Sarcoidosis

Question 1

Define sarcoidosis

Answer 1

Sarcoidosis is a chronic granulomatous disorder of unknown aetiology, commonly affecting the lungs, skin, and eyes.

• It is characterised by accumulation of lymphocytes and macrophages and the formation of non-caseating granulomas in the lungs and other organs.
• Although lungs and lymph nodes are involved in more than 90% of patients, virtually any organ can be involved.
• It has a bimodal age distribution with 2 peaks in the third and fifth decades.
• The clinical course is often heterogeneous and unpredictable.

Question 2

Which conditions must be excluded before a diagnosis sarcoidosis can be made?

Answer 2

Sarcoidosis is a diagnosis of exclusion of granulomatous lung diseases, including tuberculosis and histoplasmosis.

Question 3

What is the aetiology of sarcoidosis?

Answer 3

Aetiology is unknown.

However, several aetiological factors have been suggested, including genetic, immunological, and infectious causes

• (e.g., viruses, Borrelia burgdorferi, Propionibacterium acnes, Mycobacterium tuberculosis, and Mycoplasma

Question 4

How is sarcoidosis classified?

Answer 4

Commonly used classification according to organ/system involvement

• Systemic sarcoidosis: multisystem involvement, sometimes with chronic fatigue
• Pulmonary sarcoidosis: lungs involved in >90% of patients; further classified into stages I, II, III, and IV
• Cutaneous sarcoidosis: plaques; lupus pernio
• Ocular sarcoidosis: anterior uveitis is most common
• Cardiac sarcoidosis: 5% of patients; various types of heart block; cardiomyopathy later in course; if pulmonary arterial hypertension occurs can be debilitating
• Neurosarcoidosis: <10% of patients; headaches; seizures.

Question 5

What are the risk factors for sarcoidosis?

Answer 5

genetic

• afro-caribbean
• FHx of sarcoidosis

environmental

• prior infection w TB or borrelia burgdorferi

Question 6

Summarise the epidemiology of sarcoidosis

Answer 6

Incidence is about 6 cases per 100,000 person-years

• The lifetime risk of sarcoidosis for black people & Scandinavian in is slightly higher than for white people
• Extrathoracic manifestations are more common in certain populations, such as chronic uveitis in black people in the US, lupus pernio in Puerto Ricans, and erythema nodosum in Europeans.
• Cardiac and ocular sarcoidosis appear to be more common in Japan
• Women are more likely to have eye and neurological involvement and have erythema nodosum, whereas men are more likely to be hypercalcaemic.
• Black people are more likely to have skin manifestations (other than erythema nodosum) and have eye, liver, bone marrow, and extrathoracic lymph node involvement

Question 7

What are the presenting symptoms of sarcoidosis?

Answer 7

• SOB
• wheeze
• cough
• dyspnoea
• nodules on lower legs
  
  • (erythema nodusum)
• arthralgia
• vision changes - photophobia, red painful eye, blurred vision
• palpitations
• non specific: fever, weight loss, fatigue

Question 8

What are some uncommon symptoms of sarcoidosis?

Answer 8

• chest wall pain
• haemoptysis
• weight loss
• low-grade fever
• arrhythmias
• heart block
• hepatomegaly
• headache
• seizures
• symptoms and signs of pituitary lesion

Question 9

What are signs of sarcoidosis O/E?

Answer 9

• erythema nodusum
  
  • ​due to inflammation of lipids
  • usually on tibias
  • red, hard, painful
• uveitis
• ~ facial palsy
• arrythmias O/A?

Question 10

What is lupus pernio?

Answer 10

Indurated plaques with discoloration of the nose, cheeks, lips, and ears.

• More common in black women.
• Predictor of poor prognosis

Question 11

What are some primary investigations for ?sarcoidosis?

Answer 11

Typical history and biopsy from affected organs are essential for the diagnosis.

