Sarcoidosis

Sarcoidosis

DEAPCIT

definition

• Idiopathic, multi-system, chronic granulomatous disease characterised by noncaseating granuloma formation

epidemiology

• Prevalence = 50/100 000• Common in African Americans, not in Africans

living in Africa• Common in Japan, uncommon in rest of Asia• Clusters in health workers• Age = 20 – 40 yrs• F > M

aetiology

• Genetic predisposition + environmental trigger• Genetic– Most common allele found in sarcoidosis is HLA-B8

• ? Infectious Ag triggers CMI response & starts disease process– Many organisms have been linked to sarcoidosis:

• M Tb• Mycoplasma species; Borrelia burgdorferi; Propionibacterium

acnes• Fungi - Histoplasma and Cryptococcus species• Viruses - EBV, CMV, HSV, hepatitis C virus, and rubella

pathophysiology

• May begin with lung alveolitis• This overstimulated local cellular immune

response may involve overactive TH-cells, which release chemotactic factors to attract monocytes from blood to lungs & nose, resulting in chronic inflammation

• Macrophages transform into giant cells, which then form epithelioid cells, which form granuloma

• Mature epithelioid granulomas release ACE

pathology• Giant cells, epithelioid cells & macrophages in non-caseating

granulomas, which have fewer lymphocytes surrounding = ‘naked tubercle’

• Fibrinoid necrosis• Giant cells have prominent inclusion bodies (e.g. asteroids,

Schaumann)• Asteroid bodies are star-shaped eosinophilic structures• Schaumann bodies are round or oval, laminated structures,

which are usually calcified at the periphery• Granulomas are referred to as ‘naked’ because they only have a

sparse lymphocytic infiltrate at the margins • Giant cells are larger & have more nuclei than in TB

Schaumann Bodies

non-caseating granulomas

Asteroid bodies

Clinical (2 patterns)

• Acute

– Sudden, with remission in 2 years

– More common in Caucasians

– May present with Lofgren’s Syndrome

• Bilateral hilar LN

• Ankle arthritis

• Erythema nodosum

– Nodular, erythematous eruption on anterior LL

– Type IV hypersensitivity reaction

• Constitutional symptoms

• Chronic

– Gradual onset, with relapses

– More organ-specific symptoms, which result from irreversible fibrosis

Course of disease• Asymptomatic (30-50%)• Constitutional Symptoms (30%)• Organ-Specific Symptoms (20-40%)

– Lung LN (90%, 30% symptomatic)– LN = 30%– splenomegaly in 40 – 80%– Skin = 25%– Eye = 20 – 30%– Neuro = < 10% – Cardiac = 5%– GIT– Renal

ENT

• Occur in 9%-15% of patient with sarcoidosis• Most common with– Cervical LN– Parotidomegaly– Facial nerve palsy

Laryngeal = 1 – 5%

– Hoarseness, dyspnoea / stridor

– Rarely painful– Early stage = white-

brown mucosal nodules– Later stage = pale,

oedematous epiglottis• Lesser changes in

remaining supraglottis (arytenoids, aryepiglottic folds, false VC)

• Glottis rarely involved

• Sinonasal = 10%: – NOT often presenting symptom– Nasal obstruction, rhinorrhoea,

PND– Anosmia, recurrent sinusitis,

epiphora– Firm, raised subcutaneous

yellow papule on nose, may become confluent

– Diffuse nasal crusting & thick mucous

– Submucosal nodules on septum & IT, with dry friable mucosa • Sarcoidosis interferes with

submucosal gland function, causing dryness

– Septal perforations & polyps– Rarely, granulomas may erode

through palate

• Ear - rare– Pinna = nodules– ME = ET obstruction from

NP involvement– SNHL < 1% = sudden,

asymmetric, fluctuating, high or low frequency

– Permanent loss or complete recovery

– Vestibular involvement recovers less well than acoustic

– Vestibulo-acoustic involvement is often concurrent with facial palsy & uveitis

• Oropharyngeal– Tonsils in 2%– Pharyngeal & oesophageal

stenosis may result from fibrosis

• Neurosarcoid = 5%– CN > CNS symptoms (e.g.

pituitary involvement causes DI)– Basal Granulomatous Meningitis

• Causes multiple cranial neuropathies by involvement of nerves with perivascular lymphocytic infiltrates in IAC, causing fluctuating ischaemia

• Facial > optic > glossopharyngeal > vagus > cochlear nerves– TV channels + 8

• Fluctuating ischaemia of facial nerve caused by perivascular lymphocytic infiltration proximal to geniculate ganglion, leads to reversible neuropraxia – often sudden, bilateral palsies, which resolve

• Cervical LN = 50%– FNA has high yield

• Parotidomegaly = 6%– Usually bilateral & FNA is

useful– Heerfordt’s disease

(Uveoparotid Fever)• Uveitis, parotitis, facial

paralysis, fever

Investigation• Biopsy

– Submucosal nodules or transbronchial lung, LN, lip gland– histopath, AFB, culture

• Bronchoalveolar lavage = elevated CD4:CD8 ratio• Haematologic

– Ca (serum & urine) = elevated– Serum ACE

• Correlates with active disease in 40 – 90%• Used in monitoring

• CXR (respiratory symptoms are most common)– Bilateral hilar lymphadenopathy & lung infiltrates

• Kveim Test – Part of a spleen from a patient with known sarcoidosis is injected into skin of a

patient suspected to have the disease– If granulomas are found (4–6 weeks later), the test is positive

Management

• MEDICAL – Steroids = mainstay– Systemic steroids in eye / organ involvement– Topical steroids in skin / eye disease– Inhaled steroids in URT / LRT disease– MTX / Azathioprine

• Surgical

• Laryngeal– Steroids– Intralesional steroid injection– If unresponsive, consider low-dose RTH– Tracheostomy or RTH / laser to obstructing lesions