CHLD score, a new score based on traditional risk factor evaluation and long-term cardiovascular outcomes in patients with systemic sclerosis.

The aim of the study was to assess the predictors of major adverse cardiovascular events (MACE) in patients with systemic sclerosis (SSc) without pulmonary arterial hypertension. The study comprised 68 patients with SSc who were followed up for the median time of 99 (96; 107) months. The main exclusion criteria involved tricuspid regurgitation maximal velocity > 2.8 m/s and structural heart disease. At baseline the patients underwent clinical assessment of cardiovascular risk factors, 6-min walk test, transthoracic echocardiography and biomarker testing, including growth differentiation factor 15 (GDF-15). The primary composite endpoint was onset of MACE defined as death, myocardial infarction, myocardial revascularization and hospitalization for heart failure. The follow-up consisted of outpatient visits at 1 year intervals and telephone interview every 6 months. The baseline analysis revealed that chronic kidney disease (HR 28.13, 95%CI 4.84-163.38), lung fibrosis on high resolution computed tomography (HR 4.36, 95%CI 1.04-18.26) and GDF-15 concentration (unit HR 1.0006, 95%CI 1.0002-1.0010) were independent predictors of MACE occurrence. CHLD (Chronic kidney disease, Hypertension, hyperLipidaemia, Diabetes mellitus) score was formulated which assigned 1 point for the presence of arterial hypertension, hyperlipidaemia, diabetes mellitus and chronic kidney disease. After inclusion of CHLD score in Cox proportional model, it remained the only independent predictor of MACE onset (unit HR per 1 point 3.46; 95%CI 2.06-5.82, p < 0.0001). Joint assessment of traditional risk factors in the form of CHLD score may serve as a reliable predictor of long-term outcome in patients with SSc without pulmonary arterial hypertension.

High acute phase protein levels correlate with pulmonary and skin involvement in patients with diffuse systemic sclerosis.

Objective This study was performed to evaluate the serum amyloid A (SAA) and C-reactive protein (CRP) levels in patients with diffuse systemic sclerosis (dSSc) in relation to a control group, disease duration, and skin and pulmonary involvement. Methods This case-control study included 18 patients with early dSSc, 15 patients with late dSSc, and 15 healthy controls. The SAA and CRP levels, modified Rodnan skin score (mRSS), and diffusing capacity of the lungs for carbon monoxide (DLCO) were determined in all patients. Results The SAA and CRP levels were significantly higher in patients with early and late dSSc than in healthy controls. The frequency of detection of elevated SAA and CRP levels was approximately 66% and 85%, respectively. A significant correlation was found between the SAA and CRP levels in patients with dSSc. The SAA and CRP levels were inversely correlated with DLCO. The CRP level was positively correlated with the mRSS. Conclusions High SAA and CRP levels could serve as biomarkers for pulmonary involvement. The serum CRP level accurately reflects the extension of skin thickening in patients with dSSc.

Safety profile of autologous hematopoietic stem cell mobilization and transplantation in patients with systemic sclerosis.

Autologous hematopoietic stem cell transplantation (AHSCT) is thought to be effective therapeutic approach in patients with poor prognosis systemic sclerosis; however, the toxicity remains a challenge. Between years 2003 and 2016, we enrolled 18 patients with systemic sclerosis at median age at transplant of 52 years (range 24-68). The median duration of disease before AHSCT was 14 months (range 2-85). Peripheral blood stem cells were mobilized with cyclophosphamide (CY) and granulocyte colony-stimulating factor. Conditioning regimen included CY (200 mg/kg) and alemtuzumab (median dose, 60 mg) [n = 11], melphalan (MEL; 140 mg/m2) and alemtuzumab [n = 2], CY and rabbit anti-thymocyte globulin (rATG; 7.5 mg/kg) [n = 4], and CY alone (n = 1). Four deaths occurred early after transplant. There were three males and one female at median age at death of 51 years (range 24-68). The AHSCT-related deaths have been observed on days + 1, + 4, + 9, and + 15 after procedure. The causes of death included bilateral pneumonia followed by multi-organ failure in three patients and myocardial infarction in one. Three patients expired late during post-transplant follow-up, after 5, 21, and 42 months. The causes of death were disease progression in two patients and sudden heart attack in one. Eleven patients are alive after median follow-up after AHSCT of 42.0 months (range 0-95). Before proceeding to AHSCT in systemic sclerosis, there is a strong need to optimize patient selection to reduce toxicity. The administration of alemtuzumab should be avoided due to high risk of life-threatening infectious complications.

