DIFFUSE DISEASES OF THE LUNG PARENCHYMA

Diffuse parenchymal lung disorders (DPLD) also referred to as interstitial lung disease is a heterogenous group of lung diseases with bilateral diffuse lung injury and inflammation that can progress to lung fibrosis (Fig. 11.8). The process involves not only the interstitial space but also the alveoli, bronchi-oles and blood vessels. The diseases have common clinical, radiological and pulmonary function features. Presentation is with shortness of breath on exertion, a persistent non-productive cough, an abnormal chest X-ray (bilat-eral diffuse pulmonary infiltrates), or with pulmonary symptoms associated with another disease such as a connective tissue disease. Pulmonary infec-tion, malignancy, and pulmonary oedema may mimic interstitial lung disease.

Granulomatous lung disease

A granuloma is a mass or nodule of chronic inflammatory tissue formed by the response of macrophages and histiocytes to a slowly soluble antigen or irritant. It is characterized by the presence of epithelioid multinucleate giant cells. Sarcoidosis is the most common cause of lung granulomas.

Fig 11.8 Causes of diffuse parenchymal lung diseases.

Sarcoidosis

Sarcoidosis is a multisystem granulomatous disorder of unknown cause typi-cally affecting young and middle-aged adults. It usually presents with bilat-eral hilar lymphadenopathy (BHL) and/or pulmonary infiltrations, and skin or eye lesions. In about half of cases, the disease is detected incidentally on a routine chest X-ray in an asymptomatic individual.

Epidemiology

Sarcoidosis occurs in all ethnic groups but is uncommon in Japan. The course of the disease is more severe in African blacks than in whites.

Immunopathology

■ Typical non-caseating (compare with TB) sarcoid granuloma consists of a focal accumulation of epithelioid cells, macrophages and lymphocytes, mainly T cells.

■ Depressed cell-mediated reactivity to antigens, such as tuberculin and Candida albicans, and an overall lymphopenia with low circulating T cells, as a result of sequestration of lymphocytes within the lung and slightly increased B cells.

■ Increased number of cells (particularly CD4 helper) in bronchoalveolar lavage.

■ Transbronchial biopsies show infiltration of alveolar walls and interstitial spaces with mononuclear cells before granuloma formation.

Clinical features

Sarcoidosis can affect any organ, particularly the lung, skin and eyes (Table 11.10). Lung disease presents with a non-productive cough, breathlessness and sometimes a wheeze. Pulmonary infiltration may predominate, and, in a minority of patients there is Progressive fibrosis resulting in increasing effort dyspnoea, cor pulmonale and death. Chest examination is normal or there are fine crackles particularly anteriorly. Finger clubbing is rare and when present alterative diagnoses should be considered, e.g. other causes of pulmonary fibrosis, tuberculosis, malignancy. Lofgren's syndrome consists of the triad of erythema nodosum (p. 812), arthralgia, and bilateral hilar lymphadenopathy on chest X-ray (see later); it carries an excellent prognosis. Asymptomatic disease may be identified when a chest X-ray is performed for other reasons. Fatigue is a major problem in many patients.

Investigations

Diagnosis depends on a compatible clinical picture, exclusion of diseases with a similar presentation (see differential diagnosis) and biopsy for histo-logical diagnosis if possible. Common biopsy sites are enlarged lymph nodes, skin lesions and transbronchial biopsy at bronchoscopy.

Table 11.10 Clinical features of sarcoidosis

System

Symptoms and signs

Chest

Cough, breathlessness, wheeze, fine crackles on examination

Skin

Erythema nodosum, waxy maculopapular lesions, lupus pernio (red/blue iníiltration of the nose), iníiltration of scars by granulomas

Eye

Anterior and posterior uveitis, conjunctival nodules, lacrimal gland enlargement, uveoparotid fever (Heerfordt’s syndrome: uveitis, parotid gland enlargement and facial nerve palsy)

Bone

Arthralgias, bone cysts

Metabolic

Hypercalcaemia (sarcoid macrophages produce 1,25-dihydroxyvitamin D)

Liver

Granulomatous hepatitis, hepatosplenomegaly

Neurological

Meningeal inílammation, seizures, mass lesions, hypothalamic-pituitary iníiltration, diffuse sensorimotor neuropathy, mononeuropathy

Cardiac

Rarely: ventricular arrhythmias, conduction defects, cardiomyopathy with cardiac failure

■ Chest X-ray allows the disease to be staged. High-resolution chest CT scan provides a better assessment of pulmonary involvement and identi-fies abnormal nodes for biopsy.

