Medicine – Diseases Caused by Exposure to Asbestos

Asbestos exposure can produce several important pleural and pulmonary diseases. The main conditions are pleural plaques and diffuse pleural thickening, asbestosis, lung cancer, and malignant mesothelioma. These disorders usually have a long latency period, often developing 20 years or more after exposure.

1. Pleural Plaques and Pleural Thickening

Pleural plaques are the most common manifestation of previous asbestos exposure. They usually develop more than 20 years after exposure and are typically found on the parietal pleura, especially along the posterolateral chest wall and over the diaphragm.

They may become calcified and are often detected incidentally on chest radiography or CT.

Clinical Features

Pleural plaques are usually asymptomatic and generally do not cause major respiratory impairment.

However, some patients develop diffuse pleural thickening, in which the pleural fibrosis becomes more extensive and confluent. This can restrict expansion of the lungs and lead to exertional shortness of breath.

Lung Function

Diffuse pleural thickening may produce a restrictive ventilatory defect on spirometry.

The KCO, or carbon monoxide transfer coefficient, may remain relatively normal because the underlying alveolar-capillary membrane may be preserved. This helps distinguish pleural restriction from true interstitial pulmonary fibrosis.

2. Asbestosis

Asbestosis is a form of diffuse interstitial pulmonary fibrosis caused by substantial inhalational exposure to asbestos fibres. It also typically develops only after a long latent period, commonly more than 20 years after exposure.

The fibrosis predominantly affects the lower lobes and subpleural regions of the lungs.

Clinical Features

Patients usually present with a progressive dry cough and exertional dyspnoea.

On examination, fine bibasal or lower-zone inspiratory crepitations are common. Finger clubbing may also occur, particularly in more advanced disease.

Symptoms and functional limitation generally progress gradually.

Association with Lung Cancer

Asbestos exposure significantly increases the risk of bronchogenic carcinoma.

The risk is especially high in individuals who also smoke because smoking and asbestos exposure have a synergistic effect on lung cancer risk.

This is an important distinction from mesothelioma, for which smoking is not considered a major independent risk factor.

Chest Radiograph

The chest radiograph may show bilateral irregular reticular or linear shadowing, particularly in the lower zones.

As disease progresses, more extensive fibrotic changes may appear. Advanced fibrosis can produce architectural distortion, traction bronchiectasis, and honeycomb-type change.

High-resolution CT is more sensitive than a plain chest radiograph for detecting early asbestosis.

Pulmonary Function Tests

Asbestosis produces a restrictive pattern, with reduced lung volumes.

Unlike isolated pleural thickening, the KCO or gas transfer capacity is often reduced because fibrosis damages the alveolar-capillary interface and impairs diffusion of oxygen and carbon monoxide.

Compensation and Occupational Disease

Asbestosis is an important occupational lung disease, and affected individuals may be eligible for occupational disease compensation depending on the jurisdiction, degree of exposure, and severity of impairment.

A detailed occupational history is therefore important in anyone with suspected asbestos-related disease.

3. Malignant Mesothelioma

Malignant mesothelioma is an aggressive tumour arising from mesothelial surfaces, most commonly the pleura.

The majority of cases are associated with previous asbestos exposure, although older figures such as 85% vary between populations and studies. The latency period is often very long, frequently several decades after exposure.

Clinical Features

Patients commonly present with progressive shortness of breath, chest pain, weight loss, and recurrent unilateral pleural effusions.

As the tumour spreads along the pleural surface, it can cause diffuse pleural thickening and encasement of the lung, leading to increasing respiratory restriction.

Imaging

Chest imaging may demonstrate unilateral pleural effusion, nodular pleural thickening, pleural masses, and contraction of the affected hemithorax.

CT is more useful than plain radiography for assessing the extent of pleural disease and planning biopsy.

Key Clinical Pattern

Asbestos exposure causes several characteristic diseases. Pleural plaques are usually asymptomatic markers of previous exposure, while diffuse pleural thickening can cause restrictive breathlessness.

Asbestosis is a lower-zone interstitial pulmonary fibrosis associated with dry cough, exertional dyspnoea, bibasal crackles, clubbing, restrictive lung function, and reduced gas transfer.

Asbestos exposure also increases the risk of lung cancer and malignant mesothelioma, both of which may appear decades after the original occupational or environmental exposure.

1. Pleural Plaques and Pleural Thickening Pleural plaques are the most common manifestation of previous asbestos exposure. They usually develop more than 20 years after exposure and are typically found on the parietal pleura, especially along the posterolateral chest wall and over the diaphragm. They may become calcified and are often detected incidentally on chest radiography or CT. 

Clinical Features Pleural plaques are usually asymptomatic and generally do not cause major respiratory impairment. However, some patients develop diffuse pleural thickening, in which the pleural fibrosis becomes more extensive and confluent. This can restrict expansion of the lungs and lead to exertional shortness of breath. 

Lung Function Diffuse pleural thickening may produce a restrictive ventilatory defect on spirometry. The KCO, or carbon monoxide transfer coefficient, may remain relatively normal because the underlying alveolar-capillary membrane may be preserved. This helps distinguish pleural restriction from true interstitial pulmonary fibrosis. 

2. Asbestosis Asbestosis is a form of diffuse interstitial pulmonary fibrosis caused by substantial inhalational exposure to asbestos fibres. It also typically develops only after a long latent period, commonly more than 20 years after exposure. The fibrosis predominantly affects the lower lobes and subpleural regions of the lungs. 

Clinical Features Patients usually present with a progressive dry cough and exertional dyspnoea. On examination, fine bibasal or lower-zone inspiratory crepitations are common. Finger clubbing may also occur, particularly in more advanced disease. Symptoms and functional limitation generally progress gradually. 

Association with Lung Cancer Asbestos exposure significantly increases the risk of bronchogenic carcinoma. The risk is especially high in individuals who also smoke because smoking and asbestos exposure have a synergistic effect on lung cancer risk. This is an important distinction from mesothelioma, for which smoking is not considered a major independent risk factor. 

Chest Radiograph The chest radiograph may show bilateral irregular reticular or linear shadowing, particularly in the lower zones. As disease progresses, more extensive fibrotic changes may appear. Advanced fibrosis can produce architectural distortion, traction bronchiectasis, and honeycomb-type change. High-resolution CT is more sensitive than a plain chest radiograph for detecting early asbestosis. 

Pulmonary Function Tests Asbestosis produces a restrictive pattern, with reduced lung volumes. Unlike isolated pleural thickening, the KCO or gas transfer capacity is often reduced because fibrosis damages the alveolar-capillary interface and impairs diffusion of oxygen and carbon monoxide. 

Compensation and Occupational Disease Asbestosis is an important occupational lung disease, and affected individuals may be eligible for occupational disease compensation depending on the jurisdiction, degree of exposure, and severity of impairment. A detailed occupational history is therefore important in anyone with suspected asbestos-related disease. 

3. Malignant Mesothelioma Malignant mesothelioma is an aggressive tumour arising from mesothelial surfaces, most commonly the pleura. The majority of cases are associated with previous asbestos exposure, although older figures such as 85% vary between populations and studies. The latency period is often very long, frequently several decades after exposure. 

Clinical Features Patients commonly present with progressive shortness of breath, chest pain, weight loss, and recurrent unilateral pleural effusions. As the tumour spreads along the pleural surface, it can cause diffuse pleural thickening and encasement of the lung, leading to increasing respiratory restriction. 

Imaging Chest imaging may demonstrate unilateral pleural effusion, nodular pleural thickening, pleural masses, and contraction of the affected hemithorax. CT is more useful than plain radiography for assessing the extent of pleural disease and planning biopsy. 

