Raynaud's phenomenon-an update on diagnosis, classification and management.

Raynaud's phenomenon (RP) is used to describe a symptom complex caused by digital vascular compromise. RP is a clinical diagnosis. The typically episodic nature of RP has resulted in a reliance upon patient self-report for diagnosis. The term 'primary RP' is generally applied when no underlying pathology can be demonstrated. Whilst 'primary RP' is currently considered a distinct disorder, there is evidence that the term may comprise several entities that include a functional vasospastic disorder, a physiologically appropriate thermoregulatory response, subclinical atherosclerosis and 'cold intolerance'. Optimal management may differ depending on cause. The term 'secondary RP' encompasses a broad range of rheumatological, haematological, endocrinological and vascular pathology. RP can range from relatively benign but intrusive vasospasm, to the progressive obliterative microangiopathy of systemic sclerosis (SSc), in which severe digital ischaemia can threaten tissue viability. SSc has formed the focus of much of the research into RP but, consistent with most medical symptom complexes, the aetiopathogenesis of RP varies greatly dependent on cause. Vasospasm within the digital macro- and microvasculature occurs in SSc, but digital ischaemia is further compounded by a progressive obliterative microangiopathy. Recent work exploring the patient experience of SSc-RP is challenging the 'episodic' paradigm of 'Raynaud's', with important implications for clinical trials utilising diary-based patient-reported outcome instruments for assessing Raynaud's symptoms. This review shall examine the causes, pathogenesis, clinical features, classification and management of RP. A practical approach to the evaluation and management of RP is outlined, highlighting important knowledge gaps and unmet research needs where applicable. Key Points • Raynaud's phenomenon is a symptom complex related to digital vascular compromise secondary to broad-ranging pathology. • Raynaud's phenomenon, as currently classified, likely encompasses a number of aetiopathogenic processes. • Raynaud's phenomenon causes significant disease-related morbidity in autoimmune rheumatic diseases such as systemic sclerosis.

ESVM guidelines - the diagnosis and management of Raynaud's phenomenon.

Regarding the clinical diagnosis of Raynaud's phenomenon and its associated conditions, investigations and treatment are substantial, and yet no international consensus has been published regarding the medical management of patients presenting with this condition. Most knowledge on this topic derives from epidemiological surveys and observational studies; few randomized studies are available, almost all relating to drug treatment, and thus these guidelines were developed as an expert consensus document to aid in the diagnosis and management of Raynaud's phenomenon. This consensus document starts with a clarification about the definition and terminology of Raynaud's phenomenon and covers the differential and aetiological diagnoses as well as the symptomatic treatment.

Classification of Japanese patients with mild/early systemic sclerosis (SSc) by the 2013 ACR/EULAR classification criteria for SSc.

OBJECTIVE: To classify Japanese patients with mild/early systemic sclerosis (SSc) by the 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Classification Criteria (new 2013 criteria). METHODS: We assessed 120 patients who visited Kanazawa University Hospital suspected of SSc and who did not meet the 1980 ACR preliminary classification criteria for SSc. We clinically diagnosed 16 patients with primary Raynaud's disease and 104 with mild/early SSc prior to being assessed by the new 2013 criteria. RESULTS: None of the 16 patients with primary Raynaud's disease met the new 2013 criteria. On the other hand, 94 out of the 104 patients (90.3%) with mild/early SSc by our clinical diagnosis met the new 2013 criteria. Among the 94 SSc patients, sclerodactyly was detected in 58 (62%), puffy fingers in 62 (66%), abnormal nailfold capillaries in 89 (95%), Raynaud's phenomenon in 93 (99%), and SSc-related autoantibodies (Abs) in 85 (90%). The median (range) score of these 94 patients was 12 (9-14). Ten mild/early SSc patients who did not meet the new 2013 criteria had the following clinical features: puffy fingers in 1 (10%), abnormal nailfold capillaries in 8 (80%), Raynaud's phenomenon in 9 (90%), and SSc-related autoAbs in 8 (80%). The median (range) score of these 10 patients was 7 (5-8). CONCLUSION: The new 2013 criteria can classify most mild/early Japanese SSc patients, which may contribute to early treatment interventions.

Application of the 2013 ACR/EULAR classification criteria for systemic sclerosis to patients with Raynaud's phenomenon.

