SARCOIDOSIS

SARCOIDOSIS

Definition

• Sarcoidosis is a common multisystem disorder of unknown etiology.
• characterized by the presence of non-caseating granulomata in the lungs and other organs.
• Sarcoidosis is a T-lymphocyte-mediated non-caseating granulomatous inflammatory disorder of unknown cause.
• Sarcoidosis is a T-lymphocyte-mediated non-caseating granulomatous inflammatory disorder of unknown cause. 
• It is most common in colder climates, although it more frequently affects patients of African descent than Caucasians. (more in blacks than whites)
• The clinical spectrum of disease varies from mild single-organ involvement to potentially fatal multisystem disease which can affect almost any tissue. 
• The tissues most commonly involved are the mediastinal and superficial lymph nodes, lungs, liver, spleen, skin, parotid glands, phalangeal bones and the eye. 

Presentation

Acute-onset sarcoidosis presents in young patients (During the third decade) in one of the following ways:

• Löfgren syndrome is characterized by erythema nodosum and bilateral hilar lymphadenopathy, often accompanied by fever, anorexia and arthralgia.
  


• Heerfordt syndrome (uveoparotid fever) is characterized by uveitis, parotitis, fever and cranial nerve palsy, usually the seventh nerve.

Insidious-onset disease typically presents during the 5th decade with pulmonary involvement resulting in cough and dyspnoea, together with extrapulmonary manifestations fatigue and arthralgia .

Pulmonary disease

• Stage 1 manifests bilateral asymptomatic hilar lymphadenopathy; spontaneous resolution occurs within 1 year in most cases.
• Stage 2 consists of stage 1 and diffuse parenchymal reticulonodular infiltrates; spontaneous resolution occurs in the majority.
• Stage 3 is characterized by reticulonodular infiltrates alone; spontaneous resolution is less common.
• Stage 4 manifests pulmonary fibrosis which may result in progressive dyspnoea, pulmonary hypertension and cor pulmonale.

Skin lesions

The skin is involved in about 25% of patients by one of the following:

• Erythema nodosum is characterized by tender erythematous plaques typically involving the knees and shins and occasionally the thighs and forearms.
• Granulomatous scattered papules, plaques or nodules.
• Lupus pernio consists of indurated, violaceous lesions involving exposed parts of the body such as the nose, cheeks, fingers and ears.
• Granulomatous deposits in long-standing scars or tattoos.

Other manifestations

• Neurological disease affects 5–10% of patients. The most common lesion is unilateral facial nerve palsy; less common manifestations include seizures, meningitis, peripheral neuropathy and psychiatric symptoms.
• Arthritis in chronic sarcoidosis is typically symmetrical and may involve both small and large joints. In children the presentation can be very similar to JIA because arthropathy tends to be more prominent than pulmonary disease.
• Bone cysts typically involve the digits and are associated with swelling.
• Renal disease in the form of nephrocalcinosis, hypercalciuria and calculi.
• Miscellaneous manifestations include lymphadenopathy, granulomatous liver disease, splenomegaly and cardiac arrhythmias.

Investigations

1. Chest radiographs are abnormal in 90%.
2. Biopsy
   = Lungs give the greatest yield (90%) even in asymptomatic patients with normal chest radiograms.
   = Conjunctiva is positive in about 70% of patients with granulomatous inflammation in the form of nodules, which resemble those of follicular conjunctivitis.
   = Lacrimal glands are positive in 25% of un-enlarged and 75% of enlarged glands.
   = Superficial lymph node or skin lesion.
3. Enzyme assay for serum angiotensin-converting enzyme (ACE) and lysozyme 
4. Bronchoalveolar lavage shows a raised proportion of activated T-helper lymphocytes. Sputum examination may also show increased CD4/CD8 ratios.
5. Pulmonary function tests reveal a restrictive lung defect with reduced total lung capacity and are very useful for monitoring disease activity and the need for systemic therapy.
6. Mantoux test is negative in most patients; a strongly positive reaction to one tuberculin unit makes the diagnosis of sarcoidosis highly unlikely.
   

Ix

1. Skin test - Kweim test - Mantoux test
2. Serum Lysozyme
3. Ser. Globulin
4. Ser. ACE
5. Ser Ca -raised
6. X-ray –chest & phalanges
7. Gallium scan
8. Biopsy – Lacrimal gland & conjunctival nodules
9. BAL- bronchoalveolar lavage
10. Bronchoscopy with transbronchial biopsy

Ocular features

• The eye is involved in about 25% of patients.
• Ocular involvement may occur in patients with few, if any, systemic symptoms, as well as in those with inactive systemic disease, and the diagnosis may be missed.
• In acute sarcoidosis, the ocular inflammation is frequently Unilateral and, 
• In chronic disease, bilateral involvement is the rule.
  

External :

manifestations include KCS, conjunctival nodules, and rarely, orbital and scleral lesions.

Eyelid involvement - uncommon 

• consist of violaceous sarcoid plaques (lupus pernio) or lid granulomata which may be mistaken for small chalazia.

Conjunctiva - 

• Conjunctival granulomata - uncommon. which may be suitable for diagnostic biopsy.
• Phlyctens are very rare.

