Observational Multicenter Case-control Study to Assess Nailfold Capillary Abnormalities in Systemic Lupus Erythematosus

An Observational Multicenter International Case-control Study for the Assessment of Nailfold Capillary Abnormalities in Patients with Systemic Lupus Erythematosus

The purpose of this study is to investigate the role of nailfold capillaroscopy in the assessment of patients with Systemic Lupus Erythematosus (SLE).

Primary endpoint:

- To compare the frequency of major capillaroscopic abnormalities in patients with SLE and healthy controls.

Secondary endpoints:

• To compare the frequency of major capillaroscopic abnormalities in patients with active and non-active SLE / active SLE and healthy controls / non-active SLE and healthy controls.
• To study the association of different capillaroscopic parameters and the status of subjects (SLE / active SLE / non-active SLE / healthy controls).

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Device: nailfold capillaroscopy

Detailed Description

Background and rationale:

Nailfold capillaroscopy (NC) is a diagnostic investigation used in the routine clinical setting for the differential diagnosis of connective tissue diseases, such as Systemic Lupus Erythematosus (SLE). Among SLE clinical manifestations, vascular involvement is a common feature and a variable prevalence of NC abnormalities has been reported in SLE: typical NC changes, as well as non-specific variations as observed in healthy subjects.

At this very moment literature is interspersed with different descriptions of capillaroscopic features in SLE, and it has not been clearly defined the role of NC in SLE patients. It has been suggested that the presence of major capillary abnormalities may reflect the microvascular systemic involvement in SLE, and it may correlate to the disease activity.

Against this background, the EULAR study group on microcirculation in rheumatic diseases planned an international multicenter study.

Objective:

To investigate the role of NC abnormalities in the assessment of SLE patients.

Endpoints:

Primary endpoint:

-To compare the frequency of major capillary abnormalities in patients with SLE and healthy controls.

Secondary endpoints:

• To compare the frequency of major capillary abnormalities in patients with active and non-active SLE / active SLE and healthy controls / non-active SLE and healthy controls.
• To study the association of different capillary parameters and the status of subjects (SLE / active SLE / non-active SLE / healthy controls).

No. of subjects:

Total entered: 364 ; Cases (SLE): 182 ; Controls: 182.

Variables

NC assessment: presence of major capillary abnormalities; NC parameters/mm: number of capillaries, presence of hairpin, tortuous, crossed, bushy, ramified, enlarged, giant capillaries, microhemorrhages, architecture disorganization, visibility of the subpapillary venular plexus; presence of scleroderma patterns, normal patterns.

Clinical assessment: all subjects: date of birth, gender, race. SLE: age at disease onset, disease activity (SLEDAI-2000) and damage index (SLICC-DI), presence of antinuclear antibodies, anti-dsDNA, anti-Extractable Nuclear Antigen antibodies, lupus anticoagulant, anticardiolipin/beta2glycoprotein I antibodies, Raynaud's phenomenon, Hypertension, active smoke, diabetes mellitus, ongoing and cumulative dose steroid treatment, ongoing immunomodulatory/suppressive treatment.

Statistical methods For the primary endpoint and similar secondary endpoints, McNemar test (matching design) and a conditional odds ratio (OR). For other secondary endpoints, the Fisher's exact test and an OR, and a conditional logistic regression model (matching design) and non-conditional regression model and OR as appropriate.

• Study Type: Observational
• Enrollment (Actual): 364

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

patients ≥18 years diagnosed with SLE upon classification according to 2012 SLICC criteria and disease onset ≥16 years.

Description

Inclusion Criteria:

• At time of enrollment all subjects must be 18 years or older and give written consent.
• Patients with SLE must fulfill the 2012 SLICC classification criteria.
• SLE onset must be over 16 years of age.
• Patients with SLE and secondary anti-phospholipid syndrome will be also enrolled.
• Healthy controls will be selected according to the definition proposed in the protocol

Exclusion Criteria:

• Subject refuses to sign and/or he/she is not able to understand the patient informed consent.
• Subjects with periungual traumatic lesions that may create artifacts (i.e. recent manicure, onychophagia, or gardening).
• SLE overlapping with other rheumatic diseases such as Systemic Sclerosis, Rheumatoid Arthritis, Mixed Connective Tissue Disease, Sjögren's Syndrome, Dermatomyositis, Polymyositis

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Systemic Lupus Erythematosus; patients ≥18 years diagnosed SLE upon classification according to 2012 SLICC criteria and disease onset ≥16 years.	Device: nailfold capillaroscopy; Detection by nailfold capillaroscopy of capillary abnormalities in patients with Systemic Lupus Erythematosus and comparison with healthy controls at enrolment
Healthy controls; subjects ≥18 years fulfilling the definition proposed in the protocol.	Device: nailfold capillaroscopy; Detection by nailfold capillaroscopy of capillary abnormalities in patients with Systemic Lupus Erythematosus and comparison with healthy controls at enrolment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
major capillary abnormalities	To compare the frequency of major capillary abnormalities in patients with SLE and healthy controls.	Day 1

Collaborators and Investigators

• Sponsor: ASST Gaetano Pini-CTO
• Collaborators: EULAR study group on microcirculation in rheumatic diseases
• Investigators: Principal Investigator: Francesca Ingegnoli, MD, ASST Gaetano Pini-CTO

Publications and helpful links

General Publications

• Gladman DD, Ibanez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 2002 Feb;29(2):288-91.
• Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin PR, Bruce IN, Isenberg D, Wallace DJ, Nived O, Sturfelt G, Ramsey-Goldman R, Bae SC, Hanly JG, Sanchez-Guerrero J, Clarke A, Aranow C, Manzi S, Urowitz M, Gladman D, Kalunian K, Costner M, Werth VP, Zoma A, Bernatsky S, Ruiz-Irastorza G, Khamashta MA, Jacobsen S, Buyon JP, Maddison P, Dooley MA, van Vollenhoven RF, Ginzler E, Stoll T, Peschken C, Jorizzo JL, Callen JP, Lim SS, Fessler BJ, Inanc M, Kamen DL, Rahman A, Steinsson K, Franks AG Jr, Sigler L, Hameed S, Fang H, Pham N, Brey R, Weisman MH, McGwin G Jr, Magder LS. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012 Aug;64(8):2677-86. doi: 10.1002/art.34473.

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): February 1, 2019

Study Registration Dates

• First Submitted: June 13, 2016
• First Submitted That Met QC Criteria: June 15, 2016
• First Posted (Estimated): June 16, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 18, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Nailfold Capillaroscopy
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: SG_MC/RD4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO