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

What is the epidemiology of sarcoidosis?

Answer 2

• Prevalnce 5-64/100,000 and incidence of 1-35/100,000 worldwide
• Highest rates reported in northern European/Scandanavian and African-American individuals. Lowest rates are reported in Japan.
• It may occur at any age but is usually seen in adults under 50yrs
• Usually sporadic but familial in 4-10% of cases.

Question 3

What causes sarcoid?

Answer 3

Unknown aetiology —> non-caseating granulomas with multinucleated giant cells in the centre. Contain mainly macrophages and T-lymphocytes; CD4 throughout and CD8 in the periphery. CD4 and cytokines (If-y, IL-2, IL-12) maintain and promote granuloma formation.

Could be due to… causes.

• genetic
• immunological
• infecious (e.g., viruses, Borrelia burgdorferi, Propionibacterium acnes, Mycobacterium tuberculosis, and Mycoplasma)

Question 4

How is sarcoid commonly classfied?

Answer 4

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

Multisystem involvement is characteristic, but pulmonary involvement usually dominates. Skin, eyes, and peripheral lymph nodes are involved in 15% to 30% of patients. Clinically significant involvement of spleen, liver, heart, CNS, bone, or kidney occurs in a few patients. Incidental diagnosis on routine CXR also occurs.

Question 5

What are the risk factors for sarcoidosis?

Answer 5

• age 20 to 40 years for initial presentation
• FHx sarcoidosis
• Scandinavian origin
• female gender
• non-smokers
• black ancestry (US): uveitis
• Puerto Rican origin: lupus pernio
• European origin: erythema nodosum

Question 6

What is Lofgren syndrome?

Answer 6

Type of sarcoidosis which most commonly affects Scandanavian, Puerto Rican and Irish people.

Good prognosis.

Presents as a combination of erythema nodosum, bihilar lymphadenopathy, joint pain.

Question 7

What are the common symptoms of sarcoidosis?

Answer 7

• Non-productive cough
• Dyspnoea
• Chronic factigue
• Arthralgia (knees, ankles, wrist but no synovial thickening)
• Photophobia (uveitis)
• Red painful eye - uveitis causing superficial punctuate keratitis
• Blurred vision - uveitis

Uncommon: headache (neurosarcoidosis), low-grade fever, modest unexplained weight loss, chest wall pain (costochondritis)

Question 8

What are the signs of sarcoidosis on physical examination?

Answer 8

• Wheezing (bronchospasm)
• Rhonchi (continuous low pitched, rattling lung sounds that often resemble snoring; bronchospasm due to airway hyperactivity)
• Lymphadenopathy (cervical, submandibular non-tender)
• Erythema nodosum (tender erythematous nodules on lower extremities)
• Lupus pernio (indurated plaques wih discoloration of nose, cheeks, lips and ears)
• Conjunctival nodules
• Facial palsy (uveoparotid fever i.e. uveitis/parotitis/facial palsy)

Uncommon: arrhythmias (atrial or ventricular), hepatomegaly

Question 9

What investigations would you do for sarcoidosis?

Answer 9

History - exclude beryllium exposure (sarcoid has similar presentation to berylliosis)

• CXR, ECG, PFTs
• FBC, serum urea, creatinine, liver enzymes, serum calcium
• purified protein derivative of tuberculin (PPD)

Other:

• CT
• flexible bronchoscopy w/ transbronchial biopsy, bronchoalveolar lavage, skin biopsy, endobronchial US- transbronchial needle aspiration.
• Serum ACE, 24hr urine calcium, gallium-67 scan

Question 10

What is the CXR staging used in sarcoidosis? What else might you see on CXR of sarcoidosis?

Answer 10

• 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.

Also: hilar/paratracheal adenopathy with upper lobe predominance, bilateral infiltrates, pleural effusions (rare) and egg shell calcifications (v rare)

Question 11

What would you see in FBC/urea/creatinine/LFT/serum calcium/PFTs/PPD of sarcoid?

Answer 11

• FBC - anaemia in 4-20% and leukopenia in 40%
• Serum urea may be elevated*
• Creatinine may be elevated*
• Liver enzymes - elevated- asymptomatic aminotransferase (AST and ALT) elevation possible
• Serum calcium - hypercalcaemia due to dysregulated production of calcitriol by activated macrophages and granulomas.
• PFTs - restrictive/obstructive mixed patter but help monitor disease (FVC)
• PPD - negative (partial to complete anergy in sarcoidosis secondary to depressed cellular immunity)
  *

Question 12

What do these investigations show in sarcoid?

CT/BAL/bronch biopsy/ACE/gallium-67scan

Answer 12

• CT scan - same as CXR but ground glass(=reversible) and cystic architectual distortion (=irreversible). Calcified hilar/mediastinal lymph nodes in patients with longstanding disease.
• Bronchoscopy - usually essential for diagnosis, shows non-caseating granulomas
• BAL (lavage) - BAL lymphocytosis, with CD4-to-CD8 ratio >3.5
• Serum ACE - quite unreliable but usually elevated
• galliium-67 scan - panda sign and lambda sign (panda = lacrimal+parotid gland uptake; lambda= parahilar, infrahilar,right paratracheal/azygos node)

Question 13

Briefly, how do you treat ongoing sarcoid?

Answer 13

1. If without progressive adenopathy then observe.
2. If progressive then oral/inhaled corticosteroids(for 1-3months then taper).
3. Second line agents are cytotoxics e.g. methotrexate/azathioprine/hydroxychloroquine (used as corticosteroid sparing agents)

Question 14

What is Lofgren’s syndrome?

Answer 14

A type of acute sarcoidosis.

The triad of:

1. ankle arthritis/periarthritis
2. erythema nodosum
3. bilateral hilar lymphadenopathy

Usually good prognosis and chronic disease unlikely. Treat with NSAIDs or prednisolone.