Nailfold Capillaroscopy in Systemic Diseases: Short Overview for Internal Medicine

Abstract Nailfold capillaroscopy (NFC) is now one of the main imaging tools in systemic sclerosis and imposed over time as an easy, non-invasive method for the nailfold microvascular bed assessment. In qualitative NFC normal pattern is characterized by homogeneous, parallel fashion arrangement of the last capillaries row as well as by capillaries with hairpin or non-specific variations like tortuous and/ or crossing shape. Nailfold capillaroscopy is strongly recommended for evaluation of all patients with Raynaud phenomenon. Appearance of giant capillaries is chronologically the first finding relevant for scleroderma spectrum disorders development (systemic sclerosis, dermatomyositis, undifferentiated and mixed connective tissue disease). Collapses of the giant loops generate microhemorrhages and further capillary loss with subsequent hypoxia, and neoangiogenesis seen as ramified/ bushy capillaries. Nailfold capillaroscopy is indicated especially in systemic sclerosis, being also included in the classification criteria. Based on these major NFC pathologic findings (giant capillaries, microhemorrhages, avascularity and neoangiogenesis), three evolutive stages were described in systemic sclerosis, namely the early, active, and late scleroderma pattern. In other connective tissue diseases than those scleroderma-related, like systemic lupus erythematosus, psoriatic arthritis, or antiphospholipid syndrome, the interest for capillaroscopy is growing, but the attempts of defining specific characteristics failed until now. Besides qualitative NFC, semiquantitative and quantitative capillaroscopic assessments were proposed for more accurate evaluation. Lately, automated systems are under development. There is still need of more studies to sustain the nailfold capillaroscopy validity as diagnostic and prognostic test.

Download Full-text

Antifibrillarin autoantibodies present in systemic sclerosis and other connective tissue diseases interact with similar epitopes.

Journal of Experimental Medicine ◽

10.1084/jem.181.3.1027 ◽

1995 ◽

Vol 181 (3) ◽

pp. 1027-1036 ◽

Cited By ~ 32

Author(s):

K N Kasturi ◽

A Hatakeyama ◽

H Spiera ◽

C A Bona

Keyword(s):

Systemic Sclerosis ◽

Connective Tissue ◽

Lupus Erythematosus ◽

Competitive Inhibition ◽

Molecular Mimicry ◽

Connective Tissue Diseases ◽

Nuclear Antigen ◽

Barr Virus ◽

Recombinant Fusion Proteins ◽

Epstein Barr

Autoantibodies specific against fibrillarin, a 34-kD nucleolar protein associated with U3-snRNP, are present in patients with systemic sclerosis (SSc). To understand the mechanisms involved in the induction of these autoantibodies, we prepared a series of human fibrillarin recombinant proteins covering the entire molecule and analyzed their interaction with the autoantibodies present in various connective tissue diseases. Our results showed that antifibrillarin autoantibodies are present not only in SSc, as previously reported, but also in a variety of other connective tissue diseases. Patients with SSc (58%), mixed connective tissue diseases (60%), CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dismotility, sclerodactyly, and telangiectasia syndrome) (58%), systemic lupus erythematosus (39%), rheumatoid arthritis (60%), and Sjogern's syndrome (84%) showed presence of antifibrillarin autoantibodies. Results obtained from competitive inhibition radioimmunoassay and Western blot analyses with purified recombinant fusion proteins revealed that these autoantibodies react primarily with epitope(s) present in the NH2- (AA 1-80) and COOH-terminal (AA 276-321) domains of fibrillarin. Autoantibodies reacting with internal regions of fibrillarin are less frequent. Analysis of the hydrophilicity profiles of reactive peptides showed presence of three potential antigenic sites in the NH2- and two in the COOH-terminal regions. While a hexapeptide sequence NH2 terminus of fibrillarin is shared with an Epstein-Barr virus-encoded nuclear antigen, the COOH-terminal region shares sequence homology with P40, the capsid protein encoded by herpes virus type 1. Interestingly, these two regions of fibrillarin also contain the most immunodominant sequences, as predicted by surface probability and the Jameson and Wolf antigenic index. These observations suggest that molecular mimicry might play an important role in the induction of antifibrillarin autoantibodies.

