Diagnosis and management of connective tissue disease-associated interstitial lung disease in Australia and New Zealand: A position statement from the Thoracic Society of Australia and New Zealand.

Pulmonary complications in CTD are common and can involve the interstitium, airways, pleura and pulmonary vasculature. ILD can occur in all CTD (CTD-ILD), and may vary from limited, non-progressive lung involvement, to fulminant, life-threatening disease. Given the potential for major adverse outcomes in CTD-ILD, accurate diagnosis, assessment and careful consideration of therapeutic intervention are a priority. Limited data are available to guide management decisions in CTD-ILD. Autoimmune-mediated pulmonary inflammation is considered a key pathobiological pathway in these disorders, and immunosuppressive therapy is generally regarded the cornerstone of treatment for severe and/or progressive CTD-ILD. However, the natural history of CTD-ILD in individual patients can be difficult to predict, and deciding who to treat, when and with what agent can be challenging. Establishing realistic therapeutic goals from both the patient and clinician perspective requires considerable expertise. The document aims to provide a framework for clinicians to aid in the assessment and management of ILD in the major CTD. A suggested approach to diagnosis and monitoring of CTD-ILD and, where available, evidence-based, disease-specific approaches to treatment have been provided.

Baseline Characteristics and Survival of an Australian Interstitial Pneumonia with Autoimmune Features Cohort.

BACKGROUND AND OBJECTIVE: The research term "interstitial pneumonia with autoimmune features" (IPAF) encompasses interstitial lung disease (ILD) patients with autoimmune features not meeting diagnostic criteria for a defined connective tissue disease (CTD). It remains unclear if IPAF is a distinct disease entity with implications for management and prognosis. We describe an Australian IPAF population and compare their baseline characteristics and outcomes with distinct cohorts of idiopathic interstitial pneumonia (IIP), CTD-ILD, and unclassifiable ILD. METHODS: Review of 291 consecutive patients attending a specialist ILD clinic was performed. Patients with a diagnosis of IIP, CTD-ILD, and unclassifiable ILD by ILD-multidisciplinary meeting (ILD-MDM) were included. Patients meeting the IPAF criteria were identified. Baseline clinical data, survival, and progression were compared between ILD groups. RESULTS: 226 patients were included, 36 meeting the IPAF criteria. IPAF patients demonstrated a high prevalence of autoantibodies to tRNA synthetase (35.3%), Ro52 (27.8%), and neutrophilic cytoplasmic antigens (ANCA; 20.0%). IPAF and CTD-ILD patients demonstrated similar clinical characteristics (mean age 66.6 and 63.7 years, respectively, female predominant, frequent CTD-manifestations). Lung function did not differ between ILD groups. Disease severity, pulmonary hypertension (PH), and ILD-MDM diagnosis were strong predictors of worse transplant-free survival (TFS). Meeting the IPAF criteria was not associated with TFS. CONCLUSIONS: We identified IPAF as a heterogeneous phenotype that overlaps considerably with CTD-ILD. Disease severity, PH, and ILD-MDM diagnosis were more powerful predictors of survival outcomes than meeting the IPAF criteria.

The performance of the European League Against Rheumatism/American College of Rheumatology idiopathic inflammatory myopathies classification criteria in an expert-defined 10 year incident cohort.

