Various diagnostic criteria proposed for interstitial lung disease (ILD) in patients with features of connective tissue disease (CTD), and the diagnostic criteria for defined CTDs adapted to suit the domains of the interstitial pneumonia with autoimmune features (IPAF) criteria
| Domain | Undifferentiated CTD Kinder et al. [9] | Undifferentiated CTD Corte et al. [10] | Autoimmune-featured ILD Vij et al. [12] | Lung-dominant CTD Fischer et al. [11] | IPAF ERS/ATS [14] | RA ACR/EULAR [7] | SSc ACR/EULAR [6] | Idiopathic inflammatory myopathy EULAR/ACR [4] | Systemic lupus erythematosis EULAR/ACR [3] | Sjögren syndrome ACR/EULAR [5] |
| Entry requirements | Presence of an interstitial pneumonia. Exclusion of alternative aetiologies. Does not meet criteria for a defined CTD. | Presence of an interstitial pneumonia. Exclusion of alternative aetiologies. Does not meet criteria for a defined CTD. | Presence of an interstitial pneumonia. Exclusion of alternative aetiologies. Does not meet criteria for a defined CTD. | Presence of an interstitial pneumonia. Exclusion of alternative aetiologies. Does not meet criteria for a defined CTD. | Presence of an interstitial pneumonia. Exclusion of alternative aetiologies. Does not meet criteria for a defined CTD. | At least one joint with definite clinical synovitis. Synovitis not better explained by another disease. | Excludes skin thickening sparing the fingers or better explained by another condition. | No better explanation for the symptoms and signs. | ANA ≥1:80 on HEp-2 cells or an equivalent positive test (ever). | Ocular or oral dryness. Exclusion of other causes. |
| Clinical | Raynaud's phenomenon. Arthralgias/multiple joint swelling. Morning stiffness. Dry mouth or dry eyes. Proximal muscle weakness. Photosensitivity. Unintentional weight loss. Dysphagia. Recurrent unexplained fever. GORD. Skin changes (rash). Oral ulceration. Non-androgenic alopecia. | Raynaud's phenomenon. Arthralgias/multiple joint swelling. Morning stiffness. Dry mouth or dry eyes. Proximal muscle weakness. | Raynaud's phenomenon. Arthralgias/multiple joint swelling. Morning stiffness. Dry mouth or dry eyes. Proximal muscle weakness. Photosensitivity. Unintentional weight loss. Dysphagia. GORD. Oral ulceration. Leg/foot swelling. Hand ulcers. | Raynaud's phenomenon. Inflammatory arthritis or polyarticular morning joint stiffness ≥60 min. Distal digital tip ulceration. Palmar telangiectasia. Unexplained digital oedema. Distal digital fissuring (i.e. mechanic hands). Unexplained fixed rash on the digital extensor surfaces (Gottron's sign). | Clinical synovitis (increasing score with increasing small joint involvement). Duration of joint symptoms (</≥ weeks). | Raynaud's phenomenon. Skin thickening. Digital ulcers/pitting scars. Telangiectasia. Abnormal nailfold capillaries. | Proximal muscle weakness. Heliotrope rash. Gottron's papules. Gottron's sign. Dysphagia or oesophageal dysmotility. | Joint involvement. Oral ulcers. Non-scarring alopecia. Subacute cutaneous or discoid lupus. Acute cutaneous lupus. Unexplained fever. Neuropsychiatric (delirium, psychosis, seizure). | Ocular or oral dryness. | |
| Serological | ANA Anti-Scl70 SSA or SSB Jo-1 RF ESR >2× normal | ANA (high titre) Anti-centromere ENA Anti-Scl70 Anti-RNP SSA or SSB Jo-1 RF (high titre) | ANA ≥1:160 Anti-Scl70 Anti-RNP SSA or SSB Jo-1 Anti-Sm RF Anti-CCP Anti-dsDNA ANCA CK Aldolase | ANA >1:320 or nucleolar or anticentromere Anti-Scl70 Anti-RNP SSA or SSB Anti-tRNA synthetase Anti-Sm Anti-PM-Scl RF >60 IU·mL–1 Anti-CCP Anti-dsDNA | ANA ≥1:320 or nucleolar or anti-centromere Anti-Scl70 Anti-RNP SSA or SSB Anti-tRNA synthetase Anti-Sm Anti-PM-Scl Anti-MDA-5 RF ≥2× ULN Anti-CCP Anti-dsDNA | RF Anti-CCP Elevated CRP or ESR | Anti-centromere Anti-Scl70 Anti-RNA polymerase III | Jo-1 Elevated CK/LDH/AST/ALT | ANA ≥1:80 Anti-Sm Antiphospholipid antibody Anti-dsDNA Low C3/C4 Leukopenia Thrombocytopenia Autoimmune haemolysis Proteinuria | SSA |
| Morphological | Not specified | Not specified | Not specified | Lung histopathology: lymphoid aggregates with germinal centres. Prominent plasmacytic infiltration. Dense perivascular collagen. Extensive pleuritis. | Radiology: NSIP; OP; NSIP+OP; LIP. Lung histopathology: NSIP; OP; NSIP+OP; LIP; interstitial lymphoid aggregates with germinal centres; diffuse lymphoplasmacytic infiltration (with or without lymphoid follicles). Multi-compartment involvement: unexplained pleural effusion or thickening; unexplained pericardial effusion or thickening; unexplained intrinsic airways disease (by PFT, radiology or histopathology); unexplained pulmonary vasculopathy. | Pulmonary arterial hypertension. ILD. | Muscle histopathology: endomysial infiltration of mononuclear cells surrounding, but not invading, myofibres; perimysial and/or perivascular infiltration of mononuclear cells; perifascicular atrophy; rimmed vacuoles. | Lupus nephritis on renal biopsy. Pleural or pericardial effusion. Acute pericarditis. | Labial salivary gland with focal lymphocytic sialadenitis and focus score of ≥1. Ocular staining score. Schirmer's test. Unstimulated whole saliva flow. | |
| Required to meet definition | At least one clinical and one serological feature. | At least one clinical and one serological feature. | At least one clinical and one serological feature. | At least one serological feature or at least two histopathology features. | At least one feature from at least two of the domains. | Summed weighted scores of ≥6 for classification as definite RA. | Summed of weighted scores of ≥9 for definite SSc. | Probability score calculated by sum of weighted responses to above features. | At least one clinical criterion and ≥10 points. | Total score ≥4. |
ACR: American College of Rheumatology; ALT: alanine aminotransferase; ANA: anti-nuclear antibody; ANCA: anti-neutrophil cytoplasmic antibody; AST: aspartate aminotransferase; ATS: American Thoracic Society; CCP: cyclic citrullinated peptide; CK: creatinine kinase; CRP: C-reactive protein; dsDNA: double-stranded DNA; ENA: extractable nuclear antibody; ERS: European Respiratory Society; ESR: erythrocyte sedimentation rate; EULAR: European Alliance of Associations for Rheumatology; GORD: gastro-oesophageal reflux disease; LDH: lactate dehydrogenase; LIP: lymphoid interstitial pneumonia; NSIP: non-specific interstitial pneumonia; OP: organising pneumonia; PFT: pulmonary function test; RA: rheumatoid arthritis; RF: rheumatoid factor; RNP: ribonucleoprotein; SSA: Sjögren syndrome-related antibody A; SSB: Sjögren syndrome-related antibody B; SSc: systemic sclerosis; UIP: usual interstitial pneumonia; ULN: upper limit of normal.