Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. It commonly affects the lungs but also has extrapulmonary manifestations as well which we will take a look at.
It affects approximately 4,500 people annually in the UK (7 per 100,000).
Pathophysiology
Before we continue, let’s clarify what we mean by the term granulomatous: granulomas are simply aggregations of macrophages that form in an area due to chronic inflammation. The macrophages typically fuse together to form multinucleated giant cells which are surrounded by CD4 lymphocytes (within the granuloma) and CD8 lymphocytes (around the perimeter). They CD4 lymphocytes and macrophages release cytokines such as IFN-y, IL-2 and IL-12 which promotes and maintains the granulomas.
In sarcoid granulomas, there seems to be an antigenic stimulus which causes the T-cell mediated response and macrophage stimulation. Unfortunately, the aetiology of the disease is unknown still.
Some factors have been suggested, however:
- Viruses
- Borellia burgdorferi
- Propionibacterium acnes
- Mycobacterium tuberculosis
- Mycoplasma
⚠️ Risk factors
- Bimodal age distribution - 20 - 40 years old and then again at around 60 years old.
- Black ancestry
- Female gender
- Family history
- Scandinavian origin
- Non-smokers
😷 Presentation
Sarcoidosis is not strictly a pulmonary issue. It most commonly affects the lungs (>90%) and as such it commonly is managed by respiratory physicians, however, it has a plethora of extrapulmonary manifestations.
It can also present acutely or chronically.
Let’s look at acute sarcoidosis first:
Lofgren’s syndrome is a form of acute sarcoidosis that has a classic triad of:
- Fever
- Erythema nodosum
- Bilateral hilar lymphadenopathy
- Polyarthralgia is also a common feature of acute sarcoidosis.
Chronic sarcoidosis
Systemic symptoms that can be insidious include: fever, fatigue, weight loss.
- Dry cough
- Dyspnoea
- Mediastinal lymphadenopathy
- Pulmonary fibrosis
- Pulmonary nodules that appear on CXR.
- Rhonci and wheezing
- Uveitis - may present with a red painful eye photophobia and blurred vision.
- Conjunctivitis
- Conjunctival nodules
- Optic neuritis
- Bundle branch block
- Heart block
- Restrictive cardiomyopathy
- Kidney stones - due to hypercalcaemia. Macrophages within the granulomas increase the conversion of vitamin D to calcitriol which then increases Ca2+ uptake.
- Liver nodules
- Cirrhosis
- Cholestasis
- Hepatomegaly
- Erythema nodosum - tender, red nodules on the shins (due to inflammation of subcutaneous fat).
- Lupus pernio - these are purple skin lesions seen on the nose, cheeks, lips and ears. It is most commonly seen in black women and is a predictor of poor prognosis.
- Headache
- Seizures
- Encephalopathy
- Pituitary lesion
- Bilateral Bell’s palsy - this commonly occurs with uveoparotid fever which is uveitis, parotitis, and facial palsy. This is known as Heerfordt’s syndrome.
- Mikulicz syndrome - enlargement of parotid, salivary and lacrimal glands
- Arthralgia
- Arthritis
- Myalgia
🔍 Investigations
🏆 Tissue biopsy and histological evidence of non-caseating granulomas with epitheloid cells is the gold-standard diagnostic test
🥇 This is usually the first-line option with an imaging modality of choice.
- Serum ACE - raised. It can be used for screening. However, it is quite an unreliable test. It may be useful in monitoring disease activity. This is because sarcoidosis granulomas produce ACE and ACE levels tend to be raised in the disease.
- Serum calcium - hypercalcaemia is another sign of sarcoidosis.
- CRP/ESR - raised.
- Serum soluble IL-2 receptor (sIL-2R) - may be used as a biomarker for disease severity.
- 🥇 CXR - can classify findings into 4 stages:
- Stage 0 - normal
- Stage 1 - bilateral hilar lymphadenopathy (BHL)
- Stage 2 - BHL with pulmonary infiltrates
- Stage 3 - pulmonary infiltrates without BHL
- Stage 4 - pulmonary fibrosis with distortion.
- CT chest - looking for hilar lymphadenopathy, infiltrates, cystic changes or pulmonary nodules.
- MRI - not routinely used but may be useful in identifying neurosarcoidosis or any cardiac involvement.
- PET scan - can identify areas of ongoing inflammation.
To assess extrapulmonary involvement, we can do the following tests:
- U&Es, urine dipstick, ACR for indications of renal involvement or nephritis.
- LFTs
- Ophthalmology review
- ECG and echocardiogram
- Ultrasound can also be used for liver and kidney involvement.
🧰 Management
Most patients require no treatment, especially those with no symptoms or mild symptoms. It usually self-resolves.
If treatment is required, we have the following options:
- Stage 1 (BHL) - if patients are symptomatic, an oral or inhaled corticosteroid is the first-line option.
- 🥇 Prednisolone or budesonide
- Stage 2, 3, 4 - oral corticosteroids are first-line. However, with refractory disease or with patients unable to tolerate high doses of steroids, we can give cytotoxic agents.
- 🥇 Oral corticosteroids - prednisolone.
- 🥈 Cytotoxic - methotrexate or azathioprine (preferred in neurosarcoidosis).
- Acute respiratory failure - IV corticosteroids may be used along with ventilatory support and oxygen is also needed.
- Methylprednisolone is the option of choice
- End-stage lung disease - lung transplant is the only option.
For patients using long-term steroids, it is important to take prevention for osteoporosis such as:
- Bisphosphonates
- Be careful using vitamin D or calcium as they may already have hypercalcaemia.
- 🥇 Topical corticosteroid - first-line for anterior uveitis.
- 🥇 Oral corticosteroid - first-line for skin and neurological disease.
- For lupus pernio → oral corticosteroid (prednisolone)
- 🥉 Hydroxychloroquine - third-line for skin disease that is refractory to topical or oral corticosteroids.