Download Full-text

Ulnar artery vasculopathy: a common but nonspecific feature of systemic sclerosis

Journal of Scleroderma and Related Disorders ◽

10.5301/jsrd.5000257 ◽

2017 ◽

Vol 2 (3) ◽

pp. 221-224

Author(s):

Tae-Jong Kim ◽

Soon-Young Song ◽

Hee Chang Ahn ◽

Yoon-Kyoung Sung ◽

Sang-Cheol Bae ◽

...

Keyword(s):

Systemic Sclerosis ◽

Connective Tissue ◽

Lupus Erythematosus ◽

Connective Tissue Diseases ◽

Case Series ◽

Ulnar Artery ◽

Common Finding ◽

Clinical Factors ◽

Vessel Disease ◽

Large Vessel Disease

Introduction Systemic sclerosis (SSc) is characterized by microvascular abnormalities and fibrosis. Several studies have reported that large vessel disease is also common in SSc. The aim of this case series was to investigate whether ulnar artery involvement in patients with SSc is a disease-specific phenomenon, as compared to other connective tissue diseases (CTD). Methods A total of 28 patients, including 7 with SSc and 12 with systemic lupus erythematosus (SLE), underwent brachial arteriography due to severe Raynaud's phenomenon and/or digital ulcerations and were enrolled in the study. They were divided into two groups: an SSc/SSc-overlap group and a non-SSc group. The collection of the clinical parameters was conducted to investigate the associations between clinical factors and the ulnar artery vasculopathy. Results The SSc/SSc-overlap group (n = 10) consisted of 7 patients with SSc and 3 with features overlapping SSc. In the non-SSc group (n = 18), 12 cases of SLE, 2 of mixed connective tissue disease, 1 of dermatomyositis + SLE, 1 of rheumatoid arthritis, 1 of Sjogren's syndrome, and 1 case of skin vasculitis, were included. The relative frequencies of ulnar artery involvement were not significantly different between the SSc/SSc-overlap and non-SSc groups, respectively (n = 6, 60% vs. n = 9, 50%, p = 0.611). Conclusions Although ulnar artery involvement was frequently detected in patients with SSc/SSc-overlap, it was also a common finding in other CTDs; therefore, it is not specific to SSc or SSc-overlap diseases.

Download Full-text

Nailfold Capillaroscopy in Rheumatic Diseases

Vascular Biology - Selection of Mechanisms and Clinical Applications ◽

10.5772/intechopen.92786 ◽

2020 ◽

Author(s):

Abhishek Patil ◽

Isha Sood

Keyword(s):

Systemic Sclerosis ◽

Connective Tissue ◽

Early Diagnosis ◽

Rheumatic Diseases ◽

Connective Tissue Diseases ◽

Nailfold Capillaroscopy ◽

Indispensable Tool

Nailfold capillaroscopy (NFC) has developed into an indispensable tool for rheumatologists in the evaluation of rheumatic diseases. It offers various advantages in being rapid, noninvasive, and inexpensive. With NFC we are able to visualize the microcirculatory changes in the nail beds. These changes are key to the pathogenesis of connective tissue diseases such as systemic sclerosis. Hence NFC helps in early diagnosis of various connective tissue diseases. There is a lack of standardization in the techniques used and various capillary parameters studied, which could lead to variation in the reporting of the parameters studied. In this chapter we shall try to highlight the most common parameters studied in capillaroscopy and its utility in various connective tissue diseases.

Download Full-text

The Microbiome in Connective Tissue Diseases and Vasculitides: An Updated Narrative Review

Journal of Immunology Research ◽

10.1155/2017/6836498 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 12

Author(s):

Rossella Talotta ◽

Fabiola Atzeni ◽

Maria Chiara Ditto ◽

Maria Chiara Gerardi ◽

Piercarlo Sarzi-Puttini

Keyword(s):

Systemic Lupus Erythematosus ◽

Systemic Sclerosis ◽

Connective Tissue ◽

Lupus Erythematosus ◽

Connective Tissue Diseases ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Narrative Review ◽

Systemic Lupus ◽

Sjögren‘S Syndrome

Objective. To provide a narrative review of the most recent data concerning the involvement of the microbiome in the pathogenesis of connective tissue diseases (CTDs) and vasculitides.Methods. The PubMed database was searched for articles using combinations of words or terms that included systemic lupus erythematosus, systemic sclerosis, autoimmune myositis, Sjögren’s syndrome, undifferentiated and mixed CTD, vasculitis, microbiota, microbiome, and dysbiosis. Papers from the reference lists of the articles and book chapters were reviewed, and relevant publications were identified. Abstracts and articles written in languages other than English were excluded.Results.We found some evidence that dysbiosis participates in the pathogenesis of systemic lupus erythematosus, systemic sclerosis, Sjögren’s syndrome, and Behçet’s disease, but there are still few data concerning the role of dysbiosis in other CTDs or vasculitides.Conclusions.Numerous studies suggest that alterations in human microbiota may be involved in the pathogenesis of inflammatory arthritides as a result of the aberrant activation of the innate and adaptive immune responses. Only a few studies have explored the involvement of dysbiosis in other CTDs or vasculitides, and further research is needed.

