Sarcoidosis

Question 1

Sarcoidosis is a rare multisystem .. disorder of unknown aetiology.

Answer 1

Sarcoidosis is a rare multisystem granulomatous disorder of unknown aetiology.

Question 2

Epidemiology

Sarcoidosis

Answer 2

Sarcoidosis affects approximately 10-20 people per 100,000 in the UK.

Question 3

Pulmonary sarcoidosis

Answer 3

The lungs are affected in 90% of patients, though signs and symptoms may be absent or subtle.

Question 4

Sarcoidosis

If fibrosis develops a number of signs may be identified on examination:

Answer 4

Fine inspiratory crackles
Exertional desaturations
Clubbing

Question 5

What is the hallmark finding on chest radiograph in sarcoidosis?

Answer 5

. Bilateral hilar lymphadenopathy is the hallmark finding on chest radiograph.

Question 6

Ocular sarcoidosis

Answer 6

The eyes are affected in around 30-60% of cases most commonly in the form of uveitis.

Question 7

Uveitis is inflammation of the uvea, a structure composed of (from anterior to posterior) the iris, ciliary body and choroid.

Answer 7

Anterior uveitis is the inflammation of the iris (iritis) and may involve part of the ciliary body (cyclitis). Pain, redness and photophobia are typical.
Intermediate uveitis is the inflammation of parts of the ciliary body.
Posterior uveitis is the inflammation of the choroid (choroiditis). It may involve retinal vasculitis. Symptoms include floaters and visual loss.

Question 8

Cutaneous sarcoidosis

Answer 8

A number of rashes may be seen:

Papular sarcoidosis: multiple papules develop, generally on the head and neck or areas of trauma.
Erythema nodosum: a panniculitis (a condition with inflammation of subcutaneous adipose tissue) characterised by red, painful nodules.
Lupus pernio: a violaceous, nodular rash distributed over the nose and cheeks. It is pathognomonic but rare.

Question 9

Sarcoidosis may manifest itself in many ways.

Hypercalcaemia?

Answer 9

Hypercalcaemia is seen in around 15% of cases. This occurs due extra-renal synthesis of calcitriol causing 1-α hydroxylation of 25-hydroxyvitamin D and so increases levels of activated vitamin D. This leads to increased levels of calcium.

Question 10

… syndrome is an acute variant of sarcoidosis characterised by bilateral hilar lymphadenopathy, erythema nodosum, arthralgia and fever.

Answer 10

Löfgren’s syndrome is an acute variant of sarcoidosis characterised by bilateral hilar lymphadenopathy, erythema nodosum, arthralgia and fever.

Question 11

In cases of pulmonary sarcoidosis with pulmonary infiltrates and fibrosis a restrictive lung disease pattern is seen.

Answer 11

Spirometry measures the flow and volume of air during inhalation and exhalation.

FVC: the forced (expiratory) vital capacity is a persons maximal expiration following full inspiration.
FEV1: the forced expiratory volume in one second, i.e the volume of FVC expelled after one second.

Question 12

Restrictive pattern

The following changes are seen in restrictive lung disease such as sarcoidosis:

Answer 12

FVC: reduced
FEV1: reduced
FEV1/FVC: > 80%
Restrictive lung disease

Question 13

BILATERAL hilar lymphadenopathy is a characteristic finding in ….

Answer 13

Bilateral hilar lymphadenopathy is a characteristic finding in sarcoidosis.

Question 14

Observations

… test: both TB and sarcoidosis cause cavitating lung lesions. May be difficult to distinguish.

Answer 14

Observations

Mantoux test: both TB and sarcoidosis cause cavitating lung lesions. May be difficult to distinguish.

Question 15

A CXR in sarcoidosis may reveal:

Answer 15

Bilateral hilar and mediastinal lymphadenopathy
Reticulonodular opacities
Airspace opacities
Pulmonary fibrosis

Question 16

… needed to absolutely confirm a diagnosis of sarcoidosis, though it may not always be required.

Answer 16

Tissue biopsy is needed to absolutely confirm a diagnosis of sarcoidosis, though it may not always be required.

Question 17

Clinical diagnosis may be made without the need for biopsy following other relevant investigation and discussion at specialist MDTs. The British Thoracic Society: Sarcoidosis Clinical Statement (2020) describe two scenarios where a clinical diagnosis can be made:

Answer 17

Lofgren’s syndrome: there should be no suspicion of other diagnoses. Patients should follow close monitoring and follow-up.
Long-standing pulmonary disease: with a classical initial presentation, with no suspicion of other diagnoses, and stable, typical, imaging findings following MDT discussion.

Question 18

The classic histopathological finding in sarcoidosis is a …

Answer 18

The classic histopathological finding in sarcoidosis is a noncaseating granuloma.