Key Clinical Pattern Asbestos exposure causes several characteristic diseases. Pleural plaques are usually asymptomatic markers of previous exposure, while diffuse pleural thickening can cause restrictive breathlessness. Asbestosis is a lower-zone interstitial pulmonary fibrosis associated with dry cough, exertional dyspnoea, bibasal crackles, clubbing, restrictive lung function, and reduced gas transfer. Asbestos exposure also increases the risk of lung cancer and malignant mesothelioma, both of which may appear decades after the original occupational or environmental exposure.

Medicine – Granulomatous Lung Disease: Sarcoidosis

Sarcoidosis is a systemic granulomatous inflammatory disease that can involve almost any organ, although the lungs and intrathoracic lymph nodes are most commonly affected. Its pathological hallmark is the formation of non-caseating granulomas. The clinical course is highly variable: some patients remain completely asymptomatic and undergo spontaneous resolution, whereas others develop chronic progressive disease with irreversible organ damage.

1. Multisystem Disease

Sarcoidosis is a multisystem disorder, meaning that several organs may be affected simultaneously. Pulmonary involvement is particularly common, but disease can also occur in the skin, eyes, heart, liver, spleen, nervous system, bones, and joints.

The extent of organ involvement varies considerably between patients, making sarcoidosis a disease with a broad range of clinical presentations.

2. Cause

The precise cause of sarcoidosis remains unknown. It is thought to result from an exaggerated immune response to one or more unidentified environmental or infectious antigens in genetically susceptible individuals.

The immune response leads to accumulation of activated T lymphocytes and macrophages and ultimately to the formation of granulomas within affected tissues.

3. Age Distribution

Sarcoidosis commonly affects young and middle-aged adults, although it can occur at virtually any age.

Many patients develop the disease between approximately 20 and 40 years of age, with demographic patterns varying between populations.

4. Ethnic and Geographic Variation

The incidence and clinical severity of sarcoidosis vary considerably according to ethnicity and geographic region.

Older teaching commonly describes sarcoidosis as approximately three times more common in Black populations than White populations, particularly based on US data. More broadly, modern epidemiological studies confirm a substantially increased incidence in some populations of African ancestry, although the exact magnitude varies by location and population studied.

5. Non-Caseating Granulomas

The characteristic pathological lesion of sarcoidosis is the non-caseating granuloma. These granulomas consist predominantly of organised collections of epithelioid macrophages and multinucleated giant cells surrounded by lymphocytes.

Unlike the granulomas classically associated with tuberculosis, sarcoid granulomas usually lack central caseous necrosis.

However, finding a non-caseating granuloma is not by itself diagnostic of sarcoidosis. Other causes of granulomatous inflammation, particularly tuberculosis, fungal infection, occupational exposure, and certain drug reactions, must be excluded according to the clinical setting.

6. Genetic Associations

Sarcoidosis has a genetic component, with particular HLA alleles associated with susceptibility, clinical phenotype, and prognosis.

Older descriptions emphasised associations with HLA-A1, HLA-B8, and HLA-DR3. Modern genetic studies show that the relationship is more complex, with several HLA class II variants associated with different forms and outcomes of the disease.

Pulmonary Manifestations

7. Clinical Features

Pulmonary sarcoidosis has a highly variable presentation. Some patients have no respiratory symptoms and are diagnosed incidentally after an abnormal chest radiograph performed for another reason.

Other patients develop persistent dry cough, exertional shortness of breath, chest discomfort, fever, fatigue, and weight loss.

Respiratory Examination

Physical examination can be surprisingly normal despite significant radiological abnormalities.

Inspiratory crackles may occur when there is substantial interstitial lung involvement. Finger clubbing is uncommon in sarcoidosis; its presence should suggest advanced fibrotic disease or prompt consideration of an alternative diagnosis.

Bilateral Hilar Lymphadenopathy

Bilateral hilar lymphadenopathy (BHL) is one of the most characteristic radiological manifestations of sarcoidosis.

The combination of bilateral hilar lymphadenopathy and erythema nodosum, particularly in a young adult with compatible symptoms, is highly suggestive of sarcoidosis and may form part of the acute presentation known as Löfgren syndrome.

Pulmonary Fibrosis

Most patients do not progress to severe fibrosis, but chronic pulmonary sarcoidosis can eventually produce irreversible pulmonary fibrosis.

Fibrotic disease classically has an upper- and mid-zone predominance, unlike some other fibrotic interstitial lung diseases that predominantly affect the lung bases. Advanced disease can produce architectural distortion, traction bronchiectasis, respiratory impairment, and pulmonary hypertension.

Diagnosis

8. Establishing the Diagnosis

Diagnosis is based on a combination of a compatible clinical and radiological presentation, histological demonstration of non-necrotising granulomatous inflammation when required, and exclusion of alternative causes of granulomatous disease.

No single blood test is sufficiently specific to establish the diagnosis.

Tissue Biopsy

When histological confirmation is required, tissue should ideally be obtained from the safest and most accessible affected site.

Bronchoscopy may be used to obtain transbronchial lung biopsies. In patients with enlarged hilar or mediastinal lymph nodes, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is also widely used.

Biopsy typically demonstrates non-caseating granulomas, but infectious causes such as tuberculosis must be excluded before attributing the findings to sarcoidosis.

Hypercalcaemia

Sarcoidosis may cause hypercalcaemia and/or hypercalciuria. Activated macrophages within granulomas can increase production of active vitamin D, resulting in increased intestinal calcium absorption.

Persistent abnormalities of calcium metabolism may contribute to renal calculi and renal impairment.

Serum ACE

Serum angiotensin-converting enzyme (ACE) levels may be elevated because ACE can be produced by cells within sarcoid granulomas.

However, serum ACE has limited sensitivity and specificity and cannot reliably confirm or exclude sarcoidosis. It should therefore be interpreted only as a supportive finding in the appropriate clinical context.

Chest Radiograph Staging

Stage 0 – Normal Chest Radiograph

In Stage 0, the chest radiograph is normal despite the possibility of sarcoidosis involving extrapulmonary organs.

Stage I – Bilateral Hilar Lymphadenopathy

Stage I consists of bilateral hilar lymphadenopathy without pulmonary infiltrates. This pattern is commonly associated with a favourable prognosis and spontaneous resolution.

Stage II – BHL with Pulmonary Infiltrates

Stage II consists of bilateral hilar lymphadenopathy together with pulmonary parenchymal infiltrates.

Both the intrathoracic lymph nodes and lung tissue are therefore visibly involved.

Stage III – Pulmonary Infiltrates Without BHL

Stage III is characterised by pulmonary infiltrates without bilateral hilar lymphadenopathy.

This represents more prominent parenchymal pulmonary involvement.

Stage IV – Pulmonary Fibrosis

An important addition to the older classification in your notes is Stage IV, which represents established pulmonary fibrosis.

There may be upper-lobe volume loss, architectural distortion, fibrotic bands, traction bronchiectasis, and other features of chronic irreversible lung disease.

Extrapulmonary Manifestations

9. Liver

Hepatic involvement is relatively common and is frequently asymptomatic. Granulomas may be found within the liver even when there is little or no clinically apparent hepatic disease.

Some patients develop abnormal liver function tests, hepatomegaly, or, rarely, clinically significant chronic liver disease.

10. Cardiac Sarcoidosis

Cardiac involvement is particularly important because it can produce serious or potentially life-threatening complications.

Granulomatous inflammation and subsequent fibrosis can interfere with the cardiac conduction system and myocardium, producing atrioventricular block, ventricular arrhythmias, cardiomyopathy, heart failure, or sudden cardiac death.

The frequency of clinically apparent cardiac sarcoidosis is considerably lower than some older quoted figures of 30–70%, although occult cardiac involvement may be detected more frequently at imaging or autopsy.

11. Skin

Approximately one-quarter of patients may develop cutaneous manifestations.

Erythema nodosum produces painful, tender red nodules, typically over the shins, and is particularly associated with acute sarcoidosis.

