Derechos de remuneración

The commonest manifestation of thoracic sarcoidosis is bilateral hilar lymphadenopathy (BHL) as seen on the chest radiograph (52). In some patients it is asymptomatic and detected on a routine radiograph performed for other purposes. In others it may present with cough, breathlessness, erythema nodosum, fatigue, fever or indeed pyrexia of unknown origin (PUO), arthralgia, or a combination of any of these features. Interstitial lung involvement may be asymptomatic and physical signs absent, but breathlessness may develop. Haemoptysis and finger clubbing are rare and lung crackles are present in fewer than 20% of patients.

Extrathoracic sarcoidosis typically affects the skin, eyes, bones, heart, nervous system or kidneys (Table

30). Skin lesions include erythema nodosum (53),

nodules, lupus pernio, and scar infiltration (54). Eye disease can manifest as lacrimal gland enlargement (55), or as anterior or posterior uveitis. Posterior uveitis is the main cause of loss of vision and requires urgent treatment.

52

Table 30 Extrathoracic sarcoidosis Affected organ Frequency

Lymphoid system Palpable peripheral lymph nodes in 33%

Heart Myocardial involvement in 5%

Liver Granulomas in 50–80%

Skin 25%

Ocular lesions 11–83%; uveitis most frequent Nervous system < 10%

Musculoskeletsal Arthralgia in 25–39% system

Gastrointestinal < 1% tract

Haematological Mild leucopenia in up to 40%; manifestations mild anaemia in 4–20% Parotid glands Parotitis in < 6% Endocrine Hypercalcaemia in 2–10% manifestations

Reproductive Rare and usually asymptomatic organs

Renal tract Rarely interstitial nephritis

54 Scar infiltration in sarcoidosis 54 53 Erythema nodosum in sarcoidosis 53

Bone and joint disease includes dactylitis, osteopenic lesions (56), and arthralgia. Deforming arthritis is rare. Granulomas affecting the heart and conducting system can cause conduction defects, including third degree heart block and cardio- myopathy. Nervous system involvement may manifest as cranial and/or peripheral nerve palsies, commonly a VIIth nerve palsy, space occupying lesions which can result in seizures or diffuse CNS disease, granulo- matous meningitis, or pituitary disease causing diabetes insipidus. The kidneys may be affected by hypercalcaemic nephropathy and renal calculi, or rarely, interstitial nephritis.

INVESTIGATIONS AND DIAGNOSIS

Sarcoidosis is diagnosed on the basis of clinical symptoms and signs and on the results of investigations. There is no single diagnostic test for sarcoidosis, and no one good test exists for monitoring disease activity thereafter. Particular attention must therefore be paid to the history and examination, both at presentation and at subsequent clinic visits.

Routine blood tests include full blood count, biochemical screen, including corrected calcium and inflammatory markers, including erythrocyte sedimen- tation rate (ESR) and C-reactive protein (CRP). Mild leucopenia is common, mild anaemia may be present, and inflammatory markers may be raised. The chest radiograph may be normal, or show BHL, BHL with infiltrates, infiltrates alone, or fibrosis. Radiological staging is a guide to prognosis (Table 31).

Tuberculin skin testing helps to exclude tuberculosis; it is typically negative in sarcoidosis. A 24-hour urine calcium estimation must be performed to exclude hypercalcuria. Serum angiotensin converting enzyme (ACE) level should be measured, but a mildly raised level is nondiagnostic and in some patients ACE levels are normal at presentation and remain normal throughout the course of the disease. ECG should be performed to exclude heart block.

Full lung function testing is mandatory but must not be performed until open (smear positive) pulmonary tuberculosis is excluded because of the risk of contaminating equipment. Lung function tests may be normal or show a restrictive (small-lung) pattern with reduced gas transfer (DLCO) (see Chapter 4, page 24). Sarcoidosis can, however, also cause airflow obstruction. DLCO must be corrected for haemoglobin concentration, as an anaemia of 10 g/dl will reduce gas transfer by around 15%.

Routine HRCT scanning is not required by 55 Lacrimal gland enlargement in sarcoidosis

55

56 Bone cyst in sarcoidosis (arrowed)

56

Table 31 Chest radiograph staging of sarcoidosis

Stage Finding

0 Normal chest radiograph

I Bilateral hilar lymphadenopathy (BHL) II BHL and pulmonary infiltrates III Pulmonary infiltrates without BHL IV Pulmonary fibrosis

current North American and UK guidelines, but is recommended where there is diagnostic uncertainty, such as concern about the possibility of lymphoma, and is performed routinely in many centres. Typical HRCT features include mediastinal lympha- denopathy, nodules, and beading along broncho- vascular bundles and fissures (57).

The Kveim test, an intradermal injection of sarcoid spleen tissue resulting in granulomas at the injection site after 4–6 weeks, is not usually performed in the UK because of possible transmission of infection, including infection by slow viruses.

