OCULAR%20MANIFESTATIONS%20OF%20SARCOIDOSIS

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OCULAR MANIFESTATIONS OF SARCOIDOSIS

• Dr.Rajesh Babu B
• MS, FMRF, MSc (CEH) , DLSHTM, UK
• Consultant
• Uveitis Ocular Immunology
• Ocular Epidemiology Community Eye Health
• Narayana Nethralaya , Bangalore

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Ocular Sarcoidosis

• Definition
• Epidemiology
• Theories of pathogenesis
• Clinical manifestations
• Symptoms
• Complications
• Pathology
• Differential diagnosis
• Investigations
• Treatment
• Prognosis

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Definition

• Sarcoidosis is a chronic multisystemic
  granulomatous disorder of unknown etiology
  thought to result from an exaggerated cellular
  immune response to a variety of self antigens or
  non-self antigens that is characterized by its
  pathological hallmark, the noncaseating
  granuloma.

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• The illness can be self-limited or chronic
  Episodic recrudescence and remissions.
• Because the lungs and thoracic lymph nodes are
  almost always involved, most patients report
  acute or insidious respiratory problems, variably
  accompanied by symptoms affecting the skin, eyes,
  or other organs.

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Epidemiology

• Sarcoidosis occurs worldwide.
• Affecting persons of all races, both sexes, and
  all ages.
• It has a particular proclivity for adults lt age
  of 40 and for certain ethnic and racial groups
  (US blacks, Scandinavian and Irish white people).
  
• The lifetime risk of sarcoidosis for U.S. blacks
  is 2.4 percent, and that for U.S. whites 0.85
  percent.

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Epidemiology

• The frequency of sarcoidosis is reported to be
  low in various parts of the world.
• It is not known whether this low frequency of
  sarcoidosis is genuine or whether it represents
  an underdiagnosis owing to the frequent
  occurrence of subclinical course, similarity with
  other diseases, or absence of firm diagnostic
  criteria.

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Etiopathogenesis

• The cause of sarcoidosis remains obscure for a
  number of reasons
• The heterogeneity of the manifestations of the
  disease
• The lack of a precise definition
• Clinical overlap with other disorders
• and insensitive and nonspecific diagnostic tests
  that lead to misclassification of the disease .
• Mycobacterium remain leading suspects.
• Transmission after cardiac /bone-marrow
  transplant has been reported

1. Almenoff PL, Johnson A, Lesser M, Mattman LH.
   Growth of acid fast L forms from the blood of
   patients with sarcoidosis. Thorax
   199651530-533.
2. Burke WMJ, Keogh A, Maloney PJ, Delprado W,
   Bryant DH, Spratt P. Transmission of sarcoidosis
   via cardiac transplantation. Lancet
   19903361579-1579.
3. Heyll A, Meckenstock G, Aul C, et al. Possible
   transmission of sarcoidosis via allogeneic bone
   marrow transplantation. Bone Marrow Transplant
   199414161-164.

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Theories of pathogenesis

• The diverse manifestations of this disorder help
  fuel the prevailing hypothesis that sarcoidosis
  has more than one cause, each of which
• may promote a different pattern of illness.

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Theories of pathogenesis

• Conceptually, it appears likely that
• Genetically predisposed hosts are exposed to
  antigens that trigger an exaggerated cellular
  immune response and the formation of granulomas.
  

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PATHOLOGICAL AND IMMUNOLOGIC FEATURES
Non-caseating granuloma holds the key to the
diagnosis of sarcoidosis and provides clues to
the immunopathogenesis of the disease.
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Clinical Manifestations

• Can be widespread or may involve only one organ
  system at a time.
• Two peaks of incidence - the first at ages 2030
  years and the second at ages 5060 years.
• Ocular involvement manifests in 2560 of
  patients with systemic sarcoidosis.

Albert DM, Jakobiec FAHunter DG, Foster CS(1994)
Ocular manifestations of sarcoidosis. in
Principles and practice of ophthalmology . eds
Albert DM, Jakobiec FA(WB Saunders,
Philadelphia), pp 443450.
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Symptoms

• The majority of patients, however, present with
  systemic symptoms such as fatigue, anorexia,
  weight loss, and fever .
• Many report dyspnea on exertion, retrosternal
  chest pain, and cough .
• This may precede of come many months and years
  later.
• Ocular symptoms related to chronic granulomatous
  uveitis
• Lid nodules, conjunctival injection and nodules,
  rarely proptosis

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Symptoms

• In 20 to 50 percent of the patients with more
  acute presentations, one sees the constellation
  of
• Erythema Nodosum
• Bilateral hilar lymphadenopathy
• Polyarthralgias, known as Löfgren's syndrome.
• Parotid involvement with uveitis is called
  Herfordt syndrome.

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Examination findings

• Ophthalmic lesions develop in approximately 25
  percent of patients.
• The classic symptom of anterior uveitis has a
  rapid onset, with blurred vision, photophobia,
  and excessive lacrimation it usually clears
  spontaneously within a year.
• Conjunctival involvement with small, pale, yellow
  nodules is common.

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• The most common ocular manifestations are uveitis
  (3070) and conjunctival nodules (40)
• More than 80 of uveitis cases manifested before
  or within 1 year after the onset of systemic
  disease.

