SARCOIDOSIS

1. SARCOIDOSIS

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

3. Sarcoidosisterm is formed from - sarc meaning flesh, - oidmeaning like, and - osisfor 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 dermatologistCaesar Boeck to describe the skin nodules. Thinking thisresembled sarcoma, he called the condition "multiple benignsarcoid of the skin.”

4. 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.

6. EPIDEMIOLOGY

7. 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 inscandinavian 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.

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

9. ETHNIC HETEROGENEITY

10. 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.

11. 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.

13. ETIOLOGY • Infection • Environmental • Occupational • Autoimmune • Genetic

14. Infectious agents • Mycobacterium tuberculosis • Atypical mycobacterial species • Cell wall-deficient mycobacterial forms • Propionibacterium acnes/granulosum • Rickettsiahelvetica • Borreliaburgdorferi • Mycoplasma spp. • Viruses (e.g. human herpes viruses, Epstein–Barr)

15. With the use of polymerase-chain-reaction techniques, mycobacterialand propionibacterial DNA and RNA have been recovered from sarcoidaltissue in Japan and Europe. Investigators have reported that serum samples from patients with sarcoidosis often contain antibodies to mycobacterialantigens, including recombinant Mycobacterium tuberculosiskatG(catalaseperoxidase protein) ,M. tuberculosis heat-shock protein 70,and M. tuberculosismycolyltransferase antigen 85A. 

16. Environment and occupation • Because sarcoidosis most commonly involves the lungs, eyes,and skin, the search for environmental causes has centered onexposures to airborne antigens. • It is associated with exposures to irritantsfound in rural settings, such as emissions from wood-burningstoves and tree pollen. • More recently, associations with sarcoidosisand exposure to inorganic particles, insecticides, and moldyenvironments havebeen reported. • Occupational studies haveshown positive associations with service in the U.S. Navy,metalworking, firefighting and the handling of buildingsupplies. Recently, Izbicki et al. reported an increased incidenceof sarcoidosis among New York City Fire Department rescue workersinvolved in the 2001 World Trade Center disaster

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

18. 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.

19. 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.

20. PATHOPHYSIOLOGY

21. The development and accumulation of granulomasconstitute thefundamental 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. • Granulomasare compact, centrallyorganized collections of macrophages and epithelioid cells encircledby lymphocytes.

22. Macrophages, in the face of chronic cytokinestimulation, differentiate into epithelioid cells, gain secretoryand bactericidal capability, lose some phagocytic capacity,and fuse to form multinucleated giant cells • Inmore mature granulomas, fibroblasts and collagen encase theball-like cluster of cells, and in some cases, sclerosisensues, altering organ architecture and function • A cardinal feature of sarcoidosis is the presence of CD4+ Tcells that interact with antigen-presenting cells to initiatethe formation and maintenance of granulomas .

25. Organ Involvement • Sarcoidalgranulomas can involve any organ, but in more than90% of patients, clinical sarcoidosis is manifested as intrathoraciclymph-node enlargement, pulmonary involvement, skin or ocularsigns and symptoms, or some combination of these findings.

27. HISTOLOGY NON CASEATING GRANULOMA OF SARCOIDOSIS

30. Cutaneoussarcoidosis

34. GRANULOMA differentials • Tuberculosis of skin • Sarcoidosis • Lupus vulgaris, • Tuberculoid leprosy, • Foreign body granuloma, • Cutaneousleishmaniasis.

35. Tuberculosis of skin Sarcoidosis

36. 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.

38. Indian scenario of sarcoidosis

39. 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 tuberculintest 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.

40. 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.

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

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