Lacrimal gland infiltration is uncommon but, when severe, it may be responsible for keratoconjunctivitis sicca. Rarely, extralacrimal orbital involvement may also occur. 

Uveitis is the most common and may be in the form of anterior, posterior or intermediate.

Anterior uveitis

Anterior uveitis is by far the most common complication

The uveitis is of two types.

• Acute anterior uveitis

- unilateral and

- non-granulomatous

- occurs in young patients with acute-onset sarcoid.

- The long-term prognosis is usually good.

- typically affects patients with acute-onset sarcoid. 

• Chronic anterior uveitis

- usually bilateral,

- typically granulomatous 

- occurs in older patients with chronic lung disease.

- This is more common than the acute type.

> Iris nodules may be very large.

> The trabecular meshwork may show nodules and tent-shaped peripheral anterior synechiae.

> Mutton-fat KPs.

Intermediate uveitis

with snowballs or string-like opacities is uncommon and may antedate systemic disease.
The presence of associated granulomatous anterior uveitis should arouse suspicion.

Vitreous

• Vitreous involvement may consist of a diffuse haze or opacities
• either of the 'string of pearls' type or small 'cotton balls' which lie on the surface of the inferior retina anterior to the equator (Lander's sign).

Posterior segment

• The posterior segment is involved in about 7% of patients with chronic sarcoidosis and in 25% of patients with ocular sarcoid.
• The fundus changes are caused by granulomatous involvement of the retinal veins, the vitreous, the choroid and the optic nerve head.

Retinal vasculitis 

• Retinal vasculitis involving the peripheral retinal veins (periphlebitis) is the most frequent finding.

Periphlebitis

• Yellowish or grey-white perivenous sheathing(cuffing)
• that may also involve the optic nerve head.
• In mild cases only a few segments are involved.
• Advanced periphlebitis is characterized by 'candlewax drippings' due to perivascular accumulation of granulomatous tissue.
• (Perivenous exudates referred to as ‘candlewax drippings’ (en taches de bougie) are typical of severe sarcoid periphlebitis)
• Occlusive periphlebitis is uncommon.

Acute sarcoid retinopathy

which is rare, is characterized by vitreous haze, severe periphlebitis and haemorrhages.

Retinal granulomas: are small discrete yellow-white lesions.

Neovascularization (Peripheral retinal neovascularization)

- may develop secondary to retinal capillary dropout.

- New vessel formation on the retina and optic nerve head

- It is usually secondary to wide areas of capillary non-perfusion in some patients with acute sarcoid

retinopathy or retinal branch vein occlusion.

Choroid

Choroidal infiltrates are uncommon and vary in appearance:

Involvement of the choroid is of two types.

1. Multiple, small, pale-yellow choroidal lesions (infiltrates)
   - are the most common.
   - may have a ‘punched-out’ appearance
   - associated with mottling of the retinal pigment epithelium RPE.
   - often most numerous inferiorly.
   - Multiple large confluent infiltrates which may have amoeboid margins are less common.
2. Large, solitary, choroidal granulomata are rare

Multifocal choroiditis

• carries a guarded visual prognosis because
• it may cause loss of central vision as a result of secondary CNVM (peripapillary) or associated with a chorioretinal scar.

Optic nerve 

Granulomata of the optic nerve are uncommon.

involvement may take the following forms:

• Focal granulomas, which do not usually affect vision.
• Papilloedema due to CNS involvement may occur in the absence of other ocular manifestations.
• Persistent disc oedema is a frequent finding in patients with retinal or vitreous involvement.

ANTERIOR SEGMENT-

• KCS
• Band KP
• Conj granuloma
• Lacrimal gland enlargement
• Uveitis 
• granulomatous / non-granulomatous 
• Mutton fat KPs -Choroidal granulomas 
• Chorioretinitis
• Pars Planitis
• Cataract
• Glaucoma

POSTERIOR SEGMENT-

• Vitritis & snowballs
•  Papilloedema
•  Optic neuritis
•  Neuroretinitis
•  Retinal vasculitis
•  perivascular granulomata & optic nerve granuloma
•  Perivenous exududates with CANDLE WAX DRIPPING
•  Retinal NeoVascularization
•  VH
•  BRVO & CRVO

Treatment 

• Most anterior segment complications respond to topical steroids, although systemic steroids may be required in patients with severe involvement of the posterior segment.
• Anterior uveitis is with topical and/or periocular steroids.
  Steroids-
  Periocular - Triamcinolone acetonide 40mg or Methyl prednisone 40 mg ( ant / post subtenon)
  Systemic – oral prednisone 1 mg/kg/ day
• Posterior uveitis often requires systemic steroids and occasionally immunosuppressive agents such as methotrexate, azathioprine and ciclosporin.

Differential diagnosis of posterior segment sarcoid

1. Small choroidal lesions

• Multifocal choroiditis with panuveitis
• Birdshot chorioretinopathy
• Tuberculosis

2. Large choroidal infiltrates

• Metastatic tumour
• Large  cell  lymphoma
• Harada disease
• Serpiginous choroidopathy

3. Periphlebitis

• Tuberculosis
• Behçet syndrome
• Cytomegalovirus retinitis