Interstitial lung disease / Autoimmune Pulmonary fibrosis & Rheumatic disease 4.4/5 (10)

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Rheumatic lung disease

Impaired pulmonary function occurs in rheumatic diseases

Interstitial lung disease (ILD)


Interstitial lung disease (ILD) attacks the tissue in the lungs surrounding the aerated air sacs (interstitium) and can develop into pulmonary fibrosis by autoimmune mechanisms of rheumatic diseases. The interstitium consists of different structures (alveolar epithelium, lung capillary endothelium, basement membrane, perivascular and peri-lymphatic lymph).

Disease Causes

In some cases, rheumatic disease is the cause of ILD (please read more below)

It is essential to diagnose subgroups of ILD, because the treatment is different and can be crucial to the prognosis:

Lung fibrosis on CT image

CT lungs: Fibrosis with honeycomb pattern (A). «Airtrapping» (B). The changes are seen in Idiopathic Pulmonary Fibrosis (IPF), Chronic Hypersensitivity Pneumonia (CHrHP) and in autoimmune rheumatic diseases. Smith M, J. Clin. Pathol. (2013). CC BY-NC 3.0


Some terms

Seriously reduced lung function

  • FVC less than 70% and CT examination of lungs (HRCT) show more than 20% affected lung tissue
  • FVC and DLCO fall respectively with 10% and 15% per year


  • Widespread fibrosis (connective tissue) with cavity in the lung tissue
  • Cysts are cavities (without function) in the lung tissue
  • Knots (nodules) occur in the lung tissue in various diseases

"Interstitial Pneumonia with Autoimmune Features" (IPAF)

  • Similar to NSIP lung changes in systemic connective tissue disease, but without such a disease can be conclusively detected

Pumonary fibrosis

  • Connective tissue without special function and which usually remains despite treatment

"Frosted glass" (or "milk glass")

  • Diffuse thickened lung tissue seen on CT examinations - or X-rays. Milk glass changes may be transient or early stage towards fibrosis

Nonspecific Interstitial Pneumonitis (NSIP)

  • NSIP is the most common lung manifestation in several of them Systemic connective tissue diseases that Systemic sclerosis, Antisynthetase syndrome / myositis, hypersensitivity pnemonitis og Sarcoidosis with more.
    • NSIP can often be safely detected based on clinical assessment and CT images, so tissue testing is not always necessary
    • The prevalence of NSIP is uniform (homogeneous) and without pleural changes in contrast to UIP. Both conditions mostly affect the lower (basal) parts of both lungs
    • In order not to overlook an underlying systemic connective tissue disease, symptoms such as joint pain, skin changes, gastrointestinal symptoms, fever with multiple
      • Blood tests are recommended:
        • ANA (antinuclear antibody) with subgroups (ENA)
        • Rheumatoid factor or anti-CCP
        • Antisynthetase Antibody (Myosititis Panel)
        • Creatine kinase (CK)
        • Sedimentation rate (ESR)
        • C-reactive protein (CRP)
      • Urine specimen (protein and erythrocyte sticks)

Usual Interstitial Pneumonitis (UIP)

Lung fibrosis on x-ray

Lung fibrosis on X-ray. Illustration: Heilman J, MD. CC BY-SA 3.0,


pulmonary cysts

Differential diagnoses in multiple lung cysts (adapted to Berger I et al, Journal of Medical Research, 2020)

DiagnosisCyst contourDistributionAdditional findings in the thorax
Lymphoid interstitial pneumonia (LIP)Round, oval, irregular. The size variesDiffuse peribroncovascular, subpleural, basalMattgalssfortetninger. Noduli in acute stages. Ev. Sjögren's syndrome
Lymphangioleiomyomatosis (LAM)Round, small. Irregular in advanced diseaseDiffuse, more centralEv. nodules. Matt glass densities. Chylothorax
Neurofibromatosis Complex (NFC)Round, smallDiffuse, fewNodules
Pulmonary Lung Cell Histiocytosis (PLCH)Round, oval, Irregular / bizarreUpper and middle lung fields. Recess of costophrenic angleSmall, star-shaped nodules. Varying thickness of cyst walls
Birt-Hogg-Dube Syndrome (BHD) Round, oval. Irregular. Varies in sizeMiddle and lower lung fields. Subpleurally, peribronovascularNo

Control of lung lesions (nodules / peripheral lesions)

