Tab Application Banner
  • Users Online: 182
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
Year : 2021  |  Volume : 16  |  Issue : 5  |  Page : 116-120

Multi-disciplinary team approach in the management of connective tissue disease-interstitial lung disease: The way forward

1 Department of Respiratory Medicine, Torbay and South Devon NHS Foundation Trust, UK
2 Division of Medicine, Centre for Inflammation and Tissue Repair, UCL Respiratory and Rheumatology, University College London Hospital, UK
3 Depertment of Rheumatology, North Bristol NHS Trust, Bristol; Academic Rheumatology, University of Bristol, UK

Date of Submission17-Aug-2021
Date of Acceptance09-Sep-2021
Date of Web Publication21-Dec-2021

Correspondence Address:
Dr. Harsha Gunawardena
Autoimmune CTD and Vasculitis, North Bristol NHS Trust, Bristol
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-3698.332986

Rights and Permissions

Interstitial lung disease (ILD) is a heterogeneous group of diffuse parenchymal lung disorders and is a common manifestation of autoimmune connective tissue disease (CTD). In some patients, ILD is associated with a clinical spectrum, whereas in some cases it is the presenting or dominant feature. A prompt and correct diagnosis of CTD-ILD is paramount, as early recognition and intervention are essential to deliver an optimal patient pathway and clinical outcomes. This requires detailed clinical assessment of pulmonary and extra-pulmonary disease, robust autoimmune serological testing, review of radiological patterns, and appropriate treatment pathways. We describe the key components required for multidisciplinary evaluation of patients with CTD-ILD, highlighting the need for collaborative working between specialist teams to provide high-quality care.

Keywords: Autoimmune, connective tissue disease, interstitial lung disease, multidisciplinary, respiratory

How to cite this article:
Rowlands B, Mehta P, Gunawardena H. Multi-disciplinary team approach in the management of connective tissue disease-interstitial lung disease: The way forward. Indian J Rheumatol 2021;16, Suppl S1:116-20

How to cite this URL:
Rowlands B, Mehta P, Gunawardena H. Multi-disciplinary team approach in the management of connective tissue disease-interstitial lung disease: The way forward. Indian J Rheumatol [serial online] 2021 [cited 2022 May 28];16, Suppl S1:116-20. Available from:

  Introduction Top

Interstitial lung disease (ILD) encompasses a spectrum of fibro-inflammation diseases of the lung parenchyma that can be idiopathic or secondary to either specific exposures or another underlying pathological process; including as a manifestation of autoimmune connective tissue disease (CTD)[1],[2] ILD may be the presenting feature of CTD or present long after the initial diagnosis.[2] In some cases, ILD may be the dominant feature, while in others it be maybe milder or subclinical. The identification of phenotypic risk factors can be helpful in terms of diagnosis and prognosis, however, the influence on management strategies remains unclear.

There is no clear consensus on diagnostic methodology for determining if patients have an autoimmune CTD in the early stages of ILD diagnosis. A number of requirements must be fulfilled including clinical assessment for extra-pulmonary manifestations, robust autoimmune serological testing, with the review of radiology and/or histopathological patterns.[2] This requires specific clinical expertise to ensure appropriate interpretation and consensus diagnosis.

The risk of misinterpretation of in particular autoantibody results and potential misclassification of disease phenotype can have significant consequences. For example, patients with idiopathic pulmonary fibrosis (IPF) and positive autoantibodies (which may be clinically insignificant) could be incorrectly be relabelled as having CTD-ILD. With distinct induction treatment options available for each, correct classification of IPF and CTD-ILD patients is now critical to ensure appropriate and optimal management.[2],[3]

Some patients will not meet classification criteria for a specific CTD but will have a phenotype that falls into the recently conceived criteria for diagnosing interstitial pneumonia with autoimmune features (IPAF).[4] However, IPAF criteria have not been validated by any form of the gold standard.[5] Dogmatic application of the IPAF diagnostic criteria may lead to under-recognition of true CTD-ILD with possible clinical consequences in terms of treatment and prognosis. Conversely, positive application of IPAF criteria can identify patients with ILD predominant CTD, such as some subtypes of the anti-synthetase syndrome (ASSD), rheumatoid lung, ILD sine rheumatoid, or other formes-frustes of CTD overlap. In some respect, this simply highlights that current rheumatological classification criteria need revision. For example, the lack of well-established clinical and serological classification criteria for ASSD presents a particular challenge in this regard.

