ILD Flashcards
Young woman presenting with dyspnoea, combination of pulmonary cysts and renal angiomyolipoma (most common benign tumour of kidney) on CT
Lymphangioleiomyomatosis (LAM) -
Rare lung disease that almost always affects WOMEN, usually during reproductive years
Characterised by progressive growth of smooth muscle cells especially in the lungs, lymphatic system and kidneys.
Symptoms: dyspnoea, cough, chest pain, haemoptysis, spontaneous pneumothorax common
Antifibrotics used in ILD
Pirfenidone and Nintedanib
Only medications that have been shown to alter disease progression
Pirfenidone
Acts through TGF-B and reduces fibroblast proliferation
Slows rate of disease progression (decline in FVC)
Improves survival
Major side effects: Nausea/other upper GIT SEs Photosensitivity rash - prescribed in conjunction with sunscreen
Nintedanib
Inhibits multiple tyrosine kinases (PDGF, VEGF, FGF)
Slows rate of disease progression (change in FVC)
Reduces incidence of acute exacerbations
Improves survival
Major side effects:
- Diarrhoea (>60%)
- Nausea (25%)
- LFT derangement
Weight loss Possible cardiovascular risk Possible small increase in bleeding risk - avoid in those on anticoagulants
Lymphangioleiomyomatosis - which therapies slow lung function decline A. Pirfenidone B. Sirolimus C. Inhaled corticosteroids D. Mycophenolate E. Oestrogen
Rapamycin/sirolimus (mTOR inhibitor) has been shown to slow lung function decline in this condition.
Other Facts
- sporadic and tuberous sclerosis associated forms
- high VEGF-D levels may assist in diagnosis
Causes of drug induced ILD
Methotrexate Amiodarone Nitrofurantoin Chemotherapeutic agents/newer biologics Bleomycin (most causes ILD) - require monthly DLCO
Radiotherapy
Occupational: Silicosis, asbestosis
Smoking ILD
- Radiographic signs
- Radiographically would show ground glass opacities and thickened interstitium.
- Desquamative interstitial pneumonitis and pulmonary langerhans cell histiocytosis are other histopathologic patterns
2 ILD associated with smoking
- Desquamative interstitial pneumonia
- Respiratory bronchiolitis-interstitial lung disease
Radiological findings of usual interstitial pneumonia (UIP)
- subpleural reticulation
- apical-basal gradient
- honeycombing
- traction bronchiectasis
Radiological findings of non-specific interstitial pneumonia (NSIP)
- subpleural sparing
- ground glass changes
- apical-basal gradient
- traction bronchiectasis
Example of non-caseating granulomas
Sarcoidosis associated ILD
Hypersensitivity pneumonitis
Which of the following features are shared between Idiopathic Pulmonary Fibrosis (IPF) and Rheumatoid Arthritis associated Interstitial Lung Disease (RA-ILD)?
A. Usual interstitial pneumonia (UIP) radiological pattern
B. MUC5b genetic mutation
C. Association with a smoking history
D. Acute exacerbations
Response to anti-fibrotic therapy
The correct answers are (a), (b), (c) and (d)
• The efficacy of anti-fibrotics in RA-ILD are not yet proven –the results of the TRAIL1 study are eagerly awaited. INBUILD [ahead of print] may provide some support for nintedanib in RA-ILD.
• RA-ILD differs from other CTD-ILD in its predisposition to a UIP radiological/histological pattern.
• A gain of function mutation in MUC5b is observed in ~50% of IPF patients. The same mutation has been found to increase the risk of ILD in RA.
• The risk of RA-ILD is increased by a history of smoking.
RA-ILD acute exacerbations are similar to acute exacerbations of IPF and have a high risk for mortality.
Which of the following therapies does not have proven efficacy in systemic sclerosis associated interstitial lung disease?
A. Cyclophosphamide
B. Mycophenolate
C. Autologous stem cell transplantation
D. Nintedanib
E. Methotrexate
The correct answer is (e)
• The pivotal Scleroderma Lung Study (SLS) trials confirmed the efficacy of cyclophosphamide and mycophenolate.
• A number of recent trials have confirmed the efficacy of autologous stem cell transplantation in appropriately selected patients.
• The SENSCIS trial recently confirmed the efficacy of nintedanib on rate of FVC decline in SSc-ILD.
• Methotrexate has not been studied in SSc-ILD and would typically be avoided in SSc-ILD due to its risk of causing ILD.
