Raynaud's disease and phenomenon [keywords]
- Serum CXCL4 increase in primary Sjögren's syndrome characterizes patients with microvascular involvement and reduced salivary gland infiltration and lymph node involvement. [JOURNAL ARTICLE]
- Clin Rheumatol 2016 Aug 26.
CXCL4 is an antiangiogenic and immunomodulatory chemokine. We aimed to investigate serum levels of CXCL4 in primary Sjögren's syndrome (pSS), looking for associations with disease features. Thirty-nine consecutive pSS patients underwent clinical-serological assessment and nailfold videocapillaroscopy (NVC). Thirty-six patients and 30 controls affected by osteoarthritis were also investigated for serum levels of CXCL4 and soluble E-selectin (sE-selectin). CXCL4 was higher in pSS patients than in controls (1.79 [0.2-11.18] vs 1.023 ng/ml [0.02-14.45], p < 0.05), particularly in those without anti-La/SSB antibodies (2.89 [1.01-11.18] vs 1.69 ng/ml [0.2-2.72], p < 0.05), while it was lower in pSS patients with a focus score ≥1 at lip biopsy (1.44 [0.86-2.1] vs 2.24 ng/ml [1.64-3.25], p < 0.05) and clinically evident lymphadenopathy (1.53 [0.38-1.7] vs 2.08 ng/ml [1.45-3.03], p < 0.05). CXCL4 correlated with disease duration (r = 0.35, p < 0.05) and sE-selectin (r = 0.45, p < 0.01). Patients with Raynaud's phenomenon (RP) had more frequently abnormal CXCL4 levels than patients without RP (11/15 vs 3/21, p < 0.001), enlarged capillaries (14/16 vs 7/23, p < 0.001) and capillary loss at NVC (14/16 vs 6/23, p < 0.001). The hitherto unknown association of increased serum CXCL4 with features of microvascular impairment in pSS, along with the negative association with features of lymphocytic response (i.e., the absence of subset disease-specific autoantibodies, a low focus score, and the absence of lymphadenopathy) suggest clarifying the possible implication of this chemokine in pSS pathogenesis in larger studies.
- The Place of Nailfold Capillaroscopy Among Instrumental Methods for Assessment of Some Peripheral Ischaemic Syndromes in Rheumatology. [Journal Article]
- Folia Med (Plovdiv) 2016 Apr-Jun; 58(2):77-88.
Micro- and macrovascular pathology is a frequent finding in a number of common rheumatic diseases. Secondary Raynaud's phenomenon (RP) is among the most common symptoms in systemic sclerosis and several other systemic autoimmune diseases including a broad differential diagnosis. It should be also differential from other peripheral vascular syndromes such as embolism, thrombosis, etc., some of which lead to clinical manifestation of the blue toe syndrome. The current review discusses the instrumental methods for vascular assessments. Nailfold capillaroscopy is the only method among the imaging techniques that can be used for morphological assessment of the nutritive capillaries in the nailfold area. Laser-Doppler flowmetry and laser-Doppler imaging are methods for functional assessment of microcirculation, while thermography and plethysmography reflect both blood flow in peripheral arteries and microcirculation. Doppler ultrasound and angiography visualize peripheral arteries. The choice of the appropriate instrumental method is guided by the clinical presentation. The main role of capillaroscopy is to provide differential diagnosis between primary and secondary RP. In rheumatology, capillaroscopic changes in systemic sclerosis have been recently defined as diagnostic. The appearance of abnormal capillaroscopic pattern inherits high positive predictive value for the development of a connective tissue disease that is higher than the predictive value of antinuclear antibodies. In cases of abrupt onset of peripheral ischaemia, clinical signs of critical ischaemia, unilateral or lower limb involvement, Doppler ultrasound and angiography are indicated. The most common causes for such clinical picture that may be referred to rheumatologic consultation are the antiphospholipid syndrome, mimickers of vasculitides such as atherosclerosis with cholesterol emboli, and neoplasms.
- Recent advances in the pathogenesis and management of Raynaud's phenomenon and digital ulcers. [JOURNAL ARTICLE]
- Curr Opin Rheumatol 2016 Aug 17.
Systemic sclerosis (SSc)-related digital vasculopathy can progress from severe Raynaud's phenomenon to digital ulceration, is a major cause of pain and disability, and impacts negatively on quality of life. Current treatments are often ineffective and poorly tolerated. This review summarises some of the progress which has been made in the last 12 to 18 months in terms of our understanding of disease process, measurement and treatment.The most important findings include that we can now better predict which patients with SSc are most likely to develop digital ulcers. In terms of treatment, a multicentre trial showed that the phosphodiesterase inhibitor sildenafil confers some benefit in SSc-related digital ulceration. Topical therapies are being explored: iontophoresis of vasodilators increases local blood flow, and in an avian model, VEGF121 fibrin applied in a gel matrix improved wound healing.Progress is being made. Advances in our understanding of SSc-related vasculopathy continue to lead to exploration of new treatment approaches. Clinical trials and observational studies are challenging, but are being facilitated by developments in outcome measures and improved infrastructures and networking, allowing trials in much larger numbers of patients than have previously been possible.
