Sarcoidosis (RESP) Flashcards
Define sarcoidosis.
Chronic granulomatous multisystem disorder of unknown aetiology
Which body systems are most commonly affected in sarcoidosis? (3)
- lungs
- skin
- eyes
What is sarcoidosis a diagnosis of exclusion of?
Granulomatous lung diseases, including TB and histoplasmosis
What is sarcoidosis characterised by?
Accumulation of lymphocytes and macrophages
Formation of non-caseating granulomas (collection of histiocytes) in the lungs and other organs
What body systems are involved in >90% of patients with sarcoidosis?
Lungs and lymph nodes
Describe the epidemiology of sarcoidosis.
- F>M
- 10x more likely in African-Americans
- bimodal peak incidence:
- 25-35 years old
- 50-65 years old
What is the aetiology of sarcoidosis?
Unknown - hypotheses suggest genetic, immunological and infectious causes
HLA-DRB1 and DQB1 alleles
Describe the pathogenesis of sarcoidosis.
- unknown antigen presented on MHC-II complexes on macrophages to CD4+ T lymphocytes
- these accumulate and release cytokines
- leads to formation of non-caseating granulomas in organs
What are the clinical features of sarcoidosis? (12)
- chronic dry cough
- dyspnoea
- wheezing
- rhonchi
- swinging fever
- chronic fatigue
- facial nerve (Bell’s) palsy
- arthralgia - pain in knees, ankles and wrists
- erythema nodosum - rash on shin
- lupus pernio - indurated purple rash on face, nose, ears
- lymphadenopathy - cervical and submandibular lymph nodes
- anterior uveitis - red painful eye, photophobia, blurred vision
What pulmonary symptoms may be seen in sarcoidosis? (4)
- chronic dry cough
- dyspnoea (SOB)
- wheezing
- rhonchi
What skin symptoms may be seen in sarcoidosis? (2+1)
- lupus pernio - purple indurated rash of face, nose and ears (and terminal phalanges)
- erythema nodosum - rash on shin
- (maculopapular eruptions)
What eye symptoms are seen in sarcoidosis? (3+3)
Anterior uveitis:
- red painful eye
- photophobia
- blurred vision
(keratoconjunctivitis sicca, glaucoma, papilloedema)
What cardiac symptoms may be seen in sarcoidosis? (5)
- arrhythmias
- heart block
- pericarditis
- cardiomyopathy
- congestive heart failure
What symptom is pathognomonic for sarcoidosis?
Lupus pernio - indurated purple rash on face, nose and ears
What electrolyte disturbance can occur in sarcoidosis and why?
Hypercalcaemia - granuloma produces ectopic 1-alpha-hydroxylase, macrophages inside the granulomas cause an increased conversion of vitamin D to its active form (1,25-dihydroxycholecalciferol)
What are some risk factors for sarcoidosis? (4)
- age 20-50 years (binomial age distribution with 2 peaks 25-35 and 50-65)
- Fx sarcoidosis
- Scandinavian and African origin
- female sex
What are the first-line investigations for sarcoidosis? (7)
- CXR
- FBC
- serum urea
- serum creatinine
- PFTs
- LFTs
- serum calcium
What is the best initial test for sarcoidosis?
CXR
What does CXR show in sarcoidosis? (2)
Bilateral hilar lymphadenopathy
Bilateral pulmonary infiltrates, predominantly in upper lobes
(Pleural effusions - rare)
(Eggshell calcifications - very rare)
What are the stages of sarcoidosis by CXR? (Correlates with likelihood of spontaneous resolution)
- stage 0 - normal
- stage I - bilateral hilar lymphadenopathy
- stage II - bilateral hilar lymphadenopathy PLUS pulmonary infiltrates (and paratracheal node enlargement)
- stage III - pulmonary infiltrates WITHOUT hilar lymphadenopathy
- stage IV - extensive fibrosis with distortion (honeycombing/bulla formation, pleural involvement)
What investigation can be done if suspicious CXR for sarcoidosis?
