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Nailfold capillaroscopy by smartphone-dermatoscope for connective tissue disease diagnosis in interstitial lung disease: a prospective observational study

Adelle S. Jee, Matthew J.S. Parker, Neil McGill, Jane F. Bleasel, Susanne Webster, Lauren K. Troy, Tamera J. Corte
ERJ Open Research 2021 7: 00416-2021; DOI: 10.1183/23120541.00416-2021
Adelle S. Jee
1Dept of Respiratory, Royal Prince Alfred Hospital, Sydney, NSW, Australia
2Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
3National Health and Medical Research Council Centre of Research Excellence in Pulmonary Fibrosis, Sydney, Australia
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  • ORCID record for Adelle S. Jee
  • For correspondence: adelle.jee@health.nsw.gov.au
Matthew J.S. Parker
2Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
3National Health and Medical Research Council Centre of Research Excellence in Pulmonary Fibrosis, Sydney, Australia
4Dept of Rheumatology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
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Neil McGill
2Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
4Dept of Rheumatology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
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Jane F. Bleasel
2Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
4Dept of Rheumatology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
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Susanne Webster
1Dept of Respiratory, Royal Prince Alfred Hospital, Sydney, NSW, Australia
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Lauren K. Troy
1Dept of Respiratory, Royal Prince Alfred Hospital, Sydney, NSW, Australia
2Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
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Tamera J. Corte
1Dept of Respiratory, Royal Prince Alfred Hospital, Sydney, NSW, Australia
2Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
3National Health and Medical Research Council Centre of Research Excellence in Pulmonary Fibrosis, Sydney, Australia
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  • FIGURE 1
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    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
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    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

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  • TABLE 1

    Baseline characteristics and pulmonary physiology

    TOTALCTD-ILDNon-CTD-ILDCTD-ILD versus non-CTD-ILD
    p-value#
    IPAFIIP
    Subjects n96272742
    Age years66.4±10.361.5±8.964.2±11.171.0±8.80.003
    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 years7.4±7.711.3±10.64.3±3.06.9±6.50.002
    Respiratory symptoms years5.7±5.45.6±4.84.3±3.06.6±6.70.292
    Physiology
      SpO2 %96.6±2.597.9±2.496.7±2.395.8±2.40.003
     FVC %73.9±17.877.0±17.772.3±18.872.8±17.50.281
      DLCO %54.8±16.660.7±19.854.8±16.250.9±13.60.028
      6 MWT distance metres446.5±126.1+463.0±88.6¶421.5±138.6ƒ453.1±137.3##0.479
      6 MWT SpO2 nadir %90.0±7.1+94.3±3.6¶90.0±7.9ƒ87.6±7.2##0.001
    Composite indices
     CPI43.1±12.838.9±14.246.2±10.446.2±10.40.044
     ILD-GAP score1.9±2.20±1.61.2±1.52.5±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

      TotalCTD-ILDNon-CTD-ILDCTD-ILD versus non-CTD-ILD p-value
      IPAFIIP
      Subjects n94262741
      Density
       Number per mm6.7±1.45.6±1.66.8±1.17.3±0.9<0.001
      Giant capillaries
       Present n (%)38 (40.4)16 (61.5)12 (44)10 (24.4)0.018
       Number per patient2.9±6.37.0±1.12.8±6.10.5±8.9<0.001
      Avascular areas
       Present n (%)36 (38.3)15 (57.7)12 (44.4)9 (22.0)0.031
       Number per patient1.3±2.22.7±3.21.2±1.60.5±1.1<0.001
      Microhaemorrhages
       Present n (%)72 (76.6)24 (92.3)18 (66.7)30 (73.2)0.030
       Number per patient5.8±12.14.9±6.78.2±18.04.9±9.90.640
      Abnormal capillary shapes
       Present n (%)90 (95.7)26 (100)24 (88.9)40 (97.6)0.573
       Mode score0.7±0.81.2±0.80.7±0.80.4±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 OR95% CIp-valueAUC
        Nailfold characteristics
         Density <6/mm7.472.73–20.43<0.001#0.72
         Giant ≥3 total6.772.43–18.81<0.001#0.70
         Avascular ≥2 total5.442.02–14.680.001#0.68
         Microhaemorrhages ≥1 total5.001.08–23.180.040#0.61
        Baseline characteristics
         Age0.940.89–0.980.005#0.70
         Male0.180.06–0.470.0010.70
         Smoking0.310.12–0.790.0140.64
         FVC % predicted1.010.99–1.040.2790.59
          DLCO % predicted1.031.00–1.060.0320.64
        Clinical CTD manifestations
         Any CTD manifestation¶42.1810.80–164.74<0.001#0.86
        Serology and radiology
         ANA ≥1:3203.801.42–10.140.0080.64
         Positive ENA5.382.04–14.200.001#0.68
         Any myositis autoantibody+0.330.10–1.050.0610.60
         Radiological NSIP, OP or NSIP/OP7.482.33–23.930.001#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% CIp-value
          • A) Including CTD manifestations

          Any CTD manifestation62.8413.93–283.40<0.001
          Microhaemorrhages13.452.14–84.320.006
          • B) Excluding CTD manifestations

          Positive ENA11.591.80–74.550.010
          Microhaemorrhages22.541.89–269.050.014
          Low capillary density5.661.32–24.200.019

          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 criteriaPatternUnadjusted OR#95% CIp-value
            Ingegnoli [19]Normal1
            Minor2.150.58–7.980.254
            Major3.020.67–13.630.015
            Scleroderma15.303.37–68.99<0.001¶
            Maricq [21]Normal1
            Nonspecific2.050.58–7.220.262
            Scleroderma9.392.80–31.45<0.001¶
            Cutolo [20]Normal1
            Early2.010.57–7.040.276
            Active6.091.66–22.420.007¶
            Late15.671.46–168.070.023¶
            EULAR SG-MC [22]Scleroderma3.911.47–10.420.006¶

            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 Materials

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              Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.

              Supplementary material 00416-2021.SUPPLEMENT

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            Nailfold capillaroscopy by smartphone-dermatoscope for connective tissue disease diagnosis in interstitial lung disease: a prospective observational study
            Adelle S. Jee, Matthew J.S. Parker, Neil McGill, Jane F. Bleasel, Susanne Webster, Lauren K. Troy, Tamera J. Corte
            ERJ Open Research Oct 2021, 7 (4) 00416-2021; DOI: 10.1183/23120541.00416-2021

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            Nailfold capillaroscopy by smartphone-dermatoscope for connective tissue disease diagnosis in interstitial lung disease: a prospective observational study
            Adelle S. Jee, Matthew J.S. Parker, Neil McGill, Jane F. Bleasel, Susanne Webster, Lauren K. Troy, Tamera J. Corte
            ERJ Open Research Oct 2021, 7 (4) 00416-2021; DOI: 10.1183/23120541.00416-2021
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