  Heterogeneity of Connective Tissue Disease-Interstitial Lung Disease Top

CTD-ILD phenotypes encompass greater heterogeneity than other forms of ILD such as IPF, including presentation and progression of the disease. ASSD, idiopathic inflammatory myopathies, rheumatoid arthritis (RA), Sjogren's syndrome, systemic lupus erythematosus, and systemic sclerosis (SSc) are all associated with a range of ILD phenotypes[1],[2],[6] The highest estimated prevalence rates of diffuse parenchymal lung disease are noted in SSc, inflammatory myositis syndromes and RA when subclinical ILD is included.[1],[7]

Histology from CTD-ILD patients demonstrates a spectrum of inflammatory and fibrotic processes. Parenchymal disease is often accompanied by overlapping airways, pleural, pulmonary vascular disease. This presents increased challenge to correctly diagnose the underlying etiology and may impair response to treatment. CTD-ILD also represents a high level of uncertainty in terms of disease progression, with some diseases mild and nonprogressive while others proceed with a continuous sharp decline.[8],[9],[10] The heterogeneity of clinical progression highlights the importance of regular surveillance and re-evaluation by the multi-disciplinary team (MDT).

  Interstitial Pneumonia with Autoimmune Features Criteria Top

IPAF was the “catch-all” nomenclature coined to categorize and create consensus regarding patients with idiopathic interstitial pneumonia (IIP) and elements of autoimmune disease identified from at least two of three domains: (1) clinical signs or stigmata of CTD (2) serological markers (autoantibodies) (3) morphological evidence from either radiological ILD pattern, histopathology or specific areas of respiratory involvement in addition to ILD.[4] This enables the division of a cohort of patients that would otherwise be classified as IPF and who may respond to immunomodulatory treatments rather than supportive observational management or in some cases anti-fibrotic therapies. However, the diagnosis of a defined CTD excludes patients from the IPAF classification. This may result in scenarios where classification rather than diagnostic criteria are used to inappropriately exclude CTD. For example, would we argue that a patient with (a) mechanic's fingers | hands (one clinical domain) (b) anti-PL12 autoantibodies (one serological domain) (c) usual IIP (one morphologic domain) has lung dominant ASSD and not IPAF. Therefore, some cohorts of patients categorized with IPAF, simply have this formes-frustes or “undeclared occult” CTD reflecting the limitations of traditional rheumatology criteria as previously highlighted.

  Heterogeneity of the Multi-Disciplinary Team– Key Members Top


The British Thoracic Society (BTS) guidelines recommend that there should be specific clinics for ILD patients, with an MDT led by a respiratory consultant with a sub-specialty interest in ILD [Table 1].[3] This enables focused history taking and the identification of any risk factors, as well as facilitating resting spirometry and full pulmonary function testing, including carbon monoxide transfer factor and a 6-minute walk test. These will aid with diagnosis, prognostication, and monitoring for changes over time. Respiratory physicians will also provide the skills for bronchoalveolar lavage and transbronchial lung biopsy when indicated (where diagnostic uncertainty remains).
Table 1: Key Members of the MDT

Click here to view

Historically, respiratory clinicians are also well placed to liaise with other services. This includes thoracic surgeons when the surgical biopsy is required, regional pulmonary arterial hypertension MDTs and referral to transplant centers. They are also well placed to interact with their local colleagues who can retain ownership of ongoing routine care; which should also include acute care and long-term support services such as pulmonary rehabilitation.


