.

Clinicopathological analysis of six cases of disabling pansclerotic morphea

Objective To investigate clinical and pathological features of 6 cases of disabling pansclerotic morphea (DPM). Methods Clinical and pathological manifestations of and follow-up results in 6 patients, who were clinically and histopathologically diagnosed with DPM in the Department of Pathology, Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College from 2007 to 2017, were retrospectively analyzed. Results Among the 6 patients, 4 were male and 2 were female. The age of onset ranged from 3 to 10 years, with an average age of 6.5 years. The average duration from the occurrence to the confirmation of the diagnosis was 6.2 years (range, 2-10 years). At all the lesional sites, skin atrophy, thining and tightness occurred, and the limbs became thin. Additionally, there were muscular atrophy and visible deep thick veins on the surface of the limbs. The contracture, deformity and dysfunction of the adjacent joints occurred in 4 cases, and the lower limbs were obviously shortened in 2 cases. Peripheral blood examination showed no increase of eosinophils or hypergammaglobulinemia. Imaging examination revealed smooth cortical bone and clear trabecular bone, and no osseous abnormality was observed. Histopathological examination of contracted skin lesions of the lower limbs revealed atrophic and thinned epidermis, hyperpigmentation in the basal layer, hyperplastic, thickened, hardened and partly homogenized collagen fibers in the middle to deep dermis, subcutaneous adipose tissue region and deep tissue of the skin. Conclusions DPM usually does not affect viscera, but often involves deep tissue of the limbs. Histopathologically, DPM is mainly characterized by obviously hyperplastic and hardened collagen fibers in the dermis and subcutaneous tissue. Key words: Scleroderma, localized; Child; Skin manifestations; Pathologic processes; Therapy; Disabling pansclerotic morphea

Risk Factors for Future Scleroderma Renal Crisis at Systemic Sclerosis Diagnosis.

Systemic sclerosis (SSc) is a disease of autoimmunity, fibrosis, and vasculopathy. Scleroderma renal crisis (SRC) is one of the most severe complications. Corticosteroid exposure, presence of anti-RNA polymerase III antibodies (ARA), skin thickness, and significant tendon friction rubs are among the known risk factors at SSc diagnosis for developing future SRC. Identification of additional clinical characteristics and laboratory findings could expand and improve the risk profile for future SRC at SSc diagnosis. In this retrospective cohort study of the entire military electronic medical record between 2005 and 2016, we compared the demographics, clinical characteristics, and laboratory results at SSc diagnosis for 31 cases who developed SRC after SSc diagnosis to 322 SSc without SRC disease controls. After adjustment for potential confounding variables, at SSc diagnosis these conditions were all associated with future SRC: proteinuria (p < 0.001; OR 183, 95% CI 19.1-1750), anemia (p = 0.001; OR 9.9, 95% CI 2.7-36.2), hypertension (p < 0.001; OR 13.1, 95% CI 4.7-36.6), chronic kidney disease (p = 0.008; OR 20.7, 95% CI 2.2-190.7), elevated erythrocyte sedimentation rate (p < 0.001; OR 14.3, 95% CI 4.8-43.0), thrombocytopenia (p = 0.03; OR 7.0, 95% CI 1.2-42.7), hypothyroidism (p = 0.01; OR 2.8, 95% CI 1.2-6.7), Anti-Ro antibody seropositivity (p = 0.003; OR 3.9, 95% CI 1.6-9.8), and ARA (p = 0.02; OR 4.1, 95% CI 1.2-13.8). Three or more of these risk factors present at SSc diagnosis was sensitive (77%) and highly specific (97%) for future SRC. No SSc without SRC disease controls had ≥ 4 risk factors. In this SSc cohort, we present a panel of risk factors for future SRC. These patients may benefit from close observation of blood pressure, proteinuria, and estimated glomerular filtration rate, for earlier SRC identification and intervention. Future prospective therapeutic studies could focus specifically on this high-risk population.

