Total Skin Score Research Articles

Comparison of predictive value of FRAX, trabecular bone score, and bone mineral density for vertebral fractures in systemic sclerosis: A cross-sectional study

Assessing fracture risk is important for managing patients with systemic sclerosis (SSc). Vertebral fracture (VF) is the most common fracture and is associated with future VF and non-VF. We aimed to evaluate the predictive value of FRAX, trabecular bone score (TBS), and bone mineral density (BMD) for VFs, compared to rheumatoid arthritis (RA) patients and postmenopausal women, and to identify risk factors for VFs in SSc. In this cross-sectional study, prevalent VFs, 10-year probability of major osteoporotic fracture by FRAX (FRAX-MOF), TBS, and BMD were assessed in women with SSc (n = 69) and RA (n = 58), and postmenopausal women (n = 38). Risk factors for osteoporosis, modified Rodnan total skin score (mRSS), organ involvement, and patterns of nailfold capillaroscopy (NFC) were also evaluated. The accuracy of BMD (T-score ≤ -2.5), TBS and FRAX-MOF, with and without TBS adjustment, to detect prevalent VF was assessed by determining the area under the receiver operating characteristic (ROC) curve. Patients with SSc (14.5%) and RA (17.2%) had significantly more VFs than postmenopausal women (0%) (P = .031). Non-significant differences were observed in TBS and BMD of all groups. The FRAX-MOF were higher in RA (9.2%) than SSc group (6.1%) and postmenopausal women (5.5%) (P < .001). Based on the ROC curve, TBS-adjusted FRAX-MOF (0.803) showed largest area under curve (AUC) to detect the prevalent VFs, followed by FRAX-MOF (0.796), TBS (0.765), and BMD (0.588) in the SSc group. In the RA group, FRAX-MOF had the largest AUC (0.896), followed by TBS-adjusted FRAX-MOF (0.863), TBS (0.736), and BMD (0.686). The cutoffs for FRAX-MOF and TBS-adjusted FRAX-MOF for detecting VFs were 8.95% and 9.7% for SSc, and 14.5% and 14% for RA. No association between VFs and SSc subtypes, organ involvement, mRSS or NFC patterns was found. FRAX-MOF, with or without TBS, had better predictive value for VFs than BMD and TBS in SSc. However, FRAX-MOF underestimated the probability of VFs in SSc compared with RA.

Clinical Features and Risk Factors of Rapidly Progressive Systemic Sclerosis in a Single Center in China: Anti-RNA Polymerase III Antibodies as a Predictor.

Systemic sclerosis (SSc) have been classified in two clinical subsets (diffuse and limited) based on the extend of skin thickening. In this study, we classified a novel subset of SSc defined rapidly progressive systemic sclerosis (RPSSc), which based on the rate of skin thickening progression and the progressive of interstitial lung disease (ILD). We aimed to evaluate RPSSc clinical characteristics and predictive factors in a Chinese single center. Overall, 75 patients diagnosed with SSc, classified into RPSSc (n = 14) and non-rapidly progressive SSc (non-RPSSc, n = 61) were retrospectively included in the study. Clinical characteristics, disease severity and autoantibodies were collected. Logistic regression, least absolute shrinkage, and selection operator (LASSO) regression analysis was used to identify RPSSc predictors. Receiver operating characteristic (ROC) analysis and Delong test was conducted to evaluate and compare different indexes. RPSSc rate was 18.7%. ILD (64.3%), cardiac involvement (42.9%) were the most common organ system involvement of RPSSc, while Raynaud's phenomenon incidence significantly decreased. Disease duration (12 vs 72, months), sex (42.9% vs 11.5%, male %), SSc subset (85.7% vs 27.9%, diffuse cutaneous SSc (dsSSc) %), modified Rodnan total skin score (mRSS) (20.5 vs 6), Raynaud's phenomenon (64.3% vs 98.4%), cardiac involvement (42.9% vs 18%), higher incidence with malignancy (28.6% vs 1.6%) and positive anti-RNA polymerase III antibodies (ARA) (64.3% vs 1.6%) were statistically significant differences among the RPSSc groups and non-RPSSc groups (p < 0.05). Univariate analysis showed that positive ARA, male, dsSSc and malignancy were RPSSc risk factors, while long-disease duration, Raynaud's phenomenon was RPSSc protective factors. ARA was the strongest factor associated to RPSSc (OR 108, 95% CI 11.287-1033.327, p < 0.001). LASSO logistic regression model identified six factors: Disease duration, dsSSc, malignancy, cardiac involvement, positivity of ARA were RPSSc risk factors, Raynaud's phenomenon was RPSSc protective factors. RPSSc is an SSc clinical category which should be accounted for early detection of organ involvement and close follow-up of malignancy. ARA might be used as a predictor for RPSSc and organ involvement.

