detailed seminar on Sarcoidosis, includes- introduction, pathology, etio-pathogenesis, staging, diagnosis and its management.

1. SARCOIDOSIS
AMIT SINGH

2. INTRODUCTION
• SARCOIDOSIS HAS BEEN DEFINED AS A MULTI-
SYSTEM GRANULOMATOUS DISORDER OF
UNKNOWN CAUSE.
• AFFECTS THE LUNG IN OVER 90% OF CASES
BUT CAN AFFECT ANY PART OF THE BODY.
• DISEASE IS SELF-LIMITED AND RESOLVES
WITHIN 2 TO 5 YEARS, BUT CHRONIC FORM OF
THE DISEASE CAN LEAD TO SIGNIFICANT
MORBIDITY AND MORTALITY.

3. EPIDEMIOLOGY
• FOUND WORLDWIDE, PREVALENCE ARE UNKNOWN,
• MOST PT. ——ASYMPTOMATIC
• ESTIMATED PREVALENCE RATES BETWEEN 10 AND 40
CASES / 100,000 POPULATION ARE REPORTED IN
NORTH-AMERICA, SOUTHERN EUROPE, AND JAPAN.
• HIGHER PREVALENCE SWEDEN, DENMARK, AND US
BLACKS.
• MORE THAN 80% ———20 AND 50 YEARS OF AGE ,
• SECOND PEAK IN WOMEN MORE THAN 50 YEARS OF
AGE.

4. • IN JAPAN, OVER 50% OF PATIENTS MAY HAVE
CARDIAC SARCOIDOSIS.
• BLACK POPULATIONS MORE LIKELY TO HAVE
PERSISTENT DISEASE AND GREATER
MORTALITY .
• UNITED STATES, 40% TO 80% OF MORTALITY
FROM SARCOIDOSIS IS FROM ADVANCED
PULMONARY DISEASE, (HIGHER RATES OBSERVED IN
BLACKS AND WOMEN).
• OVERALL, MORTALITY RATES DIRECTLY
RELATED TO SARCOIDOSIS APPROXIMATE <1%
TO 5%.

5. ETIOLOGY• CAUSE OF SARCOIDOSIS REMAINS UNCERTAIN.
• ENVIRONMENTAL EXPOSURES ARE LINKED TO
SARCOIDOSIS WITH A PREDILECTION FOR WINTER AND
EARLY SPRING MONTHS IN BOTH NORTHERN AND
SOUTHERN HEMISPHERES.
• OCCUPATIONAL ASSOCIATIONS HAVE BEEN DESCRIBED
FOR HEALTHCARE PROFESSIONALS, FIREFIGHTERS,
MILITARY PERSONNEL, AND WORKERS INVOLVED IN THE
LUMBER INDUSTRY.
• CHRONIC BERYLLIUM DISEASE CAUSES A
GRANULOMATOUS PNEUMONITIS HISTOLOGICALLY
IDENTICAL TO PULMONARY SARCOIDOSIS IN LESS THAN
5% OF EXPOSED WORKERS (NO EVIDENCE THAT BERYLLIUM IS A
CAUSE OF SYSTEMIC SARCOIDOSIS ).

6. • ACCESS (A CASE CONTROL ETIOLOGIC STUDY OF SARCOIDOSIS)
COMPARED 706 NEWLY DIAGNOSED, BIOPSY-PROVEN
SARCOIDOSIS CASES TO AGE-, SEX-, AND RACE-MATCHED
CONTROLS.
• WEAK POSITIVE ASSOCIATIONS WERE FOUND FOR INSECTICIDE
USE AT WORK, MOLD/MILDEW EXPOSURES AT WORK, AND
MUSTY ODORS, SUGGESTING POSSIBLE LINKS TO MICROBIAL-
RICH ENVIRONMENTS.
• NOT ASSOCIATED WITH EXPOSURE TO HEAVY METALS
INCLUDING BERYLLIUM, WOOD DUSTS, OR RURAL RESIDENCE.
• NEGATIVE ASSOCIATION OF SMOKING AND SARCOIDOSIS RISK.
• MANY STUDIES HAVE DIRECTLY EXAMINED A ROLE FOR
INFECTIOUS AGENTS IN SARCOIDOSIS GIVEN THE CLINICAL
SIMILARITIES TO MYCOBACTERIAL DISEASE.

