|Year : 2021 | Volume
| Issue : 5 | Page : 116-120
Multi-disciplinary team approach in the management of connective tissue disease-interstitial lung disease: The way forward
Ben Rowlands1, Puja Mehta2, Harsha Gunawardena3
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 Submission||17-Aug-2021|
|Date of Acceptance||09-Sep-2021|
|Date of Web Publication||21-Dec-2021|
Dr. Harsha Gunawardena
Autoimmune CTD and Vasculitis, North Bristol NHS Trust, Bristol
Source of Support: None, Conflict of Interest: None
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: https://www.indianjrheumatol.com/text.asp?2021/16/5/116/332986
| Introduction|| |
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), ILD may be the presenting feature of CTD or present long after the initial diagnosis. 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. 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.,
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). However, IPAF criteria have not been validated by any form of the gold standard. 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|| |
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,, The highest estimated prevalence rates of diffuse parenchymal lung disease are noted in SSc, inflammatory myositis syndromes and RA when subclinical ILD is included.,
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.,, 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|| |
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. 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|| |
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]. 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).
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. However, the complexity of this differentiation is exemplified by large discrepancies in inter-observer observation. 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. 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., 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., Diagnostic agreement is higher when histopathologists are included in MDT discussions., 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., 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|| |
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., This is exemplified by 90% of patients using ILD specialist nurses as their main healthcare contact concerning their IPF. 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.
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.,,
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.,,, Recent randomized controlled trials have demonstrated that nintedanib and tocilizumab reduce deterioration of Forced vital capacity (FVC) in ILD associated with SSc., Nintedanib has also been shown to reduce progression in patients with other forms of fibrosing ILD, not just in IPF.,, 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|| |
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. 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.
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