• CXR
  
  • = hilar and/or paratracheal adenopathy with upper lobe predominant, bilateral infiltrates; pleural effusions (rare) and egg shell calcifications (very rare) may be seen
• FBC
  
  • ​Usually secondary to splenic and/or bone marrow involvement
  • = anaemia in 4%-20%; leukopenia in 40%
• serum urea
  
  • In cases of renal involvement.
  • = may be elevated
• creatinine
  
  • ​see above
• liver enzymes
  
  • ​= Asymptomatic aminotransferase (AST and ALT) elevation possible.
• serum calcium
  
  • Due to dysregulated production of calcitriol by activated macrophages and granulomas.
  • = hypercalcaemia
• PFTs
  
  • To monitor disease.
  • Persistent decline in forced vital capacity indicates disease progression.
  • = restrictive or obstructive or mixed pattern
• ECG
  
  • To exclude or confirm cardiac involvement.
  • About half of patients with cardiac sarcoidosis have abnormalities of rhythm, conduction, or repolarisation
  • = conduction abnormalities
• purified protein derivative of tuberculin (PPD)
  
  • ​Partial to complete anergy in sarcoidosis, secondary to depressed cellular immunity
  • = negative in sarcoidosis

Question 12

What are the stages of sarcoidosis seen on CXR?

Answer 12

Stage 0: normal

Stage I: bilateral hilar lymphadenopathy

Stage II: bilateral hilar lymphadenopathy plus pulmonary infiltrates

Stage III: pulmonary infiltrates without hilar lymphadenopathy

Stage IV: extensive fibrosis with distortion.

Question 13

What are some secondary investigations for ?sarcoidosis?

Answer 13

• CT scan of chest
  
  • Ground-glass appearance may indicate a potentially reversible condition.
  • Cystic architectural distortion suggests irreversible disease
  • = hilar and/or paratracheal adenopathy with upper lobe predominance, bilateral infiltrates in a bronchovascular distribution; calcified hilar or mediastinal lymph nodes in patients with longstanding disease
• flexible bronchoscopy with transbronchial lung biopsy
  
  • Essential for diagnosis in most cases.
  • Transbronchial needle aspiration from large mediastinal lymph nodes if present.
  • = non-caseating granulomas
• bronchoalveolar lavage (BAL)
  
  • ​Specificity of 94%. Sensitivity of 53%
  • BAL lymphocytosis, with CD4-to-CD8 ratio >3.5
• skin biopsy
  
  • ​Skin biopsy of lesion suspicious for sarcoidosis may histologically confirm diagnosis
  • = non-caseating granulomas
• 24-hour urine calcium
  
  • ​Hypercalciuria due to abnormal calcium and vitamin D regulation from macrophages inside granulomas
  • = hypercalciuria
• serum ACE
  
  • Elevated in about half of patients
  • May not reflect disease activity.
  • Utility is unreliable and controversial
  • = elevated
• gallium-67 scan
  
  • ​Typical patterns include panda sign: lacrimal and parotid gland uptake; lambda sign: parahilar, infrahilar, and right paratracheal or azygos node uptake
  • Lacks specificity. Serial images sometimes require 48 hours to complete.
  • The clinical value of this test remains controversial
  • may show typical uptake patterns
• endobronchial ultrasound-transbronchial needle aspiration
  
  • ​Endobronchial ultrasound-transbronchial needle aspiration is standard of care and routine practice for the diagnosis of mediastinal lymphadenopathy, with high sensitivity (88%) and specificity (100%).
  • = non-caseating granulomas

Question 14

What are some emerging tests for ?sarcoidosis

Answer 14

• MRI
  
  • ​May be useful in identifying areas of sarcoidosis involvement, including the heart and the brain
  • = heart findings include nodular lesions and/or focal myocardial thickening;
  • = brain findings are varied and non-specific, and include meningeal enhancement with or without periventricular white matter lesions
• (18)F-fluorodeoxyglucose (FDG) PET scan
  
  • ​PET scanning has been shown to have a characteristic pattern of uptake in sarcoidosis and may aid in the diagnosis of cardiac sarcoidosis.
  • This is much less invasive than endomyocardial biopsy, with minimal to no complications from the procedure
  • = heterogeneous myocardial FDG uptake