7. JAPANESE INVESTIGATORS FIND PROPIONIBACTERIUM ACNES
DNA IN 80% — 98% OF SARCOIDOSIS TISSUES FROM JAPAN AND
EUROPE .
OTHER MICROBIAL AGENTS, SUCH AS :
BORRELIA BURGDORFERI,
CHLAMYDIA PNEUMONIA,
RICKETTSIA HELVETICA
EPSTEIN–BARR VIRUS,
CYTOMEGALOVIRUS,
HUMAN HERPESVIRUS TYPE 6

8. • MYCOBACTERIA HAVE BEEN IMPLICATED AS A POTENTIAL
CAUSE OF SARCOIDOSIS.
• MORE THAN TWO DOZEN STUDIES HAVE ASSESSED THE
PRESENCE OF MYCOBACTERIAL DNA AND RNA IN
SARCOIDOSIS TISSUES.
• SARCOIDOSIS IS ASSOCIATED WITH FEATURES OF
AUTOIMMUNITY, SUCH AS ANTINUCLEAR ANTIBODIES,
RHEUMATOID FACTOR, HYPERGAMMAGLOBULINEMIA, AND
IMMUNE COMPLEXES.
• AN INCREASED INCIDENCE OF SARCOIDOSIS HAS BEEN
FOUND IN INDIVIDUALS EXPOSED TO METALS, IN
PARTICULAR, TITANIUM,33
METALWORKING, METAL MACHINING .

9. GENETICS
• THE US ACCESS STUDY FOUND SIBLINGS OF SARCOIDOSIS CASES
HAVE A HIGHER RELATIVE RISK (RR) THAN PARENTS.
• WHITES>BLACK.
• THE HLA-B8 ALLELE HAS MOST CONSISTENTLY BEEN ASSOCIATED
WITH DISEASE SUSCEPTIBILITY, INCREASING SARCOIDOSIS RISK IN
WHITES
• SCANDINAVIAN AND EUROPEAN POPULATION STUDIES SUGGEST
ROLE OF HLA CLASS II ALLELES HAS BEEN INTENSIVELY STUDIED IN
SARCOIDOSIS.
HLA-DR3 ———— SARCOIDOSIS SUSCEPTIBILITY.
HLA-DR1 & DR4 ———— DISEASE PROTECTION.

10. • ACCESS STUDY, SIGNIFICANT ASSOCIATION BETWEEN
HLA-DRB1 IN BOTH BLACK AND WHITES.
• HLA-DRB1*03 IN SARCOIDOSIS WAS STRONGLY
ASSOCIATED WITH A LÖFGREN SYNDROME , ACUTE ARTHRITIS
,STAGE I CHEST RADIOGRAPH, OR REMISSION WITHIN 2 YEARS IN
EUROPEAN AND JAPANESE POPULATIONS.
• POLYMORPHISMS OF THE TUMOR NECROSIS FACTOR
(TNF) GENE LOCATED WITHIN THE MHC LOCUS IS
ASSOCIATED WITH A 1.5-FOLD INCREASE RISK OF
DEVELOPING SARCOIDOSIS.
• GERMAN AND US INVESTIGATORS REPORTED THAT THE
BUTYROPHILIN-LIKE 2 (BTNL2) GENE IS ASSOCIATED WITH
SARCOIDOSIS. (BLACK>WHITE).

11. PATHOLOGY:
• HALLMARK OF SARCOIDOSIS IS THE PRESENCE OF
DISCRETE, NONCASEATING, EPITHELIOID CELL
GRANULOMAS
• THE DOMINANT CELL IN THE CENTRAL CORE IS THE
EPITHELIOID CELL
• CD4 LYMPHOCYTES AND MATURE MACROPHAGES ARE
TYPICALLY INTERSPERSED THROUGHOUT THE
EPITHELIOID CORE.
• BOTH CD4+ AND CD8+ T CELLS AND B LYMPHOCYTES
MAY BE SEEN IN THE PERIPHERY OF THE GRANULOMA.
• OCCASIONALLY, FOCAL FIBRINOID BUT NOT CASEATING
NECROSIS MAY BE SEEN

12. • IN THE LUNG, GRANULOMAS TEND TO FORM
ALONG PERIVASCULAR, PERIBRONCHIAL, AND
SEPTAL REGIONS, AREAS RICH IN LYMPHATIC
VESSELS.
• IN THE LUNG, A MONONUCLEAR CELL
INFILTRATION COMPOSED PREDOMINANTLY OF
LYMPHOCYTES
• GRANULOMAS IN SARCOIDOSIS MAY RESOLVE
OR UNDERGO FIBROSIS, LEAVING A STELLATE
SCAR OR HYALINIZED GHOST OF A FORMER
GRANULOMA.