■ Pulmonary function tests assess disease severity and the response to treatment. There is a restrictive lung defect in patients with pulmonary intiltration with a decrease in total lung capacity, FEV,, FVC and gas transfer.

■ Blood tests - a full blood count, liver biochemistry, serum creatinine and calcium are performed to look for abnormalities and evidence of organ involvement. Serum angiotensin-converting enzyme (ACE) is raised in most patients but it has limited sensitivity and specificity and does not provide additional information to other tests in disease monitoring.

■ Tuberculin test is negative in 80% of patients. It is of interest but of no diagnostic value.

Ditterential diagnosis

The differential diagnosis of bilateral hilar lymphadenopathy includes:

■ Lymphoma

■ Pulmonary tuberculosis

■ Bronchial carcinoma with secondary spread.

The combination of symmetrical bilateral hilar lymphadenopathy and erythema nodosum only occurs in sarcoidosis. Non-caseating granulomas also occur in lymphoma, fungal infection, tuberculosis (also caseating) and in response to foreign bodies and occupational exposure to beryllium.

Management

Hilar lymphadenopathy with no other evidence of lung involvement on chest X-ray or lung function testing does not require treatment. The disease remits spontaneously within 2 years in over two-thirds of patients.

Infiltration or abnormal lung function tests that persist for 6 months after diagnosis is treated with 30 mg prednisolone for 6 weeks, reducing to 15 mg on alternate days for 6-12 months. Other definite indications for steroid treatment are hypercalcaemia, neurological or myocardial involvement and ocular involvement (topical steroids are used in some cases). Steroid sparing agents (methotrexate, azathioprine, cyclophosphamide) are sometimes used in patients needing long-term steroids for disease control.

Prognosis

In patients of African origin the mortality rate may be up to 10%, but is less than 5% in Caucasians. Death is mainly as a result of respiratory failure or renal damage from hypercalciuria.

Granulomatous lung disease with vasculitis

There are two main groups:

■ Pulmonary vasculitis associated with primary autoimmune rheumatic diseases including rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis (Ch. 7).

■ The vasculitides associated with the presence of antineutrophil cyto-plasmic antibodies (ANCAs) including Churg-Strauss syndrome (p. 308), microscopic polyangiitis (p. 308) and Wegener's granulomatosis.

Wegener's granulomatosis is a vasculitis of unknown aetiology characterized by lesions involving the upper respiratory tract, the lungs and the kidneys. The disease often starts with rhinorrhoea, with subsequent nasal mucosal ulceration, cough, haemoptysis and pleuritic pain. Chest X-ray shows nodular masses or pneumonic infiltrates with cavitation which often show a migratory pattern. Antineutrophil cytoplasmic antibodies (p. 299) are found in the serum in over 90% of cases with active disease, and measurement is useful both diagnostically and as a guide to disease activity in the treated patient. Typical histological changes are best shown in the kidney, where there is a necro-tizing microvascular glomerulonephritis. Treatment is with cyclophospha-mide; rituximab is also being used.

Idiopathic interstitial pneumonias

This group accounts for about 40% of cases of diffuse parenchymal lung disease and, as the name suggests, no underlying causes can be identified. Idiopathic pulmonary fibrosis (previously called cryptogenic fibrosing alveolitis) is the commonest type. Other types are non-specific interstitial pneumonitis, cryptogenic organizing pneumonia, acute inter-stitial pneumonia, desquamative interstitial pneumonia and respiratory bronchiolitis.

Idiopathic pulmonary fibrosis (IFP)

There is patchy fibrosis of the interstitium and minimal or absent inflam-mation, acute fibroblastic proliferation and collagen deposition. It usually presents in the late sixties and is more common in males.

Clinical features

Presentation is with progressive breathlessness and a non-productive cough. Eventually there is respiratory failure, pulmonary hypertension and cor pul-monale. Finger clubbing occurs in two-thirds of cases, and fine inspiratory basal crackles are heard on auscultation. Rarely, an acute form known as the Hamman-Rich syndrome occurs.

Investigations

■ Chest X-ray appearances are initially of a ground-glass appearance, progressing to fibrosis and honeycomb lung. These changes are most prominent in the lower lung zones.

■ High-resolution CT scan is the most sensitive imaging technique, and shows bilateral irregular linear opacities and honeycombing.

■ Respiratory function tests show a restrictive defect (p. 509) with reduced lung volumes and impaired gas transfer.

■ Blood gases show hypoxaemia with a normal PaCO2.

