ILD and auto-immune lung disease

Question 1

Auto-immune and CTD (conn tissue disease) associated

Answer 1

Systemic sclerosis

• scleroderma is the hallmark feature of systemic sclerosis
• characterized by widespread vascular dysfunction and progressive fibrosis of the skin and internal organs.
• Patients with Diffuse Systemic sclerosis are more likely to have a rapid progression of skin thickening with early development of lung fibrosis and an increased risk of renal crisis and cardiac involvement.
• Some degree of pulmonary involvement is seen in more than 80% of patients with SSc
• The 2 principal clinical manifestations of lung disease in SSc are ILD (also called fibrosing alveolitis or pulmonary fibrosis) and pulmonary vascular disease, leading to pulmonary arterial hypertension (PAH) in 10-40% pts
• The most common symptoms are exertional dyspnoea, dry cough. In advanced disease, auscultation over the lungs reveals “velcro” rales most prominent at the lung bases.
• SSc should be suspected in patients presenting with Raynaud Phenomenon, skin thickening, puffy or swollen fingers, hand stiffness, and painful distal finger ulcers. Symptoms of GORD are often present.
• basic labs: anaemia, iron deficiency, elevated creat (renal dysfunction), elevated CK (myositis), urine sediment
• serology: ANA +ve in 95% cases; anti-Scl-70 (Anti-topoisomerase I) antibody +ve in diffuse SSc; anticentromere ab’s (ACA) are found in up to 5% pts with diffuse SSc and are rarely associated with ILD but common with PAH; Anti-RNA polymerase III antibody is found in diffuse SSc that confers higher risk of renal crisis
• PFTs: restrictive defect. Decreased TLC, FRC, RV, and DLCO (degree of DLCO decrease is proportionate to severity of ILD).
• 6MWT
• HRCT (always consider prone HRCT): mostly NSIP pattern (peripheral distribution, GGOs. Advanced disease shows volume loss, traction bronchiectasis. Honeycombing is rare). Some patients display UIP pattern (bibasal reticular opacities, traction bronchiectasis, subpleural honeycombing). Rarely, patient’s display centrilobar fibrosis (pathognomonic for recurrent aspiration).
• Bronchoscopy: exclude infection, evaluate ceff differential, +/- biopsy

Rheumatoid arthritis

Polymyositis/dermatomyositis

Vasculitis

Inflammatory bowel disease

Question 2

Hypersensitivity pneumonitis

Answer 2

Respiratory syndrome involving lung parenchyma (alveoli, terminal bronchioli, alveolar interstitium) due to delayed overactive immune response to certain substances (esp aeroallergens).

Pathophys:

• Triggers: agricultural dusts, bioaerosols (organic dust, plant/animal origin), microorganisms (fungi, bacteria, mould, protozoa), proteins, chemicals. The best studied forms of HP are farmer’s lung (breathing in mould that grows on hay) and bird fancier’s lung (breathing in bird droppings)
• Type 3 (immune-complex mediated) or type 4 (T cell mediated) immune reactions –> cellular infiltration –> granuloma formation –> diffuse cellular pneumonitis and variable degree of pulmonary fibrosis

Clues on history:

• recurrent atypical pneumonia or flu-like symptoms
• new change in lifestyle /exposure, which improves when they are away from the source
• cluster of ppl with similar symptoms in their social circle
• exposures: pets, use of feather dusters, living / working near water damaged source, use of hot tub or swimming pool (breathing in fungus/bacteria growing on humidifiers or hot tubs), occupational exposures
• occupations at risk: farmers, animal/bird breeders, cheese washers, woodworkers, wine makers
• family / genetics - familial hypersensitivity pneumonitis (FHx HP or pulm fibrosis)
• smoking can worsen chronic hypersensitivity pneumonitis
• most pts are 50-55yo

Acute / inflammatory hypersensitivity pneumonitis:

• symptoms <6months, usually abrupt onset (4-6hrs following exposure to offending agent) of flu-like symptoms (fever, chills, malaise, nausea, cough, chest tightness, dyspnoea without wheeze), diffuse fine crepitations
• reversible disease. Removal of offending antigen relieves symptoms within days (can last as short as 12hrs). Radiological findings resolve within weeks. Disease recurs with re-exposure.
• CXR: micronodular pattern in lower/mid zones
• *Subacute HP:**
• gradual development of productive cough, dyspnea, fatigue, anorexia, and weight loss
• tachypnoea and diffuse crepitations
• CXR: normal or show micronodular or reticular opacities (as in acute HP) that are typically most prominent in the middle to upper lung zones

Chronic / fibrotic hypersensitivity pneumonitis:

• symptoms >6months. Insidious onset of cough/chronic bronchitis, dyspnea, fatigue, and weight loss, and may lack a history of acute episodes.
• less reversibility, greater likelihood of progression to pulm fibrosis
• Digital clubbing (fingers/toes) may be seen in advanced disease
• reticular opacities and honeycombing, pulmonary fibrosis
• removal from exposure usually results in only partial improvement

Diagnostic criteria of HP:

Fulfils 1, 2 and 3 below OR fulfils 1 and 2, and avoidance improves symptoms.

(1) Exposure to offending antigen (history of exposure, presence of specific IgG, precipitins, micro, aerobiologic investigations).
(2) HRCT findings:
- Acute or subacute HP: upper and middle lobe predominance. Small centrilobular nodules. GGO’s.
- Chronic/fibrotic: upper and middle lobe predominance. Peribronchovascular fibrosis, honeycombing, mosaic attenuation, air trapping, centrilobular nodules, relative sparing of the bases. ….. chronic HP mimics UIP pattern radiologically
(3) BAL
- lymphocytosis >20%, often >50%. Neutrophils may also be elevated (>3%) and mast cells (>1%)
- mycobacterial stains and culture negative
(4) +ve inhalation challenge test
- only performed on selected patients

Lung biopsy is required to confirm HP if diagnosis uncertain, i.e. HRCT is more consistent with UIP, NSIP, CPFE, or OP; or HRCT consistent but serology suggests otherwise.

PFTs may show a restrictive pattern.

Note, IgE is NOT helpful in diagnosis

Eosinophil count is generally normal.

Complications of HP:

• pulmonary fibrosis
• pulmonary hypertension
• heart failure

Treatment:

• antigen avoidance usually results in regression of disease e.g. removing birds or feather bedding from the household, avoiding hot tubs and water flume slides, or sterilizing humidifiers and vaporizers. May need to resort to more extreme measures if required inc relocation to a new job or home
• re-evaluate patients after 6 to 12 weeks to ensure improvement in symptoms and lung function, or sooner if symptoms are not improving.
• a short course of oral glucocorticoids (up to 30mg daily pred, maintained for 1-2wks, then tapered over 2-4wks) in patients with subacute HP and moderate respiratory impairment can accelerate improvement. However, the long-term outcomes appears unchanged by glucocorticoid treatment.
• Azathioprine (AZA) and mycophenolate mofetil (MMF) have been used in patients with chronic HP who have not responded to antigen removal and systemic glucocorticoid use, but these agents have not been examined in clinical trials of HP
• For the patient who develops advanced lung disease due to HP, lung transplantation may be an option

Source: https://clinicalmolecularallergy.biomedcentral.com/articles/10.1186/s12948-017-0062-7