Other manifestations include papules, plaques, subcutaneous nodules, and lupus pernio. Lupus pernio consists of chronic violaceous lesions, particularly affecting the nose, cheeks, ears, and other facial areas, and tends to be associated with more chronic disease.

12. Eyes

Ocular involvement most commonly presents as uveitis, particularly anterior uveitis.

Patients may develop eye pain, redness, photophobia, and visual disturbance. Because untreated ocular inflammation can threaten vision, ophthalmological assessment is important when eye involvement is suspected.

13. Splenic Involvement

The spleen may be infiltrated by granulomas, resulting in splenomegaly.

Significant splenic involvement can occasionally contribute to cytopenias through hypersplenism.

14. Neurological Sarcoidosis

Neurosarcoidosis occurs in a minority of patients but can affect almost any part of the nervous system.

Manifestations include cranial nerve palsies, meningitis, hydrocephalus, hypothalamic or pituitary disease, peripheral neuropathy, spinal cord involvement, and mass-like intracranial lesions.

Cranial neuropathy, particularly facial nerve palsy, is a well-recognised presentation.

15. Bone and Joint Disease

Sarcoidosis may involve the bones and joints. Chronic osseous sarcoidosis can produce cystic or lytic lesions, particularly in the small bones of the hands and feet.

Musculoskeletal disease may also present with arthralgia or inflammatory arthritis, with ankle involvement being particularly characteristic of acute sarcoidosis.

Löfgren Syndrome

Löfgren syndrome is an acute and characteristic presentation of sarcoidosis. It classically consists of the triad of:

Bilateral hilar lymphadenopathy + erythema nodosum + acute arthritis or periarthritis, particularly affecting the ankles.

It usually has a favourable prognosis, and spontaneous resolution is common.

Treatment

16. Observation and Symptomatic Treatment

Not every patient with sarcoidosis requires specific treatment. Patients with mild or asymptomatic disease and preserved organ function may be monitored because spontaneous remission is common.

Symptomatic treatment can be provided when necessary, together with regular assessment for progression or important organ involvement.

17. Corticosteroids

Systemic corticosteroids are a mainstay of treatment when sarcoidosis causes significant symptoms, progressive pulmonary disease, or clinically important extrapulmonary organ involvement.

Treatment is particularly important when there is potentially serious involvement of organs such as the heart, nervous system, or eyes, although management depends on the specific manifestation.

18. Immunosuppressive Therapy

When corticosteroids are ineffective, cause unacceptable adverse effects, or prolonged steroid-sparing treatment is required, additional immunosuppressive therapy may be used.

Methotrexate is a commonly used steroid-sparing agent. Other therapies may include azathioprine, mycophenolate, or selected biologic agents such as anti-TNF therapy in difficult refractory disease.

Key Clinical Pattern

Think of sarcoidosis in a young or middle-aged adult presenting with bilateral hilar lymphadenopathy, dry cough or dyspnoea, erythema nodosum, uveitis, or ankle arthritis.

The pathological hallmark is a non-caseating granuloma, but other granulomatous diseases—especially tuberculosis and fungal infection—must be excluded.

A particularly memorable presentation is Löfgren syndrome: bilateral hilar lymphadenopathy + erythema nodosum + acute ankle arthritis/periarthritis. Pulmonary disease may resolve spontaneously, but a minority of patients develop chronic disease and irreversible pulmonary fibrosis.

Medicine – Connective Tissue Disease and the Lung

Connective tissue diseases (CTDs) frequently involve the respiratory system. Pulmonary manifestations may affect the lung parenchyma, pleura, airways, pulmonary vasculature, or respiratory muscles. In some patients, lung disease may become a major cause of morbidity and can occasionally precede the more typical systemic manifestations of the underlying connective tissue disorder.

1. Rheumatoid Arthritis

Rheumatoid arthritis (RA) can produce several different pulmonary manifestations. Lung involvement is particularly important in patients with longstanding or seropositive disease and may involve the lung parenchyma, pleura, or airways.

Pulmonary Nodules

Rheumatoid nodules can develop within the lungs, particularly in patients with severe seropositive RA. They are usually located peripherally and may be single or multiple.

Some rheumatoid nodules undergo central necrosis and cavitation, which can make them difficult to distinguish radiologically from infection, malignancy, or other causes of cavitating pulmonary nodules.

Pulmonary Fibrosis

Interstitial lung disease (ILD) is one of the most important pulmonary complications of RA. Progressive inflammation and fibrosis of the pulmonary interstitium can produce exertional breathlessness, persistent dry cough, and reduced exercise tolerance.

High-resolution CT may demonstrate several patterns, with usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia being important examples.

Bronchiectasis

Bronchiectasis occurs more frequently in patients with RA than in the general population. Permanent dilatation of the bronchi can result in chronic productive cough, recurrent respiratory infections, and haemoptysis.

Its presence is particularly important when immunosuppressive treatment is being considered because recurrent pulmonary infection may complicate therapy.

Caplan’s Syndrome

Caplan’s syndrome, also known as rheumatoid pneumoconiosis, occurs when rheumatoid arthritis is associated with occupational exposure to mineral dust, classically coal or silica.

Chest imaging typically demonstrates multiple, well-defined pulmonary nodules, which may enlarge or occasionally cavitate.

Pleural Effusion

RA can cause pleuritis with pleural effusion. The effusion is usually exudative and characteristically may have a very low glucose concentration and low pH.

Patients may experience pleuritic chest pain and breathlessness, although some rheumatoid pleural effusions are discovered incidentally.

2. Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) can affect several components of the respiratory system. Although pulmonary fibrosis and shrinking lung syndrome are recognised manifestations, SLE can also cause pleuritis, pleural effusions, acute lupus pneumonitis, and pulmonary haemorrhage.

Pulmonary Fibrosis

Chronic interstitial lung disease and pulmonary fibrosis can occur in SLE, although clinically significant fibrosis is less characteristic than in systemic sclerosis.

Patients may develop progressive exertional dyspnoea, dry cough, restrictive pulmonary function abnormalities, and impaired gas transfer.

Shrinking Lung Syndrome

Shrinking lung syndrome is a rare but distinctive pulmonary complication of SLE. It is characterised by progressive breathlessness, reduced lung volumes, and elevation of the diaphragm without significant interstitial lung disease explaining the restriction.

The mechanism is not completely understood but may involve diaphragmatic dysfunction, pleural inflammation, and abnormalities of respiratory muscle function.

3. Systemic Sclerosis

Systemic sclerosis (scleroderma) has a particularly strong association with pulmonary disease. Lung involvement is clinically important because it is a major contributor to morbidity and mortality.

The two major pulmonary complications to remember are interstitial lung disease and pulmonary arterial hypertension.

Pulmonary Fibrosis

Interstitial lung disease with pulmonary fibrosis is a major manifestation of systemic sclerosis. The most common radiological pattern is nonspecific interstitial pneumonia (NSIP).

Progressive fibrosis causes exertional dyspnoea, dry cough, restrictive lung physiology, and reduced diffusing capacity. High-resolution CT and pulmonary function tests are important for assessment and monitoring.

Bronchiectasis

Bronchiectatic changes may occur in systemic sclerosis, particularly as traction bronchiectasis secondary to pulmonary fibrosis. As fibrotic lung tissue contracts, it pulls the airways open and produces abnormal bronchial dilatation.

This differs from primary bronchiectasis caused mainly by recurrent airway infection.

Pulmonary Arterial Hypertension

An additional important manifestation is pulmonary arterial hypertension (PAH), particularly associated with limited cutaneous systemic sclerosis.

Patients may develop progressive exertional breathlessness, fatigue, syncope, and eventually right-sided heart failure. Pulmonary hypertension can occur independently of significant pulmonary fibrosis and therefore requires specific consideration during follow-up.

Key Clinical Pattern

Rheumatoid arthritis is associated with pulmonary nodules, interstitial fibrosis, bronchiectasis, Caplan’s syndrome, and pleural disease.