13. Photomicrographs of noncaseating granulomatous inflammation in sarcoidosis. A. Thoracoscopic lung biopsy showing exten

14. PATHOPHYSIOLOGY• FIRST STEP IN GRANULOMA FORMATION INVOLVES THE
TISSUE DEPOSITION OF POORLY SOLUBLE ANTIGENIC
MATERIAL.
• IT IS FOLLOWED BY RECRUITMENT AND ACTIVATION OF
ANTIGEN-PRESENTING CELLS SUCH AS MACROPHAGES
AND TOLL-LIKE RECEPTORS (TLRS). RESULTS IN THE
PHAGOCYTOSIS AND DEGRADATION OF ANTIGENIC
PROTEINS .
• THE RESULTING ADAPTIVE IMMUNE RESPONSE IS
CHARACTERIZED BY THE EXPRESSION OF EFFECTOR
CYTOKINES TYPE 1 T HELPER CELL (TH1; IFNΓ), TH2
(IL4/IL13), OR TH17 (IL17/IL21/IL22) RESPONSE, DEPENDING
ON THE NATURE OF THE ANTIGEN AND HOST.
• GRANULOMA FORMATION —>RELEASE OF CYTOKINES,
CHEMOKINES, AND OTHER MEDIATORS

15. • GRANULOMATOUS INFLAMMATION IS DOWNREGULATED
WITH CLEARANCE OF ANTIGEN ALONG WITH RELEASE OF
ANTI- INFLAMMATORY MEDIATORS (TGF-Β AND IL10 )
• SITES OF GRANULOMATOUS INFLAMMATION SUCH AS THE
LUNG CONTAIN ACTIVATED T CELLS AND MONONUCLEAR
PHAGOCYTES THAT EXPRESS THE SAME
PROINFLAMMATORY CYTOKINES AND CHEMOKINES
• LUNG T CELLS ARE PREDOMINANTLY OF THE CD4 T
HELPER, CD45R0 “MEMORY” PHENOTYPE .
• SARCOIDOSIS ALVEOLAR MACROPHAGES (AMS)
SPONTANEOUSLY PRODUCE TNF, INTERLEUKIN-6 (IL6),
IL1Α, IL15, AND THE TH1 REGULATORY CYTOKINES, IL12
AND IL18.
• TNF IS CONSIDERED TO BE A MAJOR EFFECTOR
CYTOKINE OF GRANULOMA FORMATION IN SARCOIDOSIS

16. TH1 AND TH17 IMMUNITY
• PULMONARY SARCOIDOSIS IS ASSOCIATED
WITH ENHANCED EXPRESSION OF TH1
ASSOCIATED IFN-GAMMA, IL12, AND IL18 IN THE
LUNG BUT LOW OR UNDETECTABLE LEVELS OF
IL4 OR IL5.
• THE ROLE OF TH17 RESPONSES IN
SARCOIDOSIS IS UNCERTAIN.
• STUDIES SHOW UPREGULATED TH17
RESPONSES IN SARCOIDOSIS BLOOD AND
TISSUES,WITH RELEASE OF IL17 AND IL22

17. MECHANISMS OF PULMONARY FIBROSIS
• THE MECHANISMS THAT PROMOTE
PULMONARY FIBROSIS IN SARCOIDOSIS
REMAIN UNCERTAIN.
• INCREASED EXPRESSION OF TGFΒ,
FIBRONECTIN, INSULIN-LIKE GROWTH FACTOR-
1 (IGF-1), LAMININ, AND MATRIX
METALLOPROTEASES BY SARCOIDOSIS AMS
MAY PROMOTE A FIBROSIS

18. SERUM AMYLOID A DYSAGGREGATION HYPOTHESIS• MECHANISM FOR CHRONIC GRANULOMATOUS INFLAMMATION
IN SARCOIDOSIS INVOLVING THE HOST PROTEIN SERUM
AMYLOID A (SAA).
• SAA IS AN AMYLOID PRECURSOR PROTEIN AND ACUTE PHASE
REACTANT.
• PREVIOUSLY REPORTED TO BE UPREGULATED IN THE BLOOD
OF SARCOIDOSIS PATIENTS AS AN INFLAMMATORY
BIOMARKER.
• SAA WAS HIGHLY CONCENTRATED WITHIN SARCOIDOSIS
GRANULOMAS.
• PATHOBIOLOGY OF SARCOIDOSIS IS CAUSED BY THE
INDUCTION, MISFOLDING, AND PROGRESSIVE AGGREGATION
OF INSOLUBLE SAA WITHIN GRANULOMAS IN AN AMYLOID-
LIKE PROCESS

20. Immunohistochemistry showing focal deposition of serum amyloid A (brownish stain) in
tissues from patients with sarcoidosis but little or no staining for SAA in tuberculosis,
Mycobacterium avium infection, histoplasmosis, or granulomatosis with polyangiitis
(GPA).