- Absence of Scleroderma pattern at nail fold capillaroscopy valuable in the exclusion of Scleroderma in unselected patients with Raynaud's Phenomenon. [Journal Article]
- BMC Musculoskelet Disord 2016; 17(1):342.
To report the predictive value of nail-fold capillaroscopy (NFC) patterns of vasculopathy for systemic sclerosis (Scleroderma; SSc) in an unselected cohort of patients with Raynaud's phenomenon (RP).Patients referred to a tertiary SSc clinic with RP were evaluated by light/video-NFC. Clinical diagnosis, details and serology were recorded. Primary RP was defined as RP with no features of connective tissue disease (CTD)/antibody. NFC patterns were determined: normal, non-specific, 'early', 'active' or 'late' SSc patterns. Fulfilment of the VEDOSS or 2013 ACR/EULAR criteria for SSc was determined following NFC assessment.Three hundred forty-seven patients were referred: mean (SD) age 47 (15.2) years. On clinical review, 54 (16 %) did not have RP, 69 (20 %) had primary RP, 52 (15 %) had SSc and 172 (50 %) had secondary RP. NFC SSc pattern was detected in 80 (23 %) patients; 37/52 with SSc, 30/172 with secondary RP, 9/69 with primary RP and 4/54 with no RP. For identifying patients who met either the VEDOSS or 2013 ACR/EULAR criteria for SSc, detection of a SSc NFC pattern had a sensitivity of 71 %, specificity 95 %, positive predictive value 84 % and negative predictive value 90 %.The absence of SSc NFC pattern in patients with RP or suspected CTD is very valuable in the exclusion of SSc.
- Raynaud's Phenomenon. [Journal Article, Review]
- N Engl J Med 2016 Aug 11; 375(6):556-65.
- High Prevalence of Acute Exacerbation of Interstitial Lung Disease in Japanese Patients with Systemic Sclerosis. [Journal Article]
- Tohoku J Exp Med 2016; 239(4):297-305.
Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by extensive fibrosis and autoantibodies. Its clinical manifestations are diverse and include Raynaud's phenomenon, gastrointestinal dysmotility, interstitial lung disease (ILD), pulmonary hypertension, and renal crisis. Among these, ILD is the primary cause of SSc-related death. It has been considered that acute exacerbation of ILD (AE-ILD) is not common in patients with SSc; however, little is known about the prevalence of AE-ILD in Japanese patients with SSc. In this study, we aimed to clarify the prevalence, clinical characteristics, and prognosis of patients with SSc who developed AE-ILD and to identify predictive factors for AE-ILD in our Japanese cohorts. Clinical data of patients who visited our department from 1990 to 2014 and fulfilled the 2013 classification criteria for SSc were retrospectively reviewed. A total of 139 patients were enrolled. The mean age of onset was 49.1 years, and 113 (81.3%) patients were female; 116 (83.5%) had limited cutaneous involvement, and the overall 10-year survival rate was 92.0%. Among 66 (47.5%) patients with ILD, 13 (9.4%) developed AE-ILD. Patients with AE-ILD had a significantly higher incidence of overlap with polymyositis (PM) or dermatomyositis (DM) and lower prevalence of anticentromere antibodies with higher mortality rate compared with those without AE-ILD. Multivariate Cox regression analysis identified that an overlap with PM or DM was the most significant predictive factor for AE-ILD. Our study results suggest that Japanese patients with SSc, particularly patients overlapped with PM or DM, have a high risk of AE-ILD.
- Botulinum toxin A in the treatment of Raynaud's phenomenon: a systematic review. [Journal Article]
- Arch Med Sci 2016 Aug 1; 12(4):864-70.
The management of Raynaud's phenomenon in its most severe form is challenging, and current medical and surgical treatment methods frequently do not lead to optimal symptom control and prevention of ischemic complications. The aim of the study was to critically evaluate all existing evidence on the use of botulinum toxin A in the management of Raynaud's phenomenon.We adopted the PRISMA methodology and searched Cochrane Library, MEDLINE, SCOPUS, EULAR and ACR congresses abstract archives for Raynaud* AND botulinum toxin OR onabotulinum. All studies that contained reports of botulinum toxin A use and its outcome in Raynaud's phenomenon were included in the review.Eleven studies met our inclusion criteria and involved a total of 125 patients. Two reviewers extracted data from the studies under review and achieved a consensus in their selection. The main outcomes measured were pain reduction and healing of digital ulcers. The level of evidence across studies was very low to moderate.There is insufficient evidence to assess the efficacy of botulinum toxin A in Raynaud's phenomenon. Despite many promising reports, further research in the form of randomized controlled trials is warranted in order to investigate this new treatment method for Raynaud's phenomenon.