Coexistence of systemic sclerosis and sarcoidosis.

Coexistence of systemic sclerosis (SSc) and sarcoidosis (SA) is rarely reported; 21 cases only were reported in the English medical literature before 2011. It is suggested that low incidence of overlap syndrome of SSc with SA is resulted from different immune mechanisms involved in pathogenesis of the diseases. In SSc patients, a role of Th2 lymphocytes is suggested while in patients with SA such role is attributed to Th1 lymphocytes. The paper presents a 47-year-old woman suffering from SSc for over 6 years. CT scan of the lungs revealed the nodulus of the right lung and enlarged mediastinal lymphatic nodes. Pathologic evaluation of the nodulus provided basis for diagnosis of sarcoidosis. Diagnosis of SSc was based on clinical and capilaroscopic evaluation as well as detection of anti-topoisomerase I antibodies. In the course of the disease, fibrosis of the lung, pulmonary hypertension and cardiac abnormalities with rhythm disturbances were developed. Treatment included cyclophosphamide, mycophenolate mofetil, sildenafil, losartan. Stabilization of the general state of the patient was achieved.

Calprotectin in rheumatic diseases: a review.

Calprotectin also known as MRP8/14 or S100A8/A9 is a heterodimeric complex of two S100 calcium-binding proteins: myeloid-related protein 8 (MRP-8 or S100A8) and MRP-14 (or S100A9). At present, according to many authors, it is considered that calprotectin MRP8/14 is a potentially more sensitive biomarker of disease activity in rheumatoid disease than conventional inflammatory indices such as the erythrocyte sedimentation rate, C-reactive protein and others. A review of the literature on concentration of calprotectin in patients with some rheumatic diseases (rheumatoid arthritis, juvenile idiopathic arthritis, adult-onset Still's disease, systemic vasculitis, polymyalgia rheumatica, ankylosis spondylitis, systemic lupus erythematosus, and primary Sjögren's syndrome) is presented.

Autopsy versus clinical findings in patients with systemic sclerosis in a case series from patients of the EUSTAR database.

OBJECTIVES: Subclinical organ pathology occurs regularly in systemic sclerosis (SSc) and affects correct prognosis as well as treatment choices. We aimed to evaluate autopsy data for organ involvement with subsequent correlation to clinical data in order to assess discrepancies in pathological and clinical findings in SSc. METHODS: A standardised autopsy questionnaire from diseased patients registered in the European Scleroderma Trials and Research group (EUSTAR) cohort was analysed on cause of death and various manifestations in different organ systems. Clinical data obtained from the EUSTAR database of the corresponding patients including cause of death and disease manifestations of lung, heart, kidney, gastrointestinal, skin or musculoskeletal organ involvement were retrospectively analysed and compared to autopsy data. RESULTS: 11 patients (6 women, 5 male) aged between 23 and 84 were included. Cause of death defined by pathologist and clinician were identical in 9/11 cases. In 8 individuals, cause of death was related to heart and lung pathologies. Heart and lung involvement (both 10/11) were the most frequently detected organ involvement at autopsy. Here, myocardial fibrosis occurred in 66% and lung fibrosis in 50% of the patients. Clinically, diastolic function abnormalities (6/11), conduction block (4/11), reduced DCLO (6/11) and dyspnea (8/11) were the most prevalent cardiopulmonary findings. For heart and renal involvement we found higher prevalence in autopsy than by clinical diagnosis. Especially myocardial fibrosis and renal arteriosclerosis were only obtained by autopsy in several individuals. CONCLUSIONS: Clinical diagnostic procedures are limited in detection of end-organ damage, especially for cardiac involvement. All the more post mortem examinations are needed for quality verification of clinical diagnosis and might help as to better understand the disease processes as well as to improve patient care.

