Pulmonary sarcoidosis

Consider differential diagnoses when investigating this multi-system disorder, says Dr Raj Thakkar.

Sarcoidosis is a multi-system disorder characterised histologically by noncaseating granulomas that may progress to fibrosis. It affects approximately one in 5,000 people, with those living in temperate climates more likely to be affected.

Being a black American or West Indian confers a higher risk. People living in China or India are thought to be at lower than average risk.

Although it can affect almost any organ in the body, around 85 per cent of patients will have pulmonary involvement.

Multiple factors
The exact aetiology of sarcoidosis is unknown, but people with particular human leukocyte antigen types are known to be at higher risk and genetic, immune and environmental factors are probably all involved.

Alveolar injury and subsequent alveolitis is triggered by an inhaled agent. The exact nature of this agent remains unclear, although human herpes virus 8 and mycobacteria species have been implicated in some studies.

T-helper cells accumulate at the sites of inflammation and secrete chemotactic factors. These attract monocytes and macrophages, resulting in the formation of granulomas.

Macrophages stimulated by T-lymphocytes go on to become epithelioid cells, which secrete angiotensin-converting enzyme (ACE). The accumulation of T-helper cells within the granulomas may explain the reduced circulating levels of T-lymphocytes and depressed delayed hypersensitivity reactions in these patients.

Symptoms
Acute sarcoidosis presents in younger age groups, peaking between 20 and 30 years of age.

Features include erythema nodosum and bihilar lymphadenopathy. Other symptoms include iritis, arthritis and parotitis. Lofgren's syndrome is described as erythema nodosum, hilar lymphadenopathy and polyarthralgia.

Chronic sarcoidosis peaks in the fifth decade and has a more insidious course. Features include cataracts, glaucoma, pulmonary fibrosis, hypercalcaemia, seventh nerve palsy, bone cysts and cardiac, skin, pituitary, liver and spleen infiltration.

Sarcoidosis may present non-specifically with constitutional symptoms and should be considered when investigating pyrexia of unknown origin.

The mainstay of treatment is steroid therapy. Indications for steroids include stage 2-3 lung disease, severe alveolitis, breathlessness, hypercalcaemia, eye, cardiac, salivary and nervous system involvement.

Classification
Pulmonary sarcoidosis is classified according to the appearance of the chest radiograph. At presentation, 8 per cent of patients have stage zero disease. By definition this group of patients will have a normal chest film.

Around half of patients present with stage 1 disease. Bihilar lymphadenopathy is usually found. Approximately 50 per cent of these patients are asymptomatic and 90 per cent will resolve at two years.

Cough may be a presenting feature in this group and nodes may cause chest pain. Care must be taken to exclude tuberculosis and neoplastic processes.

Between a third and half of these patients have erythema nodosum, which can also be caused by drugs such as penicillin and the contraceptive Pill, pregnancy, inflammatory bowel disease, and infection. In addition, 50 per cent of erythema nodosum has an unknown cause.

Of patients with thoracic sarcoidosis, 30 per cent have stage 2 disease at presentation. Half of these show resolution at two years.

In addition to adenopathy, pulmonary infiltrate is seen on the chest film. While some people are asymptomatic, others may complain of breathlessness on exertion. Spirometry may reveal a restrictive pattern. Treatment with steroids may be required in these patients.

About 10 per cent present with stage 3 pulmonary sarcoidosis, which is defined as infiltrate with or without fibrosis on the chest film. As well as mid- and upper-zone fibrosis, cavities may also be seen. Patients may endure significant breathlessness and can go on to develop pulmonary hypertension and enlargement of the right ventricle. Less than a third of patients show a marked improvement with steroid therapy.

Investigations
A number of differential diagnoses of presenting features should be considered. Diseases with similar features include TB, pneumonia, histoplasmosis and malignancy. Fibrotic lung disease, occupational and rheumatological diseases and allergic alveolitis should also be excluded.

The FBC in sarcoidosis patients shows leukopenia and eosinophilia. The ESR tends to be raised and 10 per cent of patients have hypercalcaemia.

ACE levels are raised in less than a third of patients in stage zero and between 50 and 80 per cent of those in later stages. This test is neither sensitive nor specific and can be raised in TB, leprosy, hyperthyroidism, diabetes, liver disease and silicosis. However, they can be used to monitor the response to steroid therapy.

Spirometry is used in general practice on a regular basis and may point toward the diagnosis. Chest radiography and CT scanning are the imaging modalities generally used.

Lavage is positive in 60-100 per cent of cases depending on the stage and shows a high lymphocyte count with a high ratio of T-lymphocytes that express the CD4 antigen to those that express the CD8 antigen. Transbronchial biopsy and liver biopsy samples are highly sensitive.

Dr Thakkar is a GP in Wooburn Green, Buckinghamshire.

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