A Randomized Controlled Study of Extracorporeal Photopheresis (ECP) Therapy with UVADEX® (Methoxsalen) for National Institutes of Health (NIH)-Graded Moderate to Severe Chronic Graft-Vs-Host Disease (cGVHD)

A Randomized Controlled Study of Extracorporeal Photopheresis (ECP) Therapy with UVADEX® (Methoxsalen) for National Institutes of Health (NIH)-Graded Moderate to Severe Chronic Graft-Vs-Host Disease (cGVHD)

Reliability and validity of the Korean version of the University of California-Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract instrument in patients with systemic sclerosis.

Background/AimsSystemic sclerosis (SSc) is associated with a wide range of gastrointestinal (GI) changes. The University of California–Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) instrument is a self-administered GI assessment instrument for patients with SSc. We developed a Korean version of the UCLA SCTC GIT 2.0 instrument and evaluated its reliability and internal consistency.MethodsThe participants were 37 Korean patients with SSc. Translation and cross-cultural adaptation of the UCLA SCTC GIT 2.0 were performed according to international standardized guidelines. We evaluated reproducibility by calculating the intraclass correlation coefficients and assessed the internal consistency of the Korean version of the UCLA SCTC GIT 2.0. We assessed its construct validity by evaluating its correlations with the Short Form Health Survey version 2 and EQ-5D scores by means of Spearman correlation analyses.ResultsPatients with SSc were mostly women (89.19%) with a mean age of 52.2 years, median disease duration of 24 months, and median modified Rodnan total skin score of 4. The median total GIT score on the UCLA SCTC GIT 2.0 was 0.3. The UCLA SCTC GIT 2.0 Korean version showed excellent internal consistency (Cronbach’s α of total GIT score = 0.863). Most domains of the ULCA SCTC GIT 2.0 were correlated with those of the EuroQol (EQ)-5D score.ConclusionsThe Korean version of the UCLA SCTC GIT 2.0 has acceptable internal consistency, reliability, and validity. Therefore, it can be used to assess GIT involvement in Korean patients with SSc.

Effect of Low Energy Far-Infrared Irradiation on Facial Skin for Healthy People

Objective: Utilizing VISIA skin tester to quantitatively evaluate the effect of low energy far-infrared irradiation on healthy people’s facial skin. Methods: 60 volunteers were selected in hospital from September 2019 to June 2020, and the total score of face, skin spots, texture, wrinkles and pores were observed before and after low energy far-infrared irradiation treatment with VISIA skin tester. Results: After 2 weeks of low energy far-infrared irradiation treatment, the total skin score of volunteers increased significantly (P < 0.01). In the itemized statistics, the moisture value, stain value and wrinkle value increased significantly (P < 0.05). Conclusion: Low energy far-infrared irradiation can significantly improve the facial skin quality of healthy people.

Myopathy is a Risk Factor for Poor Prognosis of Patients with Systemic Sclerosis: A retrospective cohort study.