SLE can cause interstitial lung disease and shrinking lung syndrome, as well as pleuritis, pneumonitis, and pulmonary haemorrhage.

Systemic sclerosis is particularly associated with interstitial pulmonary fibrosis and pulmonary arterial hypertension, while bronchiectatic changes may develop secondary to fibrosis.

Medicine – Churg–Strauss Syndrome

Churg–Strauss syndrome, now more commonly called eosinophilic granulomatosis with polyangiitis (EGPA), is a rare systemic small- to medium-vessel vasculitis characterised by asthma, eosinophilia, eosinophil-rich granulomatous inflammation, and necrotising vasculitis. It commonly affects the respiratory tract, peripheral nerves, skin, heart, gastrointestinal tract, and kidneys.

1. Classical Pathological Features

Churg and Strauss originally described the syndrome in patients with a combination of asthma, marked eosinophilia, granulomatous inflammation, necrotising systemic vasculitis, and glomerulonephritis.

The pathological hallmark is eosinophil-rich necrotising granulomatous inflammation, usually involving the respiratory tract, together with necrotising vasculitis of small and medium-sized vessels.

Renal involvement can occur, often as a pauci-immune necrotising glomerulonephritis, although kidney disease is generally less frequent and often less severe than in granulomatosis with polyangiitis.

2. ANCA Association

Approximately 30–50% of patients with EGPA are ANCA-positive. When ANCA is present, the usual pattern is p-ANCA with antibodies against myeloperoxidase (MPO-ANCA).

ANCA-positive patients tend to have more classic vasculitic manifestations such as glomerulonephritis and peripheral neuropathy, whereas ANCA-negative patients may have more eosinophilic tissue disease, including cardiac involvement.

3. Asthma

Asthma is one of the most characteristic features of EGPA and occurs in the great majority of patients.

It may develop many years before the systemic vasculitic phase, sometimes preceding vasculitis by up to a decade or more. The asthma is often persistent and may become increasingly difficult to control.

Because many patients receive corticosteroids for asthma, treatment can partially suppress eosinophilia and other inflammatory manifestations, potentially delaying recognition of the full syndrome.

4. Constitutional Symptoms

Systemic inflammation commonly produces malaise, fatigue, flu-like symptoms, fever, and weight loss.

Myalgias are also common and may occur as part of the systemic inflammatory phase. These symptoms can precede or accompany the onset of overt vasculitis.

5. Arthralgia

Arthralgia occurs in a substantial proportion of patients. Joint pain is usually non-erosive and may occur alongside myalgia and other constitutional symptoms.

True inflammatory arthritis can occur but is less characteristic than the respiratory, eosinophilic, neurological, and vasculitic manifestations.

6. Peripheral Neuropathy

Peripheral neuropathy is an important and characteristic manifestation of EGPA.

The classic pattern is mononeuritis multiplex, caused by vasculitic damage to the small blood vessels supplying peripheral nerves. Patients may develop sudden painful sensory loss, weakness, foot drop, or wrist drop involving individual peripheral nerves in an asymmetric distribution.

Over time, multiple nerves may become involved and produce a more confluent peripheral neuropathy.

7. Respiratory and Eosinophilic Features

In addition to asthma, patients often have allergic rhinitis, chronic sinusitis, nasal symptoms, and pulmonary infiltrates.

Pulmonary infiltrates may be transient or migratory and are related to eosinophilic inflammation. Marked peripheral blood eosinophilia is a central feature of the disease and may fluctuate with corticosteroid treatment.

8. Other Organ Involvement

The skin may be affected by palpable purpura, nodules, or other vasculitic lesions.

The heart is an especially important site of disease because eosinophilic myocarditis, pericarditis, or cardiomyopathy may occur and can be a major cause of morbidity.

The gastrointestinal tract may also be affected, causing abdominal pain, bleeding, or ischaemic complications.

Renal disease is less common than in some other ANCA-associated vasculitides but can present with haematuria, proteinuria, and glomerulonephritis.

Key Clinical Pattern

Think of eosinophilic granulomatosis with polyangiitis when a patient has adult-onset or difficult-to-control asthma, marked eosinophilia, sinus or pulmonary disease, constitutional symptoms, and systemic vasculitic manifestations such as mononeuritis multiplex.

A p-ANCA/MPO-ANCA may support the diagnosis, but a negative ANCA does not exclude EGPA because many patients are ANCA-negative.

1. Classical Pathological Features Churg and Strauss originally described the syndrome in patients with a combination of asthma, marked eosinophilia, granulomatous inflammation, necrotising systemic vasculitis, and glomerulonephritis. The pathological hallmark is eosinophil-rich necrotising granulomatous inflammation, usually involving the respiratory tract, together with necrotising vasculitis of small and medium-sized vessels. Renal involvement can occur, often as a pauci-immune necrotising glomerulonephritis, although kidney disease is generally less frequent and often less severe than in granulomatosis with polyangiitis. 

2. ANCA Association Approximately 30–50% of patients with EGPA are ANCA-positive. When ANCA is present, the usual pattern is p-ANCA with antibodies against myeloperoxidase (MPO-ANCA). ANCA-positive patients tend to have more classic vasculitic manifestations such as glomerulonephritis and peripheral neuropathy, whereas ANCA-negative patients may have more eosinophilic tissue disease, including cardiac involvement. 

3. Asthma Asthma is one of the most characteristic features of EGPA and occurs in the great majority of patients. It may develop many years before the systemic vasculitic phase, sometimes preceding vasculitis by up to a decade or more. The asthma is often persistent and may become increasingly difficult to control. Because many patients receive corticosteroids for asthma, treatment can partially suppress eosinophilia and other inflammatory manifestations, potentially delaying recognition of the full syndrome. 

4. Constitutional Symptoms Systemic inflammation commonly produces malaise, fatigue, flu-like symptoms, fever, and weight loss. Myalgias are also common and may occur as part of the systemic inflammatory phase. These symptoms can precede or accompany the onset of overt vasculitis. 

5. Arthralgia Arthralgia occurs in a substantial proportion of patients. Joint pain is usually non-erosive and may occur alongside myalgia and other constitutional symptoms. True inflammatory arthritis can occur but is less characteristic than the respiratory, eosinophilic, neurological, and vasculitic manifestations. 

6. Peripheral Neuropathy Peripheral neuropathy is an important and characteristic manifestation of EGPA. The classic pattern is mononeuritis multiplex, caused by vasculitic damage to the small blood vessels supplying peripheral nerves. Patients may develop sudden painful sensory loss, weakness, foot drop, or wrist drop involving individual peripheral nerves in an asymmetric distribution. Over time, multiple nerves may become involved and produce a more confluent peripheral neuropathy. 

7. Respiratory and Eosinophilic Features In addition to asthma, patients often have allergic rhinitis, chronic sinusitis, nasal symptoms, and pulmonary infiltrates. Pulmonary infiltrates may be transient or migratory and are related to eosinophilic inflammation. Marked peripheral blood eosinophilia is a central feature of the disease and may fluctuate with corticosteroid treatment. 

8. Other Organ Involvement The skin may be affected by palpable purpura, nodules, or other vasculitic lesions. The heart is an especially important site of disease because eosinophilic myocarditis, pericarditis, or cardiomyopathy may occur and can be a major cause of morbidity. The gastrointestinal tract may also be affected, causing abdominal pain, bleeding, or ischaemic complications. Renal disease is less common than in some other ANCA-associated vasculitides but can present with haematuria, proteinuria, and glomerulonephritis. 

Key Clinical Pattern Think of eosinophilic granulomatosis with polyangiitis when a patient has adult-onset or difficult-to-control asthma, marked eosinophilia, sinus or pulmonary disease, constitutional symptoms, and systemic vasculitic manifestations such as mononeuritis multiplex. A p-ANCA/MPO-ANCA may support the diagnosis, but a negative ANCA does not exclude EGPA because many patients are ANCA-negative.

