Sarcoidosis

M. Dankyau

June 2023

Outline

Case studies

Case 1 – Slide 1

• A 34-year-old woman comes to the clinic because of a 3-day history of right-sided facial droop. ROS reveals headache, blurry vision, cough, and dyspnoea. Temperature is 37.1°C, pulse 80/min, RR 16/min, and BP 136/72mmHg. Examination shows a rash on both legs (tender erythematous nodules) and plaques at the base of her neck. Right-side facial weaknesses is confirmed but no other neurological anomalies. Her eyes appear red and watery.

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• System(s) responsible
• A. CNS
• B. CVS
• C. Musculoskeletal
• D. Respiratory

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Case 1 – Slide 2

• A 34-year-old woman comes to the clinic because of a 3-day history of right-sided facial droop. ROS reveals headache, blurry vision, cough, and dyspnoea. Temperature is 37.1°C, pulse 80/min, RR 16/min, and BP 136/72mmHg. Examination shows a rash on both legs (tender erythematous nodules) and plaques at the base of her neck. Right-side facial weaknesses is confirmed but no other neurological anomalies. Her eyes appear red and watery.

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• Differential diagnoses 
• A. Bell’s palsy
• B. Dermatomyositis
• C. Sarcoidosis
• D. Stroke
• E. Systemic Lupus erythematosus

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Introduction

Sarcoidosis

• sarcoid refers to the flesh
• and osis means disorder
• sarcoidosis is an immunologic disorder that results in lots of small nodules forming throughout the body.

Introduction 1

• Sarcoidosis is a systemic, multi-organ, granulomatous disease of unknown aetiology, characterized by the presence of granuloma in various organs
• It can affect almost any organ in the body, but the most affected are the lungs

Introduction 2

• Usually associated with chest symptoms but also multiple extra-pulmonary manifestations e.g. erythema nodosum and lymphadenopathy.
• Symptoms can vary from asymptomatic (in up to 50%) to severe and life-threatening.
• Two spikes in incidence: in young adulthood and again around age 60.
• Women are affected more often, and occurs more frequently in black people compared with other ethnic groups.

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Pathophysiology

Pathophysiology 1

• Normally, cells of the immune system are ready to spot and destroy any foreign pathogens that could cause the body harm.
• In sarcoidosis, this process occurs over and over throughout the body without the presence of a specific pathogen that the body is trying to destroy.
• Immune system seems to be going haywire in the absence of a pathogen.

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Pathophysiology 2

Spirochetes & Mycobacteria

Pathophysiology 3

Pathological changes

Pathological changes 2

• Increased blood calcium level caused by excess Vitamin D produced by macrophages.
• Increased level of angiotensin converting enzyme (ACE), which is produced by T cells.
• Elevated levels of T cells in the lungs on bronchoalveolar lavage.

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Clinical features

Systemic Symptoms

Lungs (affecting over 90%)

• Mediastinal lymphadenopathy
• Pulmonary fibrosis
• Pulmonary nodules

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Liver (affecting 20%)

• Liver nodules
• Cirrhosis
• Cholestasis

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Eyes (affecting 20%)

• Conjunctivitis
• Uveitis
• Optic neuritis

Skin (affecting 15%)

• Erythema nodosum (tender, red nodules on the shins caused by inflammation of the subcutaneous fat)
• Lupus pernio (raised, purple skin lesions commonly on cheeks and nose)
• Granulomas in scar tissue

Lupus pernio

Heart (affecting 5%)

• Bundle branch block
• Heart block
• Myocardial muscle involvement

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Kidneys (affecting 5%)

• Kidney stones (due to hypercalcaemia)
• Nephrocalcinosis
• Interstitial nephritis

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Central nervous system (5%)

• Nodules
• Pituitary involvement (diabetes insipidus)
• Encephalopathy
• Facial nerve palsy

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Peripheral Nervous System (5%)

• Mononeuritis multiplex
• (painful, asymmetrical, asynchronous sensory and motor peripheral neuropathy involving isolated damage to at least 2 separate nerve areas)

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Musculoskeletal system(2%)

• Arthralgia
• Arthritis
• Myopathy

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Lofgren’s Syndrome

• Characterised by a triad of:
• Erythema nodosum
• Bilateral hilar lymphadenopathy
• Polyarthralgia (joint pain in multiple joints)

Heerfordt-Waldenström syndrome

• A rare subacute variant of sarcoidosis characterized by:
• enlargement of the parotid or salivary glands
• facial nerve paralysis
• anterior uveitis.
• Granulomas with a peripheral lymphocyte deficit are found in the affected organs.

