Sarcoidosis

Contents
Introduction
Pathology
Clinical Features
Investigations
Treatment

Introduction

Sarcoidosis is a chronic multisystem granulomatous disorder of unknown aetiology. The prevalence in the United Kingdom is around 20 to 40 per 100,000; the highest prevalence is in Sweden; the disease occurs worldwide. The age of onset is between 20 and 40 years. The disorder is slightly more common in females than males.

Pathology

The pathology of sarcoidosis can be summarised as non-caseating granulomas, chronic inflammation and fibrosis. Most of the features of the disease are attributable to the presence of one or both of these entities, especially the former.

The granulomas of sarcoidosis are usually non-necrotic although necrosis can rarely be encountered. The granulomas may feature giant cells which contain stellate concretions that are known as asteroid bodies. These are not specific to sarcoidosis. The granulomas often have only a sparse accompaniment of lymphocytes. Rarely the granulomatous inflammation can underlie a vasculitis.

The stimulus for the formation of the granulomas is unknown. Some form of mycobacterial infection has been proposed. Another theory attempted to implicate a pine tree-derived antigen, given the high incidence of the disease in Sweden. The trees are currently thought to be innocent.

Clinical Features

Sarcoidosis can produce features in many different organs and is one of a small group of diseases than can mimic the presentation of most other diseases. However, certain patterns of abnormalities are more common than others.

In around 25-40% of patients the onset is acute to subacute and develops over days to weeks. There is mild fever, malaise, anorexia and weight loss, often accompanied by features of respiratory disease. Some patients have an added constellation of abnormalities that encompasses erythema nodosum, joint symptoms and bilateral hilar lymphadenopathy and is known as Lofgren's syndrome. Other patients manifest parotid swelling, facial nerve palsy and uveitis, which can be called Heerfordt-Waldenstrom syndrome.

The remaining patients have a slower, less dramatic onset in which respiratory features are again central.

Stage one respiratory sarcoidosis comprises bilateral hilar lymphadenopathy only; this may cause a dull, central chest ache but is often asymptomatic. Stage two disease features bilateral hilar lymphadenopathy and involvement of the lung parenchyma but granulomas and ultimately fibrosis. In stage three disease only the parenchymal involvement is present. The parenchymal disease causes exertional dyspnoea and a dry cough; haemoptysis is rare.

Pleural effusions affect 5% of patients and tend to be unilateral.

Some form of respiratory disease is present in 90% of patients.

Lymphadenopathy develops in 75-90% of patients. The intrathoracic lymph nodes are the most commonly involved. Splenomegaly occurs in 5-10% although is typically of a relatively modest degree.

Sarcoidosis involves the joints in 25-50%. The larger joints are more susceptible. The arthritis is usually transient and migrates from joint to joint. Deformity of the joints is unusual. Clinically apparent muscle dysfunction is rare, although a mild degree of myositis is frequently found if a biopsy is performed.

Ocular disease is encountered in 25% of cases, of whom three quarters exhibit uveitis.

The skin is also affected in a quarter of patients. The manifestations include erythema nodosum, plaques, maculopapular eruptions and lupus pernio. The plaques are purple and tend to occur on the face, buttocks and extremeties. The maculopapular eruption prefers the face (around the eyes and nose), the back and the extremeties. Lupus pernio consists of indurated, blue-purple, shiny lesions on the nose, lips, cheeks, ears, fingers, nose and knees. Cutaneous sarcoidosis may also preferentially involve tattoos and scars.

Liver biopsy will show involvement by the disease in 60-90% of cases although hepatomegaly affects only 20-30%.

Central nervous system disease is a feature in 5%. The most frequent features centre around optic nerve and optic chiasm dysfunction, usually because the sarcoidosis has involved and enlarged the pituitary gland. However, there can also be palsies of other cranial nerves and various other lesions; the disease can resemble multiple sclerosis. Peripheral neuropathies may also develop. Psychiatric abnormalities can occur.

There are cardiac abnormalities in 5% of cases. Arrhythmias may develop if the sarcoid granulomas are located within the conducting system of the heart. Marked infiltration of the myocardium by the sarcoidosis can produce a restrictive cardiomyopathy. Pericarditis may develop.

Hypercalcaemia arises in 10% of patients and is caused by the presence of vitamin D 1-alpha-hydroxylase in the macrophages of the sarcoid granulomas. Other than hypercalcaemia the other most likely endocrine / metabolic disorder is dysfunction of the hypothalamic-pituitary system, most commonly in the form of diabetes insipidus.

Investigations

Sarcoidosis is considered to be a disease of exclusion, in that all the other disorders which could produce the clinical features in the patient should be eliminated before sarcoidosis is accepted as the diagnosis. The main concern is to avoid overlooking mycobacterial infection. Nevertheless, the clinical picture may be quite suggestive in some cases but the final diagnosis typically requires a combination of clinical features and the results of investigations.

The level of angiotensin converting enzyme (ACE) in the blood is elevated in approximately 70% of patients who have sarcoidosis and this can be a useful starting point in the set of diagnostic investigations. The concentration of calcium in the blood should also be measured.

Some form of abnormality on chest X-ray will be seen in 90% of patients while lung function tests may disclose a restrictive pattern of disease as a consequence of pulmonary fibrosis.

Demonstration of the presence of non-caseating granulomas requires a tissue sample. The predilection of sarcoidosis for the lungs often means that this must be obtained by bronchoscopy. However, if more accessible enlarged lymph nodes or skin lesions are present it is simpler to biopsy these instead. Microbiological assessment of the biopsies is essential in order to exclude the possibility of tuberculosis.

Sputum microbiology is important in order to address the differential diagnosis of tuberculosis.

A full blood count may reveal a mild anaemia, thrombocytopenia and/or leucocytopenia.

Renal dysfunction is unusual but the urea and electrolytes should be checked.

Abnormal liver function tests may be found in up to 30% of patients.

Treatment

Sarcoidosis can resolve spontaneously in 50% of patients, so treatment is not always necessary. However, if there is symptomatic lung parenchymal disease, uveitis, hypercalcaemia, neurological disease, parotid disease or cardiac disease then immunosupressive treatment with glucocorticoids is required. The use of immunosuppression explains the paranoia regarding the exclusion of tuberculosis. If somebody who has tuberculosis is immunosuppressed the mycobacteria can run amok.

The prognosis is usually good, especially if the presentation is acute. However, stage three lung disease remits in only 40%.