Thoracic radiologists with a subspecialist interest in ILD are an essential component of the MDT. High-resolution computed tomography (HRCT) imaging of the chest has become central to identifying and characterizing ILD. HRCT phenotyping leads to a change of initial diagnosis in 51% of patients.[11] However, the complexity of this differentiation is exemplified by large discrepancies in inter-observer observation.[12] This is why consistent ILD reporting is paramount, with key expert individuals that share radiology MDT responsibility. As specific patterns of ILD on HRCT correlate with disease phenotypes this can have a large effect on the correct diagnosis of CTD-ILD.[13] There is ongoing work to improve HRCT phenotyping as well as disease quantification.


Historically, surgical biopsy was considered the gold standard for the determination of ILD phenotype.[3],[14] However, there are significant limitations of patient fitness for sampling, reasonable chance of sampling error and without established criteria, there is poor inter-observer agreement amongst expert histopathologists as to disease phenotype.[15],[16] Diagnostic agreement is higher when histopathologists are included in MDT discussions.[17],[18] In general, there is good agreement IPF and CTD-ILD. However, in most cases, the benefit does not outweigh the risks of lung biopsy and radiology is sufficiently sensitive to confer diagnosis, so in the majority, this is not required.

Rheumatology (with specialist autoimmune immunology expertise)

Rheumatology physicians have expertise and experience in autoimmune CTD and valuable insights into the history and physical signs which may indicate at CTD-ILD. There is a trend towards increasing reliance on serological hallmarks of systemic autoimmune disease, which when used in conjunction with clinical features can confirm early diagnosis.[19],[20] CTD-ILD rheumatology specialists can facilitate extended autoantibody testing that may only be available in specialist centers. Moreover, interpretation of results and correlation with clinical features is paramount to ensuring accurate diagnosis. This requires a two-step process: (a) robust ANA immunofluorescence (IIF) screening, followed by (b) extended CTD autoantibody immunoblot testing utilizing new assays that include a wide array of autoantigen targets now recognized in overlap CTD, particularly SSc and myositis syndromes. It is important to highlight that serology must correlate, for example, a strong cytoplasmic stain on IIF with ASSD autoantibody on blot with the correct pattern of IIP and additional extra-pulmonary features. Whereas a “typical older patient” with UIP, with a nuclear ANA on IIF and multiple positives on immunoblot where the target autoantigen does not match the IIF staining pattern and additional clinical features has: (a) false-positive serology (b) has IPF and should not be incorrectly diagnosed as CTD-ILD. CTD-ILD rheumatologists can interpret autoantibody IIF patterns and subsequent panels within the wider clinical context. In addition, decisions about the management of CTD-ILD are often based on a rheumatologist's experience in clinical practice, in the context of limited multi-center trials.

  Other Key Members of the Wider Multi-Disciplinary Team Top

Respiratory and connective tissue disease specialist nurses and pharmacists

Nurse specialists can facilitate a more holistic approach to patients' journey. This includes education, forming part of the patients' support network, and management of symptoms or medication side-effects. They can also provide the first point of contact for patients should new problems arise, acting to gate-keep and signpost within the service.[3],[21] This is exemplified by 90% of patients using ILD specialist nurses as their main healthcare contact concerning their IPF.[22] There is also an increasing role of respiratory and rheumatology specialist pharmacists who can facilitate and help manage high-cost drug pathways, prescribing, and monitoring.

