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
Ocular Sarcoidosis
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Definition
Epidemiology
Theories of pathogenesis
Clinical manifestations
Symptoms
Complications
Pathology
Differential diagnosis
Investigations
Treatment
Prognosis
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.
• 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.
Epidemiology
• Sarcoidosis occurs worldwide.
• Affecting persons of all races, both sexes, and all ages.
• It has a particular proclivity for adults < 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.
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.
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
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2.
3.
Almenoff PL, Johnson A, Lesser M, Mattman LH. Growth of acid fast L forms from the blood of patients with sarcoidosis. Thorax 1996;51:530-533.
Burke WMJ, Keogh A, Maloney PJ, Delprado W, Bryant DH, Spratt P. Transmission of sarcoidosis via cardiac transplantation. Lancet 1990;336:1579-1579.
Heyll A, Meckenstock G, Aul C, et al. Possible transmission of sarcoidosis via allogeneic bone marrow transplantation. Bone Marrow Transplant 1994;14:161-164.
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.
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.
PATHOLOGICAL AND IMMUNOLOGIC FEATURES
Non-caseating granuloma holds the key to the diagnosis of sarcoidosis and
provides clues to the immunopathogenesis of the disease.
Clinical Manifestations
• Can be widespread or may involve only one
organ system at a time.
• Two peaks of incidence - the first at ages 20–
30 years and the second at ages 50–60 years.
• Ocular involvement manifests in 25%–60% 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 443–450.
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
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.
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.
• The most common ocular manifestations are
uveitis (30%–70%) and conjunctival nodules
(40%)
• More than 80% of uveitis cases manifested
before or within 1 year after the onset of
systemic disease.
•DIFFUSE MUTTON FAT KERATIC PRECIPITATES
•AQUEOUS FLARE ++
•AQUEOUS CELLS ++
•FIBRIN PRESENT
•IRIS NODULES
•LENS CLEAR
•NO VITREOUS REACTION
RIGHT EYE
Multiple koeppe’s and bussaca nodules
Conjunctival involvement has been reported in 6.9 - 70% of patients with ocular sarcoidosis
Sarcoidosis granulomas are described as solitary, yellow "millet-seed" nodules.
CONJUNCTIVAL NODULES
Posterior segment manifestations
Intermediate Uveitis
Posterior segment manifestations
Disc edema
Active sarcoid granulomas
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.
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.
Pathology
Small focus of necrosis.
The most common appearance of necrosis in sarcoidosis
Rather like a rugby scrum with all the players grouped around the ball;
only with sarcoidosis the ball is invisible.
Small focus of necrosis
Granulomas involving a bronchiole
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".
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.
Elevated serum ACE
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Gaucher's disease
Leprosy
Chronic pulmonary disease
Rheumatoid arthritis
Spondylitis
Primary biliary cirrhosis
Tuberculosis
Histoplasmosis
Histiocytic medullary fibrosis
Hyperthyroidism
Diabetes mellitus.
Differential diagnosis
• Any cause of chronic granulomatous diseases
– Tuberculosis
– Syphillis
– Herpetic uveitis
– Lymphoma
– Metastases
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 .
Investigations
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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
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.
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
Stage 0--No abnormality is defined.
Bilateral hilar lymphadenopathy (BHL),stage 1
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
Bilateral hilar adenopathy with Mild interstitial disease in
upper lobes.
• Stage 2-Adenopathy with parenchymal involvement.
The parenchymal involvement includes a diffuse accentuation of interstitial markings
resulting in a reticular pattern.
Sarcoidosis (with progression from stage II to stage III)
Parenchymal infiltrates, stage III
Signs of fibrosis with shrinkage, stage IV.
CT showing bilateral nodular infiltrates along bronchovascular
bundles and enlarged mediastinal lymph nodes
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.
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
Local Treatment
• Topical Prednisolone acetate eye drops
• Peri-ocular Posterior subtenons triamcinolone
acetonide
• Dexamethasone implant in very severe
recurrent cases
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
Thank You
drrajeshbabu@yahoo.com