To compare clinical characteristics and identify long-term outcomes of Chinese patients with systemic sclerosis (SSc) with and without muscle involvement.We retrospectively investigated the medical records, laboratory results, and computed tomography images of 204 consecutive SSc patients. Kaplan–Meier analysis was performed to determine survival rates. Patients were allocated into groups with and without myopathy.The prevalence of myopathy was 21.6%. The myopathy group was more likely to develop diffuse cutaneous involvement (90.9% vs 56%, P = .006), interstitial lung disease (90% vs 56%, P < .001), digestive system involvement (56.7% vs 29.3%, P = .001), pulmonary hypertension (29.5% vs 10.5%, P = .004), and pericardial effusion (25% vs. 10%, P = .019). Patients with myopathy had lower single-breath diffusing capacity of the lung for carbon oxide (46.5 ± 11.1 vs 57.1 ± 13.4, P < .001).Further, the myopathy group has similar results in interstitial lung disease associated higher resolution computed tomography score (186.8 ± 64.5 vs 152.3 ± 45.5, P = .037), Valentini score for disease activity (3.4 ± 0.9 vs 2.0 ± 0.9, P < .001) and modified Rodnan total skin score (19.4 ± 6.1 vs 15.1 ± 7.7, P = .002), compared with non-myopathy group. Kaplan–Meier survival analysis revealed decreased overall survival rate of the myopathy group (P = .028).SSc Patients with myopathy had more severe clinical manifestations and higher disease activity compared with those without, which affected survival rates and indicated worse prognosis.

Add-on tocilizumab versus conventional treatment for systemic sclerosis, and cytokine analysis to identify an endotype to tocilizumab therapy

Objectives: To evaluate the anti-interleukin (IL)-6 receptor antibody tocilizumab (TCZ) as a treatment of systemic sclerosis (SSc), a randomised parallel group study was conducted, and compared their results and baseline cytokine/chemokine profiles.Methods: Patients were assigned to a TCZ add-on group (TCZ group, n = 7) and a conventional therapy group (Conv group, n = 6). TCZ (8 mg/kg/month) for 6 months, and the modified Rodnan total skin score (mRSS) were used to compare the efficacy. The association of medical history, baseline pulmonary function tests, blood cell counts, serum C-reactive protein (CRP) and 26 cytokines/chemokines and decrease in mRSS were analysed.Results: The mean change in mRSS was larger in the TCZ group (6.3) than in the Conv group (3.4), but the difference was not statistically significant because of high variance in the TCZ group. Patients with shorter disease histories and higher CRP had larger decreases in mRSS, and the decrease in mRSS was negatively correlated with IL-13 and C–C motif chemokine ligand (CCL)5.Conclusion: Although significant between-group differences were not observed, some patients had a decrease in mRSS. Short disease duration, high CRP, low IL-13 and low CCL5 may represent an SSc endotype responsive to TCZ therapy.

Autologous haematopoietic stem cell transplantation for Japanese patients with systemic sclerosis: Long-term follow-up on a phase II trial and treatment-related fatal cardiomyopathy

Objectives: The objective of this study is to elucidate the efficacy and safety of autologous haematopoietic stem cell transplantation (HSCT) for Japanese patients with systemic sclerosis (SSc).Methods: A phase II clinical trial included SSc patients diagnosed within the last three years having at least one of the following clinical features: diffuse skin sclerosis with modified Rodman total thickness skin score (mRSS) ≥ 15, refractory digital ulcer or interstitial lung disease (ILD). HSCT were performed after conditioning using cyclophosphamide.Results: Fourteen patients were enrolled and underwent HSCT. Median follow-up period was 137 months. Overall survival or event-free survival rate was 93% or 40% at 10 years, respectively. Eight patients (57%) achieved more than a 50% decrease in mRSS from baseline within six months after HSCT. Six patients (43%) required additional immunosuppressive treatments due to progression of diffuse skin sclerosis and/or ILD during follow-up period. Adverse events related to HSCT occurred in six patients (43%). Severe cardiomyopathy occurred in two patients, and one of them had a fatal course.Conclusion: HSCT is a feasible treatment bringing favourable results to more than half of our patients with SSc. Careful selection of the patients is essential for whom benefited from HSCT, considering the risk-benefit balance of the treatment.