OBJECTIVES: To assess the performance of the EULAR/ACR idiopathic inflammatory myopathies (IIMs) classification criteria in a cohort of incident IIM cases and examine how criteria-assigned IIM subtype correlates with expert opinion. METHODS: Adults with newly diagnosed IIM attending Salford Royal NHS Foundation Trust were identified over a 10 year period. A retrospective review of all putative cases was performed and those fulfilling a consensus expert opinion diagnosis of IIM were included. Clinical, serological and histological data were collected and each case was assigned a single IIM subtype. The EULAR/ACR classification criteria were then applied and sensitivity, specificity and positive and negative predictive values were calculated, presented with 95% CIs. RESULTS: A total of 1637 cases were screened, with 255 consensus expert opinion IIM cases ultimately identified. Applying the EULAR/ACR classification criteria, the sensitivity to diagnose an IIM was 99.6% (95% CI 97.2, 100) and 80.9% (95% CI 76.0, 85.8) for the criteria cut-points of probable and definite diagnoses, respectively. In 94/255 cases the IIM subtype differed between consensus expert opinion and classification criteria, most strikingly in the group subtyped as PM by the EULAR/ACR criteria, where there was discrepancy in the majority (i.e. in 87/161). CONCLUSION: The EULAR/ACR criteria performed with high sensitivity in identifying IIM in this external cohort of incident IIM. However, substantial disagreements arose between consensus expert opinion and the criteria regarding IIM subtype assignments, resulting in a large proportion of criteria-assigned cases of PM having heterogeneous features. These results may have important implications for future use of these criteria in subsequent research.

An evaluation of two novel capillaroscopy techniques in suspected scleroderma-spectrum disorders: A single-centre cross-sectional study.

OBJECTIVES: The primary aim was to evaluate the diagnostic performance of digital photographs taken with a smartphone camera using both a lens attachment and, separately, a dermatoscope. The secondary aims were to assess the influence of prior capillaroscopy experience and familiarity with the novel techniques on diagnostic accuracy. METHODS: All patients referred for capillaroscopy between May 2016 and January 2017 were eligible for inclusion. Nailfolds were classified by widefield microscopy before proceeding double-blinded to nailfold photography using both novel techniques. Randomised photographs were assessed by three independent investigators and results were compared to widefield microscopy. Sensitivity, specificity, inter- and intra-observer variability were calculated. RESULTS: Sixty-five participants contributed over 1000 digital photographs for assessment. The 'smartphone-lens' technique performed with moderate sensitivity (65%; 58-72) and high specificity (90%; 84-96). The 'smartphone-dermatoscope' technique performed with higher sensitivity (74%; 66-82) and excellent specificity (95%; 88-100) and was used more accurately by a novice. Prior assessor experience with nailfold capillaroscopy in general and prior experience with the novel techniques positively modulated the diagnostic accuracy. CONCLUSION: New technologies, in this case utilising a smartphone camera, could help to improve accessibility to nailfold capillaroscopy, an important diagnostic tool and putative biomarker in scleroderma-spectrum disorders, whilst retaining accurate results.

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

Nailfold capillaroscopy (NFC) is a non-invasive tool validated for systemic sclerosis diagnosis. The role and interpretation of NFC in interstitial lung disease (ILD) patients for the diagnosis of connective tissue disease associated ILD (CTD-ILD) remains undefined. In a prospective study, quantitative and qualitative NFC by smartphone-dermatoscope (3M Dermlite-DL4ΤΜ attached to iPhone-6plusΤΜ) was performed in 96 patients with well-defined CTD-ILD (n=27) and non-CTD ILD (n=69; idiopathic interstitial pneumonia n=42, interstitial pneumonia with autoimmune features n=27) by ILD-multidisciplinary meeting. NFC scoring was performed by two independent, blinded specialist rheumatologists. Comprehensive baseline clinical, serological, physiological and radiological data were included. Multivariable models for CTD diagnosis in ILD, comprising nailfold characteristics at empirical thresholds determined by receiver operating characteristic curve analysis and clinical variables, were explored. In 94 patients with complete NFC data (total 687 images, median eight images per patient from eight digits), low capillary density (<6 capillaries/millimetre), increased giant capillaries (≥3), avascular areas (≥2) and microhaemorrhages all strongly enhanced the discrimination of CTD-ILD from non-CTD ILD (OR 5.00-7.47) independent of clinical covariates. In multivariable analysis, low capillary density and microhaemorrhages were independent predictors of CTD in ILD additional to the risk conferred by serology and radiology. Microhaemorrhages were also a strong predictor of CTD (adjusted OR 13.45, p=0.006) independent of clinical manifestations. All pre-specified qualitative NFC classification schemes identified CTD-ILD (OR range 3.27-8.47). NFC performed by smartphone-dermatoscope is an accessible, clinically feasible tool that may improve the identification of CTD further to routine clinical assessment of the ILD patient.