Hip resurfacing arthroplasty in treatment of avascular necrosis of the femoral head.

BACKGROUND: Hip resurfacing is a conservative type of total hip arthroplasty but its use is controversial, especially in patients with osteonecrosis. The aim of this study was analysis of the clinical and radiographic outcomes of hip resurfacing in patients with osteonecrosis. MATERIAL/METHODS: Between 2007 and 2008, 30 hip resurfacing arthroplasties were performed due to osteoarthritis secondary to avascular necrosis of femoral head staged as Ficat III and IV. Patients were qualified to resurfacing arthroplasty when the extent of avascular necrosis using Kerboul's method was <200° and the angle between avascular necrosis and head-neck junction was >20°. All patients were evaluated clinically and radiologically before and 60 months after the operation. RESULTS: The mean Harris Hip Score (HHS) score increased from 47.8 to 94.25 (p<0.05). Physical activity level (University of California, Los Angeles activity score--UCLA activity score) improved from 3.7 to 7.55 (p<0.05). No implant migration was observed. CONCLUSIONS: Management of osteonecrosis of the hip with resurfacing arthroplasty seems to be effective in strictly-selected patients.

Co-existence of lichen sclerosus and localized scleroderma in female monozygotic twins.

BACKGROUND: Etiology of lichen sclerosus (LiS) and localized scleroderma (LoS) is uncertain and probably multifactorial. CASE: We describe a case of female monozygotic twins who presented co-existence of LiS and LoS. Skin lesions typical for LoS occurred in both patients, at the age of 10. One sister was diagnosed with linear LoS of the lower limb affecting deeper situated subcutaneous tissue and muscles. The other sister was diagnosed with guttate LoS of the trunk, with slow progression of the skin lesions. In both sisters vulvar LiS developed at the age of 19. CONCLUSIONS: Co-existence of LiS and LoS in monozygotic twins indicates the possible genetic contribution to the pathogenesis of these diseases and the close relationship between them.

Subacute cutaneous lupus erythematosus in the course of rheumatoid arthritis: a relationship with TNF-α antagonists and rituximab therapy?

INTRODUCTION: Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) is caused by different medicines, first of all: calcium channel blockers, angiotensin converting enzyme inhibitors, thiazides, terbinafine, statins and antagonists of tumor necrosis factor-α (TNF-α). DI-SCLE does not distinguish from idiopathic form of the disease, clinically, histopathologically and immunologically. However, receding of symptoms is observed after recapture of the provoking drug. AIM: To present a patient with rheumatoid arthritis (RA), who developed SCLE after treatment with TNF-α antagonists and rituximab. CASE REPORT: In a 31-year-old woman with RA leucopenia due to treatment with etanercept and adalimumab was observed. Therefore, the treatment was changed to rituximab, but after starting the therapy, erythematous and oedematous skin lesions of an oval or annular shape appeared on the cheeks, auricles, lips and the decolette. Histopathological evaluation of the skin lesions revealed SCLE. Ro/SS-A and La/SS-B antibodies were detected in serum. Regression of skin lesions and hematologic disturbances was achieved after starting corticosteroid therapy. CONCLUSIONS: Co-existence of SCLE with RA should be considered in some patients. The role of TNF-α antagonists and rituximab therapy in induction of idiopathic form of SCLE requires further investigations.

Opinion of patients with ankylosing spondylitis on risk factors impairing their quality of life.

We studied 54 patients with ankylosing spondylitis with questionnaire in order to determine their view on threat to quality of their life related to the disease. We have show that pain and significant disability are the main threats associated with the disease in view of the patients. Social aspects (losing of job or decreasing of income) are also important for the patients, while management of the disease is not considered as arduous. The results of patients' opinion may be helpful in designing of educational programs for them.

Serum ghrelin in female patients with rheumatoid arthritis during treatment with infliximab.