Download Full-text

Nailfold capillaroscopy microscopy - an interdisciplinary appraisal

VASA ◽

10.1024/0301-1526/a000553 ◽

2016 ◽

Vol 45 (5) ◽

pp. 353-364 ◽

Cited By ~ 9

Author(s):

Peter Franz Klein-Weigel ◽

Cord Sunderkötter ◽

Oliver Sander

Keyword(s):

Differential Diagnosis ◽

Systemic Sclerosis ◽

Connective Tissue ◽

Critical Appraisal ◽

Connective Tissue Diseases ◽

Diagnostic Value ◽

Nailfold Capillaroscopy ◽

Technical Aspects ◽

Technical Performance ◽

Disease Specific

Abstract. Nailfold capillaroscopy is a method of great diagnostic value in the differential diagnosis of primary versus secondary Raynaud´s phenomenon, of systemic sclerosis versus other so called connective tissue diseases and of additional diagnostic value in other entities. Rheumatologists, dermatologists, and angiologists in Germany have convened in an interdisciplinary working group in which they synergistically combined their expertise to develop a common nomenclature and standards for the technical performance of nailfold capillary microscopy. The article gives an overview of historical and technical aspects of capillaroscopy, morphologic findings, and disease-specific patterns. It also provides a critical appraisal of its significance in the diagnosis and sequelae of these interdisciplinarily-managed diseases including its performance in children and gives an excursion in the potential perspectives of capillaroscopy in less common indications.

Download Full-text

Pyrophosphate Scintigraphy and other Non-Invasive Methods in the Detection of Cardiac Involvement in Some Systemic Connective Tissue Diseases

Nuklearmedizin ◽

10.1055/s-0038-1624357 ◽

1987 ◽

Vol 26 (01) ◽

pp. 28-32 ◽

Cited By ~ 2

Author(s):

P. Bradna ◽

M. Pospíšil ◽

J. Kubíček ◽

J. Vižda ◽

P. Kafka ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Blood Pressure ◽

Connective Tissue ◽

Lupus Erythematosus ◽

Cardiac Involvement ◽

Connective Tissue Diseases ◽

Systemic Lupus ◽

Non Invasive ◽

Bechterew’S Disease ◽

Spondylitis Ankylopoetica

Thirteen patients with systemic lupus erythematosus, 8 patients with polymyositis, and 6 patients with spondylitis ankylopoetica (Bechterew’s disease) underwent clinical cardiologic examination and scintigraphy of the myocardium (99mTc-pyrophosphate), ECG, echocardiography, polygraphy, and their blood pressure was taken. The aim of the study was to ascertain how such a combination of non-invasive examinations can help in recognizing a cardiac involvement. In systemic lupus erythematosus cases one or more positive findings were revealed in 9 patients (69%), in 4 patients all examinations were negative (31 %). Four patients (50%) with polymyositis had positive findings. In patients with spondylitis ankylopoetica positive findings occurred in 2 cases (33%). The study has shown that a combination of non-invasive cardiologic methods increases the probability of detecting cardiac involvement in systemic connective tissue diseases.

Download Full-text

Autoimmune connective tissue diseases

The Foot and Ankle in Rheumatology ◽

10.1093/med/9780198734451.003.0008 ◽

2019 ◽

pp. 119-134

Author(s):

Begonya Alcacer-Pitarch ◽

Edward Vital ◽

Maya Buch

Keyword(s):

Systemic Lupus Erythematosus ◽

Systemic Sclerosis ◽

Connective Tissue ◽

Lupus Erythematosus ◽

Lower Limb ◽

Connective Tissue Diseases ◽

Current Evidence ◽

Systemic Lupus ◽

Pathological Effect ◽

Potential Risks

This chapter will briefly cover the epidemiology and pathophysiology of systemic sclerosis and systemic lupus erythematosus, and, to a larger extent, their pathological effect on the lower limb. It will also discuss current evidence for foot pathology management with reference to potential risks and imaging strategies.

