Peripheral manifestations are major determinants of disease phenotype and outcome in new onset spondyloarthritis.

OBJECTIVES: To delineate the impact of peripheral musculoskeletal manifestations on stratification of disease phenotype and outcome in new-onset spondyloarthritis (SpA), using a prospective observational nationwide inception cohort, the BelGian Inflammatory Arthritis and spoNdylitis cohorT (Be-Giant). METHODS: Newly diagnosed adult SpA patients, fulfilling the Assessment of SpondyloArthritis International Society (ASAS) criteria for axial or peripheral SpA, were included in Be-Giant and prospectively followed every six months. Peripheral involvement (defined as arthritis, enthesitis and/or dactylitis) was determined in relation to clinically similar patient subsets at baseline and disease activity patterns during two-year follow-up, identified through K-means cluster analysis and latent class growth analysis. RESULTS: From November 2010 to March 2020, 367 patients were enrolled in Be-Giant, of whom 162 (44%) had peripheral manifestations. Two patient clusters [A, axial predominant (n = 248) and B, peripheral predominant (n = 119)] were identified at diagnosis. Longitudinal analysis (n = 115) revealed two trajectories of disease activity in each cluster: one with persistently high disease activity over time ('High'), the other rapidly evolving to low disease activity ('Low'). In cluster A patients, peripheral manifestations predisposed to the 'High' trajectory [odds ratio (OR) = 2.0, 95% CI: 1.3, 3.1, P = 0.001], despite more rapid initiation of biologics compared with patients without peripheral manifestations (hazard ratio (HR) = 2.1, 95% CI: 1.0, 4.4, P = 0.04 - Cox proportional-hazards model). CONCLUSION: Peripheral musculoskeletal manifestations are major determinants of phenotypical diversity in new-onset SpA. Intriguingly, stratification of axial SpA according to concomitant peripheral involvement identified an endotype with an unfavorable outcome despite more prompt therapeutic intensification with biologics. These observations justify an endotype-tailored approach beyond current ASAS/EULAR management recommendations.

A prospective, longitudinal study evaluating the baseline six-minute walk test as an individual reference value in systemic sclerosis patients.

OBJECTIVES: Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are the leading causes of death in systemic sclerosis (SSc). Although the six-minute walk test (6MWT) is used for evaluating ILD and PAH, no data are available on the evolution of the six-minute walk distance (6MWD) in SSc patients without ILD and PAH and whether the baseline 6MWD could serve as individual reference value for the management of those who will develop PAH or ILD. METHODS: Prospectively collected data of the first 6MWT (at baseline or 6-month follow-up) and the 6MWTs at 18-, 30-, 42-, 54-, and 66-month visit of 165 consecutive SSc patients without ILD and PAH, included in the Ghent University SSc Cohort between May 2006 and December 2016 were analysed. RESULTS: 96-100% of the included patients performed a 6MWT during the follow-up visits. The mean 6MWD during the baseline 6MWT of 165 SSc patients without ILD and PAH (35% limited, 56% limited cutaneous, 9% diffuse cutaneous SSc) was 484.20+/-92.65m with no significant difference in the 6MWD at different follow-up visits as compared to baseline. In 46 SSc patients without ILD and PAH who performed a 6MWT at baseline and at 66-month visit, the 6MWD walked at 66-month visit correlated with the baseline 6MWD (r=0.564, p<0.001). CONCLUSIONS: In SSc without ILD and PAH, the 6MWT is feasible and the 6MWD is clinically stable over a 66 months period. Hence, the individual 6MWD might be used as individual reference value in management of those who will develop PAH or ILD.

Screening for pulmonary arterial hypertension in an unselected prospective systemic sclerosis cohort.

Screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) improves outcomes. The DETECT screening algorithm is recommended in a high-risk SSc subgroup. This study aims to compare prospectively the positive predictive value of screening using the DETECT algorithm and the 2009 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines, and to compare their cost-effectiveness in an unselected, day-to-day SSc population. Post hoc, screening according to the 2015 ESC/ERS guidelines using echocardiographic parameters alone ("2015 echo screening") or combined with the DETECT algorithm ("2015 combined screening") in high-risk subjects was analysed.195 consecutive SSc patients included in the Ghent University Hospital SSc cohort were screened using different algorithms.The referral rate for right heart catheterisation was 32% (63 out of 195 patients) (46/4/13/34/40 patients using the DETECT algorithm/2009 guidelines/both/2015 echo screening/2015 combined screening). Right heart catheterisation was performed in 53 patients (84%) (36 (78%)/four (100%)/13 (100%)/28 (82%)/32 (80%) patients recommended by the DETECT algorithm/2009 guidelines/both/2015 echo screening/2015 combined screening). PAH was diagnosed in three patients (incidence 1.5%·year-1, 95% CI 0.5-4.4), in whom all algorithms recommended a right heart catheterisation. The positive predictive value was 6% (95% CI 2-17%; three out of 49 patients) for the DETECT algorithm, 18% (95% CI 6-41%; three out of 17 patients) for the 2009 guidelines, 23% (95% CI 8-50%; three out of 13 patients) for both, 11% (95% CI 4-27%; three out of 28 patients) for the 2015 echo screening and 9% (95% CI 3-24%; three out of 32 patients) for the 2015 combined screening. The cost was EUR224/80/90/112 per patient using the DETECT algorithm/2009 guidelines/2015 echo screening/2015 combined screening.Echocardiography may remain a candidate first step for PAH screening in SSc.

Six-minute walk test in or out in evaluation of systemic sclerosis patients?

OBJECTIVES: Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are the leading causes of death in systemic sclerosis (SSc) patients. Although the six-minute walk test (6MWT) is used for evaluating ILD and PAH in clinical practice, no data are available on six-minute walk distance (6MWD) and oxygen desaturation in SSc patients without ILD and PAH. METHODS: Prospectively collected data of the 6MWTs at baseline and 6-month follow-up of 300 consecutive SSc patients, included in the Ghent University Hospital Systemic Sclerosis Unit between May 2006 and April 2015 were analysed. RESULTS: The mean 6MWD of 165 SSc patients without ILD and PAH who performed a 6MWT at baseline or at the 6-month visit was 484±93m. Patients in the diffuse cutaneous (DcSSc) subgroup (435±94m) walked less than in the limited (LSSc) subgroup (499±91m, p=0.04) and tended to walk less than in the limited cutaneous (LcSSc) subgroup (483±92m, p=0.15). In 115 SSc patients without ILD and PAH who walked at both moments, there was no significant difference between the 6MWDs (mean difference -7.60m 95%CI [-19.93m; 4.73m], p=0.23) and the oxygen desaturation was not statistically different in 102 of them (mean difference 0.41% 95%CI [-0.49%; 1.31%], p=0.37). CONCLUSIONS: In SSc without ILD and PAH, the 6MWD and oxygen desaturation is clinically stable over a 6 months period. The DcSSc subgroup walks less than the LSSc and the LcSSc subgroup.

Nailfold Capillaroscopy and Clinical Applications in Systemic Sclerosis.

Capillary microscopy is a safe and non-invasive tool to evaluate the morphology of the microcirculation typically affected in SSc. Next to being paramount for the "(very) early" diagnosis of SSc eyes are also geared toward capillaroscopy with the aim to be able to use it as a biomarker, especially in the prediction of future occurrence of DU. The following review will explain what capillary microscopy is and will focus additionally on studies evaluating the association between capillaroscopy and DU.

Determinants of the prevalence of gout in the general population: a systematic review and meta-regression.

Studies on the occurrence of gout show a large range in estimates. However, a clear insight into the factors responsible for this variation in estimates is lacking. Therefore, our aim was to review the literature on the prevalence and incidence of gout systematically and to obtain insight into the degree of and factors contributing to the heterogeneity. We searched MEDLINE, EMBASE, and Web of Science (January 1962 to July 2012) to identify primary studies on the prevalence and incidence of gout in the general population. Data were extracted by two persons on sources of clinical heterogeneity, methodological heterogeneity, and variation in outcome reporting. Meta-analysis and meta-regression analysis were performed for the prevalence of gout. Of 1,466 articles screened, 77 articles were included, of which 71 reported the prevalence and 12 the incidence of gout. The pooled prevalence (67 studies; N = 12,226,425) based on a random effects model was 0.6% (95% CI 0.4; 0.7), however there was a high level of heterogeneity (I(2) = 99.9%). Results from a mixed-effects meta-regression model indicated that age (p = 0.019), sex (p < 0.001), continent (p < 0.001), response rate (p = 0.016), consistency in data collection (p = 0.002), and case definition (p < 0.001) were significantly associated with gout prevalence and jointly accounted for 88.7% of the heterogeneity. The incidence in the total population ranged from 0.06 to 2.68 per 1,000 person-years. In conclusion, gout is a common disease and the large variation in the prevalence data on gout is explained by sex, continent on which the study was performed, and the case definition of gout.