Ghrelin is a gastric hormone that posses multiple functions, including induction of growth hormone release, regulation of proinflammatory cytokines and control of food intake and energy homeostasis. A few reports on serum ghrelin level in chronic inflammatory states revealed contradictory results. The study was undertaken to determine ghrelin in patients with rheumatoid arthritis receiving infliximab, a TNF-α blocking agent. Serum ghrelin was determined in 18 female rheumatoid patients before the treatment with infliximab, 1 week after the first infusion and after 53 weeks of medication and compared with 15 age-matched healthy women. Serum ghrelin level was shown to be increased in the patients. A decrease in serum ghrelin level was found after the first infusion of infliximab and similarly decreased ghrelin level but still higher than in the control was shown in the 53rd week of medication. The obtained results suggest that ghrelin level is related to inflammation, and its serum level in patients with severe rheumatoid arthritis behaves similarly to acute-phase reactants.

Systemic sclerosis without antinuclear antibodies or Raynaud's phenomenon: a multicentre study in the prospective EULAR Scleroderma Trials and Research (EUSTAR) database.

OBJECTIVE: To assess patients with SSc who present without circulating ANAs or RP. METHODS: Five thousand three hundred and ninety patients who fulfilled the ACR criteria for SSc and were enrolled in the EULAR Scleroderma Trials and Research (EUSTAR) database were screened for the absence of both RP and circulating ANA. To differentiate SSc from its mimics, additional information was gathered using a standardized questionnaire. RESULTS: Five thousand three hundred and seventy-eight (99.8%) of the 5390 SSc patients in the EUSTAR database had either detectable ANA or a history of RP. Twelve (0.2%) patients lacked both circulating ANA and RP. Details of the medical history could be obtained for seven patients. Three cases were compatible with ANA-negative and RP-negative SSc and were not typical of any known SSc mimic. Four patients had a malignancy: two had breast cancer, one had multiple myeloma with possible scleromyxoedema and one had bladder carcinoma. There was no temporal relationship between the onset of skin fibrosis and that of the tumour. Although no patient with confirmed nephrogenic systemic fibrosis was identified among the cases of ANA-negative and RP-negative SSc, the presentation of one patient could be compatible with that of nephrogenic systemic fibrosis other than for the absence of chronic kidney disease or of known prior gadolinium exposure. CONCLUSION: We have identified a very small subgroup of SSc patients who lack both circulating ANA and RP, none of whom fulfils the diagnostic criteria for any known SSc mimic. Prospective studies are needed to elucidate the clinical presentation, evolution and outcome of such patients.

Femoral press-fit fixation in ACL reconstruction using bone-patellar tendon-bone autograft: results at 15 years follow-up.

BACKGROUND: If anterior cruciate ligament (ACL) reconstruction is to be performed, decision regarding graft choice and its fixation remains one of the most controversial. Multiple techniques for ACL reconstruction are available. To avoid disadvantages related to fixation devices, a hardware-free, press-fit ACL reconstruction technique was developed. The aim of this study was to evaluate clinical outcome and osteoarthritis progression in long term after ACL reconstruction with central third patellar-tendon autograft fixed to femur by press-fit technique. METHODS: Fifty two patients met inclusion/excusion criteria for this study. The patients were assessed preoperatively and at 15 years after surgery with International Knee Documentation Committee Knee Ligament Evaluation Form, Lysholm knee score, Tegner activity scale and radiographs. RESULTS: Good overall clinical outcomes and self-reported assessments were documented, and remained good at 15 years. The mean Lysholm and Tegner scores improved from 59.7 ± 18.5 and 4.2 ± 1.0 preoperatively to 86.4 ± 5.6 (p = 0.004) and 6.9 ± 1.4 (p = 0.005) respectively at follow-up. The IKDC subjective score improved from 60.1 ± 9.2 to 80.2 ± 8.1 (p = 0.003). According to IKDC objective score, 75% of patients had normal or nearly normal knee joints at follow-up. Grade 0 or 1 results were seen in 85% of patients on laxity testing. Degenerative changes were found in 67% of patients. There was no correlation between arthritic changes and stability of knee and subjective evaluation (p > 0.05). CONCLUSIONS: ACL reconstruction with patellar tendon autograft fixed to femur with press-fit technique allows to achieve good self-reported assessments and clinical ligament evaluation up to 15 years. Advantages of the bone-patellar-tendon-bone (BPTB) press-fit fixation include unlimited bone-to-bone healing, cost effectiveness, avoidance of disadvantages associated with hardware, and ease for revision surgery. BPTB femoral press-fit fixation technique can be safely applied in clinical practice and enables patients to return to preinjury activities including high-risk sports.