Download Full-text

Nailfold Capillaroscopy With USB Digital Microscopy in Connective Tissue Diseases: A Comparative Study of 245 Patients and Healthy Controls

Frontiers in Medicine ◽

10.3389/fmed.2021.683900 ◽

2021 ◽

Vol 8 ◽

Author(s):

Kumutnart Chanprapaph ◽

Wuttidej Fakprapai ◽

Preeyachat Limtong ◽

Poonkiat Suchonwanit

Keyword(s):

Connective Tissue ◽

Disease Activity ◽

Lupus Erythematosus ◽

Multinomial Logistic Regression ◽

Strong Association ◽

Prognostic Significance ◽

Connective Tissue Diseases ◽

Nailfold Capillaroscopy ◽

Healthy Controls ◽

Digital Microscopy

Background: Nailfold capillaroscopy (NFC) is a valuable tool to detect microcirculation abnormalities in connective tissue diseases (CTDs). However, whether the universal serial bus (USB) digital microscopy used as onychoscopy is as effective as the videocapillaroscopy in determining the diagnostic and prognostic values of CTDs remains to be determined.Objective: This study aims to investigate NFC features of systemic lupus erythematosus (SLE), dermatomyositis (DM), and systemic sclerosis (SSc) patients and compare with normal controls as well as examine which feature could differentiate among CTDs. Furthermore, we aim to explore different capillaroscopic abnormalities and their association with disease activity.Methods: Nailfold images were taken from patients and healthy controls using a USB digital microscopy. Patterns on the capillary morphology, diameter, architecture, and density were recorded and compared. We further determined the NFC findings in SLE, DM, and SSc and corresponded to their respective disease activity scoring system.Results: A total of 245 participants, consisting of 54 SLE, 32 DM, and 51 SSc patients, as well as 108 controls, were enrolled. All capillaroscopic features, except for tortuous capillaries, were significantly more common in CTDs than healthy control (all p < 0.05). A multinomial logistic regression analysis revealed that bushy capillaries had significantly higher odds for both SLE and DM than SSc (OR: 4.10, 95% confidence interval (CI): 1.71–9.81, p = 0.002 and OR: 7.82, 95% CI, 2.86–21.38, p < 0.001, respectively). Elongated capillaries demonstrated significant odds for SLE compared with SSc (OR: 3.35, 95% CI: 1.005–11.20, p = 0.049), while prominent subpapillary plexus showed greater odds for SLE compared with both DM and SSc (OR: 2.75, 95% CI: 1.07–7.02, p = 0.03 and OR: 5.78, 95% CI: 2.29–14.58, p < 0.001, respectively). The presence of hemorrhage, enlarged capillaries, and the low-density index had significantly higher odds in favor of SSc than SLE. Bushy capillaries were the only pattern with a strong association for DM over SSc. The presence of enlarged capillaries indicated higher SLE severity, but no specific finding was related to DM or SSc skin scores.Conclusions: Nailfold capillaroscopic examination using a digital microscope is a valuable method for the diagnosis of SLE, DM, and SSc. Several morphologic patterns can help differentiate among CTDs; however, the prognostic significance of this method requires further investigations.

Download Full-text

Systemic Sclerosis and Other Connective Tissue Diseases

Advances in Pulmonary Hypertension ◽

10.21693/1933-088x-16.2.55 ◽

2017 ◽

Vol 16 (2) ◽

pp. 55-60

Author(s):

Christopher P. Denton

Keyword(s):