Bloodless Glomeruli: A Case Report on Scleroderma Renal Crisis

Scleroderma renal crisis (SRC) is a main complication of systemic sclerosis affecting approximately one-fifth of the patient population with the disease. We present a case of a 38-year-old African American female who initially presented with findings suggestive of thrombotic thrombocytopenic purpura; however, the clinical manifestations, laboratory findings and renal biopsy confirmed the diagnosis of SRC. The case is worth reporting in medical literature because of its unique presentation and to note the findings of the kidney biopsy. SRC can present initially as thrombotic thrombocytopenic purpura; therefore, clinicians need to be more aware of this entity and it should be considered in the differential diagnosis of microangiopathic hemolytic anemia. This case also illustrates that the classic “onion skin appearance” on kidney biopsy in SRC is not always present and that patients can have “bloodless” glomeruli. J Med Cases. 2018;9(7):229-232 doi: https://doi.org/10.14740/jmc3018w

Cutaneous adverse events caused byimmune checkpoint inhibitors: classification and management

Immune checkpoint inhibitors (ICPIs) have been successfully used in the treatment of multiple malignancies. However, immune-related adverse events (irAEs) may occur during treatment. Cutaneous adverse event (CAE) is acommon type of irAE. Mild CAEs include maculopapule, lichenoid reaction, bullous pemphigoid, vitiligo, psoriasis, and scleroderma. Severe and even life-threatening CAEs include Steven-Johnson syndromeand toxic epidermal necrolysis. Other CAEs include drug reactionwith eosinophiliaand systemic symptoms, Sweet′s syndrome, alopecia, Grover′s disease, and paraneoplastic syndrome. This paper reviews the treatment of cutaneous adverse events associated with ICPIs. Key words: immune checkpoint inhibitors; immune-related adverse events; cutaneous adverse events

The stack of coins sign in scleroderma.

The stack of coins sign in scleroderma.

Skin manifestations of patients with systemic sclerosis and their clinical significance

Objective To investigate features of skin lesions of patients with systemic sclerosis (SSc) , and to analyze the relationship of skin manifestations with clinical classification, autoantibodies and internal organ involvement. Methods Clinical data were collected from 120 patients with SSc in Department of Dermatology of Zhongshan Hospital Affiliated to Fudan University and Department of Scleroderma of Shanghai TCM-integrated Hospital between 2012 and 2014, and analyzed retrospectively. Results Among the 120 patients with SSc, 118 (98.3%) had Raynaud′s phenomenon, 116 (96.7%) had skin sclerosis, including 101 (84.2%) with sclerosis of skin over the dorsum of fingers, 90 (75%) had swollen skin, including 84 (70%) with swollen fingers, 77 (64.2%) had poikiloderma, 75 (62.5%) had thinned lip, 74 (61.7%) had telangiectasia, 63 (52.5%) had radial furrowing around the mouth, 57 (47.5%) had mask-like face, 49 (40.8%) had hyperplasia of nail cuticle, 35 (29.2%) had petechiae of the nailfolds, 25 (20.8%) had depressed fingertip, 24 (20.0%) had atrophy of the finger pulp, 24 (20.0%) had distal finger shortening, and 15 (12.5%) had fingertip ulcer. Anti-Scl-70 antibody and anti-centromere antibody (ACA) were positive in 42 (35.0%) and 31 (25.8%) patients respectively. The incidence of swollen fingers, fingertip ulcer, atrophy of the finger pulp was significantly higher in the anti-Scl-70 antibody- positive group than in the-negative group (P < 0.05) , and the incidence of sclerosis of skin over the dorsum of fingers, poikiloderma, fingertip ulcer and atrophy of the finger pulp was all significantly higher in the anti-Scl-70 antibody-positive group than in the ACA-positive group (P < 0.05) . The main internal organ involvement included interstitial lung disease (50%, 44/88) , cardiac involvement (47.8%, 55/115) , pulmonary arterial hypertension (35.7%, 41/115) , esophageal involvement (28.3%, 34/120) and kidney involvement (9.2%, 11/120) . Patients with diffuse cutaneous systemic sclerosis (dcSSc) showed significantly higher incidence of cardiac involvement and poikiloderma compared with those with limited cutaneous systemic sclerosis (lcSSc) (P < 0.01) . Swollen fingers, sclerosis of skin over the dorsum of fingers, poikiloderma, telangiectasia, lip thinning, and radial furrowing around the mouth most commonly occurred in patients with early SSc, and swollen fingers and sclerosis of skin over the dorsum of fingers were highly correlated with the occurrence of pulmonary arterial hypertension. Telangiectasia, depressed fingertip and fingertip ulcer were significantly correlated with the occurrence of interstitial lung disease, and atrophy of the finger pulp was significantly correlated with the occurrence of cardiac involvement (both P < 0.05) . Conclusions Raynaud′s phenomenon, swollen fingers, sclerosis of skin over the dorsum of fingers, poikiloderma, telangiectasia, lip thinning and radial furrowing around the mouth can be helpful for the early diagnosis of SSc. Pulmonary arterial hypertension commonly occurs in the early stage of SSc. Depressed fingertip and fingertip ulcer indicate the occurrence of interstitial lung disease, and the atrophy of the finger pulp indicates cardiac involvement. Key words: Scleroderma, systemic; Skin manifestations; Antoantibodies; Early diagnosis; Fibrosis; Internal organs