INTRODUCTION: We investigated how many patients, who presented with Raynaud's phenomenon (RP) and who had not been classified as systemic sclerosis (SSc), would be reclassified as SSc, if the 2013 American College of Rheumatology (ACR)/the European League Against Rheumatism (EULAR) classification criteria were used. We also analyzed the predictive values of the reclassification as SSc in those patients. METHODS: We consecutively enrolled 64 patients with RP and 60 patients with SSc. We applied the new classification criteria to them, reclassified them, and compared variables between those who were newly classified as SSc and those who were not or previously classified as SSc. RESULTS: Seventeen of 64 patients (26.5%), who presented with RP, but did not fulfill the 1980 ACR classification criteria, were newly classified as SSc by the 2013 ACR/EULAR classification criteria. The newly classified patients as SSc showed increased frequencies of sclerodactyly, digital tip ulcer, telangiectasia, abnormal nailfold capillaries and the presence of anti-centromere antibody, compared to those not and telangiectasia and anti-centromere antibody, compared to the previously classified patients. For the reclassification as SSc, the variables with independent predictive value were sclerodactyly (odds ratio (OR) 60.025), telangiectasia (OR 13.353) and the presence of anti-centromere antibody (OR 11.168). CONCLUSIONS: Overall, 26.5% of the patients, who presented with RP, but who did not fulfill the 1980 ACR classification criteria, were newly classified as SSc according to the 2013 ACR/EULAR classification criteria. Sclerodactyly, telangiectasia, and the presence of anti-centromere antibody had independent predictive value for reclassifying patients with RP as SSc.

A Delphi exercise and cluster analysis to aid in the development of potential classification criteria for systemic sclerosis using SSc experts and databases.

OBJECTIVES: Since the 1980 ACR classification criteria for systemic sclerosis (SSc) do not identify 20% with SSc, revised criteria are necessary. METHODS: Suggested new criteria from the literature were sent in random order to 96 SSc experts. A 3-round Delphi Consensus eliminated criteria. Then cluster analysis reduced items. The Canadian Scleroderma Research Group (CSRG) database was used to determine the prevalence of each item. RESULTS: Seventy-one of 96 (71%) completed all 3 rounds; 47 items were expanded to 76 in round 2. Thirty items had at least 50% consensus and 18 had >75% agreement to include (a priori cut point). Clustering occurred for 4 categories: proximal to MCP skin involvement, vascular abnormalities, autoantibodies and tissue damage. Proximal to MCPs skin involvement identified 80% of patients. Adding one item from each of the other 3 categories or 1 or more items from 2 of 3 remaining categories increased the proportion of patients classified to 94% in CSRG patients. Categories included (1) Vascular (dilated capillaries, telangiectasia, Raynaud's phenomenon [RP]), (2) Autoantibodies (anticentromere [ACA] or antitopoisomeraseI [Topo1]) and (3) Fibrosis/damage (esophogeal dysmotility dysphagia, sclerodactyly, digital ulcers). In the CSRG, 98% were identified if using proximal skin involvement; or sclerodactyly plus one of: RP, ACA or Topo1. CONCLUSIONS: This is a first step toward developing new SSc classification criteria. A Delphi exercise alone cannot suffice for item reduction. Also, validation prospectively in SSc patients and diseases that mimic SSc is needed in order to calculate sensitivity and specificity of future criteria.

[Raynaud's syndrome, 2011]. / Raynaud-szindróma, 2011.

Raynaud's phenomenon is characterized by intense vasospasm of the digital arteries on cold exposure or emotional stress, leading to well-defined colour changes in the skin of the fingers. Behind the clinical manifestations, there is an imbalance between vasoconstrictor and vasodilator factors. It may be primary or secondary to an underlying condition, including autoimmune diseases. Physical examination, nail fold capillaroscopy and immunological tests can differentiate primary forms from secondary ones. The treatment is based on preventing exposure to cold, emotional stress and the administration of certain drugs and, if attacks are present, vasodilators, prostaglandin analogues and anticoagulants may be given. This review focuses on the characteristics of Raynaud's phenomenon and the available diagnostic and therapeutic options.

[Raynaud's phenomenon]. / La vignette diagnostique de l'étudiant. Le phénomène de Raynaud.

Raynaud's phenomenon is a vascular acrosyndrome caused by a variety of diseases. There is a distinction between the idiopathic Raynaud's disease, the secondary types and the suspicious idiopathic Raynaud's phenomenon.