Medicine – Obstructive Sleep Apnoea

Obstructive sleep apnoea (OSA) is a common sleep-related breathing disorder characterised by recurrent episodes of partial or complete upper-airway obstruction during sleep. These episodes cause intermittent hypoxaemia, sleep fragmentation, and repeated arousals, which can result in significant daytime symptoms and long-term cardiovascular and metabolic complications.

1. Epidemiology

OSA is particularly common in middle-aged men, although it can occur in both sexes and at any age. Older teaching often quoted a prevalence of approximately 1–2%, but modern studies suggest that OSA is substantially more common, particularly when milder disease is included.

Risk increases with age, obesity, male sex, and abnormalities that narrow the upper airway. In women, prevalence rises after menopause.

2. Apnoeic Episodes

An apnoea is a period of complete or near-complete cessation of airflow lasting at least 10 seconds. OSA severity is now assessed primarily using the apnoea–hypopnoea index (AHI), which measures the average number of apnoeas and hypopnoeas occurring per hour of sleep.

An AHI of 5–14 events/hour is mild, 15–29 is moderate, and ≥30 is severe OSA, when interpreted together with the clinical context. Therefore, the older definition of “10 or more apnoeas per hour” should not be used as the sole modern diagnostic criterion.

3. Relationship to Sleep Stage

Obstructive events may occur during any stage of sleep, but they can become particularly frequent or severe during rapid eye movement (REM) sleep.

During REM sleep, physiological reduction in skeletal muscle tone can further decrease the activity of muscles responsible for maintaining upper-airway patency.

4. Mechanism of Airway Obstruction

During sleep, the muscles supporting the upper airway relax. In susceptible individuals, this allows the airway to become narrowed or completely obstructed, commonly around the base of the tongue and soft palate/pharynx.

The patient continues making respiratory efforts against the obstructed airway. Falling oxygen levels and rising respiratory effort eventually trigger a brief arousal, restoring muscle tone and reopening the airway. This cycle may occur repeatedly throughout the night, causing severe sleep fragmentation.

5. Clinical Features

Heavy snoring is one of the most characteristic features of OSA. Sleep may be restless, and a partner may report episodes in which the patient stops breathing, followed by gasping, choking, or loud snoring when breathing resumes.

Repeated sleep disruption causes excessive daytime sleepiness, impaired concentration, reduced attention, irritability, and poor work performance. Severe daytime somnolence can increase the risk of road traffic and occupational accidents.

Morning headache may also occur. Other possible features include waking with a dry mouth, nocturia, reduced libido, and unrefreshing sleep despite apparently spending an adequate amount of time in bed.

6. Causes and Predisposing Factors

Obesity is the most important modifiable risk factor for OSA. Excess soft tissue around the neck and pharynx narrows the upper airway and makes it more susceptible to collapse during sleep.

Alcohol can worsen OSA because it reduces upper-airway muscle tone and may suppress normal arousal responses. Symptoms are therefore often more severe after drinking alcohol, particularly close to bedtime.

Acromegaly predisposes to OSA through enlargement of the tongue and other upper-airway soft tissues. Craniofacial and pharyngeal changes can further narrow the airway.

Hypothyroidism is another recognised association. Soft-tissue changes, weight gain, and reduced ventilatory function may contribute to upper-airway obstruction.

7. Diagnosis

The Epworth Sleepiness Scale can be used to assess the degree of daytime sleepiness, but it is a screening and symptom-assessment tool rather than a diagnostic test for OSA.

Overnight pulse oximetry may demonstrate repeated episodes of oxygen desaturation and can support further investigation. However, definitive assessment generally requires an overnight sleep study, using either home respiratory polygraphy or laboratory polysomnography depending on the clinical situation.

The sleep study allows calculation of the AHI and provides information about the frequency and severity of respiratory disturbances.

8. Treatment

Weight loss is particularly important in overweight or obese patients and can substantially reduce the severity of OSA. Patients should also reduce or avoid alcohol, particularly before bedtime, and address other contributing factors where possible.

Continuous positive airway pressure (CPAP) is a major treatment for clinically significant OSA. A mask delivers positive airway pressure during sleep, effectively acting as a pneumatic splint that prevents collapse of the upper airway.

Other selected patients may benefit from mandibular advancement devices, positional therapy, or upper-airway surgery, depending on the severity and anatomical cause of the obstruction.

Key Clinical Pattern

Think of obstructive sleep apnoea in a patient—particularly one with obesity—who has loud snoring, witnessed apnoeas or nocturnal choking, unrefreshing sleep, morning headaches, and excessive daytime sleepiness.

The underlying problem is recurrent upper-airway collapse during sleep. Diagnosis is established with appropriate sleep testing, while treatment commonly involves weight reduction and CPAP, together with management of contributing factors such as alcohol use and endocrine disorders.

1. Epidemiology OSA is particularly common in middle-aged men, although it can occur in both sexes and at any age. Older teaching often quoted a prevalence of approximately 1–2%, but modern studies suggest that OSA is substantially more common, particularly when milder disease is included. Risk increases with age, obesity, male sex, and abnormalities that narrow the upper airway. In women, prevalence rises after menopause. 

2. Apnoeic Episodes An apnoea is a period of complete or near-complete cessation of airflow lasting at least 10 seconds. OSA severity is now assessed primarily using the apnoea–hypopnoea index (AHI), which measures the average number of apnoeas and hypopnoeas occurring per hour of sleep. An AHI of 5–14 events/hour is mild, 15–29 is moderate, and ≥30 is severe OSA, when interpreted together with the clinical context. Therefore, the older definition of “10 or more apnoeas per hour” should not be used as the sole modern diagnostic criterion. 

3. Relationship to Sleep Stage Obstructive events may occur during any stage of sleep, but they can become particularly frequent or severe during rapid eye movement (REM) sleep. During REM sleep, physiological reduction in skeletal muscle tone can further decrease the activity of muscles responsible for maintaining upper-airway patency. 

4. Mechanism of Airway Obstruction During sleep, the muscles supporting the upper airway relax. In susceptible individuals, this allows the airway to become narrowed or completely obstructed, commonly around the base of the tongue and soft palate/pharynx. The patient continues making respiratory efforts against the obstructed airway. Falling oxygen levels and rising respiratory effort eventually trigger a brief arousal, restoring muscle tone and reopening the airway. This cycle may occur repeatedly throughout the night, causing severe sleep fragmentation. 

5. Clinical Features Heavy snoring is one of the most characteristic features of OSA. Sleep may be restless, and a partner may report episodes in which the patient stops breathing, followed by gasping, choking, or loud snoring when breathing resumes. Repeated sleep disruption causes excessive daytime sleepiness, impaired concentration, reduced attention, irritability, and poor work performance. Severe daytime somnolence can increase the risk of road traffic and occupational accidents. Morning headache may also occur. Other possible features include waking with a dry mouth, nocturia, reduced libido, and unrefreshing sleep despite apparently spending an adequate amount of time in bed. 

6. Causes and Predisposing Factors Obesity is the most important modifiable risk factor for OSA. Excess soft tissue around the neck and pharynx narrows the upper airway and makes it more susceptible to collapse during sleep. Alcohol can worsen OSA because it reduces upper-airway muscle tone and may suppress normal arousal responses. Symptoms are therefore often more severe after drinking alcohol, particularly close to bedtime. Acromegaly predisposes to OSA through enlargement of the tongue and other upper-airway soft tissues. Craniofacial and pharyngeal changes can further narrow the airway. Hypothyroidism is another recognised association. Soft-tissue changes, weight gain, and reduced ventilatory function may contribute to upper-airway obstruction. 

