Sarcoidosis is a multisystem granulomatous disease of unknown cause that has numerous clinical features, but mostly affects the lungs, eyes, lymph nodes and skin. Sarcoidosis is one of the commonest systemic associations of uveitis.
Sarcoidosis is a multisystem granulomatous disease of unknown aetiology, characterised by formation of non-caseating granulomas that can affect virtually any organ, but most commonly affect the eyes, lungs, skin and lymphatic system. It has a chronic course, but can undergo spontaneous remission.
The prevalence of sarcoidosis is highest in Northern Europe and colder climates. Generally, people who are of Black ethnic background are affected more frequently and severely than those who are white (10:1).
Females are more commonly affected than males.
The characteristic age of onset is 30-50 years.
It is associated with HLA-DRB1 and DBQ1 alleles.
In 20-40% of cases of sarcoidosis, the disease presents incidentally on a chest x-ray. Alternatively, patients present acutely unwell, with fever, polyarthralgia, erythema nodosum and bilateral hilar lymphadenopathy (BHL).
The clinical features of sarcoidosis are numerous, and can be classified into systemic and ocular features.
General: fever (swinging), anorexia, malaise, weight loss, fatigue, lymphadenopathy
Upper respiratory: otitis, sinusitis
Lower respiratory (seen in 90%): dry cough, progressive dyspnoea, chest pain, reduced lung function, pulmonary fibrosis
Musculoskeletal: polyarthralgia, dactylitis
Cardiac (5%): restrictive cardiomyopathy (secondary to granulomas and fibrosis), pericardial effusion, arrhythmias
Neurological: peripheral and cranial polyneuropathy (especially facial nerve palsy, also known as Bell’s palsy), meningitis, transverse myelitis. Pituitary involvement can cause hormonal abnormalities.
Urological: hypercalcaemia —> renal stones, nephrocalcinosis, diabetes insipidus. The hypercalcaemia is caused by macrophages inside the granulomas metabolising vitamin D to its active form more quickly than usual.
Dermatological: erythema nodosum (painful erythematous plaques commonly on the shins - caused by lumps of inflamed fat under the skin), lupus pernio (raised, dusky purple plaques on the nose, cheeks and fingers), granulomatous papules and macule
Sarcoidosis can involve almost any structure around or within the eye. Moreover, eye disease is often the first clinical manifestation of sarcoidosis.
Granulomatous anterior uveitis is the most common ocular feature, typically affecting patients with acute-onset sarcoidosis. Chronic anterior uveitis (typically granulomatous) tends to affect older patients with chronic lung involvement.
The International Workshop on Ocular Sarcoidosis (IWOS) in 2009 reported 7 key signs for diagnosing intraocular sarcoidosis:
“Mutton fat” KPs (keratic precipitates) and/or small granulomatous KPs and/or iris nodules
Trabecular meshwork nodules
Vitreous opacities: snowballs and/or “strings of pearls”
Multiple chorioretinal peripheral lesions (active and/or atrophic). These vary in appearance, but are typically many small pale-yellow infiltrates, sometimes with a punched-out appearance. Retinal granulomas (discrete small yellow-white lesions) can also occur.
Nodular and/or segmental periphlebitis (± “candle drippings”) and/or retinal macroaneurysm in an inflamed eye. Periphlebtiis is seen as yellowish or grey-white perivenous sheathing. Perivenous exudates known as “candle wax drippings” indicate severe sarcoid periphlebitis.
Optic disc nodule/granuloma and/or solitary choroidal nodule. Optic nerve granulomas do not usually affect vision.
Other ocular manifestations including:
Lacrimal gland inflammation, nasolacrimal gland obstruction and dry eye
Orbital and scleral lesions
Complications of ocular involvement are the same complications typically seen in idiopathic uveitis:
Posterior and peripheral anterior synechiae
Maculopathy (including cystoid macular oedema and choroidal neovascularisation)
Sarcoidosis is adiagnosed histopathologically, with a biopsy typically from the lung, lymph nodes, liver or skin nodules, showing non-caseating granulomas. It is also important to rule out other differentials, and to rule out alternative causes of uveitis by appropriate investigation:
Blood tests: ↑ESR, ↑ calcium (in 10%), lymphocytopaenia, deranged LFTs, ↑ serum ACE (angiotensin converting enzyme), ↑ serum lysozyme
Urine: ↑ calcium
Imaging: chest x-ray (abnormal in 90%), high-resolution CT (if chest x-ray is negative), cardiac MRI
Fibreoptic bronchoscopy with biopsy
ECG: may show arrhythmias or bundle branch blood
Lung function testing: may show a restrictive pattern (due to reduced lung volumes) and a reduced transfer factor (due to impaired gas transfer)
Negative tuberculin skin test (to rule out tuberculosis)
Sarcoidosis is staged according to the findings on chest x-ray.
BHL + interstitial infiltrates
Diffuse interstitial infiltrates only
Diffuse fibrosis, honeycombing (due to bullae) and pleural involvement
BHL alone with no symptoms:
No treatment required, recovers spontaneously
Usually resolves spontaneously
Bed rest + NSAIDs
Corticosteroids - oral prednisolone for 6 weeks, then taper over 1 year. Indications for steroids: (1) patients with stage 2 or 3 disease on chest x-ray who are symptomatic; (2) hypercalcaemia; (3) ocular, cardiac or neurological involvement
Oxygen therapy if needed
For pulmonary disease: oral/inhaled corticosteroids, anti-TNF⍺, possibly lung transplantation
Additional immunosuppression can be considered: methotrexate, cyclosporin, cyclophosphamide
Treating ocular disease:
Anterior and intermediate uveitis: steroid drops and cyclopentolate (see our ‘Classification of Uveitis’ notes)
Posterior uveitis: systemic steroids ± immunosuppressive agents
Cystoid macular oedema: topical NSAID
Peripheral retinal neovascularisation: scatter photocoagulation to ischaemic areas
Inflammation should ideally be suppressed for ≥3 months prior to cataract surgery
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