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Interstitial Lung Disease Associated With Collagen-Vascular Disease Differential Diagnoses

  • Author: Isabel F Pedraza, MD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
 
Updated: Aug 12, 2016
 
 

Diagnostic Considerations

Proper diagnosis of interstitial lung disease (ILD) in persons with collagen-vascular disease (CVD) is important. In most cases, treatment is not very successful, and the medications themselves can cause ILD.

Methotrexate-induced pulmonary toxicity can manifest as an acute onset of fever, dyspnea, hypoxia, and patchy interstitial infiltrates, making it indistinguishable from rheumatoid arthritis (RA)-related ILD. The presence of lymphocytes in bronchoalveolar lavage (BAL) fluid, granuloma in lung biopsy specimens, and peripheral eosinophilia can distinguish methotrexate toxicity from RA-related ILD.

In addition to the conditions listed in the differential diagnosis, other problems to be considered include the following:

  • Human immunodeficiency virus
  • Antiphospholipid antibody syndrome
  • Undifferentiated connective-tissue disease

Differential Diagnoses

 
 
Contributor Information and Disclosures
Author

Isabel F Pedraza, MD Director, Respiratory Intensive Care Unit, Faculty Physician, Department of Medicine, Division of Pulmonary/Critical Care Medicine, Women's Guild Lung Institute, Cedars-Sinai Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

Daniel R Ouellette, MD, FCCP Associate Professor of Medicine, Wayne State University School of Medicine; Chair of the Clinical Competency Committee, Pulmonary and Critical Care Fellowship Program, Senior Staff and Attending Physician, Division of Pulmonary and Critical Care Medicine, Henry Ford Health System; Chair, Guideline Oversight Committee, American College of Chest Physicians

Daniel R Ouellette, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, Society of Critical Care Medicine, American Thoracic Society

Disclosure: Nothing to disclose.

Arshad Ali, MD Attending Physician, Department of Pulmonary and Critical Care Medicine, Mercy General Hospital of Sacramento

Arshad Ali, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Danilo A Enriquez, MD, FCCP Clinical Assistant Professor of Medicine, State University of New York Health Science Center at Brooklyn; Associate Program Director of Internal Medicine Residency Program, Interfaith Medical Center

Danilo A Enriquez, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association

Disclosure: Nothing to disclose.

Hina Arif, MD 

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.

Acknowledgements

Om Prakash Sharma, MD, FRCP, FCCP, DTM&H Professor, Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Southern California Keck School of Medicine

Om Prakash Sharma, MD, FRCP, FCCP, DTM&H is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Osler Society, American Thoracic Society, New York Academy of Medicine, and Royal Society of Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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Pulmonary hypertension is complication of various collagen-vascular diseases. Lung biopsy specimen demonstrates severe interstitial fibrosis and medial fibrosis and smooth muscle hyperplasia of pulmonary arteriole, compatible with pulmonary hypertension.
Heliotrope rash in woman with dermatomyositis.
Gottron papules and nail-fold telangiectasia in patient with dermatomyositis.
Classic malar rash (butterfly rash) with distribution over cheeks and nasal bridge. Note that fixed erythema (sometimes associated with mild induration, as here) characteristically spares nasolabial folds.
High-resolution CT scan of advanced-stage pulmonary fibrosis demonstrating reticular opacities with honeycombing in predominantly subpleural distribution. This pattern can be present in rheumatoid arthritis–related interstitial lung disease, Sjögren syndrome, and scleroderma.
Ground-glass opacification (GGO) may correlate with active alveolitis and favorable response to therapy. GGO is among earliest features of rheumatoid arthritis–induced interstitial lung disease.
Patient with lymphocytic interstitial pneumonia.
Usual interstitial pneumonitis. Subpleural and paraseptal inflammation are present, with appearance of temporal heterogeneity. Patchy scarring of lung parenchyma and normal (or nearly normal) alveoli interspersed between fibrotic areas are hallmarks of this disease. In addition, lung architecture is completely destroyed. This pattern can be present in rheumatoid arthritis–induced interstitial lung disease and generally is associated with poor prognosis.
Table 1. Important Physical Findings in Collagen-Vascular Diseases
CVD Skin and Musculoskeletal System Lungs Heart Salivary Glands Eyes
RA*Subcutaneous nodules, digital ulcers, nail-fold infarctsBibasilar Velcro crackles, signs of pulmonary hypertension, pleural effusionPericarditis, myocarditisN/AN/A
SLE*Malar rash, alopecia, livedo reticularis, erythema, telangiectasia, capillary infarcts, polyarthritisPleural effusion or rub, pneumonitis, cor pulmonale, diaphragmatic weaknessPericarditis, myocarditis, CADN/AN/A
SDThickening of skin of face, fingers, and hands; Raynaud phenomenon and ischemic changes of fingertipsCor pulmonale, inspiratory Velcro crackles at lung basesRestrictive pericardial disease, conduction defects, CHFN/AN/A
SS*Secondary SS can manifest similarly to RA and SLESecondary SS can manifest similarly to RA and SLEN/AXerostomia, parotid gland swellingKeratoconjunctivitis sicca
PMProximal muscle weaknessRespiratory muscle failureN/AN/AN/A
DMHeliotrope rash of eyelids, Gottron papules,Respiratory muscle failureN/AN/AN/A
ASSacroiliitisRestriction in chest expansion, pulmonary apical fibrosisAortic insufficiencyN/AAnterior uveitis
* MCTD can manifest with the signs and symptoms of RA, SLE, or SS.