Question 19

In those with suspected pulmonary sarcoidosis bronchoalveolar lavage ± transbronchial biopsy may be arranged. The classic histopathological finding in sarcoidosis is a noncaseating granuloma. These are collections of macrophages, epithelioid cells, t-lymphocytes (normally CD4 +ve) and giant cells that are noncaseating (or non-necrotising) - that is the centre has not undergone caseating necrosis. This is then surrounded by both T- and B- lymphocytes, mast cells and fibroblasts.

Brochoalveolar lavage can show features supportive of sarcoidosis including raised lymphocytes and a CD4/CD8 ratio > …

Answer 19

In those with suspected pulmonary sarcoidosis bronchoalveolar lavage ± transbronchial biopsy may be arranged. The classic histopathological finding in sarcoidosis is a noncaseating granuloma. These are collections of macrophages, epithelioid cells, t-lymphocytes (normally CD4 +ve) and giant cells that are noncaseating (or non-necrotising) - that is the centre has not undergone caseating necrosis. This is then surrounded by both T- and B- lymphocytes, mast cells and fibroblasts.

Brochoalveolar lavage can show features supportive of sarcoidosis including raised lymphocytes and a CD4/CD8 ratio > 4.

Question 20

Scadding staging

Answer 20

Scadding staging may be used to stage pulmonary sarcoidosis based upon chest radiograph findings.
The Scadding staging system was first published in the early 1960’s. It is based on chest radiograph findings and is used to predict the chance of spontaneous resolution. Though widely used it does have its limitations - it correlates relatively poorly with the severity of patients symptoms and does not predict well those who will need treatment.

Question 21

Managing pulmonary disease - sarcoidosis

Answer 21

Many patients will not require active treatment for sarcoidosis.
Patients should be counselled on the condition, its prognosis and both the benefits and risks of treatment. It is known that disease will regress in a significant cohort of patients without treatment. Additionally, the treatments themselves carry their own risks.

As such the British Thoracic Society (BTS) state treatment should only be started if:

Potential danger of a fatal outcome or permanent disability or
Unacceptable loss of quality of life
As with all chronic diseases, patients should be offered support and counselling. The optimisation of lifestyle factors may involve smoking cessation, weight loss and dietary advice.

Question 22

Pharmacological treatment - sarcoidosis

Answer 22

Prednisolone has been the mainstay of management for many years. Typically initial treatment consists of:

High-dose induction: typically 20 - 40mg each day for 4 - 6 weeks
Dose tapering: the initial dose is gradually reduced (e.g. 5mg every two weeks)
Maintenance dose: typically 5 - 10mg each day

Classical immunosuppressants

These are generally considered to be second-line agents. Options include methotrexate, azathioprine, leflunomide and mycophenolate They may be used in patients:

With significant side-effects from steroids
Co-morbidities putting patients at greater risk of steroid-related side effects
Progressive pulmonary disease / unacceptable ongoing symptoms
Inability to taper steroids to an acceptable maintenance dose
Patient aversion to steroid therapy - may be used as initial therapy

Biologics

Biologic agents are considered third-line therapy. They are indicated after treatment failure and use is directed by specialist tertiary centres.

Question 23

What is generally the first choice of the second-line agents in sarcoidosis?

Answer 23

Methotrexate, an antimetabolite, is generally the first choice of the second-line agents. Doses are given weekly alongside folic acid supplementation to reduce the risk of myelosuppression. Side effects include the aforementioned myelosuppression, rashes, alopecia and pneumonitis.

Question 24

Classical immunosuppressants - sarcoidosis contraindications?

Answer 24

All second-line therapies have significant side effect profiles. Baseline full blood count, renal function, liver function and viral hepatitis screen should be arranged. Contraindications to treatment include an eGFR < 30, ALT greater than two times the upper limit of the normal range (unless cause is sarcoidosis) or chronic hepatitis B/C.

Question 25

It is estimated there is a reduction in life expectancy in ..-..% of those with sarcoidosis.

Answer 25

It is estimated there is a reduction in life expectancy in 6-8% of those with sarcoidosis.

Question 26

Prognosis-sarcoidosis

Answer 26

Many patients with sarcoidosis will experience spontaneous regression and resolution of the disease. In those with pulmonary disease the chance of this can be predicted with the scadding staging (see above). The disease is known to be more severe in certain races, in black Americans mortality rates of 10% have been seen.

Pulmonary disease (including pulmonary fibrosis and pulmonary hypertension) is the predominant cause of sarcoidosis related death, implicated in around 70% of cases. Cardiac disease accounts for much of the remaining deaths.

Question 27

Lung transplant - sarcoidosis

Answer 27

Lung transplantation is a significant procedure that may be indicated in those with:

Advanced pulmonary fibrosis
Pulmonary hypertension