7. Diagnosis The Epworth Sleepiness Scale can be used to assess the degree of daytime sleepiness, but it is a screening and symptom-assessment tool rather than a diagnostic test for OSA. Overnight pulse oximetry may demonstrate repeated episodes of oxygen desaturation and can support further investigation. However, definitive assessment generally requires an overnight sleep study, using either home respiratory polygraphy or laboratory polysomnography depending on the clinical situation. The sleep study allows calculation of the AHI and provides information about the frequency and severity of respiratory disturbances. 

8. Treatment Weight loss is particularly important in overweight or obese patients and can substantially reduce the severity of OSA. Patients should also reduce or avoid alcohol, particularly before bedtime, and address other contributing factors where possible. Continuous positive airway pressure (CPAP) is a major treatment for clinically significant OSA. A mask delivers positive airway pressure during sleep, effectively acting as a pneumatic splint that prevents collapse of the upper airway. Other selected patients may benefit from mandibular advancement devices, positional therapy, or upper-airway surgery, depending on the severity and anatomical cause of the obstruction. 

Key Clinical Pattern Think of obstructive sleep apnoea in a patient—particularly one with obesity—who has loud snoring, witnessed apnoeas or nocturnal choking, unrefreshing sleep, morning headaches, and excessive daytime sleepiness. The underlying problem is recurrent upper-airway collapse during sleep. Diagnosis is established with appropriate sleep testing, while treatment commonly involves weight reduction and CPAP, together with management of contributing factors such as alcohol use and endocrine disorders.

Medicine – Causes of Cavitation on a Chest Radiograph

Pulmonary cavitation refers to an air-containing space within an area of lung consolidation, a pulmonary nodule, or a mass. It usually develops when lung tissue undergoes necrosis and then drains into the bronchial tree. Important causes include infection, malignancy, vascular disease, occupational lung disease, inflammatory disorders, and advanced fibrotic lung disease.

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1. Bullae

Pulmonary bullae are thin-walled, air-filled spaces caused by destruction and enlargement of distal air spaces, most often in association with emphysema. They are not true necrotic cavities, but they may resemble cavitary lesions on a chest radiograph.

Large bullae can compress adjacent normal lung and may rupture, occasionally leading to a spontaneous pneumothorax.

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2. Cavitating Pneumonia

Certain bacterial pneumonias can cause necrosis of lung tissue and subsequent cavitation. Important organisms include Klebsiella species, Staphylococcus aureus, and anaerobic bacteria.

Anaerobic infection is particularly associated with aspiration, while staphylococcal pneumonia can produce multiple areas of necrosis, abscess formation, or pneumatoceles.

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3. Pulmonary Tuberculosis

Tuberculosis is a classic cause of pulmonary cavitation, especially in post-primary or reactivation TB. Cavities are often found in the upper lobes and may have irregular walls.

Cavitary TB is clinically important because these lesions may contain a high concentration of organisms, making the patient potentially highly infectious.

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4. Lung Abscess

A lung abscess is a localised collection of pus caused by necrosis and destruction of lung tissue. When the abscess communicates with a bronchus, an air–fluid level may be visible on an erect chest radiograph.

Aspiration is an important cause, particularly in patients with impaired consciousness, swallowing difficulty, or poor dental hygiene.

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5. Tumour

Certain lung tumours may undergo central necrosis and cavitate. Squamous cell carcinoma is the primary lung cancer most classically associated with cavitation.

Pulmonary metastases can also occasionally cavitate. A thick-walled or irregular cavity should therefore raise suspicion of malignancy, particularly in an older patient or someone with a smoking history.

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6. Pulmonary Embolism

A pulmonary embolism can occasionally cause pulmonary infarction. If the infarct undergoes necrosis, cavitation may develop, although this is relatively uncommon.

Pulmonary infarction more commonly appears as a peripheral pleural-based opacity before any cavitation occurs.

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7. Pneumoconiotic Nodule

Occupational lung diseases such as silicosis and coal workers’ pneumoconiosis can produce large fibrotic nodules or masses. These lesions may occasionally cavitate.

In a patient with silicosis, the development of cavitation should also raise concern for superimposed tuberculosis, because silica exposure increases susceptibility to TB.

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8. Rheumatoid Nodule

Patients with rheumatoid arthritis may develop pulmonary rheumatoid nodules, particularly in severe seropositive disease.

These nodules may undergo central necrosis and cavitation. Infection and malignancy should still be excluded because they can produce a similar radiographic appearance.

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9. Granulomatosis with Polyangiitis

Granulomatosis with polyangiitis, formerly called Wegener’s granulomatosis, is a necrotising granulomatous vasculitis affecting mainly the respiratory tract and kidneys.

It commonly causes multiple pulmonary nodules or masses, and these lesions may cavitate. Other features may include sinus disease, haemoptysis, haematuria, and glomerulonephritis.

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10. Eosinophilic Granulomatosis with Polyangiitis

Eosinophilic granulomatosis with polyangiitis, formerly called Churg–Strauss syndrome, is a small-vessel vasculitis associated with asthma and eosinophilia.

Pulmonary infiltrates are common, but true cavitation is not a typical feature. If marked cavitation is present, alternative diagnoses such as granulomatosis with polyangiitis, infection, or malignancy should be considered.

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11. Honeycomb Lung

Honeycombing is seen in advanced pulmonary fibrosis and consists of multiple clustered, usually subpleural cystic air spaces caused by severe architectural distortion of the lung.

These spaces may look like multiple small cavities on imaging, but they are fibrotic cystic spaces rather than true necrotic cavities. High-resolution CT is much better than a plain chest radiograph for demonstrating this pattern.

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Key Clinical Pattern

Important causes of a cavitary appearance on chest imaging include tuberculosis, necrotising pneumonia, lung abscess, and cavitating squamous cell carcinoma.

Multiple cavitating nodules may suggest granulomatosis with polyangiitis, metastatic malignancy, septic embolic disease, or rheumatoid nodules, while bullae and honeycombing are important structural mimics of true cavitation.

Medicine – Causes of Calcification on a Chest Radiograph

Calcification on a chest radiograph can arise from several structures within the thorax, including the lungs, pleura, lymph nodes, pericardium, heart valves, and major blood vessels. The pattern and location of calcification can provide useful clues to the underlying diagnosis. Some causes reflect previous infection or inflammation, while others are related to occupational exposure, malignancy, or degenerative disease.

1. Pulmonary Calcification

Tuberculosis

Previous tuberculosis (TB) infection can leave areas of calcification within the lungs. Healed granulomas may become densely calcified, and calcified hilar or mediastinal lymph nodes can occur at the same time. These findings usually indicate old, inactive disease rather than active infection.

Carcinoma

Some lung carcinomas may contain calcification, although this is less common than in benign pulmonary lesions. Calcification within a lung mass does not automatically indicate benign disease, so the overall radiological appearance and clinical context remain important.

Chickenpox

Previous varicella (chickenpox) pneumonia can rarely heal with multiple small, scattered calcified pulmonary nodules. This gives a characteristic appearance on chest imaging and usually represents a remote complication of prior varicella infection.

Sarcoidosis

Sarcoidosis can produce pulmonary and lymph node calcification, particularly in longstanding disease. Calcification may occur in hilar or mediastinal lymph nodes and may sometimes have a characteristic eggshell-like pattern.

Asbestos Exposure

Long-term asbestos exposure is more strongly associated with pleural plaques, but pulmonary fibrosis and other parenchymal abnormalities may also be present. The presence of calcified pleural plaques is particularly suggestive of previous asbestos exposure.

Silicosis

Silicosis results from chronic inhalation of silica particles, usually through occupational exposure. It can produce multiple pulmonary nodules and characteristic calcification of hilar or mediastinal lymph nodes, sometimes described as eggshell calcification.

Pneumoconiosis

Other forms of pneumoconiosis can also lead to chronic pulmonary inflammation, fibrosis, and calcification. The exact radiographic pattern depends on the type and duration of occupational dust exposure.