AS = ankylosing spondylitis; CAD = coronary artery disease; CHF = congestive heart failure; CVD = collagen-vascular disease; DM = dermatomyositis; PM = polymyositis; RA = rheumatoid arthritis; SD = scleroderma; SLE = systemic lupus erythematosus; SS = Sjögren syndrome.



Table 2. Autoantibodies in Collagen-Vascular Diseases
Autoantibody RA SLE SD SS PM/DM AS MCTD
RF++++Rare-+
ANA++++Rare-+



(speckled)



ds-DNA-+-----
Anticentromere--+ (limited)RareRare--
Scl-70--+ (diffuse) Rare--
Anti-Jo---Rare+ (ILD)--
ANCARareRare-----
Smith antibody-+-----
Anti-Ro/SSA and anti-La/SSB---+---
Anti-U1-RNP and anti-UN-70 kd------+
Anti-CCP+------
ANA = antinuclear antibody; ANCA = antineutrophilic cytoplasmic antibody; AS = ankylosing spondylitis; DM = dermatomyositis; ds-DNA = double-stranded DNA antibody; ILD = interstitial lung disease; MCTD = mixed connective-tissue disease; PM = polymyositis; RA = rheumatoid arthritis; RF = rheumatoid factor; RNP = ribonucleoprotein; SD = scleroderma; SLE = systemic lupus erythematosus; SS = Sjögren syndrome; CCP = cyclic citrullinated peptide.
Table 3. Radiographic Patterns of Collagen-Vascular Diseases
Radiologic Pattern RA SLE SD Secondary SS PM/DM AS MCTD
Pleural effusion+++±--+
Interstitial pneumonitis, fibrosisUIP and NSIP patterns+LIP pattern±+Upper apical fibrosis[49] +
BOOP±++++±±
Pulmonary nodulesRheumatoid pulmonary nodules; uncommon, may be 1-5 mm, single or multiple, may cavitate--Follicular lymphoid hyperplasia or lymphoma can present as lung nodules+--
Bronchiectasis+++++++
Caplan syndromeCoal worker’s pneumoconiosis, rheumatoid nodules-----±
Diffuse pulmonary hemorrhage-+----±
Shrinking lung syndrome-Loss of lung volume at bases with no parenchymal pathology----±
Diaphragmatic dysfunction-+-May be present+-±
Cysts, honeycombing10% of patients have subpleural honeycombing; compared with IPF, it is more anterior and involves upper lobesUncommon+Present, especially in LIP+Upper-lobe cyst may become infected with Aspergillus species-
GGOPresent, especially in NSIP++++-±
AS = ankylosing spondylitis; BOOP = bronchiolitis obliterans organizing pneumonia; DM = dermatomyositis; GGO = ground-glass opacification; IPF = idiopathic pulmonary fibrosis; LIP = lymphoid interstitial pneumonia; MCTD = mixed connective-tissue disease; NSIP = nonspecific interstitial pneumonia; PM = polymyositis; RA = rheumatoid arthritis; SD = scleroderma; SLE = systemic lupus erythematosus; SS = Sjögren syndrome; UIP = usual interstitial pneumonia.
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