High resolution CT (check for diffuse lung involvement)
What is the gold-standard investigation for sarcoidosis diagnosis?
Bronchoscopy with lung biopsy –> showing non-caseating granulomas
What does FBC show in sarcoidosis? (2)
- anaemia
- leukopenia - due to lymphocyte sequestration in lungs
What would U&Es show in sarcoidosis? (2)
- hypercalcaemia (macrophages in granuloma increase 1,25-dihydroxycholecalciferol as granulomatous tissue produces ectopic 1a-hydroxylase)
- urea and creatinine elevated if renal involvement
What does spirometry/PFTs show in sarcoidosis?
Restrictive defect
- low FEV1
- FVC shows restrictive/obstructive/mixed picture
- persistent decline in FVC indicates disease progression
What do LFTs show in sarcoidosis?
High ALP and GGT
What enzyme is raised in sarcoidosis?
Raised serum ACE
What are some differential diagnoses for sarcoidosis? (6)
- TB - caseating granulomas
- histoplasmosis - fungus isolation on silver stain from lung biopsy
- NSCLC - smoking Hx
- lymphoma - extra-thoracic involvement
- berylliosis - exposure in nuclear and aerospace industries
- hypersensitivity pneumonitis
What syndromes are associated with sarcoidosis? (3)
- Lofgren’s syndrome - acute form of disease characterised by bilateral hilar lymphadenopathy, erythema nodosum, fever and polyarthralgia
- Mikulicz syndrome - enlarged parotid and lacrimal glands due to sarcoidosis, TB or lymphoma
- Heerfordt’s syndrome (uveoparotid fever) - parotid enlargement, fever and uveitis secondary to sarcoidosis
What are the indications for treatment of sarcoidosis? (4)
- CXR stage 2/3+ and symptomatic
- hypercalcaemia
- eye, heart or neurological involvement
- deteriorating PFTs/CXR changes
Give an example of a patient we would not give corticosteroid treatment to with sarcoidosis?
Patient with asymptomatic bilateral hilar lymphadenopathy
(No pulmonary infiltrates)
What is the first-line treatment for symptomatic sarcoidosis?
Corticosteroids - prednisolone, (hydrocortisone)
What other medications can we give for sarcoidosis, alongside corticosteroids? (2)
- immunosuppressive therapy: methotrexate, azathioprine (check thiopurine methyltransferase [TPMT] deficiency first)
- antimalarial drugs - chloroquine, hydroxychloroquine
What is given for symptomatic relief in sarcoidosis?
NSAIDs
What is the last resort in severe sarcoidosis?
Lung transplant
How do we manage the different stages of pulmonary disease in sarcoidosis?
- stage I asymptomatic - no treatment
- stage I symptomatic - oral/inhaled prednisolone
- stage II/III/IV - oral/inhaled prednisolone, methotrexate (cytotoxic), oxygen
- end stage - lung transplant
How do we manage lupus pernio with scarring in sarcoidosis?
Prednisolone + methotrexate/azathioprine
How do we manage acute respiratory failure in sarcoidosis?
IV/oral methylprednisolone + ventilatory support and oxygen
What are some complications of sarcoidosis? (8)
- increased risk of malignancy
- bronchiectasis
- lung fibrosis
- chronic renal failure
- haemoptysis
- glaucoma
- corticosteroid-related conditions (hyperglycaemia, osteoporosis, infection)
- cytotoxic-related conditions (hepatic toxicity, marrow toxicity)
What indicates poorer prognosis of sarcoidosis?
Chronic hypercalcaemia (renal failure), chronic pulmonary involvement, lupus pernio, black ancestry
Describe the % of spontaneous remissions in different stages of sarcoidosis.
- stage I 55-90%
- stage II 40-70%
- stage III 20%
- stage IV - remission not expected