Gallium scanning is expensive and involves the patient making two hospital visits, one for injection and one for scanning. It involves significant radiation exposure and has limited value in diagnosing sarcoidosis. It is, however, sometimes used to assess disease activity, and to help diagnose sarcoidosis in extrathoracic disease not accessible to biopsy.

Current North American and UK guidelines recommend histological confirmation of the diagnosis. Initially, a bronchoscopy with bronchoalveloar lavage (BAL) and bronchial and transbronchial biopsies is usually performed. Transbronchial biopsy carries a small risk (< 10%) of pneumothorax. Analysis of the cellular constituents of BAL typically reveals a lymphocytosis with increased CD4:CD8 T-cell ratio. Bronchial and/or transbronchial biopsies typically show noncaseating granulomas without evidence of acid-fast bacilli. In some patients granulomas are not detectable

in these small tissue samples and further means of histological confirmation has to be sought. This may involve proceeding to mediastinoscopy or biopsy of skin, lymph node, or other lesions. Biopsy of erythema nodosum is usually not recommended.

MANAGEMENT

The natural history of sarcoidosis is highly variable and disease activity tends to wax and wane, either spontaneously or in response to therapy. In asympto- matic disease with no lung function abnormalities, treatment is not indicated and the patient can be monitored at 3–6 monthly intervals.

In patients with vital organ involvement, including progressive deterioration in lung function, prompt treatment with oral corticosteroids is indicated. The usual starting dose is 20–40 mg of oral prednisolone daily for between 1 and 3 months, with subsequent gradual reduction of the dose to the lowest possible maintenance dose. The usual length of initial treatment is up to 2 years, with around half of those patients who require steroids initially requiring further courses subsequently. Patients must be warned about the common side-effects of systemic corticosteroid treatment, including weight gain, osteoporosis, diabetes, hypertension, and cataracts. A rare but potentially serious complication is avascular necrosis of the hip.

Some patients require additional treatment with alternative immunosuppressants, although there are limited data on their efficacy. Frequently used agents include methotrexate, azathioprine, and hydroxy- chloroquine. Methotrexate and azathioprine confer a risk of potentially serious side-effects, including bone marrow suppression and teratogenicity. These must be discussed fully with the patient before starting treatment. Monitoring is required as recommended by manufacturers’ and national guidelines, and includes, as a minimum, regular full blood count, urea, and electrolytes and liver function tests.

57 Typical HRCT appearances of parenchymal nodularity and bronchovascular beading in sarcoidosis

Summary of sarcoidosis ❏ It is the commonest DPLD. ❏ Prevalence is higher in

Blacks and Afro- Caribbeans, who suffer more severe disease. ❏ It is a multisystem disease

of unknown aetiology; it affects the lungs in over 90% of cases.

❏ Biopsy showing

noncaseating granulomas in the absence of acid-fast bacilli is required to confirm diagnosis. ❏ Patients with vital organ

involvement or progressive lung function deterioration require treatment with oral

corticosteroids. CASE STUDY

good data on genotypes predisposing to the illness, but current evidence suggests that genetic factors may influence its severity. The condition may be familial.

Recent estimates of prevalence give figures of 13–20 per 100,000 of the population with an incidence of 7–11 per 100,000 per year. The incidence rises steeply with age, being approximately six times more frequent in those aged over 75 than in the age range 55–64. Prognosis is poor despite treatment, with 5- year survival < 25% and median survival of 2.8 years. Respiratory failure and cardiovascular disease are the commonest causes of death, but CFA is also associated with an increased risk of lung cancer.

CASE STUDY1

A 32-year-old woman attends the chest clinic complaining of red, tender lumps over her shins and painful ankles. Closer questioning

reveals that she has been feeling unwell for the last 6 weeks with enlarged glands and intermittent fevers. She has a non-productive cough. She recently returned from a trip to visit her family in

Pakistan but is not aware of any contact with tuberculosis. Examination reveals a pyrexia of 37.5°C, erythema nodosum, and

cervical lymphadenopathy. The chest is clear

. Initial investigations reveal abnormal liver function (mild transaminitis) and BHL on

chest radiography.

The differential diagnosis includes tuberculosis and

sarcoidosis. Lymphoma is less likely; Hodgkin’

s disease rarely causes erythema nodosum. A Heaf test should be performed. If

negative, this supports a diagnosis of sarcoidosis and makes

tuberculosis less likely. BAL should be performed and lavage

fluid sent to the microbiology laboratory to look for acid-fast bacilli, as well as to cytology for a cell count. If no acid-fast bacilli are found on Ziehl–Neelsen (ZN) stain or after 8 weeks'

culture, this makes tuberculosis much less likely

. Endobronchial and transbronchial biopsies may reveal noncaseating granulomas

typical of sarcoidosis. Finally

, HRCT scan may help if it shows parenchymal disease typical of sarcoidosis, but absence of

parenchymal disease does not exclude the diagnosis. Lung function testing should not be performed before excluding open

(smear positive) tuberculosis as far as possible. Queries about when and how to perform lung function tests should be addressed to the lung function laboratory

, and local hospital guidelines strictly followed.

CRYPTOGENIC FIBROSING ALVEOLITIS