Flemish network on rare connective tissue diseases (CTD): patient pathways in systemic sclerosis. First steps taken.

Despite the low prevalence of each rare disease, the total burden is high. Patients with rare diseases encounter numerous barriers, including delayed diagnosis and limited access to high-quality treatments. In order to tackle these challenges, the European Commission launched the European Reference Networks (ERNs), cross-border networks of healthcare providers and patients representatives. In parallel, the aims and structure of these ERNs were translated at the federal and regional levels, resulting in the creation of the Flemish Network of Rare Diseases. In line with the mission of the ERNs and to ensure equal access to care, we describe as first patient pathways for systemic sclerosis (SSc), as a pilot model for other rare connective and musculoskeletal diseases. Consensus was reached on following key messages: 1. Patients with SSc should have multidisciplinary clinical and investigational evaluations in a tertiary reference expert centre at baseline, and subsequently every three to 5 years. Intermediately, a yearly clinical evaluation should be provided in the reference centre, whilst SSc technical evaluations are permissionably executed in a centre that follows SSc-specific clinical practice guidelines. In between, monitoring can take place in secondary care units, under the condition that qualitative examinations and care including interactive multidisciplinary consultations can be provided. 2. Patients with early diffuse cutaneous SSc, (progressive) interstitial lung disease and/or pulmonary arterial hypertension should undergo regular evaluations in specialised tertiary care reference institutions. 3. Monitoring of patients with progressive interstitial lung disease and/or pulmonary (arterial) hypertension will be done in agreement with experts of ERN LUNG.

Nailfold Video Capillaroscopy in Pregnant Women With and Without Cardiovascular Risk Factors.

Objective: To evaluate microvasculature in pregnant women with and without cardiovascular risk factors. Design: Cross-sectional, observational study. Population: Women were recruited at the outpatient clinic for high risk prenatal care. Out of a total of 345 women assessed at first and/or second and/or third trimester, 169 women without and 176 with cardiovascular risk factors were included. Methods: Nailfold video capillaroscopy (NVC) measurements were performed at magnification of 200x at all fingers except thumbs. Images were stored for offline measurement of capillary density (CDe) and capillary diameters (CDi). Maternal anthropometrics, obstetric, and medical history were used for categorization in low and high cardiovascular risk. Comparison between groups and trimesters, with respect to pregnancy outcome, was performed using linear mixed model analysis. Results: Women with a high risk cardiovascular profile show higher CDe, regardless of pregnancy outcome. CDi drops during pregnancy, with lowest CDi in third trimester in patients with preeclampsia. Capillary bed (CB), as a composite of CDe and CDi, is stable during pregnancy in women with low risk cardiovascular profile. In women with high risk cardiovascular profile, CB drops from the first to the second trimester, regardless of pregnancy outcome. Only in women with pre-eclampsia, the CB is lower in the third trimester as compared to the first trimester.There is an inverse association between CDe and mean arterial pressure (MAP) in women with high cardiovascular risk and pre-eclampsia. Conclusion: Microcirculation is altered during the course of pregnancy and microcirculatory behavior is different in patients with low and high cardiovascular risk profile, as well as in patients with preeclampsia.

Corrigendum: Nailfold video capillaroscopy in pregnant women with and without cardiovascular risk factors.

[This corrects the article DOI: 10.3389/fmed.2022.904373.].

Laboratory evaluation of anti-dsDNA antibodies.

Antibodies to dsDNA are an important laboratory parameter for diagnosis, monitoring and classification of systemic lupus erythematosus (SLE). In clinical laboratories, several techniques are used to detect and quantify anti-dsDNA antibodies. Each technique has its advantages and disadvantages regarding sensitivity, specificity, avidity and assay procedure. Assays differ with respect to the antigen source (native versus synthetic versus molecular biological) used and the way the antigen is presented (e.g. in solution, covalently linked to a solid phase,…). Consequently, correlation between assays can be poor and standardization of anti-dsDNA antibody tests is challenging. We here provide an overview of the currently available anti-dsDNA tests frequently used in clinical laboratories [Crithidia luciliae immunofluorescence test (CLIFT), Enzyme linked immune sorbent assay (ELISA), fluoroenzyme immunoassay (FEIA), chemiluminisence immunoassay (CIA), multiplexed bead-based assays and Farr-RIA] and their performance characteristics. From this literature study, we concluded that performance characteristics differ between assays. Often, a combination of techniques is necessary for the best result interpretation.

