Contents
- 1 Interstitial lung disease (ILD)
- 2 Definition
- 3 Disease Causes
- 4 Some terms
- 5 Control of lung lesions (nodules / peripheral lesions)
- 6 Rheumatic diseases with interstitial lung disease (ILD)
- 7 Systemic connective tissue diseases
- 8 Systemic vasculitis
- 9 Rheumatoid arthritis
- 10 Other diseases with interstitial lung disease (ILD)
- 11 Medical examination of interstitial lung disease (ILD)
- 12 Literature
Interstitial lung disease (ILD)
Definition
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:
- Chronic hypersensitivity pneumonia may be caused by a strong reaction to various substances that are breathed (fungi, bacteria, chemical products with more)
- Autoimmune ILD in rheumatic diseases
- ILD related to Systemic connective tissue diseases: or Vasculitis
- Rheumatoid Arthritis (Arthritis)
- Sjögren's syndrome
- Systemic sclerosis (scleroderma) (about 50%)
- Antisyntetase syndrome (100%)
- Myositis
- Systemic lupus erythematosus (SLE)
- Inflammatory bowel disease (Crohn's disease, Ulcerative colitis)
- Interstitial Pneumonia with Autoimmune Features (IPAF)
- ILD related to Systemic connective tissue diseases: or Vasculitis

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
- Sarcoidosis in chronic stage
- Idiopathic interstitial pneumonia
- Other ILD
- Medication associated
- Cytoctatics against cancer
- Drugs for heart disease, especially amiodarone (Cordarone)
- Methotrexate
- Antibiotics, especially nitrofurantoin (Furadantin)
- Biological drugs for the treatment of cancer or rheumatic diseases
- Lymphangioleiomyomatosis (LAM)
- Langerhans histiocytosis
- Eosinophilic pneumonia
- Vasculitis diseases / granulomatous ILD
- Other rare ILD
- Medication associated
- Infections (Opportunistic infections) may give similar symptoms, especially among patients with impaired immune system. The treatment is antibiotics with cures for healing
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
Honeycombing
- 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)
- Blood tests are recommended:
Usual Interstitial Pneumonitis (UIP)
- The radiological image (CT examination), among other things, on idiopathic pulmonary fibrosis (IPF) which is the most common condition of pulmonary fibrosis. IPF also has the worst prognosis. UIP also occurs at Systemic connective tissue diseases: that Systemic sclerosis, Antisynthetase syndrome / myositis with multiple drug side effects, Sarcoidosis and inhaled harmful substances.
- Upon examination, auscultatory krepitations are detected basalt in the lungs and lung function tests shows reduced DLCO and FVC
- There have appeared drugs (pirfenidone and nintedanib) that can stop the development of pulmonary fibrosis. Early diagnosis is therefore important.
Lung fibrosis on X-ray. Illustration: Heilman J, MD. CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=11110205
Control of lung lesions (nodules / peripheral lesions)
Rheumatic diseases with interstitial lung disease (ILD)
Systemic connective tissue diseases
- IPAF (Interstitial pneumonia with autoimmune features
- MDA5 antibody syndrome
- Rapidly increasing lung disease
- Arthritis or joint pain
- Skin abnormalities
- Please read more about the MDA5 syndrome on a separate page here
- Myositis / dermatomyositis / Antisynthetase syndrome
- In particular, in the antisynthetase syndrome, lung changes can be rapidly increasing and very severe. Early treatment is important to maintain lung function
- Sjögren's syndrome (primary form)
- Various types of changes in lung tissue, usually not serious
- LIP (lymphocytic interstitial pneumonia) mostly consist of partly large cysts. Histologically infiltrations with lymphocytes, plasma cells, histiocytes and lymphoretic cells in the interstitium and in alveoli are detected. Multi-nuclear giant cells with granulomas possible. polyclonal B cells differ from pulmonary Lymphoma. Mostly slow progression. About 25% of all people with LIP also have Sjögren's syndrome.