What full blood count and biochemistry abnormalities may be encountered in the context of telomere shortening? Select one or more: a. Anaemia b. Microcytosis c. Thrombocytopenia d. Lymphopenia e. Deranged liver function tests
The most common blood test abnormalities in the context of telomere shortening are: • Anaemia (28%) • Macrocytosis (24-45%) • Thrombocytopenia (9-55%) • Lymphopenia (8%) • Deranged liver function tests (4%)
What other features raise the possibility of shortened telomeres in a patient with pulmonary fibrosis? Select one or more: a. Liver cirrhosis b. Premature hair greying c. Opportunistic infections d. Emphysema e. Osteoporosis
The correct answers are (a) –(e) (all are correct)
The clinical features of telomere shortening can involve multiple organs; the effects are in part dependent on the rapidity of tissue turnover
Manifestations in rapid turnover tissues include:
• Premature greying of the hair (20-30 years of age)
• Aplastic anaemia, macrocytosis, thrombocytopenia, lymphopenia
• B, T and NK cell immunodeficiency resulting in opportunistic infections
Manifestations in slow turnover tissues include:
• Pulmonary fibrosis
• Premature onset emphysema
• Cirrhosis
• Coronary artery disease
• Osteoporosis
Additional manifestations include an increased risk of epithelial and haematological malignancies
What genetic phenomenon explains the occurrence of aplastic anaemia in the son and pulmonary fibrosis in the father? A. Autosomal dominant inheritance B. X-linked recessive inheritance C. Mosaicism D. Anticipation
• The telomere complex mutations are inherited in an autosomal dominant fashion.
• Shortened telomeres are carried in germ cells to offspring such that telomeres start from a shortened length in successive generations. This leads to an anticipation effect with the onset of disease becoming earlier in successive generations.
• Phenotype transition can occur, as exemplified in this case, with offspring presenting with haematological manifestations rather than respiratory disease –this explains the interesting occurrence of pulmonary fibrosis in this patient developing after the onset of haematological disease in his son.
The disease phenotype can also become more severe in successive generations. This phenomenon raises important issues for genetic counselling in affected families.
A 55-year-old non-smoking male gentleman was referred with an abnormal chest radiograph and an 18-month history of progressive breathlessness. His previously unlimited exercise tolerance had diminished to 300 metres on level ground. He had no infective symptoms, haemoptysis, orthopnoea or paroxysmal nocturnal dyspnoea. He did not have any symptoms of an underlying connective tissue disease (for example Raynaud’s phenomenon, joint or muscle ache, skin tightening, rash, sicca symptoms, mucosal ulcers, alopecia or gastro-oesophageal reflux symptoms). There was no family history of pulmonary disease but his teenage son suffered with chronic aplastic anaemia
What is the relevance of this patient’s family history?
Select one or more:
a. The absence of a family history of lung disease suggests that the aplastic anaemia affecting his son is not important
b. Childhood aplastic anaemia has no relevance to adult respiratory disease
c. Childhood aplastic anaemia may be related to underlying dyskeratosis congenita (DKC)
d. The family may carry a genetic mutation in the telomerase complex
C+D
• The occurrence of childhood aplastic anaemia raises the possibility of an inherited bone marrow failure syndrome.
• Dyskeratosis congenita is caused by mutations in genes encoding proteins involved in the maintenance of telomere length (e.g. telomerase) and manifests with a triad of mucocutaneous features in infancy: nail dystrophy, patchy skin hyperpigmentation and oral leukoplakia.
• Aplastic anaemia complicates dyskeratosis congenita in the first or second decade of life.
• Telomere shortening as a result of similar mutations has been associated with familial pulmonary fibrosis and emphysema.
A 45 year old lady presents with type 1 respiratory failure and the CT scan attached. She has no known medical history. Examination of the hands reveals erythematous lesions symmetrically over the meta-carpophalangealjoints. Her CK is not elevated. She is started on high flow oxygen therapy at 60% FiO2 and stabilized on the ward. What is the most important next step in management of this patient?
A. Await ENA result
B. Await myositis panel result
C. Bronchoscopy with bronchoalveolar lavage
D. Commence immunosuppression
E. Start broad spectrum antibiotic therapy
Answer: Commence immunosuppression
EXPLANATION
This lady has a severe dermatomyositis associated interstitial lung disease. In this particular case the patient has an anti-MDA5 antibody which is typically amyopathic (hence the negative CK, amyopathic is dermatomyositis characterised by presence of typical skin findings without muscle weakness) and a pneumomediastinum (a common complication of this disease). The constellation of skin and lung findings is sufficient for the diagnosis and therefore the antibody panel is not necessary before the commencement of treatment. A bronchoscopy is not required to make the diagnosis and would also be highly risky in the patient’s current clinical circumstance.
