Table 3. Summary of recommendations of on the clinical applications and interpretations of the NFC.

Statement	Level of evidence	Mean±SD	Percent of agreement	Level of agreement
indications of NFC: 1. Differentiating between primary and secondary Raynaud’s 2. Monitoring the transition from primary to secondary RP; 3. Early diagnosis of SSc; 4. Differential diagnosis of SSc-related conditions, such as localized SSc and eosinophilic fasciitis, which usually have a normal capillaroscopic pattern; 5. Detection of severe microangiopathy and prognostic evaluation in SSc; 6. Monitoring treatment and disease activity in dermatomyositis. 7. Evaluating cases of idiopathic pulmonary fibrosis for possible underlying connective tissue diseases	2	7.8±2.9	90.9	H
Device: The gold standard device is the digital videocapillaroscope that combines a microscope with a digital video camera.	3	8.1±2.4	90.9	H
Targeted patients: NFC should be performed in almost all patients with RP even primary or secondary type.	4	7.6±2.4	90.9	H
Who should do the NFC procedure and interpret the results? Specialists who have the experience in NFC. These include: 1. Working in National/University Hospital/Ministry of Health hospital providing NFC service and having regular scientific meetings. 2. In solo practice: -if less than 3 years, a log book showing traceable record of NFC cases and diagnosis/management outcomes; and -if practice more than 3 years, the specialist should provide an audit comparing his/her service with gold standards as national guidelines showing the outcome of his service. 3. Preferable if healthcare professional have publications in peer-reviewed journal whether national or international	2	8.2±2.7	90.9	H
Terminology in NFC: Counting the capillaries number: All the capillaries present in the distal row are considered for counting, even if they are not at the same levels. Capillary density (the number of capillaries in the distal row of each finger or toe in a 1 mm length. Low Capillary density: Less than 9 capillaries per mm Intercapillary distance: defined as the longest distance that H exists between two neighboring capillary loops (Normal <110 μm) Drop out zone (Avascular Areas): Region with intercapillary distance over 500 μm with no apparent cause of visual field obstruction Capillary dimension The width and height of a capillary are the main parameters. Capillary width is the width of a capillary loop at its widest section Capillary length is the distance between the apex of a capillary loop and the point where the capillary loop is no longer visible Cut off measures Dilated Capillary: The arterial limb diameter larger than 15 μm or whose venous limb wider than 20 μm Giant Capillary: Capillaries with an apical diameter >50 μm (afferent, apical, efferent) Capillary elongation: Over 295 μm length Capillary Morphology (shape of individual capillaries): The shape of a regular capillary: like a hair pin or the letter “U” upside-down, with a slimmer arterial arm, an upper part, and a venous arm. Other shapes include: tortuous, branched, bushy, dilated, and giant capillaries. Capillary direction is the angle between a vertical line and the vector associated with the highest proper value Capillary polarity is the standard deviation of all the capillary directions in an image Neo angiogenesis: Newly formed irregular, branching capillaries usually in an avascular area replacing the older ones that were lost Hemorrhage(s): Extravascular deposits consisting of fresh, bright-red blood or old blood containing hemosiderin deposits (present/absent) Microhemorrhage: Reddish brown rounded well defined hemorrhage blotches outside the capillary	4	8.1±2.4	90.9	H
Relevance of capillaroscopy for assessment of patients with Raynaud's phenomenon: NFC findings are usually normal in primary RP, and abnormal in secondary RP (abnormal findings differ according to the underlying rheumatic disease).	4	8±2.4	90.9	H
In case of primary Raynaud's It is recommended to perform capillaroscopy every 12-24 months in primary RP, since up to 10% of these patients will develop a connective tissue disease, sometimes after decades.	4	8±2.4	90.9	H
Abnormal NFC findings in primary RP have a positive predictive value for the development of systemic rheumatic disease.	4	8±2.4	90.9	H
Relevance of capillaroscopy for systemic sclerosis The pattern of NFC in SSC is specific and is characterized by presence of loss of capillaries, dilated capillaries, avascular areas, hemorrhages and neoangiogeneis.	4	8.2±2.4	90.9	H
There are three phases of capillaroscopic changes during the course of SSc: 1. An early phase: presence of few dilated and/or giant capillaries and few hemorrhages without loss of capillaries. 2. An active phase: (a marker of disease progression) presence of frequent giant capillaries, frequent (more than 6 per millimetre) capillary microhemorrhages, moderate (20-30%) capillary loss, absent or mild ramified capillaries and a mild disorganization of the capillary architecture. 3. A late phase: it is characterized by, irregular enlargement of the capillaries, severe (>50%) capillary loss with evident extensive avascular areas, ramified or bushy capillaries, severe disorganization of the capillary array, and almost absence of giant capillaries and microhemorrhages.	4	8.2±2.4	90.9	H
Diagnostic parameters: Capillaroscopy has diagnostic parameters (irregularly enlarged capillaries, giant capillaries, microhemorrhages) and progression parameters (reduced capillary number, capillary ramifications and capillary architectural disorganization	4	7.6±2.8	81.8	H