Inhibitory regulation of apelin on fibrosis in systemic sclerosis

The secreted protein apelin and its receptor APJ signaling mainly regulates angiogenesis and cardiovascular functions. Recently, it has been identified that apelin: APJ signaling also regulates cardiac and arterial fibrosis. However, the mechanisms and roles of apelin in skin fibrosis in systemic sclerosis (SSc) are not well characterized. The aim of this study was to elucidate the role of apelin in skin fibrosis in SSc. We first demonstrated that the plasma apelin levels were negatively correlated with modified Rodnan total skin score in SSc patients. Expression of apelin in SSc fibroblasts was significantly lower than that in normal fibroblasts. In addition, decreased apelin synthesis in fibroblasts was induced by stimulation with TGF-β, suggesting that the activation of TGF-β signaling in SSc might be responsible for the reduced apelin expression in SSc fibroblasts. siRNA depletion of apelin from fibroblasts significantly enhanced collagen type I, αSMA and sphingosine kinase 1 (SPHK1) expressions. Furthermore, treatment with apelin protein significantly inhibited TGF-β-induced overexpression of collagen type I, αSMA and SPHK1 in fibroblasts. These results suggest that apelin might have an inhibitory action against TGF-β-induced skin fibrosis. Finally, we demonstrated that administration of apelin significantly inhibited bleomycin-induced dermal fibrosis in mice. Collectively, TGF-β signaling and apelin signaling may counteract each other in the fibrotic process of SSc. Apelin signaling may be involved in the pathogenesis of SSc, and have therapeutic potential for fibrosis in SSc.

Possible association of elevated serum collagen type IV level with skin sclerosis in systemic sclerosis.

Collagen type IV is the primary collagen in the basement membranes around blood vessels and in the dermoepidermal junction in the skin. Perivascular collagen type IV is synthesized by endothelial cells and pericytes, and contributes to the homeostasis and remodeling of blood vessels. It has been well recognized that elevated serum collagen type IV levels are associated with the liver fibrosis. The objective was to examine serum collagen type IV levels and their clinical associations in patients with systemic sclerosis (SSc), and to examine the expression of collagen type IV in the fibrotic skin in SSc. Serum collagen type IV levels in SSc patients and diffuse cutaneous type SSc patients were significantly higher than those in healthy individuals. Serum collagen type IV levels were positively correlated with modified Rodnan total skin score. Serum collagen type IV levels in early stage (disease duration ≤3 years) diffuse cutaneous SSc patients were significantly elevated. Serum collagen type IV levels in SSc patients with digital ulcers (DU) were significantly elevated. In immunohistochemical staining, the expression of collagen type IV around dermal small vessels in the affected skin was reduced compared with those of normal individuals. These results suggest that elevated serum collagen type IV levels may be associated with the skin sclerosis in the early stage of SSc. The measurement of serum collagen type IV levels in SSc patients may be useful as a disease activity marker in skin sclerosis and DU.

Skin fibrosis correlates with circulating thyrotropin levels in systemic sclerosis: translational association with Hashimoto's thyroiditis.

Systemic sclerosis (SSc) is a connective tissue disease, characterized by cutaneous and multi-organ fibrosis, and vascular abnormalities. Skin thickening is a characteristic feature of SSc and resembles myxedematous skin. Our aim was to correlate the degree of skin involvement in SSc patients with serum TSH levels, since TSH receptors are widely expressed in human tissues, including the skin. In this cross-sectional study, we enrolled 70 SSc patients, all females with a mean age of 47 ± 11 year. Thirty-five age- and sex-matched HT patients were recruited, as controls. Subjects under L-thyroxine therapy and/or with positive anti-TSH receptor antibodies were excluded. In all subjects, we measured serum TSH, FT4, and free tri-iodothyronine (FT3) levels. Skin thickness was evaluated using the modified Rodnan total skin score (mRSS). mRSS averaged 14 ± 9 for SSc and 4 ± 6 for HT patients. TSH levels positively correlated with skin scores in both SSc and HT patients groups. In SSc patients, FT3 and FT4 showed an inverse correlation with mRSS, while in HT only FT4 levels showed this inverse significance. When divided by cutaneous extent, SSc patients with diffuse disease form had higher TSH serum levels compared to those with the limited form; additionally, the correlations between TSH, FT4, and mRSS reached statistical significance. Our preliminary data clearly indicate that serum TSH is higher in SSc patients with more severe skin disease, and significantly correlate with the mRSS. Therefore, TSH could play a role in the development of cutaneous changes in SSc patients.