Diagnostic and predictive value of acute-phase reactants in adult undifferentiated peripheral inflammatory arthritis: a systematic review.

OBJECTIVE: To review the available literature on the diagnostic and predictive value of acute-phase reactants in adult undifferentiated peripheral inflammatory arthritis (UPIA) as an evidence base for generating multinational clinical practice recommendations in the 3e Initiative in Rheumatology. METHODS: A systematic literature search was carried out using Medline, Embase, the Cochrane Library, and abstracts presented at the 2007 and 2008 meetings of the American College of Rheumatology and European League Against Rheumatism, searching for prognostic and diagnostic markers of acute-phase reactants in adult UPIA. Articles that fulfilled predefined inclusion criteria were systematically reviewed, and the quality was appraised. Likelihood ratios (LR), sensitivity, and specificity for diagnostic and prognostic outcomes were calculated. RESULTS: A total of 18 publications out of 3699 identified references were included in the review. Only a small number of studies with significant heterogeneity, including different outcome measures and different cutoff values, were eligible for review, so pooling data was not possible. Overall, LR showed poor diagnostic and prognostic performance for most investigated acute-phase reactants. Available data showed some value for erythrocyte sedimentation rate in establishing a diagnosis in patients with undifferentiated arthritis; some prognostic and diagnostic value for C-reactive protein; some prognostic value for plasma viscosity in predicting persistence of arthritis; and some diagnostic value for sulfhydryl levels and matrix metalloproteinase-3 in establishing a diagnosis of rheumatoid arthritis. CONCLUSION: There is little published evidence concerning the diagnostic and predictive value of acute-phase reactants in patients with UPIA. Studies were heterogeneous, and "undifferentiated arthritis" was not well defined or was equivocally defined. The role of acute-phase reactants in diagnosing and predicting outcome in patients presenting with undifferentiated arthritis is limited.

Diagnostic and prognostic value of synovial biopsy in adult undifferentiated peripheral inflammatory arthritis: a systematic review.

OBJECTIVE: Our aim was to systematically review the literature on the diagnostic and prognostic value of synovial biopsy in undifferentiated peripheral inflammatory arthritis (UPIA) as an evidence base for generating clinical practice recommendations. The results lead to multinational recommendations in the 3e Initiative in Rheumatology. METHODS: We performed a systematic literature review according to the PICO strategy (Patients, Intervention, Comparator, and Outcome). Using a designed search strategy we ran literature searches using Medline, Embase, the Cochrane Library, and abstracts presented at the 2007 and 2008 meetings of the American College of Rheumatology and European League Against Rheumatism. Articles fulfilling predefined inclusion criteria were reviewed, and quality appraisal was performed. RESULTS: Six publications from a total of 3265 diagnostic and 3271 prognostic studies were included, of which 2 were review articles. Data pooling was impossible because of significant clinical and statistical heterogeneity. Three themes of outcome were identified: anti-citrullinated peptide antibody (ACPA) staining in synovium, immunohistochemistry (CD22, CD38, CD68), and vascular patterns. Prognostic and diagnostic value was poor for these themes, although diagnostic trends favoring a particular diagnosis were identified. In contrast to serological ACPA testing, ACPA staining was shown not to be specific for diagnosis of rheumatoid arthritis (RA). Synovial CD22 and CD38 positivity seem to differentiate between RA and non-RA, while synovial CD38 and CD68 positivity can differentiate among RA, spondyloarthritis (SpA), and other diagnoses. Vascular patterns in undifferentiated arthritis are insufficiently specific to differentiate between SpA and RA. CONCLUSION: There is sparse evidence that synovial biopsy has diagnostic or prognostic value in patients with UPIA in clinical care. We urgently need systematic studies investigating the diagnostic and prognostic potential of synovial markers. A clear, broadly accepted, and unequivocal definition of undifferentiated arthritis is required as a starting point.

Algorithm for identification of undifferentiated peripheral inflammatory arthritis: a multinational collaboration through the 3e initiative.

