Sarcoidosis - Granulomatous/vasculitic lung disorders

Granulomatous/vasculitic lung disorders

Sarcoidosis

Definition

Multisystem chronic granulomatous disorder of unknown origin.

Incidence

19 per 100,000 in United Kingdom.

Age

Under 40 years; peak 20–30 years.

Sex

F > M

Geography

Affects American Afro Caribbeans more than Caucasians. Uncommon in Japan.

Aetiology

No HLA association but familial cases seen, suggesting environmental factors.

Because of the granulomata, atypical mycobacterium, Epstein–Barr virus or other infections have been suggested but never proven.

Beryllium poisoning can cause an identical clinical picture.

Pathophysiology

Unknown but there is strong evidence for an immunopathological basis:

1.     The granulomas consist of macrophages and mainly T lymphocytes, particularly helper (CD4+) cells, and even before granulomas form bronchoalveolar lavages reflect this cell mix.

2.     Peripheral blood has decreased T cells and relatively increased B cells (overall lymphopenia).

3.     Depressed cell mediated immunity is demonstrated by the depressed responses to tuberculin or other immunological skin testing (this is called ‘anergy’).

Clinical features

Around half present with respiratory symptoms or are diagnosed following an incidental finding of bilateral hilar lymphadenopathy or lung infiltrates on chest X-ray. Next most common are skin and ocular presentations. Other presentations include arthralgias, non-specific symptoms of weight loss, fatigue and fever.

Pulmonary manifestations:

·        Bilateral hilar lymphadenopathy with or without pulmonary infiltration.

·        Pulmonary infiltration may be progressive leading to fibrosis, increasing effort dyspnoea and eventually corpulmonale and death.

Extra pulmonary manifestations:

Any organ of the body can be affected, most commonly:

·        Skin: Sarcoid is the commonest cause of erythema nodosum, when associated with bilateral hilar lymphadenopathy it is diagnostic. Violaceous plaques on the nose, cheeks, ears and fingers known as lupus pernio or skin nodules may occur.

·        Eyes: Anterior uveitis is common.

·        Enlargement of lacrimal and parotid glands.

·        Arthralgia and joint swelling with associated bone cysts.

·        Cranial nerve involvement particularly facial nerve palsy occurs but is uncommon.

·        Hepatosplenomegaly often present though rarely clinically relevant.

·        Cardiac involvement is relatively common: ventricular dysrhythmias, conduction defects and cardiomyopathy with congestive cardiac failure.

·        Ten per cent of patients with established sarcoidosis have hypercalcaemia and hypercalciuria which can lead to renal calculi. This is thought to be due to 1α-hydroxylation of vitamin D in sarcoid macro-phages, which results in raised levels of 1,25-dihydroxy vitamin D3.

Microscopy

Non-caseating granulomas consisting of focal accumulation of epithelioid cells, macrophages, (mainly T) lymphocytes and giant cells.

Investigations

Chest X-ray: Bilateral hilar lymphadenopathy (differential: lymphoma, TB, Ca). Pulmonary infiltration: mottling of mid and lower zones proceeding to bilateral fine nodular shadowing. May be normal even with infiltration.

Lung function tests show a restrictive pattern with infiltration.

Full blood count: Mild normochromic, normocytic anaemia with raised ESR and/or CRP.

Serum angiotensin converting enzyme (ACE): In 75% of patients with untreated sarcoid ACE is >2sd above the mean. Not diagnostic but useful to assess activity of pulmonary infiltrates.

Transbronchial biopsy: Infiltration of the alveolar walls and interstitial space with lymphocytes. Positive in 90% with or without X-ray evidence.

Tuberculin test: 80% show anergy, but this is not helpful diagnostically.

Kveim test: Intradermal injection of sarcoid tissue is not used now due to risk of infection.

Management

1.     1 Acute sarcoidosis, e.g. hilar lymphadenopathy with erythema nodosum usually resolves spontaneously over 2 years and usually does not require treatment if asymptomatic. If symptomatic responds well to steroid therapy.

2.     The more chronic form with evidence of infiltration or abnormal lung function is unlikely to improve with-out treatment and is initially treated with steroids and monitored with lung function tests, ESR, CRP and/or serum ACE levels.

Indications for systemic steroids:

·        Progressive deterioration in lung function or symptomatic pulmonary lesions.

·        Cardiac, CNS or severe ocular involvement. Hypercalcaemia.

·        Hepatitis (rare).

·        Skin lesions such as erythema nodosum respond rapidly to a short course.

·        Constitutional symptoms may also respond.

Prognosis

Once on steroids, many patients require long-term medium dose prednisolone; however, many patients are able to stop steroids after ∼2 years. The disease has a high spontaneous remission rate.

·        Sarcoidosis is more severe in Black Americans where the death rates are up to 10%.

·        In the United Kingdom the death rate is approximately 1 in 20 often due to respiratory problems.

·        The chest X-ray provides a guide to prognosis:

1.        In patients with only hilar lymphadenopathy two thirds will remit in 2 years.

2.        In patients with lymphadenopathy and infiltration one half will remit in 2 years.

3.        In patients with infiltration alone only one third will remit in 2 years.