Validation of potential classification criteria for systemic sclerosis.

OBJECTIVE: Classification criteria for systemic sclerosis (SSc; scleroderma) are being updated jointly by the American College of Rheumatology and European League Against Rheumatism. Potential items for classification were reduced to 23 using Delphi and nominal group techniques. We evaluated the face, discriminant, and construct validity of the items to be further studied as potential criteria. METHODS: Face validity was evaluated using the frequency of items in patients sampled from the Canadian Scleroderma Research Group, 1000 Faces of Lupus, and the Pittsburgh, Toronto, Madrid, and Berlin connective tissue disease (CTD) databases. Patients with SSc (n = 783) were compared to 1,071 patients with diseases similar to SSc (mimickers): systemic lupus erythematosus (n = 499), myositis (n = 171), Sjögren's syndrome (n = 95), Raynaud's phenomenon (RP; n = 228), mixed CTD (n = 29), and idiopathic pulmonary arterial hypertension (PAH; n = 49). Discriminant validity was evaluated using odds ratios (ORs). For construct validity, empirical ranking was compared to expert ranking. RESULTS: Compared to mimickers, patients with SSc were more likely to have skin thickening (OR 427); telangiectasias (OR 91); anti-RNA polymerase III antibody (OR 75); puffy fingers (OR 35); finger flexion contractures (OR 29); tendon/bursal friction rubs (OR 27); anti-topoisomerase I antibody (OR 25); RP (OR 24); fingertip ulcers/pitting scars (OR 19); anticentromere antibody (OR 14); abnormal nailfold capillaries (OR 10); gastroesophageal reflux disease symptoms (OR 8); antinuclear antibody, calcinosis, dysphagia, and esophageal dilation (all OR 6); interstitial lung disease/pulmonary fibrosis (OR 5); and anti-PM-Scl antibody (OR 2). Reduced carbon monoxide diffusing capacity, PAH, and reduced forced vital capacity had ORs of <2. Renal crisis and digital pulp loss/acroosteolysis did not occur in SSc mimickers (OR not estimated). Empirical and expert ranking were correlated (Spearman's ρ = 0.53, P = 0.01). CONCLUSION: The candidate items have good face, discriminant, and construct validity. Further item reduction will be evaluated in prospective SSc and mimicker cases.

Classification of Raynaud's disease based on angiographic features.

Accurate diagnosis and timely management are crucial to avoid an ischaemic consequence in Raynaud's disease. There is, however, no objective classification of this disorder which guides surgical planning in refractory cases. We propose a new classification system to achieve this. From 2003 to 2009, we treated 178 patients (351 hands) who underwent surgical intervention due to an ischaemic consequence. We analysed the angiographic features of the arterial supply of the hand at three levels: (1) radial or ulnar, (2) palmar arch and common digital and (3) digital vessels. Subsequent surgical interventions were tailored according to disease types, and these included combinations of: digital sympathectomy, balloon angioplasty and end-to-end interposition venous or arterial grafting. We classified Raynaud's disease into six types: type I and II involve the radial or ulnar arteries. Type I (27.3%) showed complete occlusion, while type II (26.2%) involved partial occlusion. Type IIIa (27.1%) showed tortuous, narrowed or stenosed common digital and digital vessels. Type IIIb (1.4%) is a subset which involved the digital vessel of the index finger related to exposure to prolonged vibration. Type IV and V showed global involvement from the main to digital vessels. Type IV (13.7%) showed diffused tortuosity, narrowing and stenosis. Type V (4.3%) is the most severe, with paucity of vessels and very scant flow. Nearly half (47%) of the patients had associated systemic disease. This new classification provides objective and valuable information for decision making regarding choice of surgical procedures for the treatment of patients with Raynaud's disease which had failed conservative therapy.

Raynaud's phenomenon.

Raynauds phenomena (RP) is a commonly encountered clinical manifestation which may be primary or secondary to underlying disease. There is imbalance between vasoconstricting and vasodilating factors. Physical examination, nailfold capillaroscopy and immunological tests can differentiate primary from secondary RP. Treatment involves prevention of RP so that permanent ischemic damage i.e. gangrene can be avoided. Avoidance of exposure to cold, emotional stress and certain drugs is mandatory and if attacks are occurring then vasodilators, prostaglandin analogues, anticoagulants and antiplatelet drugs may be added. An attempt has been made to guide the clinician to diagnose and treat a patient of RP through this article.