OBJECTIVE: To develop an algorithm for identification of undifferentiated peripheral inflammatory arthritis (UPIA). METHODS: An algorithm for identification of UPIA was developed by consensus during a roundtable meeting with an expert panel. It was informed by systematic reviews of the literature used to generate 10 recommendations for the investigation and followup of UPIA through the 3e initiative. The final recommendations from the 3e UPIA Initiative were made available to the panel to guide development of the algorithm. The algorithm drew on the clinical experience of the consensus panel and evidence from the literature where available. RESULTS: In patients presenting with joint swelling a thorough evaluation is required prior to diagnosing UPIA. After excluding trauma, the differential diagnosis should be formulated based on history and physical examination. A minimum set of investigations is suggested for all patients, with additional ones dependent on the most probable differential diagnoses. The diagnosis of UPIA can be made if, following these evaluations, a more specific diagnosis is not reached. Once a diagnosis of UPIA is established, patients should be closely followed as they may progress to a specific diagnosis, remit, or persist as UPIA, and additional investigations may be required over time. CONCLUSION: Our algorithm presents a diagnostic approach to identifying UPIA in patients presenting with joint swelling, incorporating the dynamic nature of the condition with the potential to evolve over time.

Fever and an abnormal chest X-ray during the COVID-19 pandemic.

During the COVID-19 pandemic, a 56-year-old man presented at our emergency department with fever and shortness of breath; Diffuse pulmonary nodular vascular spread lesions were found. Detailed history taking showed a four-week history of fever and night sweats. The man had been under treatment for 2 years with Adalimumab, a tumor-necrosis-factor (TNF) inhibitor, for ulcerative colitis. Before start, screening by tuberculin skin test was negative. Cultures en PCR on BAL and urine were positive for mycobacterium tuberculosis also ocular findings were present. The diagnosis of military tuberculosis was made.

Nailfold capillaroscopy in systemic lupus erythematosus: A systematic review and critical appraisal.

Nailfold capillaroscopy is an easy, non-invasive technique to assess microvascular involvement in rheumatic diseases. Multiple studies describe capillaroscopic changes in systemic lupus erythematosus (SLE), including a wide range of non-specific findings. On behalf of the European League Against Rheumatism (EULAR) study group on microcirculation in rheumatic diseases, a systematic review was done to obtain all original research studies (in English) in which SLE patients had capillaroscopy. Forty such studies are identified. This article firstly provides a résumé of the results of these studies according to capillaroscopic parameters (density, dimensions, morphology, haemorrhages), semi-quantitative assessment and qualitative assessment of capillaroscopy in SLE patients. Secondly, the correlations between capillaroscopic parameters in SLE patients and clinical and laboratory parameters (including auto-immune parameters) are outlined. The following capillaroscopic parameters are found to be significantly more prevalent in SLE patients compared to healthy controls: tortuous capillaries, abnormal morphology and haemorrhages. Hairpin-shaped capillaries are significantly less prevalent than in healthy persons. The semi-quantitatively determined nailfold capillaroscopic score (NFC score) in SLE patients is also higher than in healthy controls. Several correlations between clinical and laboratory parameters and capillaroscopic parameters are identified in the review. Disease activity is correlated with NFC score in seven studies, with abnormal morphology (i.e. "meandering") in one study and with haemorrhages in one study. Frequent attacks of Raynaud's phenomenon (RP) and gangrene are significantly correlated with dilated capillaries. In two studies a possible correlation between anti-SSA antibodies and lower density of capillaries is withheld. About other immune parameters conflicting results are found. In one study a significant negative correlation is found between 24-hour proteinuria and abnormal morphology (i.e. "meandering"). For the first time, an overview of the nailfold capillaroscopic changes that have been described in SLE and their correlations with clinical and laboratory findings is given. Further large-scale research on the identification of capillaroscopic changes in SLE and their correlations with standardised clinical and laboratory parameters, is ongoing at the EULAR study group on microcirculation in rheumatic diseases.

Association of Inflammatory Bowel Disease and Acute Anterior Uveitis, but Not Psoriasis, With Disease Duration in Patients With Axial Spondyloarthritis: Results From Two Belgian Nationwide Axial Spondyloarthritis Cohorts.