21. CLINICAL FEATURES

22. • CONSTITUTIONAL SYMPTOMS (50% OF PATIENTS)
FEVER,
FATIGUE,
MALAISE, AND
WEIGHT LOSS ARE SEEN IN OVER
• THE LUNGS OR INTRATHORACIC LYMPH NODES
ARE INVOLVED IN MORE THAN 90% OF
PATIENTS WITH SARCOIDOSIS.

23. • ONE CLASSIFICATION SCHEME WITH
PROGNOSTIC INFORMATION CATEGORIZES
PATIENTS BASED ON THEIR INITIAL
MANIFESTATIONS AS FOLLOWS:
ASYMPTOMATIC,
ACUTE SARCOIDOSIS WITH OR WITHOUT ERYTHEMA NODOSUM,
SARCOIDOSIS WITH SYMPTOMS OR SIGNS OF PULMONARY
DISEASE FOR LESS THAN 2 YEARS,
CHRONIC PULMONARY SARCOIDOSIS OF MORE THAN 2 YEARS,
AND
DOMINANT EXTRAPULMONARY SARCOIDOSIS.

24. ACUTE SARCOIDOSIS WITH OR WITHOUT ERYTHEMA NODOSUM
• ACUTE ONSET OF ERYTHEMA NODOSUM
ASSOCIATED WITH BILATERAL HILAR
ADENOPATHY, FEVERS, POLYARTHRITIS, AND
OFTEN UVEITIS, KNOWN AS LÖFGREN
SYNDROME.
• ERYTHEMA NODOSUM IS CHARACTERIZED BY
TENDER REDDISH NODULES SEVERAL
CENTIMETERS IN DIAMETER, USUALLY
LOCATED ON THE LOWER EXTREMITIES
• APPROXIMATELY 10% OF PATIENTS WITH THIS
SYNDROME HAVE A NORMAL CHEST
RADIOGRAPH.

25. PULMONARY SARCOIDOSIS
• COUGH AND BREATHLESSNESS(USUALLY OF A
PROGRESSIVE, INSIDIOUS NATURE).
• HEMOPTYSIS
• BRONCHIECTASIS.
• CHEST TIGHTNESS AND WHEEZING
• THESE SYMPTOMS ARE USUALLY POORLY
RESPONSIVE TO BRONCHODILATORS

26. CHEST IMAGING
• CHEST RADIOGRAPHS ARE CATEGORIZED BY INTERNATIONAL
CONVENTION:
STAGE 0 (<15%) :-DENOTES A NORMAL CHEST X-RAY.
STAGE I (30% TO 50%) :-SHOWS SYMMETRIC BILATERAL HILAR
ADENOPATHY OFTEN WITH RIGHT PARATRACHEAL
ADENOPATHY.
STAGE II (40% TO 60%) :-INDICATE THE PRESENCE OF
PULMONARY INFILTRATES WITH BILATERAL HILAR
ADENOPATHY.
STAGE III (10% TO 20%) :-INDICATE THE PRESENCE OF
PULMONARY INFILTRATES WITHOUT BILATERAL HILAR
ADENOPATHY.
STAGE IV (<15%) SHOWS OBVIOUS SCARRING WITH
FIBROCYSTIC CHANGES WITH CEPHALAD HILAR RETRACTION .

27. There is bilateral hilar (white arrows) and right paratracheal (yellow
arrow) adenopathy, the classical triad of adenopathy in pulmonary
sarcoid. Notice how adenopathy produces a lobulated, lumpy
contour.

28. Stage II sarcoidosis pattern with prominent, discrete “stand-away” hilar
nodes, right paratracheal adenopathy, and fine reticulonodular
infiltrates.