■ Autoantibodies, such as antinuclear factor and rheumatoid factor, are present in one-third of patients.

■ Histological confirmation is necessary is some patients. Transbronchial lung biopsy is rarely diagnostic but can exclude other conditions that present similarly, e.g. sarcoidosis. A video-assisted thoracoscopic lung biopsy is performed to obtain a larger specimen and a clear histological diagnosis.

Differential diagnosis

This is from other causes of diffuse parenchymal lung disease (Fig 11.8). A detailed history, including occupational exposure (past and present) and drug history, is required to exclude other causes of pulmonary fibrosis.

Treatment

Large doses of prednisolone are used (30 mg daily); azathioprine and cyclophosphamide may also be tried. Single lung transplantation is now an established treatment for some individuals.

Prognosis

The median survival without lung transplantation is approximately 5 years. Hypersensensitivity pneumonitis

This condition was previously called extrinsic allergic alveolitis and character-ized by a widespread diffuse inflammatory reaction in the alveoli and small airways of the lung as a response to inhalation of organic dusts (Table 11.11). By far the most common is farmer's lung, which affects up to 1 in 10 of the farming community in poor wet areas around the world.

Clinical features

There is fever, malaise, cough and shortness of breath several hours after exposure to the causative antigen. Physical examination reveals tachypnoea, and coarse end-inspiratory crackles and wheezes. Continuing exposure leads to a chronic illness with weight loss, effort dyspnoea, cough and the features of pulmonary fibrosis.

Investigations

■ Chest X-ray shows fluffy nodular shadowing with the subsequent devel-opment of streaky shadows, particularly in the upper zones.

Table 11.11 Hypersensitivity pneumonitis - some causes

Disease

Situation

Antigens

Farmer’s lung

Forking mouldy hay or other vegetable material

Micropolyspora faeni

Bird fancier’s lung

Handling pigeons, cleaning lofts or budgerigar cages

Proteins present in feathers and excreta

Malt worker’s lung

Turning germinating barley

Aspergillus clavatus

Humidiíier fever

Contaminated humidifying systems in air conditioners or humidifiers

A variety of bacteria or amoebae

Mushroom workers

Turning mushroom compost

Thermophilic

actinomycetes

Cheese washer’s lung

Mouldy cheese

Penicillium casei Aspergillus clavatus

Wine maker’s lung

Mould on grapes

Botrytis

■ High-resolution CT shows reticular and nodular changes with ground-glass opacity.

■ Full blood count shows a raised white cell count in acute cases.

■ Lung function tests show a restrictive defect with a decrease in gas transfer.

■ Precipitating antibodies to causative antigens are present in the serum (these are evidence of exposure and not disease).

■ Bronchoalveolar lavage shows increased T lymphocytes and granulocytes.

Management

Prevention is the aim, with avoidance of exposure to the antigen if possible.

Prednisolone in large doses (30-60 mg daily) may be required to cause

regression of the disease in the early stages.

Other types of diffuse lung disease

Intrapulmonary haemorrhage can produce diffuse infiltrates on the chest X-ray. In Goodpasture's syndrome antibodies are directed against the base-ment membrane of both kidney and lung. There is cough, haemoptysis and tiredness followed by acute glomerulonephritis. Treatment is usually with corticosteroids. Diffuse alveolar haemorrhage is similar but tends to occur in children, the kidneys are less frequently involved and there are no anti-basement membrane antibodies. Other rarer causes of diffuse parenchymal lung disease are Langerhan's cell histiocytosis and pulmonary alveolar proteinosis.

Ebook Essentials of Kumar and Clark's Clinical Medicine, 5e

1. Ethics and communication

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2. Infectious diseases

Infectious diseases

3. Gastroenterology and nutrition

Gastroenterology and nutrition

4. Liver, biliary tract and pancreatic disease

Liver, biliary tract and pancreatic disease
LIVER BIOCHEMISTRY AND LIVER FUNCTION TESTS
SYMPTOMS AND SIGNS OF LIVER DISEASE
JAUNDICE
HEPATITIS
NON - ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
CIRRHOSIS
COMPLICATIONS AND EFFECTS OF CIRRHOSIS
LIVER TRANSPLANTATION
TYPES OF CHRONIC LIVER DISEASE AND CIRRHOSIS
PRIMARY SCLEROSING CHOLANGITIS
BUDD - CHIARI SYNDROME
LIVER ABSCESS
LIVER DISEASE IN PREGNANCY
LIVER TUMOURS
GALLSTONES
THE PANCREAS
CARCINOMA OF THE PANCREAS
NEUROENDOCRINE TUMOURS OF THE PANCREAS