OBJECTIVE: To determine the link between extraarticular manifestations (EAMs) and baseline characteristics in patients with axial spondyloarthritis (SpA), and to define their potentially differential prognostic value in 2 large, independent Belgian axial SpA cohorts with distinct recruitment periods. METHODS: Information on demographic and clinical characteristics and extraarticular manifestations (EAMs) was obtained from patients with axial SpA originating from the (Be)Giant (Belgian Inflammatory Arthritis and Spondylitis) cohort, which includes consecutive axial SpA patients whose data have been collected since 2010, and from the ASPECT (Ankylosing Spondylitis Patients Epidemiological Cross-sectional Trial) cohort, a Belgian registry of cross-sectional data collected between February 2004 and February 2005 from consecutive patients with ankylosing spondylitis (AS) or probable AS. RESULTS: Among the 1,250 Belgian patients studied, disease duration was associated with risk of developing inflammatory bowel disease (IBD), with an increase in risk by 20% per 10 years of disease duration (relative risk [RR] 1.2, P = 0.026), and associated with risk of developing acute anterior uveitis, with an increase in risk by 30% per 10 years of disease duration (RR 1.3, P < 0.001). In the subgroup of 171 newly diagnosed patients with prospective follow-up data, higher mean C-reactive protein levels over time were demonstrated in those with acute anterior uveitis or IBD compared to those without EAMs or those with psoriasis alone (each P = 0.01). CONCLUSION: The risk of developing acute anterior uveitis or IBD, but not psoriasis, in patients with axial SpA seems to increase with disease duration and appears to be linked to a higher cumulative exposure to inflammation, thus providing a possible explanation for the differential structural progression observed in those with axial SpA.

Two years follow-up of an open-label pilot study of treatment with rituximab in patients with early diffuse cutaneous systemic sclerosis.

OBJECTIVES: Following results in open-label studies of rituximab in patients with systemic sclerosis, a Belgian three-centre initiative was launched to explore safety and efficacy of rituximab in early, diffuse cutaneous systemic sclerosis (dcSSc). METHODS: Open-label study of 17 patients with early dcSSc, treated with two courses of rituximab, at month 0 and 6. Clinical examination, lung function testing, echocardiography, disease activity score (DAS) and functional status were performed at baseline and over 24 months of follow-up. RESULTS: Modified Rodnan skin score (MRSS) changed significantly over time, with a mean of 25.5 (standard deviation [SD] 6.0) at baseline to 12.6 (SD 5.1) at month 24 (Mixed Model Analysis [MMA] p < 0.0001), which is a decrease of 51% at month 24 vs. baseline. DAS showed significant decrease over the total study period, with a score of 4.1 (SD 1.7) at baseline to 1.5 (SD 1.8) at month 24 (MMA p < 0.0001). Additionally, this was significant at all time points vs. baseline, both for MRSS and DAS. Internal organ status remained clinically stable throughout the study period. No statistically significant differences compared to baseline were found at the follow-up time points. Seven serious adverse events took place, all except for one, considered unrelated to study medication. CONCLUSIONS: This is the first multicentre Belgian collaboration investigating potential efficacy of rituximab in early dcSSc. Rituximab appears to be safe and tolerable and it may have beneficial effects on skin involvement, on overall disease activity and on stabilization of internal organ status in early dcSSc.

Capillaroscopy in pregnancy.

INTRODUCTION: In pregnancy, the circulatory system undergoes profound adaptation to meet the requirements in blood supply for the mother and the foetus. With the development of new techniques, research of the microcirculatory changes becomes available. This expert review gives an overview of the current evidence in the field of capillaroscopy. The aim of this review is to summarize the available techniques in the assessment of the microcirculation during pregnancy. Areas covered: A literature search was done, using the strategy: (microcirculation OR capillary OR capillaries OR capillaroscopy) AND pregnancy AND (density OR diameter OR count OR number). All articles were screened and all English articles were considered, when containing information regarding imaging of capillaries. Only structural parameters were considered, functional parameters (e.g. flow velocity) were not considered. Reference search was undertaken after reading full text articles. Articles from reference search underwent same selection criteria as in the primary search. Expert commentary: With growing insight in microcirculatory changes in hypertensive pregnancy conditions, the field of capillaroscopy will become more important in future. The technique is feasible and easy to use in clinical practice as well as in research setting. The first step, necessary to perform further research in this field in future, is to get consensus in technique to perform capillaroscopy and in methods to quantitatively and qualitatively describe the observed changes in microvasculature.