SARCOIDOSIS

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SARCOIDOSIS

SARCOIDOSISEpidemiology ,etiology ,pathophysiology

Dr. ADITI GUPTA

Junior Resident

Chest & TB

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Sarcoidosis term is formed from - sarc meaning flesh, - oid meaning like, and - osis for diseased or abnormal condition.

It is also called sarcoid, Besnier-Boeck disease or Besnier-Boeck-Schaumann disease.

The term sarcoidosis was coined by a Norwegian dermatologist Caesar Boeck to describe the skin nodules. Thinking this 

resembled sarcoma, he called the condition "multiple benign sarcoid of the skin.”

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Sarcoidosis is a multisystem disorder of unknown origin characterized by noncaseating granulomatous inflammation affecting lungs and intrathoracic lymph nodes, most commonly.

Diagnosis is establised most securely from clinicoradiologic findings together with histologic evidence of noncaseating epithelioid granulomas in more than one organ and exclusion of granulomatous disorders of known cause.

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EPIDEMIOLOGY

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INCIDENCE & PREVALENCE

It is found worldwide, although the frequency varies among different geographic regions.

Exact prevalence is not certain, as many people are asymptomatic and there is no sensitive nor specific test.

Highest prevalence is noted in scandinavian countries namely Sweden, Denmark, Norway & Finland.

The annual incidence(cases per 100,000 people) in decreasing order is :-Scandinavian(5-40) > US blacks(35.5) >whites of North America(10) > Southern Europe > Japan(1-2).

However, these values are greatly underestimated as majority patients are asymptomatic.

Geographic distribution of sarcoidosisScandinavian countries namely Sweden, Denmark, Norway & Finland.

North America (Blacks>whites)

Southern Europe

“The farther from the equator , the more patients.”

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ETHNIC HETEROGENEITY

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AGE & SEX incidence

It is slightly more common in females.

More than 80% cases occur in 20 and 40 years of age, with a second peak in women >50 yrs .

Very rare in preadolescent period.

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ETHNIC FACTORS Erythema nodosum is more common in

scandinavian countries. Lupus pernio is m/c in blacks Cardiac sarcoidosis is m/c in Japan Blacks have more persistent & severe

disease than whites. In US, majority deaths are due to advanced

pulmonary disease but in Sweden & Japan, its due to cardiac involvement.

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ETIOLOGY

1. Infection

2. Environmental

3. Occupational

4. Autoimmune

5. Genetic

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Infectious agents Mycobacterium tuberculosis Atypical mycobacterial species Cell wall-deficient mycobacterial forms Propionibacterium acnes/granulosum Rickettsia helvetica Borrelia burgdorferi Mycoplasma spp. Viruses (e.g. human herpes viruses,

Epstein–Barr)

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With the use of polymerase-chain-reaction techniques, mycobacterial and propionibacterial DNA and RNA have been recovered from sarcoidal tissue in Japan and Europe. 

Investigators have reported that serum samples from patients with sarcoidosis often contain antibodies to mycobacterial antigens, including recombinant Mycobacterium tuberculosis katG (catalase peroxidase protein) , M. tuberculosis heat-shock protein 70,and M. tuberculosismycolyl transferase antigen 85A. 

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Environment and occupation Because sarcoidosis most commonly involves the lungs, eyes, and skin,

the search for environmental causes has centered on exposures to airborne antigens.

It is associated with exposures to irritants found in rural settings, such as emissions from wood-burning stoves and tree pollen.

More recently, associations with sarcoidosis and exposure to inorganic particles, insecticides, and moldy environments have been reported.

Occupational studies have shown positive associations with service in the U.S. Navy,  metalworking, firefighting and the handling of building supplies. Recently, Izbicki et al. reported an increased incidence of sarcoidosis among New York City Fire Department rescue workers involved in the 2001 World Trade Center disaster

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Inorganic substances

Aluminum Zirconium Man-made mineral fibers Silica Silicone Clay Talc

Organic substances Pine tree pollen Starch

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Genetics Genetic factors have a greater influence in susceptibility to

sarcoidosis in whites than blacks.

Familial clustering is more in blacks.

Siblings have higher relative risk (5.8)than parents(3.8).