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Haematological disease
ANAEMIA
Assessment and treatment of suspected neutropenic sepsis
HAEMOLYTIC ANAEMIA
INHERITED HAEMOLYTIC ANAEMIAS
ACQUIRED HAEMOLYTIC ANAEMIA
MYELOPROLIFERATIVE DISORDERS
THE SPLEEN
BLOOD TRANSFUSION
THE WHITE CELL
HAEMOSTASIS AND THROMBOSIS
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Malignant disease
MYELOABLATIVE THERAPY AND HAEMOPOIETIC STEM CELL TRANSPLANTATION
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Clinical features, Investigations
INFECTION OF JOINTS AND BONES
AUTOIMMUNE RHEUMATIC DISEASES
SYSTEMIC INFLAMMATORY VASCULITIS
DISEASES OF BONE
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BODY FLUID COMPARTMENTS
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PLASMA OSMOLALITY AND DISORDERS OF SODIUM REGULATION
DISORDERS OF POTASSIUM REGULATION
DISORDERS OF MAGNESIUM REGULATION
DISORDERS OF ACID - BASE BALANCE
THERAPEUTICS

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Renal disease
INVESTIGATION OF RENAL DISEASE
GLOMERULAR DISEASES
NEPHROTIC SYNDROME
URINARY TRACT INFECTION
TUBULOINTERSTITIAL NEPHRITIS
HYPERTENSION AND THE KIDNEY
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CHRONIC KIDNEY DISEASE
RENAL REPLACEMENT THERAPY
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TUMOURS OF THE KIDNEY AND GENITOURINARY TRACT
DISEASES OF THE PROSTATE GLAND
TESTICULAR TUMOUR
URINARY INCONTINENCE

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COMMON PRESENTING SYMPTOMS OF HEART DISEASE
INVESTIGATIONS IN CARDIAC DISEASE
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HEART FAILURE
ISCHAEMIC HEART DISEASE
RHEUMATIC FEVER
VALVULAR HEART DISEASE
PULMONARY HEART DISEASE
MYOCARDIAL DISEASE
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ARTERIAL AND VENOUS DISEASE
ELECTRICAL CARDIOVERSION
DRUGS FOR ARRHYTHMIAS
DRUGS FOR HEART FAILURE
DRUGS AFFECTING THE RENIN - ANGIOTENSIN SYSTEM
NITRATES, CALCIUM - CHANNEL BLOCKERS AND POTASSIUM - CHANNEL ACTIVATORS

11. Respiratory disease


Respiratory disease
TUBERCULOSISnd
DIFFUSE DISEASES OF THE LUNG PARENCHYMA
OCCUPATIONAL LUNG DISEASE
CARCINOMA OF THE LUNG
DISEASES OF THE CHEST WALL AND PLEURA
DISORDERS OF THE DIAPHRAGM

12. Intensive care medicine

Intensive care medicine

13. Drug therapy, poisoning, and alcohol misuse

Drug therapy, poisoning, and alcohol misuse

14. Endocrine disease

Endocrine disease
PITUITARY HYPERSECRETION SYNDROMES
THE THYROID AXIS
MALE REPRODUCTION AND SEX
FEMALE REPRODUCTION AND SEX
THE GLUCOCORTICOID AXIS
THE THIRST AXIS
DISORDERS OF CALCIUM METABOLISM
DISORDERS OF PHOSPHATE CONCENTRATION
ENDOCRINOLOGY OF BLOOD PRESSURE CONTROL
DISORDERS OF TEMPERATURE REGULATION
THERAPEUTICS

15. Diabetes mellitus and other disorders of metabolism

DIABETES MELLITUS
DIABETIC METABOLIC EMERGENCIES
COMPLICATIONS OF DIABETES
SPECIAL SITUATIONS
HYPOGLYCAEMIA IN THE NON - DIABETIC
DISORDERS OF LIPID METABOLISM
THE PORPHYRIAS

16. The special senses

THE EAR
THE NOSE AND NASAL CAVITY
THE THROAT
THE EYE

17. Neurology

COMMON NEUROLOGICAL SYMPTOMS
COORDINATION OF MOVEMENT
THE CRANIAL NERVES
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EPILEPSY AND LOSS OF CONSCIOUSNESS
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DEGENERATIVE NEURONAL DISEASES
DISEASES OF THE PERIPHERAL NERVES
MUSCLE DISEASES
MYOTONIAS
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Dermatology

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