Palliative care

Certain ILD phenotypes are associated with a significant decline in quality of life and survival. Palliative care specialists can offer effective pharmacological and psychosocial management strategies. They can not only improve quality of life throughout the disease course but also facilitate sensitive and appropriate advanced care planning leading to timely patient-centered end-of-life care.[3],[21],[23]

The role of the multi-disciplinary team and treatment pathways

Complex CTD-ILD treatment decisions require a combination of consensus MDT experience and judgment alongside clinical evidence and guidelines to formulate an appropriate holistic approach for patients. There remains a paucity of well-controlled trials of existing and novel therapeutic agents in CTD-ILD relative to other autoimmune diseases; this is largely a consequence of the heterogeneity that CTD-ILD presents. There remains a significant challenge to recruit enough patients of a particular phenotype to be certain of outcomes. However, centralized MDT assessment of CTD-ILD patients can considerably increase recruitment into these trials. There is a real opportunity to develop CTD-ILD network MDTs who can bring clinical subgroups together to facilitate larger-scale registries. This will enable harnessing of observational cross-sectional and longitudinal data to assess natural history, response to treatment, and survival as well as inclusion in novel therapeutic trials.

Most patients with CTD-ILD will stabilize on recognized immunosuppression, which includes cyclophosphamide, mycophenolate, calcineurin inhibitors (cyclosporin and tacrolimus), and rituximab regimes.[24],[25],[26],[27] Recent randomized controlled trials have demonstrated that nintedanib and tocilizumab reduce deterioration of Forced vital capacity (FVC) in ILD associated with SSc.[28],[29] Nintedanib has also been shown to reduce progression in patients with other forms of fibrosing ILD, not just in IPF.[30],[31],[32] Some patients may have undiagnosed CTD-ILD, and this would represent an adjunctive combination treatment option, as a number will progress despite immunosuppression. Therefore, access to continuing evaluation by the MDT can adapt treatments to a patient's clinical response. The MDT capture of larger numbers of patients with these rare conditions can lead to optimal standardized treatment regimens; that can be continued and monitored by peripheral centers. This will encompass novel and high-cost therapies that these peripheral centers might not have access to, widening the care that can be offered to individuals.

Individualized MDT treatment decisions involving balancing the potential benefits and risks should occur following informed discussion with the patient. It can prove challenging for patients to access centralized MDT assessment, but remote virtual consultations will improve patient care.

  Summary Top

This heterogenic nature of this cohort of patients presents varied challenges for classification, diagnosis, treatment, prognostication, and research. Early recognition of the often rare and complex disease is essential as this influences management and prognosis; poor outcomes have been demonstrated with delays in specialist assessment.

A mechanism for managing this complexity sits with an equally diverse MDT of experts available at specialist centers, whose primary aim is optimal care of patients with ILD [Figure 1]. Bringing together this level of expertise can help to mitigate some of the pitfalls of formulaic criteria, but may come at a cost of accessibility to patients within a region. Single center trials have shown that the CTD-ILD MDT is sensitive and specific for CTD-ILD or IPAF diagnosis.[5] Further work has also highlighted the frequency of reclassification following MDT review after initial diagnosis and period of treatment. Ultimately, this is leading to a paradigm shift from the traditional gold standard of histopathological diagnosis of ILD with lung biopsy to integrated and dynamic MDT interaction.
Figure 1: A connective tissue disease interstitial lung disease multi-disciplinary team model | the rheumatology - respiratory interface CTD: Connective tissue disease, ILD: Interstitial lung disease (respiratory), PH: Pulmonary hypertension

