SARCOIDOSIS 1 SARCOIDOSIS Epidemiology etiology pathophysiology Dr ADITI

SARCOIDOSIS 1

SARCOIDOSIS Epidemiology , etiology , pathophysiology Dr. ADITI GUPTA Junior 2 Resident Chest & TB

� 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. ” 3

� 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. 4

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EPIDEMIOLOGY 6

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(12). However, these values are greatly underestimated as majority patients are asymptomatic. 7

Geographic distribution of sarcoidosis North America (Blacks>whites) Scandinavian countries namely Sweden, Denmark, Norway & Finland. Southern Europe “The farther from the equator , the more patients. ” 8

ETHNIC HETEROGENEITY 9

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. 10

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. 11

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ETIOLOGY 1. Infection 2. Environmental 3. Occupational 4. Autoimmune 5. Genetic 13

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) 14

� 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 kat. G (catalase peroxidase protein) , M. tuberculosis heat-shock protein 70, and M. tuberculosismycolyl transferase antigen 85 A. 15

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 16

Inorganic substances Aluminum � Zirconium � Man-made mineral fibers � Silica � Silicone � Clay � Talc � Organic substances Pine tree pollen � Starch � 17

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-B 8 increases the risk in whites HLA-B 07 &08 in Scandinavians whereas HLA-DR 1 &DR 4 are associated with disease protection in Scandinavians. � � HLA DR 0301/0201 are associated with good outcome whereas HLA DRBI 1501/DQBI 0602 are associated with severe disease. 18

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. 19

PATHOPHYSIOLOGY 20

� 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. 21

� 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 CD 4+ T cells that interact with antigen-presenting cells to initiate the formation and maintenance of 22 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. 25

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HISTOLOGY NON CASEATING GRANULOMA OF SARCOIDOSIS 27

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Cutaneous sarcoidosis 30

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GRANULOMA differentials �Tuberculosis of skin � Sarcoidosis �Lupus vulgaris, �Tuberculoid leprosy, �Foreign body granuloma, �Cutaneous leishmaniasis. 34

Tuberculosis of skin Sarcoidosis 35

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. 36

Indicator Sarcoidosis Tuberculosis Clinical course Remission & exacerbation Progressive granuloma Caseating Noncaseating cough Mainly dry, hemoptysis rare. Usually productive, hemoptysis is common Pleural effusion Rare Very common Tuberculin test Nearly always negative Positive Serum ACE Raised Normal Clinico-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. 37

Indian scenario of sarcoidosis 38

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 -5 th 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. 39 �

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. 40

Patient dependent factors � Reluctance to accept diagnosis. � Doctor shopping � Reluctance to undergo invasive procedure � Partial symptomatic relief with intermittent unregulated steroid therapy 41

Physician dependent factors � Lack of knowledge � Lack of ease, standardized diagnostic criterion � Reluctance to perform invasive procedure � Lack of standard treatment protocol 42

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