Diagnosis of myositis-associated interstitial lung disease: Utility of the myositis autoantibody line immunoassay.

OBJECTIVES: The detection of myositis autoantibodies (MA) in patients with interstitial lung disease (ILD) has major implications for diagnosis and management, especially amyopathic and forme frustes of idiopathic inflammatory myositis-associated ILD (IIM-ILD). Use of the MA line immunoblot assay (MA-LIA) in non-rheumatological cohorts remains unvalidated. We assessed the diagnostic performance of the MA-LIA and explored combined models with clinical variables to improve identification of patients with IIM-ILD. METHODS: Consecutive patients referred to a specialist ILD clinic, with ILD-diagnosis confirmed at multidisciplinary meeting, and MA-LIA performed within six months of baseline were included. Pre-specified MA-LIA thresholds were evaluated for IIM-ILD diagnosis. RESULTS: A total 247 ILD patients were included (IIM-ILD n = 12, non-IIM connective tissue disease-associated ILD [CTD-ILD] n = 52, idiopathic interstitial pneumonia [IIP] n = 115, other-ILD n = 68). Mean age was 64.8 years, with 45.3% female, mean FVC 75.5% and DLCO 59.2% predicted. MA were present in 13.8% overall and 83.3% of IIM-ILD patients. The most common MA in IIM-ILD and non-IIM ILD patients were anti-Jo-1 (prevalence 40%) and anti-PMScl (29.2%) autoantibodies respectively. The pre-specified low-positive threshold (>10 signal intensity) had the highest discriminative capacity for IIM-ILD (AUC 0.86). Combining MA-LIA with age, gender, clinical CTD-manifestations and an overlap non-specific interstitial pneumonia/organising pneumonia pattern on HRCT improved discrimination for IIM-ILD (AUC 0.96). CONCLUSION: The MA-LIA is useful to support a diagnosis of IIM-ILD as a complement to multi-disciplinary ILD assessment. Clinical interpretation is optimised by consideration of the strength of the MA-LIA result together with clinical and radiological features of IIM-ILD.

Increasing incidence of adult idiopathic inflammatory myopathies in the City of Salford, UK: a 10-year epidemiological study.

OBJECTIVES: The aim was to identify and characterize all incident adult cases of idiopathic inflammatory myopathies (IIM) between 1 January 2007 and 31 December 2016 in the City of Salford, UK. METHODS: Adults first diagnosed with IIM within the study period were identified by: a Salford Royal NHS Foundation Trust (SRFT) inpatient episode IIM-specific ICD-10 coding search; all new patient appointments to SRFT neuromuscular outpatient clinics; and all Salford residents enrolled within the UKMYONET study. All patients with definite IIM by the 2017 EULAR/ACR classification criteria were included, as were probable cases if consensus expert opinion agreed. Cases were excluded if <18 years of age at disease onset, if they did not meet probable criteria or when probable but expert opinion concluded a non-IIM diagnosis. RESULTS: The multimodal case ascertainment identified 1156 cases which, after review and application of exclusion criteria, resulted in 32 incident cases during the study period. Twenty-three of 32 were female, with a mean age of 58.1 years. The mean incidence of adult IIM was 17.6/1 000 000 person years, and higher for females than for males (25.2 vs 10.0/1 000 000 person years, respectively). A significant incidence increase over time was apparent (13.6 vs 21.4/1 000 000 person years; P = 0.032). Using EULAR/ACR classification criteria, the largest IIM subtype (21/32) was PM, followed by DM (8/32), IBM (2/32) and amyopathic DM (1/32). Expert opinion subtype differed from EULAR/ACR classification criteria in 19/32 cases. CONCLUSION: The incidence of adult IIM in Salford is 17.6/1 000 000 person years, higher in females, and is increasing over time. Disagreement exists between EULAR/ACR-derived and expert opinion-derived IIM subtype assignments.