Staging based on Chest radiograph

• 0: No lung involvement�I: Bilateral lymphadenopathy (LAD)�II: LAD + infiltrates�III: Parenchymal disease but no LAD�IV: Pulmonary fibrosis

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Differential diagnosis: Granulomatous lung disease

• Infectious conditions
• Tuberculosis
• Atypical mycobacterial infections
• Invasive fungal infections - histoplasmosis, aspergillosis, blastomycosis, or Pneumocustis Jirovecii

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Differential diagnosis: Granulomatous lung disease

• Hypersensitivity pneumonitis
• Pneumoconiosis
• Drug-induced hypersensitivity pneumonitis

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Differential diagnosis: Granulomatous lung disease

• Foreign body granulomatosis

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Differential diagnosis: Granulomatous lung disease

• Vasculitides
• Granulomatosis with polyangiitis
• Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
• Pulmonary lymphomatoid granulomatosis

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Investigations

Histology

Caseating vs Noncaseating granuloma

Langhans giant cell

Blood Tests

• Raised serum ACE.
• Often used as a screening test.
• Hypercalcaemia is a key finding.
• Raised serum soluble interleukin-2 receptor
• Raised C-Reactive Protein
• Raised immunoglobulins

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Imaging

Chest radiograph in sarcoidosis

High Resolution CT - Hilar lymphadenopathy

Tests for other organ involvement

• U&E for kidney involvement
• Urine dipstick or urine albumin-creatinine ratio for proteinuria indicating nephritis
• LFTs for liver involvement
• ECG and echocardiogram for heart involvement
• Ultrasound abdomen for liver and kidney involvement
• Ophthalmology review for eye involvement

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Treatment and prognosis

Treatment

• No treatment is considered as first line in patients with no or mild symptoms as the condition often resolves spontaneously.
• Oral steroids are usually first line where treatment is required and given for between 6 to 24 months.
• Patients should be given bisphosphonates to protect against osteoporosis while on such long-term steroids.
• Second line options are methotrexate or azathioprine
• Lung transplant is rarely required in severe pulmonary disease

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Prognosis

Summary

Flash cards

Questions

Flashcard 1

• What is the most common sign of sarcoidosis?
• Lymphadenopathy

Flashcard 2

• What is the characteristic pathologic feature of sarcoidosis?
• Non-caseating granuloma

Flashcard 3

•  List 5 organs most commonly affected by sarcoidosis.
• Lymph node
• Lungs
• Liver
• Skin
• Eyes

Flashcard 4

• Angiotensin converting enzyme levels (decrease/increase)            in sarcoidosis.

Summary

•  Sarcoidosis is a systemic disease that can affect any organ, with the lungs and intrathoracic lymph nodes being the most frequently affected sites.
• Diagnosis relies on the presence of noncaseating granuloma on histopathologic examination, compatible clinical presentation, and exclusion of other causes of granulomatous inflammation.
• Treatment is reserved for patients with disabling symptoms or progressive organ damage/dysfunction because spontaneous remission is frequent.
• Glucocorticoids are first-line therapy, whereas glucocorticoid-sparing agents and biologic agents are used in refractory/recurrent cases

Conclusion

Bibliography

• Gupta R et al (2021). Sarcoidosis: An FP’s primer on an enigmatic disease
• Kaloga M et al. (2015). Epidemiological, Clinical, and Paraclinic Aspect of Cutaneous Sarcoidosis in Black Africans
• Osmosis.org. (2021). Sarcoidosis
• Ungprasert P et al (2019). Clinical Manifestations, Diagnosis, and Treatment of Sarcoidosis
• Zerotofinals.com. (2019). Sarcoidosis