Click here to view

Multidisciplinary team care of CTD-ILD patients will improve disease awareness, leading to earlier disease detection, diagnosis, and access to treatment with established and novel therapeutic agents. Improved exposure to rare subsets of patients will also improve understanding of individual disease phenotypes and how this influences their prognosis. Overall, this will lead to improvements in patient care pathways, clinical and psychosocial outcomes.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Fischer A, du Bois R. Interstitial lung disease in connective tissue disorders. Lancet 2012;380:689-98.  Back to cited text no. 1
Vij R, Strek ME. Diagnosis and treatment of connective tissue disease-associated interstitial lung disease. Chest 2013;143:814-24.  Back to cited text no. 2
Bradley B, Branley HM, Egan JJ, Greaves MS, Hansell DM, Harrison NK, et al. Interstitial lung disease guideline: The British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society. Thorax 2008;63 Suppl 5:v1-58.  Back to cited text no. 3
Fischer A, Antoniou KM, Brown KK, Cadranel J, Corte TJ, Du Bois RM, et al. An official European Respiratory Society/American Thoracic Society research statement: Interstitial pneumonia with autoimmune features. Eur Respir J 2015;46:976-87.  Back to cited text no. 4
Hernandez-Gonzalez F, Prieto-González S, Brito-Zeron P, Cuerpo S, Sanchez M, Ramirez J, et al. Impact of a systematic evaluation of connective tissue disease on diagnosis approach in patients with interstitial lung diseases. Medicine (Baltimore) 2020;99:e18589.  Back to cited text no. 5
Fischer A, Strek ME, Cottin V, Dellaripa PF, Bernstein EJ, Brown KK, et al. Proceedings of the American College of Rheumatology/Association of Physicians of Great Britain and Ireland connective tissue disease – Associated interstitial lung disease summit: A multidisciplinary approach to address challenges and opportunities. Arthritis Rheumatol 2019;71:182-95.  Back to cited text no. 6
Castelino FV, Varga J. Interstitial lung disease in connective tissue diseases: Evolving concepts of pathogenesis and management. Arthritis Res Ther 2010;12:213.  Back to cited text no. 7
Liu H, Xie S, Liang T, Ma L, Sun H, Dai H, et al. Prognostic factors of interstitial lung disease progression at sequential HRCT in anti-synthetase syndrome. Eur Radiol 2019;29:5349-57.  Back to cited text no. 8
Park JH, Kim DS, Park IN, Jang SJ, Kitaichi M, Nicholson AG, et al. Prognosis of fibrotic interstitial pneumonia: Idiopathic versus collagen vascular disease-related subtypes. Am J Respir Crit Care Med 2007;175:705-11.  Back to cited text no. 9
Navaratnam V, Ali N, Smith CJ, McKeever T, Fogarty A, Hubbard RB. Does the presence of connective tissue disease modify survival in patients with pulmonary fibrosis? Respir Med 2011;105:1925-30.  Back to cited text no. 10
Aziz ZA, Wells AU, Bateman ED, Copley SJ, Desai SR, Grutters JC, et al. Interstitial lung disease: Effects of thin-section CT on clinical decision making. Radiology 2006;238:725-33.  Back to cited text no. 11
Aziz ZA, Wells AU, Hansell DM, Bain GA, Copley SJ, Desai SR, et al. HRCT diagnosis of diffuse parenchymal lung disease: Inter-observer variation. Thorax 2004;59:506-11.  Back to cited text no. 12
Cottin V. Significance of connective tissue diseases features in pulmonary fibrosis. Eur Respir Rev 2013;22:273-80.  Back to cited text no. 13
Ozasa M, Ichikawa H, Sato S, Tanaka T, Johkoh T, Kataoka K, et al. Proposed method of histological separation between connective tissue disease-associated interstitial pneumonia and idiopathic interstitial pneumonias. PLoS One 2018;13:e0206186.  Back to cited text no. 14
Flaherty KR, Travis WD, Colby TV, Toews GB, Kazerooni EA, Gross BH, et al. Histopathologic variability in usual and nonspecific interstitial pneumonias. Am J Respir Crit Care Med 2001;164:1722-7.  Back to cited text no. 15