A preliminary study of acoustic radiation force impulse quantification for the assessment of skin in diffuse cutaneous systemic sclerosis.

To investigate skin elasticity using acoustic radiation force impulse (ARFI) quantification in systemic sclerosis (SSc), and compare the modified Rodnan skin score (mRSS) with measured shear wave velocity (SWV) and thickness of the skin. Fifteen patients with diffuse cutaneous SSc (dcSSc) and 15 age-matched and sex-matched healthy controls were evaluated. The SWV and thickness of skin were measured at 17 sites corresponding to those assessed in the mRSS in each participant. The SWV measurements of skin were compared between patients with dcSSc and healthy controls. The correlations between the mRSS and the skin SWV and thickness were explored using Spearman's correlation. The SWV values were higher in patients with dcSSc compared with healthy controls at right hand dorsum, right forearm, left hand dorsum, left forearm, right foot dorsum, and left foot dorsum (p < 0.05). In patients with dcSSc, the SWV values of uninvolved skin were higher than those of controls (p < 0.001), and the SWV values increased with increasing skin scores except for skin score 3 (p < 0.05). The sum of the SWV values correlated with total clinical skin score (r = 0.841, p < 0.001), and the sum of the skin thickness correlated with total clinical skin score (r = 0.740, p = 0.002). ARFI quantification is feasible and reliable for assessing the skin involvement in dcSSc. ARFI quantification could identify early skin change that may precede palpable skin involvement, and may be a valuable adjunct to skin evaluation in patients with SSc.

QTc interval prolongation in systemic sclerosis: Correlations with clinical variables

Systemic sclerosis (SSc) is an autoimmune disease characterized byendothelial dysfunction and fibrosis of the skin and internal organs [1].Cardiac involvement in the course of SSc could be primary or sec-ondary to pulmonary arterial hypertension and kidney pathology. Pri-mary cardiac involvement may manifest as myocardial involvement,arrhythmias,fibrosisoftheconductionsystem,pacemakerandintracar-diac defibrillator implantation, sudden death and autonomic dysfunc-tion [2,3].Amongtheabnormalities in SSc,QTc intervalprolongation hasbeenreportedandassociatedwithanti-RNApolymeraseIIIantibodies,longerdisease duration, and greater disease severity [4].Accordingly,theaimofthestudyistoassessQTcprolongationinSScand evaluate correlations with clinical variables and complications ofthe disease.The protocol is in accordance with the Declaration of Helsinki andwas approved by the Ethics Committee at our Institution. Twenty Cau-casian subjects fulfilling the American Rheumatism Association (ARA)criteria for classification and diagnosis of SSc [5] and twenty healthysubjectswereexaminedbeforeinclusioninthestudy.All examined pa-tientsunderwentclinicalevaluation,ambulatory24-hourECGmonitor-ing, transthoracic echocardiogram.Scleroderma patients with coronary artery disease, congestiveheartfailure, left ventricular dysfunction, significant valvular abnormalitiesand arrhythmias were not included in the study.Patients with pulmonary function abnormalities were not includedeither. Patients with diabetes mellitus, renal failure, hepatic or thyroiddysfunction, and anemia were excluded.Patients were not takingβ-blockers, antiarrhythmic drugs,ACE-inhibitors or angiotensin receptor antagonists. QTc interval,assessed by 24-hour Holter ECG recording, was defined as prolongedwhen N440 ms [6].Nailfold videocapillaroscopy (NVC) was performed by an opticalprobe, equipped with magnification 200× contact lens and connectedto image analysis software (Pinnacle Studio Version 8). The identifiedpatterns were classified as early, active or late [7]. Skin thickening wasassessed by a modified Rodnan total skin score (mRSS) [8]. In all pa-tientswemeasuredtheDiseaseActivityIndex(DAI)andDiseaseSever-ity Scale (DSS) [9].Thedatawereexpressedasmedianandrange.Multivariateanalysiswas applied for the estimation of relationship of QTc with disease vari-ables. The Mann–Whitney U-test or Kruskal–Wallis were used to testdifferences between two individual study groups. Spearman's rankorder correlation coefficient (r) was used to test for an association be-tweennumericalvariables.p-Valuesb0.05wereconsideredsignificant.Commercial software (SPSS version 20.0) was used for statisticalanalysis.Twentysclerodermapatientswereenrolledinthecurrentstudy.Theepidemiological and clinical features of SSc are shown in Table 1.ThemedianvalueofQTcissignificantly(pb0.0001)increasedinSScpatients than healthy controls [447 (414–566) vs 386 (342–447)].The medianvalueof QTc is significantly (p b 0.01) different in threecapillaroscopicgroups:early425(421 –454),active437(416–467),late471 (445–566).ThemedianvalueofQTcissignificantly(pb 0.05)augmentedin SScpatients with digital ulcers than in SSc patients without digital ulcers[459(422–566)vs436(416–454)].Apositivecorrelation (p b0.05)ex-ists between QTc and mRSS (r = 0.53).NocorrelationswerefoundbetweenQTcanddiseasesubset,diseaseduration, Disease Activity Index, and Disease Severity Scale.Amongthe causes of suddencardiacdeath in SScpatients,ventricu-lar late potentials, autonomic dysfunction, pro-arrhythmogenic drugsand increased QT dispersion were found.