2. Pleural Calcification

Asbestos-Related Pleural Plaques

Calcified pleural plaques are a classic marker of previous asbestos exposure. They commonly involve the parietal pleura and diaphragmatic surfaces and may appear as well-defined calcified areas along the chest wall.

Empyema

A previous empyema, or infected pleural collection, can heal with marked pleural thickening and calcification. In longstanding cases, the pleura may become heavily calcified and restrict expansion of the underlying lung.

Haemothorax

An old haemothorax can organise and undergo fibrosis and calcification. The resulting pleural thickening may remain visible on chest radiographs long after the original bleeding episode has resolved.

Tuberculosis

Pleural involvement by tuberculosis can produce chronic pleural inflammation and fibrosis, which may eventually calcify. This is more likely after longstanding or previously treated tuberculous pleuritis.

Recurrent Pneumothorax

Repeated episodes of pneumothorax, particularly when associated with pleural inflammation or previous pleurodesis, may lead to pleural thickening and calcific change.

3. Calcified Lymph Nodes

Tuberculosis

Healed tuberculosis commonly causes calcification of hilar or mediastinal lymph nodes. These calcified nodes may coexist with calcified pulmonary granulomas and usually represent previous granulomatous infection.

Carcinoid Tumour

Some carcinoid tumours or associated lymph node metastases may contain calcification. Calcification can sometimes be seen within a central pulmonary lesion or involved lymph nodes.

Silicosis

Silicosis can cause characteristic calcification of the hilar and mediastinal lymph nodes. The classic pattern is eggshell calcification, in which a thin rim of calcium outlines the periphery of the lymph node.

4. Other Thoracic Causes

Pericardial Calcification

Pericardial calcification usually reflects previous chronic inflammation of the pericardium. It may be seen in patients with constrictive pericarditis and can follow previous tuberculosis, cardiac surgery, radiation, or other forms of pericardial injury.

Heart Valve Calcification

Calcification may occur in the aortic or mitral valves, particularly with advancing age or longstanding valvular disease. Aortic valve calcification is commonly associated with degenerative aortic stenosis, while mitral annular calcification may also be visible on chest imaging.

Calcified Aorta

The aortic wall may become calcified as a result of atherosclerosis and age-related degenerative change. Calcification is commonly seen along the aortic arch or descending thoracic aorta and may serve as a marker of systemic vascular disease.

Key Clinical Pattern

When calcification is seen on a chest radiograph, it is useful to first determine whether it lies in the lung parenchyma, pleura, lymph nodes, pericardium, heart valves, or aorta. Pulmonary and nodal calcification often reflects old granulomatous infection such as TB or occupational disease such as silicosis, while calcified pleural plaques strongly suggest previous asbestos exposure. Cardiac and vascular calcification is more often related to chronic inflammation, valvular degeneration, or atherosclerosis.

Medicine – Common Causes of an Acute Monoarthritis

Acute monoarthritis refers to the sudden onset of pain, swelling, and inflammation affecting a single joint. It is an important clinical presentation because some causes, particularly septic arthritis, require urgent diagnosis and treatment to prevent irreversible joint damage. The differential diagnosis includes crystal arthropathies, trauma, infection, inflammatory arthritis, and bleeding into the joint.

1. Gout

Gout is a common cause of acute monoarthritis and results from deposition of monosodium urate crystals within the joint. The classic site is the first metatarsophalangeal joint, producing podagra, although the ankle, knee, wrist, and other joints may also be affected. The joint is typically extremely painful, red, swollen, and tender. Diagnosis is confirmed by identifying needle-shaped, negatively birefringent crystals in synovial fluid.

2. Pseudogout

Pseudogout, or calcium pyrophosphate deposition disease, can also present as an acute monoarthritis. It most commonly affects large joints, especially the knee, although the wrist and other joints may be involved. Synovial fluid examination shows calcium pyrophosphate crystals that are weakly positively birefringent, and radiographs may demonstrate chondrocalcinosis.

3. Trauma

Traumatic injury can produce acute pain and swelling in a single joint. Causes include ligament injury, meniscal damage, fracture, dislocation, or direct soft-tissue injury. A careful history of recent injury, examination for instability or deformity, and appropriate imaging can help distinguish trauma from inflammatory or infectious causes.

4. Acute Septic Arthritis

Septic arthritis is one of the most important causes of acute monoarthritis because it can rapidly destroy articular cartilage. Patients usually present with a severely painful, hot, swollen joint with markedly restricted movement, often accompanied by fever or systemic illness. The knee is commonly affected, although any joint can be involved. Urgent joint aspiration, Gram stain, culture, and prompt antimicrobial treatment are essential.

5. Seronegative Spondyloarthritides

The seronegative spondyloarthritides may occasionally present with acute inflammation of a single peripheral joint. This is more likely in disorders such as reactive arthritis or psoriatic arthritis. Associated features such as enthesitis, sacroiliitis, psoriasis, uveitis, or a recent gastrointestinal or genitourinary infection may help identify the underlying diagnosis.

6. Rheumatoid Arthritis

Although rheumatoid arthritis usually presents as a symmetrical polyarthritis, it can occasionally begin with inflammation of a single joint, particularly early in the disease. Persistent synovitis, later involvement of additional joints, and serological findings such as rheumatoid factor or anti-CCP antibodies may support the diagnosis.

7. Haemarthrosis

Haemarthrosis refers to bleeding into a joint and can produce sudden pain, swelling, and restricted movement. It may result from trauma, anticoagulant therapy, or inherited bleeding disorders such as haemophilia. Joint aspiration may reveal bloody synovial fluid, and management depends on the underlying cause of bleeding.

Key Clinical Point

The main causes of acute monoarthritis are gout, pseudogout, trauma, septic arthritis, seronegative spondyloarthritis, rheumatoid arthritis, and haemarthrosis. Among these, septic arthritis must always be considered urgently, especially when the joint is hot, swollen, and very painful or the patient is systemically unwell.

Medicine – Causes of an Acute Polyarthritis

Acute polyarthritis refers to the relatively sudden development of inflammatory symptoms affecting several joints. It may result from autoimmune disease, infection, crystal deposition, systemic inflammatory disorders, or less commonly other multisystem conditions. The pattern of joint involvement, associated systemic symptoms, age of the patient, and laboratory findings help distinguish the underlying cause. Conditions marked with an asterisk are among the more common causes.

1. Rheumatoid Arthritis*

Rheumatoid arthritis (RA) is a common cause of inflammatory polyarthritis. Although RA more often develops gradually, some patients can present with a relatively acute onset of symmetrical pain, swelling, and morning stiffness, particularly involving the MCP, PIP, wrist, and MTP joints. Persistent synovitis and serological findings such as rheumatoid factor or anti-CCP antibodies help support the diagnosis.

2. Generalised Osteoarthritis*

Generalised osteoarthritis can produce pain and stiffness in multiple joints, particularly in older adults. Although osteoarthritis is usually chronic and non-inflammatory, symptoms can sometimes worsen abruptly, especially when several joints become symptomatic at the same time. Typical sites include the knees, hips, spine, DIP joints, PIP joints, and first carpometacarpal joints of the thumbs.

3. Seronegative Spondyloarthritides*

The seronegative spondyloarthritides can present with acute peripheral polyarthritis or oligoarthritis. This group includes ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and enteropathic arthritis. Joint involvement is often asymmetrical and predominantly affects the lower limbs, although the exact pattern varies. Enthesitis, sacroiliitis, uveitis, psoriasis, or bowel disease may provide additional diagnostic clues.

4. Viral Infections*

Several viral infections can cause an acute polyarthritis, often as part of a systemic viral illness. The joint symptoms may be transient and can closely resemble an autoimmune inflammatory arthritis.