[Capillaroscopy. Procedure and nomenclature]. / Kapillarmikroskopie. Durchführung und Nomenklatur.

Capillaroscopy has high diagnostic and prognostic value in autoimmune connective tissue diseases, in particular systemic sclerosis (SSc). Our working group has developed a consensus on nomenclature, technical equipment, procedure, and diagnostic interpretation of results. The following are required: binocular microscopes with at least 20-/50- and 160-/200-fold magnification and digital archiving. Documentation of defined findings is mandatory. The simultaneous occurrence of, e.g. caliber variations, ectasia, ramifications, elongation (length > 350 microm), torsion (at least two crossing segments per capillary loop), sludge, hemorrhage, and edema is of pathological significance. The isolated occurrence of bushy capillaries (multiple ramifications), thrombosis, giant capillary (capillary lumen > 50 microm), and avascular areas also indicates disease. The latter two findings are highly specific for SSc. Other findings are consistent with connective tissue diseases. These standardized definitions increase quality and comparability of nailfold capillaroscopy in Germany.

[Raynaud's phenomenon]. / El fenómeno de Raynaud.

Raynaud's phenomenon is a frequent reason for seeking of medical attention, since it affects 3-5% of the population. It is characterized by sudden, transient and recurrent episodes of pallor and/or digital cyanosis, after exposure to cold or stressful situations. No known underlying illness is identified in over 80% of cases and consequently these cases are classified as primary Raynaud's phenomenon. Connective tissue diseases, particularly systemic sclerosis, are the main causes of the phenomenon. Once a complete clinical and physical evaluation rule out other causes, a nailfold capillaroscopy and antinuclear antibodies determination are the most useful adjunctive tests. Mild Raynaud's phenomenon can be managed almost exclusively with conservative non-pharmacological lifestyle modifications. However, if a patient develops a severe vascular condition a suitable vasodilator treatment is needed. When critical digital ischemia develops, intravenous treatment with prostaglandin analogues and surgery may be useful.

Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud's phenomenon to systemic sclerosis: a twenty-year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis.

OBJECTIVE: To identify in patients with Raynaud's phenomenon (RP) independent markers that predict progression to definite systemic sclerosis (SSc) and to determine in patients with progression to SSc the type and sequence of microvascular damage and its relationship to SSc-specific autoantibodies. METHODS: Consecutive patients referred for evaluation of RP who had no definite connective tissue disease were evaluated for microvascular damage by nailfold capillary microscopy (NCM) and for anticentromere (anti-CENP-B), anti-Th/To, anti-topoisomerase I, and anti-RNA polymerase III (anti-RNAP III) autoantibodies by specific assays. Patients were studied prospectively. RESULTS: Of the 586 patients who were followed up for 3,197 person-years, 74 (12.6%) developed definite SSc. A characteristic sequence of microvascular damage was identified, starting with enlarged capillaries, followed by capillary loss, and then by capillary telangiectases. Definite SSc was diagnosed in close temporal relationship to capillary loss. Enlarged capillaries, capillary loss, and SSc-specific autoantibodies independently predicted definite SSc. Anti-CENP-B and anti-Th/To antibodies predicted enlarged capillaries; these autoantibodies and anti-RNAP III predicted capillary loss. Each autoantibody was associated with a distinct time course of microvascular damage. At followup, 79.5% of patients with 1 of these autoantibodies and abnormal findings on NCM at baseline had developed definite SSc. Patients with both baseline predictors were 60 times more likely to develop definite SSc. The data validated the proposed criteria for early SSc. CONCLUSION: In RP evolving to definite SSc, microvascular damage is dynamic and sequential, while SSc-specific autoantibodies are associated with the course and type of capillary abnormalities. Abnormal findings on NCM at baseline together with an SSc-specific autoantibody indicate a very high probability of developing definite SSc, whereas their absence rules out this outcome.

[Definition and terminology of Raynaud's syndrome]. / Definition und Terminologie von Raynaud-Syndromen.