In a systemic disease in which vascular damage is one of the pathogenetic factors, abnormalities in capillary morphology can be observed long before the onset of clinical symptoms. In patients already diagnosed with a systemic disease, damage to the capillaries may reflect the involvement of internal organs and help determine the stage of the disease”.	3	7.6±2.8	81.8	H
The link between Capillaroscopic and Serological Findings: There is association between NFC, disease specific autoantibodies and cardiopulmonary complications.	4	8±1.9	81.8	H
The combination of autoantibodies and NFC-defined microvascular lesions identified patients at higher risk for cardiopulmonary disease more accurately	4	8±1.9	81.8	H
NFC and comorbidities Loss of capillary density is linked with higher mortality rate in SSC patients.	3	7.8±2.1	81.8	H
Nailfold videocapillaroscopy has a relation with visceral organ involvement in SSc; especially PAH, digital ulcers & ILD.	4	7.8±2.1	81.8	H
Using NFC could be of value for the evaluation of treatment response.	4	7.8±2.1	81.8	H
Technique: The NVC technique with 200x magnification, capturing at least two adjacent fields of 1 mm in the middle of the nailfold finger, is the gold standard capillaroscopic technique to perform nailfold capillaroscopy	2	7.9±2.1	90.9	H
Preparation: 1. Patient preparation: Artificial nails and nail polish are contraindicated. Patients should have no history of recent (at least 2 weeks) trauma to the distal phalanges (including manicure), and the nail beds should appear normal with no evidence of recent or old infection, wound, etc. 2. Environment preparation: Room temperature should be between (22-25°C), and the patient should be present for at least 15 minutes before the examination so the nail fold capillary network can adapt to the room temperature	3	8.2±1.6	90.9	H
Procedure: 1. Nailfolds are prepared by rubbing on a thin layer of herbal oil, preferably cedar oil (olive oil and sesame oil can also be used). Emulsion oil used in microscopes is not recommended as it reduces the visual field. 2. All fingertips, except for the thumbs, should be studied. Thumbs often show irregularities in their capillary network due to repeated trauma in everyday task. The best fingers are often the 4th (ring), but it is better to study all eight fingers. 3. Three high quality pictures of each finger are taken from the medial and lateral corners of the nail bed and from the midpoint. These pictures increase the sensitivity of the diagnosis. A total of 24 images are recorded which is very important in scoring (quantitative assessment) and follow-up, but the average of the three readings for each nail is recorded in the table for the final report.
How to read NFC: 1. Transparency 2. Density 3. Dimension 4. Morphology 5. Hemorrhage 6. Angiogenesis 7. Venous plexus 8. Flow
Reporting: 1. Relevant patient’s data (reason for referral, occupation, patient’s habits e.g. smoking, comorbidities, medications, rheumatologic diagnosis, antibody positivity) 2. Description of patient preparation before NVC 3. Details of device description (make and model of the NFC, use of oil, PC software for image analysis, the use of automated grid.) 4. Description of examination: 5. Details of experience or qualifications of personnel responsible for image acquisition and interpretation should be reported 6. In case of more than one examiner, training for each examiner should be specified 7. The number of fingers examined should be reported 8. Which fingers have been examined 9. Each finger should be analyzed separately and reported separately or together 10. Reasons for finger exclusion should be reported 11. Number of images collected at each nailfold should be reported 12. Details of image quality (and missing data) should be reported 13. Details of global condition of the hands (e.g. flexion contractures) should be reported 14. Details on image reading (e.g. blind reading) should be reported (if part of a research study) 15. Report the overall pattern (i.e. normal: stereotype normal and non-specific abnormalities vs abnormal: scleroderma patterns)9 16. Report the validated scleroderma patterns (i.e. early, active, late or scleroderma-like)12 How to interpret results Based on the abnormalities, results are reported in three main categories: 1. Normal capillaroscopy. When all five groups of findings are negative except for some degree of tortuosity, the term of “normal capillaroscopic findings” is applied. Tortuosity is relatively frequent in healthy subjects following microtrauma to the nailfold. 2. Nonspecific morphological abnormalities: The presence of one abnormal finding, except severe capillary density loss. 3. scleroderma pattern The existence of more than one abnormal finding in NFC is named “scleroderma pattern” or “SSD.”
Statement Level of Mean±SD Percent of Level of evidence agreement agreement
Microvascular alterations detected by NFC in patients with ssc were reclassified into three different subgroups: Early: 1. Very mild architectural derangement 2. No changes in capillary density 3. Slightly enlarged loops and giant capillaries 4. Rare occurrence of microhemorrhage 5. Angiogenesis Active: 1. Mild architectural derangement 2. Moderate changes in capillary density 3. Moderately enlarged loops and giant capillaries 4. Moderate to severe microhemorrhages 5. Moderate angiogenesis Late: 1. Severe architectural derangement 2. Severe changes in capillary density 3. Enlarged loops or giant capillaries 4. Microhemorrhage 5. Angiogenesis
Recommendations/suggestions and images	3
NFC: Nailfold capillaroscopy; RP: Raynaud’s phenomenon; SSc: Systemic sclerosis; PAH: Pulmonary artery hypertension; SSD: Scleroderma spectrum disorder; ILD: Interstitial lung disease; PC: Personal computer.