Hypersensitivity Pneumonitis DR.S.H.HASHEMI 1. INTRODUCTION HP known as extrinsic allergic alveolitis Granulomatous, interstitial, bronchiolar and.

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Hypersensitivity Pneumonitis

DR.S.H.HASHEMI

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INTRODUCTION

HP known as extrinsic allergic alveolitis

Granulomatous, interstitial, bronchiolar and alveolar-filling lung diseases

Caused by repeated exposure and subsequent sensitization to a variety of organic and chemical antigens.

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ETIOLOGYThree main categories:

Microbial agents Bacteria

Farmer’s lung Bagassosis Mushroom

worker’s lung Fungi

Wood pulp worker’s lung

Cheese washer lung

Ameba Humidifier lung

Animal proteinsAvian proteins

Bird breeder’s lung

Urine,Serum,Pelts Animal handler’s lung

Wheat weevil Wheat weevil lung

Chemicals Isocyanate

TDI,MDI,HDI

TMA Trimellitic

anhydride

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PATHOGENESIS

Immunology: Cell-mediated immunity

Repeated inhalation of antigens → sensitization → immunology response(type III,IV) → influx of neutrophiles → shift T lymphocytes (~70%)(predominantly of CD8)(↓CD4/CD8 )

BAL → activated T lymphocytes

Lung biopsy: Interstitial mononuclear cell infiltration Granulomatous inflammatory response

Antibodies in HP are IgG class

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PATHOGENESIS . . .

Host factors: Host susceptibility or resistance factors may

influence individual responses to inhaled antigens. Non smokers > smokers No association with HLA

Exposure factors: Ag concentration Duration of exposure Frequency & intermittency of exposure Particle size Use of respiratory protection

Farmer's lung disease: winter Bird breeder's lung: summer

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CLINICAL FEATURES

Acute HP: Fever ,chills ,myalgia ,cough , dyspnea (4-12 h

after heavy exp. )

Ph/E : basilar rales , peripheral leukocytosis

Recurrent febrile episodes (most frequent presentation)

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CLINICAL FEATURES . . .

Subacute and chronic HP: Temporal relationship between symptoms and

exposure is difficult to elicit.

Insidious onset of respiratory symptoms

Non-specific systemic symptoms Malaise, fatigue, weight loss, cough, dyspnea, low

grade fever

Ph/E: normal or basilar crackles & wheezing

End-stage disease: cyanosis & right-sided HF

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L/D

↑ Specific IgG ( no sensitive , no specific ) ↑ ESR & CRP ↑ IgM , IgA, IgG ↑ ACE ↑ ANA

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PFT

There is no single characteristic pattern of pulmonary function abnormalities .

Acute HP : restrictive pattern

Subacute and chronic HP : air way obstruction or mixed

↓ DLCO (most sensitive physiologic test in early HP )

Methacholine challenge test : increased non-specific bronchial hyper-reactivity

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CXR

Acute HP: Diffuse ground glass opacification Fine nodular or reticulonodular pattern( lower lung

field) Consolidation ( rarely )

Subacute HP: Reticulonodular pattern

Chronic HP: Fibrosis with upper lobe retraction Reticular opacity Volume loss Honeycombing Mediastinal lymphadenopathy (up to 50%)

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Ground glass pattern

Most common in acute HP (but may also be seen in subacute and chronic HP)

Middle lung zone PFT: restrictive , ↓DLCO May resolve with removal from exposure

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Acute HP: pigeon breeder’s lung shows ground-glass haziness and associated air-trapping

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Airspace consolidation

Only reported in acute HP

Bilateral ill-defined areas of consolidation

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Subacute HP: bilateral alveolar and reticular pattern

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Centrilobular nodules

Round, poorly defined, less than 5 mm in diameter

Typically centrilobular

Profuse throughout the lung,but a middle to lower lung zone predominance.

Most frequent HRCT finding in HP

Centrilobular nodules + ground glass opacification are highly suggestive for HP.

PFT : normal

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Fibrosis

Chronic HP (subacute HP) Irregular linear opacities Traction bronchiectasis Honeycombing

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Emphysema

Chronic HP Emphysema occurred more commonly than

fibrosis in chronic farmer’s lung.

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Chronic HP: upper lobe fibrosis

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Chronic HP: farmer’s lung disease showing bibasilar end-stage fibrosis

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HRCT

Sensitivity of HRCT is significantly better than CXR Ground glass Centrilobular nodules Fibrosis Emphysema Mediastinal lymphadenopathy (> 20 mm )

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Centrilobular ground-glass nodules uniformly distributed throughout the lung.Lobular air-trapping also frequently present.

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Multiple low density ill-defined centrilobularnodules

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Extensive areas of grand-glass attenuation.Decreased perfusion (arrows)representing associated air-trapping.

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Chronic HP: Honeycombing, intralobular and septal fibrosis, architectural distorsion

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Mosaic pattern

Patchwork of regions of differing attenuation Due to patchy areas of ground glass or

airtrapping

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Histopathology

Classic triad: Cellular bronchiolitis Lympho-plasmocytic interstitial infiltration Non-necrotizing granulomas

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Diagnosis

Temporal relationship between symptoms and certain activities is often the first clue to the diagnosis of HP

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Diagnostic criteria

Required Appropriate exposure Dyspnea on exertion Inspiratory crackles Lymphocytic alveolitis

Supportive Recurrent febrile episodes Infiltration on CXR Decreased DLCO Precipitating antibodies Granulomatous on lung

biopsy Improvement with contact

avoidance

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DDx

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Comparison HP& Inhalation fever

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Comparison HP& Inhalation fever . . .

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Comparison HP& Inhalation fever . . .

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PROGNOSIS

The clinical course of HP is variable

Acute HP generally resolves without sequelae But progressive impairment may occur with recurrent

attacks or with a single severe attack.

Subacute or chronic forms of HP present with insidious symptoms More subtle clinical abnormalities Frequently recognized later in the disease course

Long-term mortality rates for patients with chronic HP range from 1% to 10%.

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Prognostic factors

Age Duration of exposure after onset of symptoms Time of exposure prior to diagnosis

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TREATMENT

Cornerstone of therapy → removal from exposure

Respirators are used when removal from exposure is impossible.

Oxygen (hypoxemic patients)

Airflow limitation: Inhaled steroids β-agonists

Oral corticosteroids (40–60 mg/day of oral prednisone) in severe or progressive disease.

In refractory cases: Cyclophosphamide & Azathioprine

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