Nicholson AG, Addis BJ, Bharucha H, Clelland CA, Corrin B, Gibbs AR, et al. Inter-observer variation between pathologists in diffuse parenchymal lung disease. Thorax 2004;59:500-5.  Back to cited text no. 16
Flaherty KR, King TE Jr., Raghu G, Lynch JP 3rd, Colby TV, Travis WD, et al. Idiopathic interstitial pneumonia: What is the effect of a multidisciplinary approach to diagnosis? Am J Respir Crit Care Med 2004;170:904-10.  Back to cited text no. 17
Walsh SL, Wells AU, Desai SR, Poletti V, Piciucchi S, Dubini A, et al. Multicentre evaluation of multidisciplinary team meeting agreement on diagnosis in diffuse parenchymal lung disease: A case-cohort study. Lancet Respir Med 2016;4:557-65.  Back to cited text no. 18
Barratt SL, Adamali HH, Cotton C, Mulhearn B, Iftikhar H, Pauling JD, et al. Clinicoserological features of Antisynthetase Syndrome (ASyS)-associated interstitial lung disease presenting to respiratory services: Comparison with idiopathic pulmonary fibrosis and ASyS diagnosed in rheumatology services. BMJ Open Respir Res 2021;8:e000829.  Back to cited text no. 19
Gunawardena H. The clinical features of myositis-associated autoantibodies: A review. Clin Rev Allergy Immunol 2017;52:45-57.  Back to cited text no. 20
Russell AM, Ripamonti E, Vancheri C. Qualitative European survey of patients with idiopathic pulmonary fibrosis: patients' perspectives of the disease and treatment. BMC Pulm Med 2016;16:10.  Back to cited text no. 21
Russell AM, Ripamonti E, Vancheri C. Qualitative European survey of patients with idiopathic pulmonary fibrosis: Patients' perspectives of the disease and treatment. BMC Pulm Med 2016;16:10.  Back to cited text no. 22
Kreuter M, Bendstrup E, Russell AM, Bajwah S, Lindell K, Adir Y, et al. Palliative care in interstitial lung disease: Living well. Lancet Respir Med 2017;5:968-80.  Back to cited text no. 23
Hoyles RK, Ellis RW, Wellsbury J, Lees B, Newlands P, Goh NS, et al. A multicenter, prospective, randomized, double-blind, placebo-controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma. Arthritis Rheum 2006;54:3962-70.  Back to cited text no. 24
Volkmann ER, Tashkin DP, Li N, Roth MD, Khanna D, Hoffmann-Vold AM, et al. Mycophenolate mofetil versus placebo for systemic sclerosis – Related interstitial lung disease: An analysis of scleroderma lung studies I and II. Arthritis Rheumatol 2017;69:1451-60.  Back to cited text no. 25
Allenbach Y, Guiguet M, Rigolet A, Marie I, Hachulla E, Drouot L, et al. Efficacy of rituximab in refractory inflammatory myopathies associated with anti-synthetase auto-antibodies: An open-label, phase II trial. PLoS One 2015;10:e0133702.  Back to cited text no. 26
Sharp C, McCabe M, Dodds N, Edey A, Mayers L, Adamali H, et al. Rituximab in autoimmune connective tissue disease-associated interstitial lung disease. Rheumatology (Oxford) 2016;55:1318-24.  Back to cited text no. 27
Distler O, Highland KB, Gahlemann M, Azuma A, Fischer A, Mayes MD, et al. Nintedanib for systemic sclerosis – Associated interstitial lung disease. N Engl J Med 2019;380:2518-28.  Back to cited text no. 28
Khanna D, Denton CP, Jahreis A, van Laar JM, Frech TM, Anderson ME, et al. Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate): a phase 2, randomised, controlled trial. Lancet 2016;387(10038):2630-40.  Back to cited text no. 29
Flaherty KR, Wells AU, Cottin V, Devaraj A, Walsh SL, Inoue Y, et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med 2019;381:1718-27.  Back to cited text no. 30
Richeldi L, Costabel U, Selman M, Kim DS, Hansell DM, Nicholson AG, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med 2011;365:1079-87.  Back to cited text no. 31
Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med 2014;370:2071-82.  Back to cited text no. 32


  [Figure 1]

  [Table 1]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Heterogeneity of...
Interstitial Pne...
Heterogeneity of...
Other Key Member...
Article Figures
Article Tables

 Article Access Statistics
    PDF Downloaded61    
    Comments [Add]    

Recommend this journal