Reporting items for capillaroscopy in clinical research on musculoskeletal diseases: a systematic review and international Delphi consensus.

OBJECTIVES: The level of detail included when describing nailfold videocapillaroscopy (NVC) methods varies among research studies, making interpretation and comparison of results challenging. The overarching objective of the present study was to seek consensus on the reporting standards in NVC methodology for clinical research in rheumatic diseases and to propose a pragmatic reporting checklist. METHODS: Based on the items derived from a systematic review focused on this topic, a three-step web-based Delphi consensus on minimum reporting standards in NVC was performed among members of the European League against Rheumatism (EULAR) Study Group on Microcirculation in Rheumatic Diseases and the Scleroderma Clinical Trials Consortium. RESULTS: A total of 319 articles were selected by the systematic review, and 46 items were proposed in the Delphi process. This Delphi exercise was completed by 80 participants from 31 countries, including Australia and countries within Asia, Europe, North America and South America. Agreement was reached on items covering three main areas: patient preparation before NVC (15 items), device description (5 items) and examination details (13 items). CONCLUSION: Based on the available evidence, the description of NVC methods was highly heterogeneous in the identified studies and differed markedly on several items. A reporting checklist of 33 items, based on practical suggestions made (using a Delphi process) by international participants, has been developed to provide guidance to improve and standardize the NVC methodology to be applied in future clinical research studies.

Position article and guidelines 2018 recommendations of the Brazilian Society of Rheumatology for the indication, interpretation and performance of nailfold capillaroscopy.

Nailfold capillaroscopy (NFC) is a reproducible, simple, low-cost, and safe imaging technique used for morphological analysis of nail bed capillaries. It is considered to be extremely useful for the investigation of Raynaud's phenomenon and for the early diagnosis of systemic sclerosis (SSc). The capillaroscopic pattern typically associated with SSc, scleroderma ("SD") pattern, is characterized by dilated capillaries, microhemorrhages, avascular areas and/or capillary loss, and distortion of the capillary architecture. The aim of these recommendations is to provide orientation regarding the relevance of NFC, and to establish a consensus on the indications, nomenclature, the interpretation of NFC findings and the technical equipments that should be used. These recommendations were formulated based on a systematic literature review of studies included in the database MEDLINE (PubMed) without any time restriction.

Prospective evaluation of the capillaroscopic skin ulcer risk index in systemic sclerosis patients in clinical practice: a longitudinal, multicentre study.

BACKGROUND: Nailfold capillaroscopy (NC) is an important tool for the diagnosis of systemic sclerosis (SSc). The capillaroscopic skin ulcer risk index (CSURI) was suggested to identify patients at risk of developing digital ulcers (DUs). This study aims to assess the reliability of the CSURI across assessors, the CSURI change during follow-up and the value of the CSURI in predicting new DUs. METHODS: This multicentre, longitudinal study included SSc patients with a history of DUs. NC images of all eight fingers were obtained at baseline and follow-up and were separately analysed by two trained assessors. RESULTS: Sixty-one patients were included (median observation time 1.0 year). In about 40% of patients (assessor 1, n = 24, 39%; assessor 2, n = 26, 43%) no megacapillary was detected in any of the baseline or follow-up images; hence the CSURI could not be calculated. In those 34 patients in whom CSURI scores were available from both assessors (26% male; median age 57 years) the median baseline CSURI was 5.3 according to assessor 1 (IQR 2.6-16.3), increasing to 5.9 (IQR 1.3-12.0) at follow-up. According to assessor 2, the CSURI diminished from 6.4 (IQR 2.4-12.5) to 5.0 (IQR 1.7-10.0). The ability of a CSURI ≥ 2.96 category to predict new DUs was low (for both assessors, positive predictive value 38% and negative predictive value 50%) and the inter-assessor agreements for CSURI categories were fair to moderate. CONCLUSIONS: In this study, around 40% of patients could not be evaluated with the CSURI due to the absence of megacapillaries. Clinical decisions based on the CSURI should be made with caution. TRIAL REGISTRATION: Current Controlled Trials, ISRCTN04371709 . Registered on 18 March 2011.

Automated assessment of absolute nailfold capillary number on videocapillaroscopic images: Proof of principle and validation in systemic sclerosis.