- Evidence for the Use of Epoprostenol to Treat Raynaud's Phenomenon With or Without Digital Ulcers: A Review of the Literature. [REVIEW, JOURNAL ARTICLE]
- Ann Pharmacother 2016 Jul 26.
To review the evidence for using intravenous (IV) epoprostenol to treat Raynaud's phenomenon (RP).The databases MEDLINE (1946 to March 2016), PubMed, and International Pharmaceutical Abstracts were searched using the terms epoprostenol, Flolan, Raynaud's disease, and CREST syndrome. Further literature sources were identified by reviewing article citations.All English-language, clinical trials and case series evaluating IV epoprostenol for the management or treatment of RP were included. Lower-quality evidence were incorporated due to limited information.Seven small uncontrolled studies/case series, 1 small placebo controlled study, and 1 larger randomized trial were identified and included. There was no consistent measurement of efficacy utilized, but improvements in hand temperature, RP attack duration and frequency were commonly associated with IV epoprostenol treatment (5 trials). There were conflicting data regarding effect sustainability, with 5 trials showing long-term effects and 3 showing immediate effects. Fewer ischemic ulcers developed during treatment with IV epoprostenol in 1 trial compared to conventional treatment. Ulcer healing ocurred in 2 trials. Common adverse effects included hypotension, headache, flushing, gastrointestinal symptoms, and jaw pain.Available evidence supports the use of IV epoprostenol for treatment of severe RP in patients refractory or intolerant to standard therapies. The dose, titration schedule, and duration of IV epoprostenol utilized in studies varied, but a conservative approach to initiation should be considered. Patients who do not respond to intermittent infusions and have severe digital ischemia may require more aggressive regimens.
- Prevalence and predictors of hand involvement in Thai patients with systemic sclerosis. [JOURNAL ARTICLE]
- Int J Rheum Dis 2016 Jul 26.
Data regarding the clinical and radiographic hand involvement in Asian patients with systemic sclerosis (SSc) are limited. Thus, we determined the prevalence of clinical and radiographic hand involvement in Thai SSc patients, comparing diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc). We also determined the factors associated with arthritis, contracture of fingers and digital ulcers.SSc patients seen at the Rheumatology Clinic, Chiang Mai University, Thailand, from December 2012 to June 2013 were consecutively invited to enroll in the study. After study entry, demographic data, clinical features and hand radiographs were evaluated.We studied 110 SSc patients (73 dcSSc) with mean ± SD age of 53.2 ± 9.2 years and disease duration from non-Raynaud's phenomenon of 4.9 ± 4.8 years. The prevalence of arthritis, finger contractures and digital ulcers were 10 (9.1%), 47 (42.7%), and 14 (12.7%), respectively. DcSSc patients had significantly more of the following hand complications than lcSSc patients: digital pitting scar (53.4% vs. 27.0%, P = 0.008), digital ulcer (17.8% vs. 2.7%, P = 0.032), traumatic ulcer (27.4% vs. 0%, P < 0.001), acrolysis (45.2% vs. 18.9%, P = 0.007) and flexion contracture (60.3% vs. 8.1%, P < 0.001). Radiographic finger contractures were more prevalent in the dcSSc subset. In multivariate logistic regression analysis, a positive rheumatoid factor was associated with arthritis; dcSSc, arthritis and modified Rodnan skin score (MRSS) > 18 were associated with contracture of fingers. Furthermore, hand MRSS > 4 was associated with digital ulcers.Our results confirm that dcSSc patients had more severe clinical hand complications than lcSSc. However, radiographic findings were similar among subgroups, except that more finger contractures were seen in dcSSc. Finally, the presence of rheumatoid factor is associated with arthritis, and high MRSS is associated with finger contractures and digital ulcers.
- Acute Respiratory Distress Syndrome as the Initial Clinical Manifestation of an Antisynthetase Syndrome. [Journal Article]
- Tuberc Respir Dis (Seoul) 2016 Jul; 79(3):188-92.
Antisynthetase syndrome has been recognized as an important cause of autoimmune inflammatory myopathy in a subset of patients with polymyositis and dermatomyositis. It is associated with serum antibody to aminoacyl-transfer RNA synthetases and is characterized by a constellation of manifestations, including fever, myositis, interstitial lung disease, mechanic's hand-like cutaneous involvement, Raynaud phenomenon, and polyarthritis. Lung disease is the presenting feature in 50% of the cases. We report a case of a 60-year-old female with acute respiratory distress syndrome (ARDS), which later proved to be an unexpected and initial manifestation of anti-Jo-1 antibody-positive antisynthetase syndrome. The present case showed resolution of ARDS after treatment with high-dose corticosteroids. Given that steroids are not greatly beneficial in the treatment of ARDS, it is likely that the improvement of the respiratory symptoms in this patient also resulted from the prompt suppression of the inflammatory systemic response by corticosteroids.