Physicians have for a long time used different definitions, terminology and differential diagnoses for Raynaud's syndromes, which has resulted in diagnostic, therapeutic and prognostic problems. In order for difficulties of understanding to be prevented, the terminology should be restricted to the most common terms in international use, i. e. primary, secondary and suspected secondary Raynaud's syndrome. The characteristics of those three forms of Raynaud's syndrome are outlined.

Sparing of the thumb in Raynaud's phenomenon.

OBJECTIVES: To conduct a prospective study to determine which digits are affected (and whether the thumb is spared or not) in a cohort of patients with RP as assessed by symptoms and thermography and to determine whether the degree of thumb involvement differs between primary (PRP) and secondary Raynaud's phenomenon (SRP). METHODS: This was a cross-sectional study of 44 patients with RP. The following characteristics were recorded to allow comparisons between digits: symptoms of RP in each digit (graded on a scale of 'never', 'sometimes' and 'always' affected during an attack of RP) and thermography at 23 degrees C. A distal-dorsal difference (DDD) in temperature at 23 degrees C of -1 degree C or less was considered to be clinically relevant. RESULTS: Symptom scores in the thumb were significantly better, i.e. less severe than in each finger (P < 0.001). As only three participants had any finger better than the thumb, there was no power to compare whether the thumb was spared more in PRP compared with SRP. Mean DDD was significantly higher (i.e. better) in the thumb compared with each finger (P < 0.001). Although DDD scores were higher in PRP compared with SRP (P = 0.01), there was no evidence that the relative effect of the thumb differed between the two groups (P = 0.26). CONCLUSIONS: Our findings confirm that the thumbs are spared in RP, both primary and secondary, as demonstrated by both symptoms and thermography. The reasons for sparing of the thumb were not addressed in this study but raised questions regarding pathophysiology.

Differential diagnosis of scleroderma and pseudoscleroderma.

The different forms of scleroderma and the pseudosclerodermas, which clinically partially imitate scleroderma, are rare. Due to the large variety and variability of the clinical course, particularly at the onset of disease, diagnosis may be difficult. For differential diagnosis, the presence of Raynaud phenomenon, antinuclear antibodies and the distribution of sclerosis play essential roles. Besides discussing the diseases that should be considered in the differential diagnosis, we present an algorithm which should facilitate the diagnosis and allow one to promptly initiate appropriate treatment.

Pathophysiology and clinical consequences of Raynaud's phenomenon related to systemic sclerosis.

According to the so-called vascular hypothesis, Raynaud's phenomenon (RP) is one initial event in the pathophysiological cascade leading to sclerosis in systemic sclerosis (SSc). It is characterized by recurrent, reversible spasms of small arterioles and digital arteries, usually triggered by cold and emotional stress. Clinical signs of RP are a sudden pallor of single digits of fingers followed by reactive hyperaemia and in severe cases also by cyanosis. Besides imbalances between vasoconstrictive and vasodilatory processes, structural alterations of the involved vessels are fundamental to secondary RP in SSc. The latter is the reason why secondary RP in SSc, in contrast to primary RP, often leads to ischaemia and re-perfusion injuries. New insights into the pathophysiology of RP feature a special role for alpha2c-adrenoreceptors, Rho-kinase signalling pathways and soluble mediators. They have resulted in promising therapeutic options, including antagonism of endothelin receptors, inhibition of phosphodiesterases or selective blockade of alpha2c-adrenoreceptors. They should also have a positive impact on the course of SSc in general.

[Systemic sclerosis - diagnosis and classification]. / Systemische Sklerose - Diagnose und Klassifikation.

Systemic sclerosis (SSc) is a polymorphic and heterogenic systemic disorder with inflammation, fibrosis and vascular damage. Early diagnosis and classification may be difficult if disease expression is oligosymptomatic (undifferentiated), presenting with only Raynaud's phenomenon or limited scleroderma. Scleroderma specific antinuclear autoantibodies, which are present early and persistently in about 90% of the patients with SSc, play an important taxonomic role. Scleroderma specific findings in nailfold capillary microscopy are sensitive and predictive for evolving SSc. An algorithm will be presented for the diagnosis and classification of SSc using clinical, capillaroscopic and serologic criteria, which are also useful for mixed or special forms of SSc. The 6th Outcome Measures in Rheumatology Clinical Trials (OMERACT) conference proposed different outcome measurements for clinical studies, however, for daily clinical practice there is as yet no consensus on status indices for disease activity, disease related damage or suitable prognostic criteria.