Figures
- FIGURE 1
Nailfold patterns, characteristics and technique. a) Normal nailfold capillaroscopy pattern; b) “scleroderma” pattern with (i) abnormal capillary shape, (ii) avascular area, (iii) giant capillary and (iv) microhaemorrhages; c) capillaroscopy by widefield stereomicroscopy; d) nailfold capillaroscopy by “smartphone-dermatoscope”.
- FIGURE 2
Study flowchart and ILD diagnoses. ILD-MDM: interstitial lung disease multidisciplinary meeting; CTD-ILD: connective tissue disease associated ILD; IIP: idiopathic interstitial pneumonia; IPAF: interstitial pneumonia with autoimmune features; SSc: systemic sclerosis; IIM: idiopathic inflammatory myositis; MCTD: mixed connective tissue disease; RA: rheumatoid arthritis; SLE: systemic lupus erythematosus; PsA: psoriatic arthritis; IPF: idiopathic pulmonary fibrosis; iNSIP: idiopathic nonspecific interstitial pneumonia; iOP: idiopathic organising pneumonia. #: IPAF – “working diagnosis” based on clinical, serological and radiological features as per ILD-MDM discussion. ¶: Undifferentiated CTD = features of autoimmune disease without an identifiable provisional phenotype.
Tables
- TABLE 1
Baseline characteristics and pulmonary physiology
TOTAL CTD-ILD Non-CTD-ILD CTD-ILD versus non-CTD-ILD
p-value#IPAF IIP Subjects n 96 27 27 42 Age years 66.4±10.3 61.5±8.9 64.2±11.1 71.0±8.8 0.003 Female n (%) 43 (44.8) 20 (74.1) 15 (55.6) 8 (19.0) <0.001 Smoking ever n (%) 55 (57.3) 10 (37.0) 16 (59.3) 29 (69.1) 0.021 Caucasian n (%) 79 (82.3) 19 (70.4) 23 (85.2) 37 (88.1) 0.075 Disease duration years 7.4±7.7 11.3±10.6 4.3±3.0 6.9±6.5 0.002 Respiratory symptoms years 5.7±5.4 5.6±4.8 4.3±3.0 6.6±6.7 0.292 Physiology SpO2 % 96.6±2.5 97.9±2.4 96.7±2.3 95.8±2.4 0.003 FVC % 73.9±17.8 77.0±17.7 72.3±18.8 72.8±17.5 0.281 DLCO % 54.8±16.6 60.7±19.8 54.8±16.2 50.9±13.6 0.028 6 MWT distance metres 446.5±126.1+ 463.0±88.6¶ 421.5±138.6ƒ 453.1±137.3## 0.479 6 MWT SpO2 nadir % 90.0±7.1+ 94.3±3.6¶ 90.0±7.9ƒ 87.6±7.2## 0.001 Composite indices CPI 43.1±12.8 38.9±14.2 46.2±10.4 46.2±10.4 0.044 ILD-GAP score 1.9±2.2 0±1.6 1.2±1.5 2.5±1.5 <0.001 Data represented as mean±sd unless otherwise stated. CTD-ILD: connective tissue disease associated ILD; IPAF: interstitial pneumonia with autoimmune features; IIP: idiopathic interstitial pneumonia; SpO2: peripheral oxygen saturation; FVC %: percentage predicted forced vital capacity; DLCO %: percentage predicted diffusing capacity for carbon monoxide; 6MWT: 6-min walk test; CPI: composite physiological index; ILD-GAP ILD: gender–age–physiology index. #: p-value for CTD-ILD versus non-CTD-ILD; ¶: n=22; +: n=82; §: n=60; ƒ: n=24; ##: n=36.
- TABLE 2
Nailfold capillaroscopy characteristics by interstitial lung disease (ILD) group
Total CTD-ILD Non-CTD-ILD CTD-ILD versus non-CTD-ILD p-value IPAF IIP Subjects n 94 26 27 41 Density Number per mm 6.7±1.4 5.6±1.6 6.8±1.1 7.3±0.9 <0.001 Giant capillaries Present n (%) 38 (40.4) 16 (61.5) 12 (44) 10 (24.4) 0.018 Number per patient 2.9±6.3 7.0±1.1 2.8±6.1 0.5±8.9 <0.001 Avascular areas Present n (%) 36 (38.3) 15 (57.7) 12 (44.4) 9 (22.0) 0.031 Number per patient 1.3±2.2 2.7±3.2 1.2±1.6 0.5±1.1 <0.001 Microhaemorrhages Present n (%) 72 (76.6) 24 (92.3) 18 (66.7) 30 (73.2) 0.030 Number per patient 5.8±12.1 4.9±6.7 8.2±18.0 4.9±9.9 0.640 Abnormal capillary shapes Present n (%) 90 (95.7) 26 (100) 24 (88.9) 40 (97.6) 0.573 Mode score 0.7±0.8 1.2±0.8 0.7±0.8 0.4±0.6 <0.001 Data represented as mean±sd unless otherwise stated. CTD-ILD: connective tissue disease associated ILD; IPAF: interstitial pneumonia with autoimmune features; IIP: idiopathic interstitial pneumonia.
