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Although there is substantial histologic overlap among the pulmonary manifestations of different connective tissue diseases (CTDs), certain patterns may favor 1 CTD over another; occasionally, distinctive histologic clues may be present.
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CTDs may present with acute, subacute, and/or chronic pleuropulmonary manifestations, often mixed within the same biopsy, representing ongoing disease.
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Patients with CTD may be taking immunosuppressive medications and are vulnerable to certain infections; both of
Histopathology of Lung Disease in the Connective Tissue Diseases
Section snippets
Key points
Histology of lung disease in rheumatoid arthritis
Perhaps more so than any of the other CTDs, lung disease in patients with RA exhibits a wide variety of histopathologic patterns that can affect all of the major compartments of the lung. Pleural effusion and pleuritis are common initial pleuropulmonary manifestations of RA and may be appreciated grossly and microscopically as acute fibrinous pleuritis, fibrous pleural thickening, and/or pleural adhesions.8, 9, 10 Cytologic preparations of pleural fluid may have characteristic aggregates of
Histology of lung disease in systemic sclerosis (scleroderma)
ILD occurs in up to 80% of patients with systemic sclerosis (SSc), making ILD more prevalent in SSc than in any other CTD. The most characteristic histologic features of ILD in SSc are dense interstitial fibrosis and pulmonary hypertensive vascular changes.24, 25 The most common pattern of interstitial fibrosis in SSc is fibrotic NSIP (Fig. 5), manifesting as dense, paucicellular interstitial fibrosis that maintains the underlying lung architecture and often spares the immediate subpleural area.
Histology of lung disease in myositis
Chronic pulmonary disease in polymyositis and dermatomyositis (PM-DM) consists of varying degrees of cellular interstitial pneumonitis that are best characterized as NSIP (Fig. 7).2, 6, 22, 31, 32, 33, 34, 35 Most case series have described varying degrees of fibrosis accompanying the cellular interstitial infiltrates of PM-DM, including 1 study indicating approximately a 40% prevalence of cellular NSIP and 53% prevalence of mixed cellular and fibrotic NSIP in myositis patients, with only rare
Histology of lung disease in systemic lupus erythematosus
Pleuritis is the most frequent pleuropulmonary manifestation of systemic lupus erythematosus (SLE), and it appears histologically as nonspecific inflammation, fibrin deposition, and pleural fibrosis (Fig. 9).39, 40, 41, 42, 43 Cytologic preparations of pleural fluid from SLE patients may show pathognomonic lupus erythematosis cells consisting of neutrophils or macrophages with intracytoplasmic remnants of degenerated nuclei.
Pulmonary involvement in SLE is usually acute in nature and presents
Histology of lung disease in Sjögren syndrome
Sjögren syndrome (SjS)-associated ILD (SjS-ILD) presents with a spectrum of cellular chronic interstitial pneumonia and airway disease that ranges from a minimally cellular NSIP pattern to more florid patterns of lymphoplasmacytic infiltration such as follicular bronchiolitis, lymphoid interstitial hyperplasia, and LIP. NSIP as a cellular, fibrotic, or mixed pattern is the more commonly reported histologic pattern of SjS-ILD in recent studies.22, 55, 56 LIP (Fig. 12) lies on the other end of
Histology of lung disease in mixed connective tissue disease
Patients who have anti-(U1)snRNP antibodies manifesting some features of DM, PM, SLE, or SSc (but not meeting formal diagnostic criteria) are labeled as having mixed CTD (MCTD). Many of these patients will develop additional clinical and laboratory findings and eventually declare themselves as having one of the specific CTDs. Consistent with the clinical phenotype, the pulmonary manifestations of MCTD in any given patient may reflect any of the patterns discussed previously for the specific
Histologic differential diagnosis of lung disease in connective tissue diseases
The histologic differential diagnosis in cases of suspected pulmonary involvement by CTD can be broad and is compounded by the significant histologic overlap among pulmonary manifestations of CTD, by the immunosuppressed nature of the patients, and by various treatments that may induce histologic changes in the lung.5, 66 Each of the patterns of lung disease (ie, UIP, NSIP, OP, LIP) mentioned previously carries its own differential diagnosis that includes pulmonary involvement by one or more of
Summary
ILD is common in patients with CTDs. Many of the histologic patterns of the idiopathic interstitial pneumonidites such as UIP, cellular and/or fibrotic NSIP, LIP, DAD, and OP can also be seen in patients with CTD; occasionally, the pulmonary manifestations of CTD may precede formal diagnosis of the underlying CTD. The pulmonary manifestations of CTD can result from the direct involvement of the CTD on the lung, from drug reactions from the patient’s medications, or from infections to which the
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Cited by (32)
Interstitial lung disease in systemic lupus erythematosus: state of the art search
2023, Revista Colombiana de ReumatologiaConnective tissue disease-related interstitial lung disease (CTD-ILD) and interstitial lung abnormality (ILA): Evolving concept of CT findings, pathology and management
2022, European Journal of Radiology OpenCitation Excerpt :Most often only nonspecific reactive patterns are identified [28,29], the most common reactive histologic patterns by compartment are compiled in Table 1. ILD is encountered in the majority of CTDs and is indistinguishable from the IIPs [30]. Fibrosing NSIP is the most common pattern identified across all CTDs [31,32], with PM/DM demonstrating OP, RA demonstrating follicular bronchiolitis and occasionally OP, and SSc demonstrating cellular bronchiolitis either separately or in conjunction with fibrosing NSIP [31].
Lung involvement in SLE
2022, Handbook of Systemic Autoimmune DiseasesCitation Excerpt :Bronchoalveolar lavage (BAL) or transbronchial lung biopsy may be useful to evaluate for alternative causes such as hypersensitivity pneumonitis or associated infection or neoplasm. Histological studies have reported the presence of lymphocytic and mononuclear interstitial and peribronchiolar infiltrates in biopsies taken from those with SLE-related NSIP [22]. In terms of treatment, there is a lack of clinical trials assessing the efficacy of immunosuppressive agents for the ILD in the context of SLE, a lack of data about the potential role of new antifibrotic therapies and finally, a lack of biomarkers to assess from the pathogenic point of view, the therapeutic response to all these treatments.
Connective Tissue Disease Related Interstitial Lung Disease
2020, Surgical Pathology ClinicsCitation Excerpt :Pulmonary involvement is observed in the majority (85%) of patients.43 ALI, including acute interstitial pneumonia, diffuse alveolar hemorrhage, OP, and DAD, has been reported, but are rare.45–47 The literature is sparse on the patterns of pulmonary interstitial damage seen in MCTD.
Systemic Lupus Erythematosus and Antiphospholipid Antibody Syndrome
2019, Clinics in Chest MedicineCitation Excerpt :Lung function tests show a restrictive pattern with reduced lung volumes and reduced diffusing capacity for carbon monoxide (DLCO).5 Nonspecific interstitial pneumonia (NSIP) (both cellular and fibrotic) (Fig. 1) appears to be the most common pattern in SLE–ILD, but usual interstitial pneumonia (UIP) (Fig. 2), organizing pneumonia (Fig. 3), lymphocytic interstitial pneumonia (LIP), follicular bronchiolitis, and lymphoid hyperplasia have also been reported.15,17 There have been no controlled treatment trials for chronic ILD in SLE.
The authors have no disclosures to make.