Rubella may cause arthralgia or polyarthritis, particularly in adults. Mumps can occasionally be associated with joint inflammation. Parvovirus B19 is a particularly important cause because it may produce an acute symmetrical small-joint polyarthritis resembling rheumatoid arthritis. Coxsackie viruses may also cause musculoskeletal symptoms. Hepatitis B and hepatitis C can produce inflammatory polyarthritis as part of their extrahepatic manifestations.

5. Reactive Arthritis

Reactive arthritis, formerly called Reiter’s syndrome, develops after an infection elsewhere in the body, particularly a gastrointestinal or genitourinary infection. It typically causes an asymmetrical inflammatory arthritis of the lower limbs, although several joints may be involved. Conjunctivitis, urethritis, enthesitis, and mucocutaneous lesions may accompany the arthritis.

6. Gonococcal Arthritis

Disseminated gonococcal infection caused by Neisseria gonorrhoeae can produce migratory polyarthralgia or polyarthritis. Patients may also develop tenosynovitis and pustular skin lesions. In some cases, the illness progresses to a more localised purulent monoarthritis. Recognition is important because antimicrobial treatment is required.

7. Adult- and Childhood-Onset Still’s Disease

Still’s disease can occur in both children and adults and may present with acute inflammatory polyarthritis. It is typically associated with high spiking fever, an evanescent salmon-pink rash, and systemic inflammation. Arthritis may appear after the constitutional symptoms have already begun.

8. Rheumatic Fever

Acute rheumatic fever can cause a characteristic migratory polyarthritis, particularly affecting large joints such as the knees, ankles, elbows, and wrists. The arthritis is usually very painful but transient, with inflammation resolving in one joint as another becomes affected. Other features may include carditis, chorea, erythema marginatum, and subcutaneous nodules.

9. Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) commonly causes inflammatory polyarthralgia or polyarthritis. The arthritis is usually non-erosive and often affects the small joints of the hands and wrists. Associated manifestations such as rash, photosensitivity, oral ulcers, serositis, renal disease, or haematological abnormalities may help establish the diagnosis.

10. Gout

Although gout usually presents as an acute monoarthritis, particularly of the first MTP joint, approximately a minority of patients may develop polyarticular gout, especially in longstanding or severe disease. Multiple joints can become acutely inflamed, sometimes making the presentation difficult to distinguish from septic or autoimmune arthritis. Synovial fluid examination reveals needle-shaped, negatively birefringent monosodium urate crystals.

11. Pyrophosphate Arthropathy

Calcium pyrophosphate deposition disease (CPPD or pseudogout) can also cause an acute polyarthritis, although large-joint monoarthritis or oligoarthritis is more typical. The knees, wrists, and other large joints are frequently involved. Joint aspiration demonstrates weakly positively birefringent calcium pyrophosphate crystals, and radiographs may show chondrocalcinosis.

12. Acute Sarcoidosis

Acute sarcoidosis can present with polyarthritis, particularly involving the ankles. A classic acute presentation is Löfgren syndrome, which consists of bilateral hilar lymphadenopathy, erythema nodosum, and acute arthritis or periarthritis. This form of sarcoidosis often has a relatively favourable prognosis.

Key Clinical Approach

Common causes of acute polyarthritis include rheumatoid arthritis, seronegative spondyloarthritis, and viral infection. Important alternatives include reactive arthritis, gonococcal infection, Still’s disease, rheumatic fever, SLE, crystal arthropathies, and acute sarcoidosis. The diagnosis is guided by the distribution of affected joints, duration of symptoms, systemic manifestations, infection history, serology, inflammatory markers, and synovial fluid analysis when appropriate.

Medicine – Risk Factors for Osteoarthritis

Osteoarthritis (OA) is a chronic degenerative joint disorder characterised by progressive loss of articular cartilage, changes in subchondral bone, and varying degrees of synovial inflammation. Although ageing is one of the strongest risk factors, osteoarthritis usually develops through a combination of mechanical stress, genetic susceptibility, previous joint damage, metabolic factors, and abnormalities of joint structure.

1. Increasing Age

Age is one of the most important risk factors for osteoarthritis. With advancing age, articular cartilage becomes less able to repair itself after repeated mechanical stress. Changes in cartilage composition, subchondral bone, muscle strength, and joint mechanics all contribute to the increasing prevalence of OA in older adults.

2. Female Sex

Women have a higher risk of osteoarthritis, particularly after middle age and after menopause. The reason is likely multifactorial and may involve hormonal influences, anatomical differences, and differences in joint biomechanics. Hand and knee osteoarthritis are especially common in women.

3. Genetic Predisposition

A family history and genetic susceptibility can increase the likelihood of developing OA. Genetic factors appear particularly important in osteoarthritis of the hands, hips, and spine. Inherited differences in cartilage structure, bone shape, or connective tissue may make certain joints more vulnerable to degeneration.

4. Obesity

Obesity is a major modifiable risk factor, especially for osteoarthritis of weight-bearing joints such as the knees and hips. Excess body weight increases the mechanical load passing through these joints and accelerates cartilage wear. Adipose tissue may also contribute through metabolic and inflammatory mediators, so the effect is not purely mechanical.

5. Joint Hypermobility

Hypermobility can increase abnormal movement and mechanical stress within a joint. Repeated excessive movement may reduce joint stability and expose articular surfaces to uneven loading, thereby increasing the risk of degenerative change over time.

6. Previous Joint Trauma

A history of significant joint injury is an important cause of secondary osteoarthritis. Fractures that extend through the articular surface are particularly important because they can permanently alter joint congruity and load distribution. Ligament injuries and meniscal damage may also increase later OA risk by producing chronic instability or abnormal biomechanics.

7. Chondrocalcinosis

Chondrocalcinosis, usually related to calcium pyrophosphate deposition, is associated with osteoarthritic change. Crystal deposition can damage cartilage and alter joint mechanics, sometimes producing a pattern of degeneration that differs from typical primary OA.

8. Previous Septic Arthritis

Septic arthritis can cause rapid and severe destruction of articular cartilage. Even after the infection has been successfully treated, residual cartilage damage and joint deformity can predispose the affected joint to secondary osteoarthritis.

Developmental Conditions

9. Congenital or Developmental Hip Abnormalities

Abnormal joint development can produce uneven loading of articular surfaces and markedly increase later OA risk. Developmental dysplasia or congenital dislocation of the hip can alter the relationship between the femoral head and acetabulum, leading to premature degeneration of the hip joint.

Perthes’ disease, in which childhood avascular necrosis affects the femoral head, can also leave residual deformity. The altered shape of the hip may cause abnormal mechanical stress and predispose to osteoarthritis in adult life.

Bone Disorders

10. Paget’s Disease of Bone

Paget’s disease produces abnormal bone remodelling and can change the shape and mechanical alignment of bones near a joint. These structural abnormalities alter the distribution of forces across articular cartilage and may lead to secondary osteoarthritis.

Endocrine and Metabolic Conditions

11. Acromegaly

In acromegaly, excess growth hormone and insulin-like growth factor 1 cause enlargement of bones, cartilage, and soft tissues. These changes alter joint structure and mechanics and may eventually result in a characteristic degenerative arthropathy.

12. Haemochromatosis

Haemochromatosis can produce a characteristic arthropathy through iron deposition and associated metabolic effects on cartilage. It is also strongly associated with calcium pyrophosphate deposition, which can further contribute to joint degeneration.

13. Wilson’s Disease

Wilson’s disease has historically been associated with degenerative joint abnormalities in some patients. Disturbances in copper metabolism may contribute to skeletal and joint changes, although this is a much less common risk factor than age, obesity, prior trauma, or developmental abnormalities.

Key Clinical Concept

The major risk factors for osteoarthritis include increasing age, female sex, genetic predisposition, obesity, hypermobility, and previous joint injury. Secondary OA can also result from conditions that damage cartilage or alter joint anatomy, including septic arthritis, chondrocalcinosis, developmental hip disorders, Paget’s disease, and selected endocrine or metabolic diseases.