- TABLE 3
Univariable logistic regression for connective tissue disease associated interstitial lung disease (CTD-ILD) diagnosis
Unadjusted OR 95% CI p-value AUC Nailfold characteristics Density <6/mm 7.47 2.73–20.43 <0.001# 0.72 Giant ≥3 total 6.77 2.43–18.81 <0.001# 0.70 Avascular ≥2 total 5.44 2.02–14.68 0.001# 0.68 Microhaemorrhages ≥1 total 5.00 1.08–23.18 0.040# 0.61 Baseline characteristics Age 0.94 0.89–0.98 0.005# 0.70 Male 0.18 0.06–0.47 0.001 0.70 Smoking 0.31 0.12–0.79 0.014 0.64 FVC % predicted 1.01 0.99–1.04 0.279 0.59 DLCO % predicted 1.03 1.00–1.06 0.032 0.64 Clinical CTD manifestations Any CTD manifestation¶ 42.18 10.80–164.74 <0.001# 0.86 Serology and radiology ANA ≥1:320 3.80 1.42–10.14 0.008 0.64 Positive ENA 5.38 2.04–14.20 0.001# 0.68 Any myositis autoantibody+ 0.33 0.10–1.05 0.061 0.60 Radiological NSIP, OP or NSIP/OP 7.48 2.33–23.93 0.001# 0.71 Odds ratios (OR) are shown for the bivariate relationship of each variable with CTD-ILD diagnosis. FVC %: percentage predicted forced vital capacity; DLCO %: percentage predicted diffusing capacity for carbon monoxide; ANA: antinuclear antibodies; ENA: extractable nuclear antibodies; NSIP: nonspecific interstitial pneumonia pattern on radiology; OP: organising pneumonia pattern on radiology; #: remains significant adjusted for age, sex, smoking, FVC%, treatment and pulmonary hypertension; ¶: including any of inflammatory arthritis, Raynaud's phenomenon, digital oedema, palmar telangiectasia, digital tip ulceration, mechanic's hands, Gottron's papules/sign, sclerodactyly; +: patients with positive myositis autoantibody and no clinical features of myositis classified as IPAF (non-CTD-ILD).
- TABLE 4
Independent predictors for connective tissue disease (CTD) diagnosis in interstitial lung disease (ILD) identified by exploratory multivariable regression
Predictors# Adjusted OR¶ 95% CI p-value A) Including CTD manifestations
Any CTD manifestation 62.84 13.93–283.40 <0.001 Microhaemorrhages 13.45 2.14–84.32 0.006 B) Excluding CTD manifestations
Positive ENA 11.59 1.80–74.55 0.010 Microhaemorrhages 22.54 1.89–269.05 0.014 Low capillary density 5.66 1.32–24.20 0.019 A) Independent predictors for CTD diagnosis in ILD respective to retained nailfold characteristics, clinical, serological and radiological variables. B) Independent predictors for CTD diagnosis in ILD excluding CTD manifestations, respective to remaining nailfold characteristics, serological and radiological variables. ENA: extractable nuclear antibodies. #: all retained variables in initial multivariable regression shown in supplementary table S8; ¶: adjusted for age, sex, smoking, FVC%, treatment and pulmonary hypertension.
- TABLE 5
Association of qualitative nailfold capillaroscopy pattern with connective tissue disease associated interstitial lung disease (CTD-ILD) diagnosis
Proposed criteria Pattern Unadjusted OR# 95% CI p-value Ingegnoli [19] Normal 1 Minor 2.15 0.58–7.98 0.254 Major 3.02 0.67–13.63 0.015 Scleroderma 15.30 3.37–68.99 <0.001¶ Maricq [21] Normal 1 Nonspecific 2.05 0.58–7.22 0.262 Scleroderma 9.39 2.80–31.45 <0.001¶ Cutolo [20] Normal 1 Early 2.01 0.57–7.04 0.276 Active 6.09 1.66–22.42 0.007¶ Late 15.67 1.46–168.07 0.023¶ EULAR SG-MC [22] Scleroderma 3.91 1.47–10.42 0.006¶ EULAR SG-MC: European League Against Rheumatism Study Group on Microcirculation. #: odds ratios (OR) relative to a normal pattern for each classification criteria; ¶: p-value remains <0.05 adjusted for age, sex, smoking, FVC %, treatment, pulmonary hypertension.
Supplementary Material
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Supplementary material 00416-2021.SUPPLEMENT