Demographic and clinical features of systemic sclerosis patients with anti-RNA polymerase III antibodies.

Anti-RNA polymerase III antibody (RNAP) is primarily detected in diffuse cutaneous type systemic sclerosis (dcSSc) patients and strongly associated with renal crisis. Additionally, there has been increasing evidence that cancer in SSc patients is associated with RNAP. The aim of this study was to examine the demographic and clinical features of SSc patients with RNAP. Among 246 SSc patients, 5.7% were positive for RNAP, 20.7% were positive for anti-topoisomerase I antibody (Topo I) alone and 39.4% were positive for anticentromere antibody (ACA) alone. The modified Rodnan total skin score (mRTSS) in SSc patients with RNAP (19.1±2.6) was significantly higher than those in SSc patients with Topo I (11.5±1.1) and patients with ACA (4.4±0.4). Furthermore, among SSc patients with RNAP, the levels of RNAP were positively correlated with mRTSS. Renal crisis is also significantly more prevalent in SSc patients with RNAP than patients without RNAP. Male sex, dcSSc subtype, digital vasculopathy, including digital ulcers and acro-osteolysis, interstitial lung disease and rheumatoid arthritis complications were prevalent in SSc patients with RNAP and patients with Topo-I. Primary biliary cirrhosis and Sjögren's syndrome were more in SSc patients with RNAP and patients with ACA compared with patients with Topo 1. No significant difference in the frequency of complications, including Raynaud's phenomenon, pulmonary artery hypertension and malignancy was observed between the three groups. Thus, measurement of RNAP in SSc patients is useful for the diagnosis and risk stratification of severe manifestation, such as renal crisis and severe skin sclerosis.

Elevated plasma homocysteine level is possibly associated with skin sclerosis in a series of Japanese patients with systemic sclerosis.

Homocysteine is a sulfhydryl-containing amino acid that is derived from dietary methionine, and there has been increasing evidence that elevated plasma homocysteine levels are associated with increased risk of cardiovascular diseases, including carotid, coronary and peripheral arterial disease (PAD). The association of plasma homocysteine levels with peripheral vascular involvements, such as Raynaud phenomenon (RP), digital ulcers (DU) in systemic sclerosis (SSc) patients has not been well studied. The objective of this study was to examine plasma homocysteine levels and their clinical associations in patients with SSc. Plasma homocysteine levels in 151 Japanese patients with SSc and 20 healthy controls were examined. No significant differences were observed in plasma homocysteine levels between SSc patients and healthy individuals. Demographic and clinical features of the SSc patients revealed that severe skin sclerosis, anti-topoisomerase I antibody positivity, complications of DU, acro-osteolysis (AO) and interstitial lung disease (ILD) were significantly more prevalent among the patients with elevated plasma homocysteine levels. The plasma homocysteine levels were positively correlated with modified Rodnan total skin score. The plasma homocysteine levels in the SSc patients with DU, AO and ILD were significantly higher than those in the SSc without DU, AO and ILD, respectively. Plasma homocysteine levels did not correlate with either the mean or max intima-media thickness (IMT) or plaque score, suggesting that plasma homocysteine levels might not be associated with carotid artery atherosclerosis in SSc patients. The measurement of plasma homocysteine levels in SSc patients might be useful for the risk stratifications of severe skin sclerosis, DU and AO.

Potential effect of Sildenafil beyond pulmonary hypertension in a patient with diffuse systemic sclerosis and cryoglobulinemic vasculitis.

IntroductionPulmonary arterial hypertension (PAH) is a serious complication of systemic sclerosis (SSc), has a dramatic impact on prognosis and survival and is a leading cause of death.Case descriptionA 40 years old female patient with difuse cutaneous SSc (dcSSc) presented with progressive dyspnea, choking sensation, cough, abdominal distension, constipation and dysphagia to solids. The muscle power was mildly reduced and multiple purpuric eruptions were present on the legs of variable sizes. The patient was ANCA negative and had positive cryoglobulinemia. The hepatitis C virus test was positive and the skin biopsy histopathology proved small vessel (leucocytoclastic) vasculitis. The modified Rodnan total skin score (MRSS) was 37. There was deterioration of the pulmonary function tests and transesophageal echocardiography revealed PAH (RVSP 60 mmHg). Sildenafil 50 mg/day resulted in a remarkable improvement of the dyspnea and Raynauds’ with a significant improvement of the skin tightness as the MRSS became 22. The small vessel vasculitic rash remarkably improved and the RVSP became 34 mmHg with a dramatic improvement of the PAH.Discussion and evaluationSildenafil enhances vasodilatation, has antiproliferative effects and is effective in the treatment of PAH. The remarkable improvement in the vasculitic skin lesions in this case after sildenafil is the second report after the described dramatic improvement of small vessel vasculitis in a case with Takayasu arteritis. The emerging trends make it necessary to exploit the full therapeutic potential of Sildenafil in scleroderma and PAH with other extrapulmonary manifestations.ConclusionWe report a very rare association of dcSSc with small vessel cryoglobulinemic vasculitis with a remarkable improvement after sildenafil.

Human chorionic gonadotropin and indolamine 2,3-dioxygenase in patients with GVHD

GVHD is a major complication following allogeneic hematopoietic SCT, and is associated with substantial morbidity and mortality. Based on the results of our previous clinical study with females treated with human chorionic gonadotropin (hCG) as preconditioning therapy for in vitro fertilization, we hypothesized that low-dose hCG stimulates indoleamine-2,3-dioxygenase (IDO), IL 10 and regulatory T cells (Treg), thereby suppressing clinical manifestations of chronic GVHD. Active chronic GVHD localized at skin, subcutaneous tissue, joints or gastrointestinal tract that was refractory or intolerant to glucocorticoid therapy improved substantially in 12 of 20 patients treated with hCG for 8 weeks (off-label), enabling a glucocorticoid dose reduction of 28% (average). Twelve of 19 patients with chronic GVHD of the skin responded to hCG therapy with a reduction of 25% (average) in their total skin score. HCG treatment increased IDO expression at median by sevenfold in peripheral mononuclear cells and IL10 levels in serum up to twofold at median from the pretreatment baseline. Further, an expansion of the Treg cell population was measured in one patient, which is also associated with the induction of tolerance. This novel application of low-dose hCG was well tolerated and is of clinical interest for GVHD treatment.