BACKGROUND: Absolute nailfold capillary number should be a putative biomarker in selected rheumatic diseases but could be time-consuming and not highly repeatable. OBJECTIVE: To validate an automated software for absolute nailfold capillary number and density evaluation, on NVC images in SSc. METHODS: An automated software to count nailfold capillary number (AUTOCAPI) had been constructed, through an exploratory image set. Subsequently, application rules have been created to define the ROI in NVC images, through a training images set. The software reliability was assessed through calculation of the ICC between automatic and manual counting, by four independent observers, on the same NVC images. RESULTS: The following ICC's were obtained per observer, for the patients with SSc (40 images), the healthy (20 images), and the PRP subgroups (20 images), respectively: 0.94, 0.81, and 0.62 (observer 1); 0.94, 0.91, and 0.67 (observer 2); 0.88, 0.56, and 0.64 (observer 3); and 0.88, 0.85, and 0.85 (observer 4). CONCLUSIONS: The validation of an automated software for measuring absolute nailfold capillary number and density in SSc was achieved. The integration into the pre-existing imaging software should make the assessment of the capillary number in NVC easier, quicker, and standardized.

An evaluation of two novel capillaroscopy techniques in suspected scleroderma-spectrum disorders: A single-centre cross-sectional study.

OBJECTIVES: The primary aim was to evaluate the diagnostic performance of digital photographs taken with a smartphone camera using both a lens attachment and, separately, a dermatoscope. The secondary aims were to assess the influence of prior capillaroscopy experience and familiarity with the novel techniques on diagnostic accuracy. METHODS: All patients referred for capillaroscopy between May 2016 and January 2017 were eligible for inclusion. Nailfolds were classified by widefield microscopy before proceeding double-blinded to nailfold photography using both novel techniques. Randomised photographs were assessed by three independent investigators and results were compared to widefield microscopy. Sensitivity, specificity, inter- and intra-observer variability were calculated. RESULTS: Sixty-five participants contributed over 1000 digital photographs for assessment. The 'smartphone-lens' technique performed with moderate sensitivity (65%; 58-72) and high specificity (90%; 84-96). The 'smartphone-dermatoscope' technique performed with higher sensitivity (74%; 66-82) and excellent specificity (95%; 88-100) and was used more accurately by a novice. Prior assessor experience with nailfold capillaroscopy in general and prior experience with the novel techniques positively modulated the diagnostic accuracy. CONCLUSION: New technologies, in this case utilising a smartphone camera, could help to improve accessibility to nailfold capillaroscopy, an important diagnostic tool and putative biomarker in scleroderma-spectrum disorders, whilst retaining accurate results.

Raynaud's syndrome in children: systematic review and development of recommendations for assessment and monitoring.

OBJECTIVES: To develop recommendations for investigation and monitoring of children with Raynaud's syndrome, based on paediatric evidence collated by a systematic review. METHODS: A systematic review was undertaken to establish the paediatric evidence for assessment and monitoring of Raynaud's syndrome. An expert panel including members of the Paediatric Rheumatology European Society (PRES) Scleroderma Working Group, were invited to a consensus meeting where recommendations were developed based on evidence graded by the systematic review and where evidence was lacking, consensus opinion. A nominal technique was used where 75% consensus was taken as agreement. RESULTS: The expert panel recommended testing anti-nuclear antibody (ANA), more specific antibodies associated with connective tissue disease and nail-fold capillaroscopy in all children presenting with Raynaud's syndrome as data suggests these can be risk factors for evolution into a connective tissue disease. The frequency of follow-up recommended depends on presence of these risk factors with the aim to detect evolving connective tissue disease early in high risk individuals. Those with no abnormalities on capillaroscopy and negative autoantibodies were deemed low risk of progression, whereas those with ANA positivity, specific autoantibodies and/or nailfold capillary changes were deemed high risk and more frequent follow-up was recommended. CONCLUSIONS: Recommendations, primarily based on consensus opinion, were agreed regarding investigation and monitoring of children who present with Raynaud's syndrome. Further prospective studies are needed to better define the risk factors for progression to connective tissue disease.

An EULAR study group pilot study on reliability of simple capillaroscopic definitions to describe capillary morphology in rheumatic diseases.