Systemic Sclerosis ◽

Connective Tissue ◽

Lupus Erythematosus ◽

Lung Fibrosis ◽

Connective Tissue Diseases ◽

Right Heart Catheterization ◽

World Health ◽

Heart Catheterization ◽

Pulmonary Arterial ◽

Group 1

Pulmonary hypertension (PH) is an important and relatively frequent complication of connective tissue disease (CTD). It is most often seen as a complication of systemic sclerosis and mixed CTD, but is also recognized in systemic lupus erythematosus and other related conditions. Although PH is defined hemodynamically by mean pulmonary arterial pressure (mPAP) of ≥25 mm Hg at right heart catheterization, and may have a variety of mechanisms, it is World Health Organization (WHO) Group 1 pulmonary arterial hypertension (PAH) that has deservedly received the most attention in CTD. The inclusion of cases of precapillary PH without other explanation or concurrent lung fibrosis in WHO Group 1 led to availability of licensed therapies and increased the need for screening and treatment. Approaches are now available that detect PAH, and optimal approaches to therapy are included in expert and evidence-based recommendations. Challenges include borderline elevation of mPAP, comorbidity, and mixed-etiology cases. Overall outcomes have improved, and new clinical trials are being performed that will hopefully build on recent progress to further improve outcomes. Other aspects of PH in CTD to consider include forms related to cardiac disease and lung fibrosis or hypoxia, as these may occur as complications of the underlying CTD. Thromboembolic disease may also occur and represents another important differential diagnosis. Finally, it has been reported that pulmonary veno-occlusive disease may occur, which raises diagnostic and treatment difficulties. Overall, there are major challenges in CTDPH, but also opportunities for effective multispecialty care and early detection and diagnosis of potentially treatable cases of PAH.

Download Full-text

AB0605 CLINICAL PROFILE AND CHEST HIGH-RESOLUTION COMPUTED TOMOGRAPHY (HRCT) FINDINGS IN PATIENTS WITH CONNECTIVE TISSUE DISEASES AND INTERSTITIAL LUNG DISEASE: EXPERIENCE OF A SINGLE REFERENCE RHEUMATOLOGY CENTER

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3758 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1598.2-1599

Author(s):

I. Rusu ◽

L. Muntean ◽

M. M. Tamas ◽

I. Felea ◽

L. Damian ◽

...

Keyword(s):

Computed Tomography ◽

Systemic Sclerosis ◽

High Resolution ◽

Interstitial Lung Disease ◽

Connective Tissue ◽

Lung Disease ◽

Interstitial Pneumonia ◽

Connective Tissue Diseases ◽

High Resolution Computed Tomography ◽

Hrct Patterns

Background:Interstitial lung disease (ILD) is a common manifestation of connective tissue diseases (CTDs), and is associated with significant morbidity and mortality. Chest high-resolution computed tomography (HRCT) play an important role in the diagnosis of ILD and may provide prognostic information.Objectives:We aimed to characterize the clinical profile and chest HRCT abnormalities and patterns of patients diagnosed with CTDs and ILD.Methods:In this retrospective, observational study we included 80 consecutive patients with CTDs and ILD referred to a tertiary rheumatology center between 2015 and 2019. From hospital charts we collected clinical data, immunologic profile, chest HRCT findings. HRCT patterns were defined according to new international recommendations.Results:Out of 80 patients, 64 (80%) were women, with a mean age of 55 years old. The most common CTD associated with ILD was systemic sclerosis (38.8%), followed by polymyositis (22.5%) and rheumatoid arthritis (18.8%). The majority of patients had dyspnea on exertion (71.3%), bibasilar inspiratory crackles were present in 56.3% patients and 10% had clubbing fingers. Antinuclear antibodies (ANA) were present in 78.8% patients, and the most frequently detected autoantibodies against extractable nuclear antigen were anti-Scl 70 (28.8%), followed by anti-SSA (anti-Ro, 17.5%), anti-Ro52 (11.3%) and anti-Jo (7.5%). Intravenous cyclophosphamide therapy for 6-12 months was used in 35% of patients, while 5% of patients were treated with mycophenolate mofetil.The most frequent HRCT abnormalities were reticular abnormalities and ground glass opacity. Non-specific interstitial pneumonia (NSIP) was identified in 46.3% CTDs patients. A pattern suggestive of usual interstitial pneumonia (UIP) was present in 32.5% patients, mainly in patients with systemic sclerosis. In 21.3% patients the HRCT showed reticulo-nodular pattern, micronodules and other abnormalities, not diagnostic for UIP or NSIP pattern.Conclusion:Nonspecific interstitial pneumonia (NSIP) is the most common HRCT pattern associated with CTDs. Further prospective longitudinal studies are needed in order to determine the clinical and prognostic significance of various HRCT patterns encountered in CTD-associated ILD and for better patient management.References:[1]Ohno Y, Koyama H, Yoshikaua T, Seki S. State-of-the-Art Imaging of the Lung for Connective Tissue Disease (CTD). Curr Rheumatol Rep. 2015;17(12):69.[2]Walsh SLF, Devaraj A, Enghelmeyer JI, Kishi K, Silva RS, Patel N, et al. Role of imaging in progressive-fibrosing interstitial lung diseases. Eur Respir Rev. 2018;27(150)Disclosure of Interests:None declared

Download Full-text