Sarcoidosis
Sarcoidosis is a multisystem disorder and, although predominantly respiratory (>90%), many tissues can be affected (see
below). It usually presents in young adults, 20-40 years old, and is most
frequent in Afro-Caribbeans, Scandinavians, the Irish and relatives of patients
with sarcoidosis. Black people are more susceptible to aggressive, systemic
disease. Incidence varies
geographically from 5 to 00/ 05 population.
Aetiology: unknown, but it often follows exposure of a genetically susceptible
person (e.g. HLA-DR) to an antigenic trigger which may be infective (e.g.
mycobacteria and propionibacteria), geographical (e.g. pine pollen) or
occupational (e.g. beryllium and talc). Autoimmune causes are less likely. Histopathology is characterized by non-
caseating granulomata (NCG) and an abnormal, antigen-triggered CD4 (helper) T-cell
response. Interferon-γ release stimulates granuloma formation, fibroblast and fibrosis. Activated
macrophages release serum angiotensin-converting enzyme (SACE), and B-cell
stimulation produces immunoglobulin and immune complex formation. Delayed hypersensitivity
(e.g. to tuberculin) is reduced due to T-cell migration. Figure 3 a illustrates
other causes of lung granuloma.
Clinical features: pulmonary
(>90%), systemic or both:
1 Pulmonary sarcoidosis may
be asymptomatic ( 30%) or associated with constitutional (e.g. fever, malaise,
weight loss 30% and fatigue 70%) and/or respiratory (e.g. non-productive cough,
dyspnoea and chest discomfort 30-50%) symptoms. Physical finding (e.g. club-
bing) are rare and despite CXR infiltrate crepitations occur in less than 20%
of cases. There are two distinct pulmonary presentations:
(a) Acute sarcoidosis (Lo·fgren's syndrome) occurs mainly in Caucasians
with fever, erythema nodosum (EN), arthralgia, pulmonary infiltrate and bihilar
lymphadenopathy (BHL; Fig. 3 c(i)). The CXR f ndings may be asymptomatic.
Exclude other causes of BHL (Fig. 3 b). About 0% develop progressive lung
fibrosi (Fig. 3 c).
(b) Progressive, interstitial lung disease causes increasing dyspnoea
and cough. Infiltrate ( +BHL) are seen on CXR (Fig. 3 c(iii)) and
may progress to lung fibrosi and respiratory failure.
Diagnosis: requires a compatible clinical (+CXR) picture-histological
confirmatio of NCG and exclusion of other causes (e.g. TB). Figure 3 d
summarizes evaluation. Disease progression is monitored by serial clinical
assessment, CXR, spirometry ( +DLco)
and SACE.
SACE is raised in 80% of acute sarcoidosis and is
suppressed by steroids. It aids monitoring but is not specifi (i.e. raised in
TB).
CXR is abnormal in more than 85% of lung sarcoid, but
30-60% are asymptomatic (i.e. incidental CXR finding) BHL occurs in 50-85%,
unilateral hilar lymphadenopathy in < 0% and pulmonary infiltrates usually
central or in the upper lobes, in 25-50% of cases (Fig. 3 c). Figure 3 e shows
the CXR staging system.
High-resolution CT scans are not required for routine evaluation. They are
useful if the CXR is normal, to discriminate between inflammatio and fibrosi
and to detect complications. Characteristic early features include
bronchovascular micronodules (Fig. 3 f), inflammatio with ground glass
opacificatio and septal thickening. Later disease causes traction
bronchiectasis and f brosis.
Histological confirmation is not always needed in asymptomatic or acute
disease but is recommended in symptomatic cases or if BHL is asymmetrical or
massive to exclude malignancy ( 0%). Transbronchial lung biopsies
histologically confir approximately 70% of cases. Bronchoalveolar lavage
CD4:CD8 ratio of more than 3.5 is also specifi for sarcoidosis. Tissue biopsies
(e.g. skin and salivary/parotid gland) also confir the diagnosis, but liver
biopsies are not specific A positive Mantoux test makes sarcoidosis unlikely.
Pulmonary function tests (PFTs) are abnormal in 20% of stage I and 40-70%
of stage II-IV radiographic disease (Fig. 3 e). Typically, the defect is
restrictive, but obstructive lesions occur in approximately 40% of cases. Gas
transfer (DLco) and FVC are reduced despite a normal CXR in 5-50% of cases.
Management: Most pulmonary sarcoidosis resolves spontaneously
and treatment is not required (Fig. 3 e). Asymptomatic BHL and CXR infiltrate
(stage II and III) should be monitored.
a. Steroid
therapy alleviates acute
symptoms but does not prevent progressive pulmonary fibrosis Figure 3 g
summarizes indications for treatment. The initial response to high-dose
steroids (e.g. pred- nisolone 30-60 mg daily) is evaluated after -2 months and
gradually tapered over 6-24 months. Relapse is common (>33% within 2 years)
and is managed with prolonged low-dose steroid therapy. Prophylaxis against
osteoporosis and peptic ulcers is required. Inhaled steroids have a limited
role.
b. Immunosuppressive
therapy is indicated for
steroid-insensitive disease and as steroid sparing agents. Methotrexate and
azothioprine are beneficia in approximately 50% of steroid-resistant cases.
Other cytotoxic agents include cyclophosphamide and cyclosporine. All cause
toxicity and must be monitored. Hydroxychloroquine inhibits macrophage TNF-α
production and granuloma formation. It is effective for hypercalcaemia, skin,
lung and neurosarcoid.
c. Lung
transplant is considered in
end-stage lung disease. NCG may recur in transplanted lung.
2 Extrathoracic disease is associated with fever, weight loss,
malaise and arthralgia. Other features include hepatic NCG (60%), renal impairment
(35%), splenomegaly, bone cysts and parotid, lacrimal or salivary gland
swelling. Hypercalcaemia is common in men and Caucasians.
a.
Skin is often affected in women ( 25%). EN describes
painful, inflame plaques usually on the shins. Lupus pernio (LP) produces
indurated 'bluish', nose, ear or cheek lesions in chronic sarcoidosis. Topical
steroids may be effective in EN, but LP requires oral steroids,
hydroxychloroquine or methotrexate therapy.
b.
Eye (e.g. uveitis and scleritis) involvement is more
common in women and Afro-Caribbeans (>25%). Ophthalmology assessment is
essential. Treatment is with oral steroids ( steroid eye drops).
c. Cardiac
disease (e.g. arrhythmias and
heart failure) is uncom- mon ( 5%) in the USA and Europe but causes more than
70% of sarcoid-related deaths in Japan. Treatment is with high-dose steroids,
antiarrhythmics and pacemakers.
d. Neurosarcoid (5- 5% cases) causes nerve (e.g. mononeuritis
multiplex) and focal cerebral (e.g. diabetes insipidus) lesions. Steroid and
immunosuppressive therapy is often required.
Prognosis: factors associated with a relapsing course and
poor out-come include age more than 40 years at onset, ethnic origin (e.g.
Afro- Caribbean), extrathoracic disease and CXR stage (Fig. 3 e). Spontaneous
remission usually occurs within 3 years and failure to remit within this time
predicts a chronic course ( 0-30%) with death in 2-5% of cases. PFT have little
prognostic value, but serial FVC and DLco detect progressive fibrosi which
accounts for 87% of sarcoid-related deaths in the USA.