Evaluation of visceral involvement and detection of autoantibodies in patients with systemic sclerosis

Objective To investigate clinical characteristics of systemic sclerosis (SSc) , and to explore the correlation between visceral involvement and autoantibodies. Methods Clinical data, laboratory examination and auxiliary examination findings were collected from 63 patients with SSc in the Department of Dermatology of Zhongshan Hospital affiliated to Fudan University between 2012 and 2015, and the correlation of autoantibodies with visceral involvement and clinical phenotypes was analyzed. Results The 63 patients with SSc included 29 with diffuse SSc, 29 with limited SSc and 5 with overlap syndrome. Of the 63 patients, 30 had pulmonary interstitial fibrosis, 32 had lung function impairment which manifested as reduced diffusing capacity for carbon monoxide, and 12 had increased pulmonary arterial pressure. Among 29 patients with anti- DNA topoisomerase Ⅰ (SCL-70) antibody, 19 (65.52%) had pulmonary interstitial fibrosis, while 11 (32.35%) of 34 patients without anti-SCL-70 antibody had pulmonary interstitial fibrosis. Pulmonary interstitial fibrosis also occurred in 13 (68.42%) of 19 patients with anti-Sjogren′s syndrome antigen A (SSA) antibody, as well as in 17 (38.64%) of 44 patients without anti-SSA antibody. The incidence of pulmonary interstitial fibrosis was significantly higher in the patients with anti-SCL-70 or anti-SSA antibody than in the patients without anti-SCL-70 or anti-SSA antibody respectively (χ2= 6.901, 4.720, respectively, both P < 0.05) . Among the 63 patients, 22 had fingertip ulcers, and 16 (72.73%) of the 22 patients had pulmonary interstitial fibrosis, while 14 (34.15%) of 41 patients without fingertip ulcers had pulmonary interstitial fibrosis, and the incidence of pulmonary interstitial fibrosis significantly differed between the two groups (χ2= 8.544, P < 0.01) . Of the 63 patients, 50 (79.40%) initially presented with Raynaud′s phenomenon, and the average duration between the occurrence of Raynaud′s phenomenon and the diagnosis of SSc was 48.3 months. Conclusions Patients with SSc usually present with a high incidence of pulmonary interstitial fibrosis, which is complicated by lung function impairment and pulmonary hypertension. Raynaud′s phenomenon usually occurs as the initial symptom. There is a high incidence of pulmonary interstitial fibrosis in the patients with fingertip ulcers and anti-SCL-70 and anti-SSA antibodies. Key words: Scleroderma, systemic; Lung diseases, Interstitial; Autoantibodies; Hypertension, pulmonary