Efficacy of low-dose imatinib mesylate for cutaneous involvement in systemic sclerosis: a preliminary report of three cases

In this pilot study, the effect of low-dose imatinib mesylate (100 mg/day) on cutaneous involvement in patients with systemic sclerosis (SSc) was analyzed. Three patients with SSc were treated with 100 mg/day of imatinib mesylate for 6 months because of pulmonary arterial hypertension refractory to conventional treatments, including beraprost, bosentan, sildenafil, and epoprostenol. Changes in cutaneous involvement were evaluated at 1, 3, and 6 months. During the treatment, the total skin score gradually improved in all of the patients. Contracture of phalanges was attenuated in two patients, one of whom also experienced the partial restoration of large-joint mobility. Nailfold bleeding, initially seen in two patients, was gradually attenuated and had completely disappeared at 6 months. In all patients, Raynaud’s phenomenon was attenuated at around 3 months and had completely disappeared at 6 months. Although transient renal dysfunction was observed in one patient, none of the patients experienced common adverse effects of imatinib, such as edema, nausea, rash, and musculoskeletal pain. These clinical data indicate the tolerability and efficacy of low-dose imatinib in SSc, especially against cutaneous vascular involvement, including Raynaud’s phenomenon and nailfold bleeding.

Serum Levels of Galectin-3: Possible Association with Fibrosis, Aberrant Angiogenesis, and Immune Activation in Patients with Systemic Sclerosis

Galectin-3 is a multifunctional protein implicated in a variety of biological processes including fibrosis, angiogenesis, and immune activation, all of which are associated with the development of systemic sclerosis (SSc). We investigated the clinical significance of serum galectin-3 levels in SSc. Serum galectin-3 levels were determined by a specific ELISA in 58 patients with SSc and 19 healthy controls. Serum galectin-3 levels were significantly lower in patients with diffuse cutaneous SSc (dcSSc) than in controls (3.29 ± 3.27 ng/ml vs 4.91 ± 2.67 ng/ml, respectively; p < 0.05), while being comparable between limited cutaneous SSc (3.70 ± 2.39 ng/ml) and healthy controls. In dcSSc, serum galectin-3 levels significantly correlated with total skin score (r = 0.45, p < 0.05). Serum galectin-3 levels were significantly decreased in early dcSSc (disease duration < 1 year; 1.64 ± 1.74 ng/ml; p < 0.05), but not in mid-stage dcSSc (1 to 6 years; 3.22 ± 3.16 ng/ml) or late-stage dcSSc (> 6 years; 4.86 ± 4.10 ng/ml), compared with controls. Serum galectin-3 levels were higher in SSc patients with both digital ulcers (DU) and elevated right ventricular systolic pressure (RVSP) than in those without each symptom (DU: 5.44 ± 3.74 ng/ml vs 2.99 ± 2.36 ng/ml, p < 0.05; elevated RVSP: 4.44 ± 3.14 ng/ml vs 2.82 ± 2.64 ng/ml, p < 0.05). Galectin-3 may be related to the developmental process of skin sclerosis in dcSSc and of DU and pulmonary vascular involvements in total SSc.

Evaluation of skin thickness lesions in patients with Lyme disease measured by modified Rodnan total skin score

Recently, a possible etiological connection between infection with Borrelia burgdorferi and various skin lesions, including morphea and systemic sclerosis (SSc), has been discussed. The aim of our study was the evaluation of frequency of skin thickening typical of SSc or morphea in the group of patients with Lyme disease (LD) with frequent exposition to tick bites. The group consisted of 110 patients with LD frequently exposed to tick bites form the northeastern Poland, which is an endemic area for this disease. To measure the skin lesions, the modified Rodnan total skin score (RTSS) was used. In the analyzed group, no skin changes typical of morphea or skin thickening were found. According to RTSS, all patients scored 0 points. Raynaud's phenomenon in all patients was not found. The relationship between scleroderma or morphea and LD is still a matter of controversy. Described by some authors, cases with LD and scleroderma may be associated with co-existence of B. burgdorferi infection with autoimmune process.