Rheumatic diseases with interstitial lung disease (ILD)

Systemic connective tissue diseases

Systemic vasculitis

Rheumatoid arthritis

  • Carpet glass and fibrosis in lung tissue (reference: Kelly C, 2014)
    • Occurs in 4 - 10%
    • Divided in NSIP (often good treatment response)
    • UIP (Responding poorer to medication)
  • Rheumatoid nodules (nodules) in the lung tissue (α-CCP positive Rheumatoid arthritis)
    • 2mm-5cm large opacities
    • Rarely symptoms
    • Increased incidence under treatment with methotrexateand possibly by aTNF and leflunomide treatment
    • Appears on X-rays (rare; <1%). During CT examinations, several cases are detected
    • PET / CT with 18FDG investigations may be useful if cancer is a differential diagnosis
    • Subpleural (at the pleura) or in the lung gaps are the most common location
    • Little or no growth at controls
    • Final diagnosis by tissue sample (fibrinoid necrosis, cellular palisade / fencing pattern)
  • Medications (methotrexate, leflunoid (Arava) and TNF inhibitors can rarely cause lung symptoms

 Other diseases with interstitial lung disease (ILD)

  • Lymphomatoid granulomatosis is a rare lympho-proliferative disease with lymphoma-like granulomatosis. Biopsy (tissue sample) is crucial for the diagnosis: (histology: polymorphic lymphoid infiltrates with focal necrosis). Reactivation (by immunosuppression and / or impaired immune system) can be triggered by infection with Ebstein-Bar virus (Mononucleosis)
  • Niemann-Pick Disease (various forms)
    • Sphing myelin cholesterol lipidosis
    • Splenomegaly
    • Neurological symptoms
      • Cognitive changes
      • Hepatosplenomegaly
  • Nitrofurantoin (Furananthin)
    • May cause long-term lung fibrosis (6 months), most commonly in women
  • Reflux Disease
  • SAVI (Autoinflammatory fever syndrome with vasculitis and lung disease)

Medical examination of interstitial lung disease (ILD)

  • Case history:
    • Other illness, exposure (infections, drugs, chemical substances, radioactive radiation). Other signs of active rheumatic disease (medical history, clinical, blood and urine tests)
  • Clinical assessment:
    • Dry cough, heavy breathing under load (load deep). Signs of hypoxemia (low oxygen): Lip cyanosis (blue lips), hourglass nails, drumstick fingers (enlarged outer phalanges). Crepitations by auscultation. Signs of right-sided heart strain: leg edema (water in the legs), stewing in the jugular veins.
  • Lung function tests (FEV1, FVC, DLCO)
  • CT examinations:
    • High Resolution CT (HRCT) display the pulmonary tissue well without using high radiation dose. Fixed nodes (tumor-like) are best investigated with normal CT)
    • NSIP og UIP are really lung-Tissue samples diagnoses, but suspicion is often also described in CT
  • 6 Minutes walking Test shows the pulmonary and cardiac function (besides joints and muscular strength) of the individual and is suitable for following the course of time
  • Blood tests: Hemoglobin (often increased by chronic lung disease, sinks at lung hemorrhage), Platelets (high in inflammation, low values ​​can cause pulmonary edema). Liver and kidney function, CK (myositis with lung changes?). Serological tests: Rheumatoid arthritis: a-CCP, systemic connective tissue disease: ANA (with subgroups), Vasculitis diseases: ANCA vasculitis (GPA / Wegener's): PR3 and MPO-ANCA
  • Bronchio-alveolar lavage (BAL) is done by a pulmonologist: Rinse fluid from the lungs is obtained via a bronchoscope for diagnosis of infection (pneumocystis with more) and pulmonary bleeding
  • Tissue test (biopsy) trans bronchial via bronchoscope is taken by the lung doctor, especially where tissue sample is important for determining treatment.
  • Open lung biopsy can be done if tissue changes are located so that transbronal tissue sample is not possible and a closer assessment is needed for the treatment.

Regardless of the cause of illness and special treatment, the following applies:

  1. Nicotine (smoking) must stop
  2. Other concomitant diseases must be treated as best as possible, including:
    1. Stomach acid reflux (acid reflux)
    2. Heart disease
  3. Obesity must be reduced


Pleuritis in rheumatic conditions, please read here (in Danish)

Lung disease and rheumatic diseases

Grans Compendium in Rheumatology

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