Plasma leptin and neuropeptide Y concentrations in patients with rheumatoid arthritis treated with infliximab, a TNF-α antagonist.

TNF-α is one of the key proinflammatory cytokines in pathogenesis of rheumatoid arthritis (RA). TNF-α was also found to enhance synthesis of leptin. Leptin is mainly adipocyte-derived hormone controlling appetite and energy expenditure. It acts through inhibition of neuropeptide Y secretion. It is possible that TNF-α-induced leptin secretion contributes to body mass reduction in patients with RA. The study was designed to determine the influence of inactivation of the TNF-α with infliximab on plasma leptin and neuropeptide Y concentrations in patients with RA. Sixteen female patients with RA treated with infliximab and 16 healthy women were investigated. Plasma leptin and neuropeptide Y concentrations were determined before, during and after 1 year management of the patients with infliximab and were compared with body mass index and body fatty and lean mass. There was no difference in plasma leptin concentration between the rheumatoid patients before therapy and the controls (15.6 ± 1.85 and 14.5 ± 2.15 ng/ml, respectively). Neuropeptide Y concentration was higher in the patients than in the controls (54.5 ± 3.96 and 24.8 ± 2.80 pmol/l, respectively). Treatment with infliximab resulted in enhancement in leptin concentration (18.5 ± 2.34 ng/ml) and a slight increase in neuropeptide Y concentration (58.7 ± 4.66 pmol/l). Physiological relationship between leptin and body mass was shown in the patients and was not altered during the treatment. There was no significant correlation between the disease activity and plasma leptin or neuropeptide Y concentrations.

Exacerbated course of atrophoderma of Pasini and Pierini in patient with papillary cancer of the thyroid gland.

Atrophoderma of Pasini and Pierini is a benign cutaneous atrophy skin to morphea en plaques on repression and is considered as systemic sclerosis-like disorder. A case of female patient with atrophoderma of Pasini and Pierini in whom rapid eruption of new plaques was found after many years of stable disease in described. Papillary cancer of the thyroid gland was diagnosed and acceleration of atrophoderma should be considered as paraneoplastic syndrome.

Serum human cartilage glycoprotein-39 in patients with systemic sclerosis: relationship to skin and articular manifestation.

Human cartilage glycoprotein-39 (HC gp-30) is a secretory protein of several types of cells including chondrocytes. It has been suggested to be a laboratory index of joint damage. Thirty-two patients with systemic sclerosis (SSc) and 22 age-matched controls were investigated. An increased serum HC gp-39 level was shown in SSc patients and was found to correlate with inflammatory indices. There was no correlation with modified Rodnan score, joint involvement, or duration of symptoms of SSc. The obtained results indicate for possible relationship of HCgp-39 to inflammation but do not suggest determination of HC gp-39 as clinically applicable index of articular involvement in SSc patients.

[Biological agents in treatment of psoriatic arthritis]. / Zastosowanie leków biologicznych w leczeniu tuszczycowego zapalenia stawów.

Psoriatic arthritis was reported in approximately 6-39% of patients with psoriasis. It is a chronic disease that commonly leads to disability. The paper reviews TNF-alpha inhibitors, the drugs which resulted in a substantial progress in management of psoriatic arthritis. Numerous studies have shown efficacy of these medical agents including inhibition of the disease progress, improvement of skin changes, inhibition of bone destruction, and improvement in quality of life. Other agents which can be used in psoriatic arthritis treatment are being tested in clinical trials.