OBJECTIVE: To propose simple capillaroscopic definitions for interpretation of capillaroscopic morphologies and to assess inter-rater reliability. METHODS: The simple definitions proposed were: normal--hairpin, tortuous or crossing; abnormal--not hairpin, not tortuous and not crossing; not evaluable--whenever rater undecided between normal and abnormal. Based upon an aimed kappa of 0.80 and default prevalences of normal (0.4), abnormal (0.4) and not evaluable (0.2) capillaries, 90 single capillaries were presented to three groups of raters: experienced independent raters, n = 5; attendees of the sixth EULAR capillaroscopy course, n = 34; novices after a 1-h course, n = 11. Inter-rater agreement was assessed by calculation of proportion of agreement and by kappa coefficients. RESULTS: Mean kappa based on 90 capillaries was 0.47 (95% CI: 0.39, 0.54) for expert raters, 0.40 (95% CI: 0.36, 0.44) for attendees and 0.46 (95% CI: 0.41, 0.52) for novices, with overall agreements of 67% (95% CI: 63, 71), 63% (95% CI: 60, 65) and 67% (95% CI: 63, 70), respectively. Comparing only normal vs the combined groups of abnormal and not evaluable capillaries did increase the kappa: 0.51 (95% CI: 0.37 ,: 0.65), 0.53 (95% CI: 0.49, 0.58) and 0.55 (95% CI: 0.49, 0.62). On the condition that the capillaries were classifiable, the mean kappa was 0.62 (95% CI: 0.50, 0.74) for expert raters (n = 65), 0.76 (95% CI: 0.69, 0.83) for attendees (n = 20) and 0.81 (95% CI: 0.74, 0.89) for novices (n = 44). CONCLUSION: This multicentre, international study showed moderate reliability of simple capillaroscopic definitions for describing morphology of capillaries by rheumatologists with varying levels of expertise. Novices were capable of distinguishing normal from abnormal capillaries by means of a 1-h training session. In future studies, the class not evaluable may be obsolete.

Measuring microangiopathy abnormalities in systemic sclerosis patients: the role of capillaroscopy-based scoring models.

Capillaroscopy is a noninvasive imaging technique for the in vivo study of microcirculation. The role of a qualitative evaluation of capillaroscopy in the assessment of Raynaud's phenomenon secondary to scleroderma spectrum disorder, particularly systemic sclerosis (SSc), is well defined. The usefulness of capillaroscopy in the follow-up of SSc patients and the possible prognostic role for the appearance of typical SSc vascular and visceral involvement, namely, digital ulcers, pulmonary arterial hypertension, and mortality, is suggested by many authors but still under debate. In this regard, and for a reliable and repeatable longitudinal evaluation of SSc microangiopathy, a quantitative analysis should be required. In this review, we describe the current classifications proposed to define the SSc microvascular involvement and the scoring methods suggested for a semiquantitative and quantitative analysis of microangiopathy and its correlation with clinical manifestations of disease.

Capillaroscopic Skin Ulcers Risk Index (CSURI) calculated with different videocapillaroscopy devices: how its predictive values change.

INTRODUCTION: Digital ulcers (DU) occur in about 50% of systemic sclerosis (SSc) patients. Scleroderma DU are responsible for chronic pain and disability with the need of systemic and local treatments. Recently, capillaroscopic skin ulcer risk index (CSURI) has been validated as useful tool in predicting the appearance of new scleroderma ulcers and/or persistence of non-healing lesions, within 3 months from capillaroscopy evaluation. OBJECTIVES: Since the image length of 1.57 mm might represent a critical factor for CSURI calculation, the present study aimed to evaluate the reliability of CSURI using three different videocapillaroscopy devices with distinct image widths. METHODS: One hundred and seventy-six unselected SSc patients were consecutively enrolled for the study during a six-month period, using three different capillaroscopy devices (image widths of 1.33, 1.57, and 1.70 mm). RESULTS: After a three month-follow-up new DU or persisting non-healing ulcers were observed in 46/176 patients (26.1%). The receiver operating characteristic curve analysis for CSURI showed an area under curve respectively of 0.705 for the image width of 1.33 mm, 0.786 for the image of 1.70 mm, and 0.888 for the image width of 1.57 mm. CONCLUSIONS: The good sensitivity, specificity and positive predictive value of CSURI was confirmed in the whole patients' series, as well as in the three subgroups on different image widths obtained with various available devices. In addition, the negative predictive value of the capillaroscopic index remained very high regardless of the picture length adopted.

Nailfold capillaroscopy in systemic sclerosis: is there any difference between videocapillaroscopy and dermatoscopy?