Role of HLA class I and II have been extensively studied HLA-B8 increases the risk in whites HLA-B07 &08 in Scandinavians whereas HLA-DR1 &DR4 are

associated with disease protection in Scandinavians.

HLA DR0301/0201 are associated with good outcome whereas HLA DRBI 1501/DQBI 0602 are associated with severe disease.

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ETIOLOGICAL CONCLUSION

Given the multiple environmental risk factors and potential causes reported to date, it seems plausible that sarcoidosis is the end result of an altered or incomplete immune response to various ubiquitous environmental triggers in genetically susceptible hosts, and that specific HLA gene–environmental interactions play a fundamental role.

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PATHOPHYSIOLOGY

The development and accumulation of granulomas constitute the fundamental abnormality in sarcoidosis.

Although the inciting event in sarcoidosis is unknown, in principle. Infectious, organic, and inorganic agents are possible antigens in sarcoidosis . Granulomas are generally formed to confine pathogens, restrict inflammation, and protect surrounding tissue.

Granulomas are compact, centrally organized collections of macrophages and epithelioid cells encircled by lymphocytes.

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Macrophages, in the face of chronic cytokine stimulation, differentiate into epithelioid cells, gain secretory and bactericidal capability, lose some phagocytic capacity, and fuse to form multinucleated giant cells

In more mature granulomas, fibroblasts and collagen encase the ball-like cluster of cells, and in some cases, sclerosis ensues, altering organ architecture and function

A cardinal feature of sarcoidosis is the presence of CD4+ T cells that interact with antigen-presenting cells to initiate the formation and maintenance of granulomas .

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Organ Involvement Sarcoidal granulomas can involve

any organ, but in more than 90% of patients, clinical sarcoidosis is manifested as intrathoracic

lymph-node enlargement, pulmonary involvement, skin or ocular signs and symptoms, or some combination of these findings.

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HISTOLOGY

NON CASEATING GRANULOMA OF SARCOIDOSIS

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Cutaneous sarcoidosis

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GRANULOMA differentials Tuberculosis of skin Sarcoidosis Lupus vulgaris, Tuberculoid leprosy, Foreign body granuloma, Cutaneous leishmaniasis.

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SarcoidosisTuberculosis of skin

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Similarities between TB & Sarcoidosis

Both are chronic multisystem diseases.

Both are characterized by granulomatous inflammation.

Both can have acute presentation.

Both present with constitutional symptoms like fever, weight loss, anorexia, malaise, chronic cough etc.

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Indicator Sarcoidosis TuberculosisClinical course Remission &

exacerbationProgressive

granuloma Caseating Noncaseatingcough Mainly dry, hemoptysis

rare.Usually productive, hemoptysis is common

Pleural effusion Rare Very commonTuberculin test Nearly always negative PositiveSerum ACE Raised NormalClinico-radiological dissociation

Often seen Rare

Intrathoracic LAP Symmetrical, bihilar, paratracheal smooth, discrete, solid.

Asymmetrical, large, conglomerate, with central area of hypodensity.

Extrathoracic LAP In 10% only Cervical &axillary LAP is very common.

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Indian scenario of sarcoidosis

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Sarcoidosis is a rare clinical entity in india. In India, almost all patients are symptomatic

on presentation unlike in west where 50% are asymptomatic at the time of diagnosis.

Age -5th decade but in west it is 20-40 yr. Sex-males>females. In India, healthy adults are commonly

tuberculin test positive. Sarcoidosis is infrequently recognized & is

often mistaken for tuberculosis. Case reports are seen on TB with sarcoidosis.It

can be a concomitent occurrence OR is followed by TB or TB followed by it.

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Treatment issues & difficulties in INDIA

Risk of precipitation of TB following steroid therapy for sarcoidosis.

Occasionally, patient is misdiagnosed as sarcoidosis may later develop TB due to delay in diagnosis rather than steroid therapy.

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Patient dependent factors

Reluctance to accept diagnosis.

Doctor shopping

Reluctance to undergo invasive procedure

Partial symptomatic relief with intermittent unregulated steroid therapy

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Physician dependent factors

Lack of knowledge

Lack of ease, standardized diagnostic criterion

Reluctance to perform invasive procedure

Lack of standard treatment protocol

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