- Systemic lupus erythematosus (SLE) with or without Antifosfolipid syndrome (ApLs) High disease activity can cause lung tissue abnormalities
- Pneumonitis with diffuse pulmonary opacities
- Pulmonary Haemorrhage with frosted glass-like abnormalities occur
- Lung changes at SLE are relatively unusual. It is always important to rule out infection as an alternative cause
- Systemic sclerosis (scleroderma)
- Lung abnormalities usually occur early and increase gradually. Often drugs can stop or slow down development
Systemic vasculitis
- Behcet's disease
- Aneurism-bleeding (also in the lungs)
- Thromboembolisms (blood clots), pulmonary embolisms
- Eosinophil granulomatosis with angiitis (EGPA, Churg-Strauss syndrome)
- Varying pulmonary opacities
- Emphysema (often after many years with Asthma and / or COPD)
- Granulomatosis with polyangiitis (GPA, Wegener's granulomatosis)
- Pulmonary Haemorrhage (Frosted glass-like)
- Granulomas (Tumor-like)
- Microscopic Polyangiitis (MPA)
- MPO-ANCA: Elevated in ILD Cohorts
- ILD may precede vasculitis symptoms
- The occurrence of ILD can affect the prognosis adverse to MPA
- Pulmonary Haemorrhage (frosted glass-like opacities) occurs
Rheumatoid arthritis
- Carpet glass and fibrosis in lung tissue (reference: Kelly C, 2014)
- 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)
- Alveolar proteinosis
- Storage of PAS positive lipoproteins in the lungs
- Heavy breathing and coughing
- CT with infiltrates in the central, middle and basal (lower) parts of the lungs
- «Bats distribution»
- Amyloidosis
- Asbestosis
- Aspiration (chronic aspiration pneumonia)
- Berylliosis
- Mining, occupational disease
- Bronchiolitis (obliterative bronchiolitis)
- Obstructive pulmonary disease
- No effect of asthma drugs
- HRCT shows "air trapping" in expiration
- Many possible reasons
- COPA (Autoinflammatory fever syndrome: Small children with polyarticular arthritis and lung disease)
- Fistula (connection between esophagus and trachea)
- Gaucher's disease
- Pulmonary infiltrates
- Liver disease (Hepato-pulmonary syndrome)
- Goodpastures (anti-glomerular basal membrane antibody) disease
- Kidney disorders
- Hemosiderosis / iron deposits in lungs (idiopathic)
- Hemorrhagia / Pneumonia
- Hypersensitivity alveolitis (allergy)
- Hypersensitivity pneumonia (chronic)
- Idiopathic pulmonary fibrosis (unknown cause)
- Infections
- Aspergillosis (overlap)
- Aspiration pneumonia
- Atypical bacterial pneumoniae
- Pneumocystis jirovecii (Frosted glass opacities by immunosuppressed)
- Viral pneumoniae
- MERS (Middle East Respiratory Syndrome)
- Fever, cough, dyspnoea and muscle aches
- MERS (Middle East Respiratory Syndrome)
- Langerhans histiocytosis
- Eosinophils granulomas
- Pulmonary edema (chronic)
- Lymphangioleio myomatosis (LAM)
- Young women
- Lymphangic carcinomatosis
- Late stage of cancer in which cancer cells create congestion in the lungs
- 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)
- Sarcoidosis
- Diffuse opacities
- Enlarged lymph nodes in the lung hilus
- Silicosis
- Work in stone industry or porcelain
- Veno-occlusive lung disease (reference: Holocomb BW Jr., 2000)
- Causes Pulmonary hypertension with elevated postcapillary pressure measured at right heart catheter (other treatment than PAH related to Systemic sclerosis)
- Heavy breathing / dyspnea (> 95%)
- Right-sided heart failure (> 50%) 18%)
- Chest pain
- Hemoptysis (8%)
- Most often idiopathic (unknown cause), but some are genetic
- Some cases of possible association with autoimmune diseases have been published
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:
- Nicotine (smoking) must stop
- Other concomitant diseases must be treated as best as possible, including:
- Stomach acid reflux (acid reflux)
- Heart disease
- Obesity must be reduced
Literature
Pleuritis in rheumatic conditions, please read here
Lung disease and rheumatic diseases
Grans Compendium in Rheumatology