BACKGROUND: Vasculopathy is known to destroy nailfold capillary pattern (NCP) in systemic sclerosis (SSc). There are several methods for the evaluation of NCP of which the most common are dermatoscopy and videocapillaroscopy (VCAP). No study has been reported in the literature comparing these two techniques for their diagnostic value. OBJECTIVE: To compare the diagnostic value of dermatoscopy and VCAP which are widely used to determine changes in the NCP in SSc patients. METHODS: A total of 382 nailfolds were visualized. NCP was evaluated in 39 SSc patients using dermatoscopy and VCAP. Defined dermatoscopic groups were matched with early, active and late phase NCP groups determined by VCAP for comparisons. RESULTS: Both dermatoscopy and VCAP demonstrated distinct NCP of SSc efficiently. According to dermatoscopic NCP, capillary dilatation, giant capillaries and disrupted vascular configuration were able to be visualized. VCAP revealed early phase NCP in N = 8 (20,5%), active phase in N = 18 (46,2%) and late phase NCP in N = 13 (33.3%) of the patients. Statistical evaluation of grouped data resulted a Cohen kappa value (K) = 0,527. Although VCAP was able to facilitate a more detailed evaluation of NCP, there was no difference between dermatoscopy and VCAP for the identification of distinct NCP in SSc. CONCLUSION: We suggest that dermatoscopy is efficient enough to identify pathognomonic changes in NCP in SSc as well as VCAP and find dermatoscopy as a very easy applicable and convenient method than VCAP although VCAP facilitates a more detailed evaluation of NCP.

[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.

Confocal laser-scanning capillaroscopy: a novel approach to the analysis of skin capillaries in vivo.

BACKGROUND: New techniques for diagnostics and therapy in dermatology are becoming increasingly non-invasive, among which confocal laser-scanning microscopy (CLSM) is the most prevalent. It allows visualization of cellular structures of the skin up to a depth of 300 microm in vivo. Until now, most studies have been conducted on pathologically altered skin, mostly oncologic lesions. We now present a detailed analysis of capillaries located in the upper dermal papillae. METHODS: Multiple measurements were performed on the dorsal and ventral surface of the right forearm of 30 healthy volunteers (22-88 years) under standard conditions (room temperature, body position, time of day). Images were obtained with the Vivascope 1500 (Lucid) under standard settings and analyzed using the freeware ImageJ with a customwritten macro plugin. The following parameters of the capillaries in vivo were measured: area, perimeter, circularity and maximum diameter. RESULTS: Statistical analysis showed that all four parameters were constant within a narrow range, regardless of the body site, sex and age. In this physiological study, we can clearly demonstrate that by confocal laser-scanning capillaroscopy (CLSC), it is possible to visualize and measure skin capillaries at the extremities in a reproducible manner. CONCLUSION: This new approach offers a considerable advantage compared with nailfold capillaroscopy, which can only be performed at the proximal nail segment, and over histological analysis, which can be hampered by fixation artifacts resulting in altered size and shape of the vessels to be analyzed. CLSC could allow for precise analysis of in vivo skin vasculature in systemic and proliferative diseases of the skin.

Capillaroscopy of the dorsal skin of the hands in hereditary hemorrhagic telangiectasia.

BACKGROUND: Cutaneous telangiectases are manifestations of hereditary hemorrhagic telangiectasia (HHT), a dominantly inherited disorder. Telangiectases have been studied by skin biopsy, and recently by nailfold capillaroscopy. AIM: To confirm the diagnostic role of nailfold capillaroscopy, and assess the value of skin capillaroscopy of the dorsum of the hands in HHT. DESIGN: Prospective clinical investigation. METHODS: Using a Wild Heerbrugg-M650 microscope, we studied the nailfolds and dorsum of the hands of 88 patients (37 females, 51 males, mean age 39.7 +/- 18.4 years), including 85 with positive genetic testing and three with clinical diagnosis (at least three clinical criteria but a negative genetic test) and 27 controls (13 females, 14 males, mean age 38.6 +/- 19.6 years). RESULTS: Microscopic telangiectases were observed on the dorsum of the hands in 80/88 patients (91%): 77 with positive and three with negative genetic tests. No control showed vascular abnormalities. In six patients (7%), nailfold capillaroscopy showed pseudo-megacapillaries and megacapillaries; the remaining 82 (93%) and all controls, had normal capillaroscopic patterns. DISCUSSION: HHT can induce morphological changes in microcirculation that are more easily detectable on the dorsum of the hands than in the nailfold. Microscopic lesions without macroscopic telangiectases were also noted, suggesting the need for further research. Capillaroscopy may provide an additional non-invasive diagnostic criterion for HHT.

Capillaroscopic observations in childhood rheumatic diseases and healthy controls.