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• DIFFUSE MUTTON FAT KERATIC PRECIPITATES
• AQUEOUS FLARE
• AQUEOUS CELLS
• FIBRIN PRESENT
• IRIS NODULES
• LENS CLEAR
• NO VITREOUS REACTION

RIGHT EYE
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Multiple koeppes and bussaca nodules
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Conjunctival involvement has been reported in 6.9
- 70 of patients with ocular sarcoidosis Sarcoido
sis granulomas are described as solitary, yellow
"millet-seed" nodules.
CONJUNCTIVAL NODULES
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Posterior segment manifestations
Intermediate Uveitis
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Posterior segment manifestations
Disc edema
Active sarcoid granulomas
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Complications

• The clinical impact of sarcoidosis is directly
  related to the extent of granulomatous
  inflammation and its effect on the function of
  vital organs.
• Specimens should be obtained from the most
  readily accessible organ with the least invasive
  method.

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Complications

• The clinical impact of sarcoidosis is directly
  related to the extent of granulomatous
  inflammation and its effect on the function of
  vital organs.
• Specimens should be obtained from the most
  readily accessible organ with the least invasive
  method.

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Pathology
Small focus of necrosis. The most common
appearance of necrosis in sarcoidosis
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Rather like a rugby scrum with all the players
grouped around the ball only with sarcoidosis
the ball is invisible.
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Small focus of necrosis
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Granulomas involving a bronchiole
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Angiotensin converting enzyme (ACE)

• ACE is normally present in the vascular
  endothelium of many organs (lung, kidney, small
  intestine, uterus, prostate, thyroid, testes,
  adrenals) and in macrophages.
• The macrophages accounts for elevated ACE levels
  in patients with sarcoidosis.
• ACE is elevated in 60-90 of patients with active
  sarcoidosis.
• A normal serum ACE does not exclude the
  diagnosis, especially if the disease is in its
  early stages, localized to a small area (e.g. the
  eye), and therefore with a small epithelioid cell
  "burden".

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False low values of ACE

• Patients taking ACE inhibitors
• Endothelial abnormalities, such as deep vein
  thrombosis
• Patients who have had chemotherapy or radiation.
• Treatment with systemic steroids or other
  immunosupressive agents can also affect ACE
  levels with values normalizing with adequate
  control of intraocular inflammation.

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Elevated serum ACE

• Gaucher's disease
• Leprosy
• Chronic pulmonary disease
• Rheumatoid arthritis
• Spondylitis
• Primary biliary cirrhosis
• Tuberculosis
• Histoplasmosis
• Histiocytic medullary fibrosis
• Hyperthyroidism
• Diabetes mellitus.

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Differential diagnosis

• Any cause of chronic granulomatous diseases
• Tuberculosis
• Syphillis
• Herpetic uveitis
• Lymphoma
• Metastases

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Investigations

• In the absence of a known causative agent,
  sarcoidosis remains a diagnosis of exclusion.
• There are no definitive diagnostic blood, skin,
  or radiologic imaging tests specific for the
  disorder.
• Even serum ACE and galluium 67 Scan s are not
  specific to Sarcoidosis
• Gold standard is demonstration of non caseating
  granulomas from tissue .

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Investigations

• CBC, ESR
• Mantoux test
• Chest X Ray
• Serum ACE levels
• Lymph Node Biopsy
• Broncheo Alveolar Lavage
• Trans Bronchial Lung Biopsy
• Other tests
• TPHA
• Sputum for AFB
• Gallium 67 Scan

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Gold standard

• In most centers, skin and transbronchial lung
  biopsies have supplanted biopsy of mediastinal
  lymph nodes and the liver because of their high
  yield, greater specificity, and low morbidity.

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Lungs and thoracic lymph nodes are affected in
90 of patients with sarcoidosis Clinical staging
is based on the pattern of chest radiographic
findings
Radiographic Staging of Pulmonary Sarcoidosis
Using Conventional Chest Radiography
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• Stage 0--No abnormality is defined.

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Bilateral hilar lymphadenopathy (BHL),stage 1
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• Stage 1- Hilar and paratracheal adenopathy
  without parenchymal involvement.
• Bilateral hilar adenopathy is most common,
  followed by adenopathy in the right paratracheal
  area or aortopulmonary window area on the left.
•  

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BHL with parenchymal infiltrates, stage II
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Bilateral hilar adenopathy with Mild interstitial
disease in upper lobes.
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• Stage 2-Adenopathy with parenchymal involvement.
• The parenchymal involvement includes a diffuse
  accentuation of interstitial markings resulting
  in a reticular pattern.
•  

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Sarcoidosis (with progression from stage II to
stage III)
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Parenchymal infiltrates, stage III
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Signs of fibrosis with shrinkage, stage IV.
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CT showing bilateral nodular infiltrates along
bronchovascular bundles and enlarged mediastinal
lymph nodes
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Treatment

• The optimal therapy for sarcoidosis is not well
  defined therapeutic decisions are dictated by
  the localisation of the disease and severity of
  organ involvement.
• The mainstay of treatment is corticosteroid
  therapy, which exhibits especially short term
  beneficial effects.

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Treatment

• Steroid sparing drugs for longer term treatment
• Methotrexate 10-22.5mg/week
• Cyclosporin B 3-5 mg/kgBW/day
• Azathioprine 1-3mg/kgBW BID/TID

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Local Treatment

• Topical Prednisolone acetate eye drops
• Peri-ocular Posterior subtenons triamcinolone
  acetonide
• Dexamethasone implant in very severe recurrent
  cases

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Prognosis

• The poor visual prognosis was associated with the
  advanced age of the patients, black race, female
  sex, chronic systemic disease, and also with
  posterior segment involvement, peripheral punched
  out lesions, and the presence of cystoid macular
  oedema and glaucoma.
• CME is leading cause of visual loss in sarcoid
  patients

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Thank You
drrajeshbabu_at_yahoo.com