OBJECTIVE: To describe, by using video nailfold capillaroscopy (NFC), microvascular abnormalities in children with rheumatic diseases and to evaluate the capillary changes over a follow up period. METHODS: 118 children suffering from rheumatic diseases: 55 juvenile idiopathic arthritis (JIA), 7 mixed connective tissue disease (MCTD), 6 primary Raynaud's phenomenon (PRP), 34 systemic lupus erythematosus (SLE), 8 juvenile systemic sclerosis (JSSc) and 8 juvenile dermatomyositis (JDM) were included in the study. Patients with major capillaries abnormalities or scleroderma pattern were followed up for at least 12 months. 70 age- and sex-matched healthy controls (HC) were also examined. RESULTS: In HC there was a significant correlation between age and capillary length (p = 0.001). JIA patients showed capillary number, size, shape and arrangement similar to HC. Minor abnormalities were frequently observed. The percentage of major abnormalities were significantly increased compared to HC in MCTD (p = 0.008), SLE (p = 0.0002) and JDM patients (p < 0.0001). 5/8 of JSSc had a scleroderma pattern from the onset of the disease. The serial observations in connective tissue diseases also showed that the evolution of capillaroscopic pattern was not unidirectional. In fact, in some nailfolds there was an increase in capillary loss and in avascular areas, whereas sometimes it remained stable on repeated examination. CONCLUSION: NFC can be used as a simple, inexpensive, non-invasive method to evaluate the microvascular abnormalities in childhood rheumatic conditions, and it may be useful in early recognition and monitoring scleroderma spectrum disorders.

Prosthesis intolerance in patients with transfemoral amputation: a videocapillaroscopic study.

Videocapillaroscopy is a new technique allowing a noninvasive examination of the capillary framework of the skin by using a contact probe with magnifying lenses and a cold-light epiluminescence system. The aim of this article was to investigate, by videocapillaroscopy, the microcirculation of the skin of the stump in 70 consecutive patients with unilateral transfemoral amputation. Patients were divided into two subgroups according to their tolerance (A) or intolerance (B) to a prosthesis with an Icelandic-Swedish-New York socket. Subgroup A included 48 patients, 17 diabetic and 31 nondiabetic, and subgroup B included 22 patients, 16 diabetic and 6 nondiabetic. In subgroup B, the caliber of capillary loops was significantly larger (mean +/-standard deviation, 23.6 +/-2.04 vs. 16.2 +/-1.96 microm; P < 0.001), neoangiogenesis was significantly more frequent (82%vs. 25%, P < 0.001), and the presence of microaneurysms (64%vs. 15%, P < 0.001) and microhemorrhages (36%vs. 4%, P < 0.001) was also more frequent. Surprisingly, some such diabetes-like microvascular changes were also found in the six nondiabetic patients of subgroup B. By using multiple logistic regression analysis, intolerance to the prosthesis was significantly related to microvascular changes (P = 0.001) but not to diabetes (P = 0.601), although diabetes was unequally distributed in the two subgroups.

Hemorragia ungueal / Nail Hemorrhage

La hemorragia ungueal se presenta como una cromoniquia adquirida. Su etiología puede ser traumática, medicamentosa, por enfermedades sistémicas o dermatológicas o iatrogénica por internación prolongada en UTI. El diagnóstico diferencial se deberá hacer con infecciones locales del aparato ungueal así como con tumores nevos y otras cromoniquias. El objetivo del presente trabajo es plantear una metodología diagnóstica que ayude a determinar la causa de la hemorragia ungueal y/o hacer el diagnóstico diferencial con otros cuadros clínicamente semejantes. La metodología de este estudio comprende: historia clínica, exámenes hematológicos, autoanticuerpos, capilaroscopía convencional periungueal y de la hemorragia, cultivo de gérmenes y eventual biopsia del lecho ungueal

Hemorragia ungueal / Nail Hemorrhage

La hemorragia ungueal se presenta como una cromoniquia adquirida. Su etiología puede ser traumática, medicamentosa, por enfermedades sistémicas o dermatológicas o iatrogénica por internación prolongada en UTI. El diagnóstico diferencial se deberá hacer con infecciones locales del aparato ungueal así como con tumores nevos y otras cromoniquias. El objetivo del presente trabajo es plantear una metodología diagnóstica que ayude a determinar la causa de la hemorragia ungueal y/o hacer el diagnóstico diferencial con otros cuadros clínicamente semejantes. La metodología de este estudio comprende: historia clínica, exámenes hematológicos, autoanticuerpos, capilaroscopía convencional periungueal y de la hemorragia, cultivo de gérmenes y eventual biopsia del lecho ungueal (AU)