29. • CHEST COMPUTED TOMOGRAPHY (CT)
TYPICALLY DEMONSTRATES THAT INFILTRATES
TEND TO BE CENTRAL, FOLLOWING
BRONCHOVASCULAR STRUCTURES.
• GROUND-GLASS INFILTRATES OR
HONEYCOMBING CAN ALSO BE SEEN.
• THE ADENOPATHY OF SARCOIDOSIS TYPICALLY
APPEARS AS MULTIPLE DISCRETE ENLARGED
LYMPH NODES RATHER THAN AMORPHOUS,
MASS-LIKE GROWTHS MORE SUGGESTIVE OF
MALIGNANCY.

30. Computed tomographic image of pulmonary sarcoidosis with bilateral
hilar lymphadenopathy and micronodules with a perilymphatic distribution
including spreading along the fissures.

31. Pulmonary Function Tests
• PULMONARY FUNCTION MAY BE NORMAL EVEN WHEN THE
CHEST RADIOGRAPH DEMONSTRATES PULMONARY
INFILTRATES.
• RESTRICTIVE IMPAIRMENT WITH REDUCTION IN LUNG
VOLUMES, FORCED VITAL CAPACITY (FVC) AND FORCED
EXPIRATORY VOLUME IN 1 SECOND (FEV1
), IS COMMON,
PARTICULARLY WHEN PULMONARY INFILTRATES ARE
PRESENT ON CHEST RADIOGRAPH.
• OBSTRUCTIVE IMPAIRMENT IS AS COMMON AS RESTRICTIVE
IMPAIRMENT, PARTICULARLY IN ADVANCED FIBROCYSTIC
DISEASE
• CO2
RETENTION IS UNUSUAL EXCEPT IN ADVANCED
PULMONARY DISEASE.

32. EXTRAPULMONARY
SARCOIDOSIS

33. SARCOIDOSIS OF THE UPPER
RESPIRATORY TRACT AND ORAL CAVITY
(SURT)• OCCURS IN 5%- 10% OF PATIENTS INVOLVING
THE NASAL SINUSES OR LARYNGEAL
STRUCTURES.
• SYMPTOMS OF NASAL CONGESTION, SINUSITIS,
AND INTERMITTENT EPISTAXIS ARE OFTEN
CHRONIC, UNRESPONSIVE TO
DECONGESTANTS OR INHALED STEROIDS.
• CHRONIC DISEASE OR SURGICAL
INTERVENTION MAY RESULT IN DESTRUCTION
OF THE NASAL SEPTUM AND A “SADDLE NOSE”
DEFORMITY.

34. LARYNGEAL SARCOIDOSIS :-
• MAY MANIFEST WITH SEVERE HOARSENESS,
STRIDOR, OR ACUTE RESPIRATORY FAILURE
SECONDARY TO UPPER AIRWAY OBSTRUCTION.
• LARYNGEAL SARCOIDOSIS IS ASSOCIATED WITH
CHRONIC SKIN LESIONS, LUPUS PERNIO, OR SINUS
DISEASE.
ORAL AND PHARYNGEAL SARCOIDOSIS:-
• IS RARE, BUT MAY MANIFEST WITH MACROGLOSSIA ,
TONGUE MASS, OR PALATAL MASS WITH
CARTILAGINOUS OR BONE DESTRUCTION.

35. OCULAR SARCOIDOSIS
• 20% - 30% OF PATIENTS, MORE FREQUENTLY IN BLACK
POPULATIONS.
• UVEITIS IS THE MOST COMMON MANIFESTATION AND IS
OFTEN ASSOCIATED WITH BILATERAL HILAR ADENOPATHY.
• THE UVEITIS IS MORE COMMONLY ANTERIOR, AND MAY BE
UNILATERAL OR BILATERAL, WITH EITHER
GRANULOMATOUS OR NONGRANULOMATOUS FEATURES.
• GRANULOMATOUS CONJUNCTIVITIS IS LESS COMMON.
• OPTIC NEURITIS, OR SEVERE CHORIORETINITIS, MAY
PRESENT WITH BLINDNESS.

37. CUTANEOUS SARCOIDOSIS
• 25 % OF PATIENTS
• THE CLASSIC CUTANEOUS LESIONS INCLUDE
• ERYTHEMA NODOSUM
• MACULOPAPULAR LESIONS
• HYPER- AND HYPOPIGMENTATION
• KELOID FORMATION
• SUBCUTANEOUS NODULES
• MORE COMMON AND SEVERE IN BLACKS.
• THE PLAQUES ARE LOCATED AROUND THE HAIRLINE, EYELIDS,
EARS, NOSE, AND EXTENSOR SURFACES OF THE ARMS AND
LEGS.

38. HEPATIC SARCOIDOSIS
• 50% OF PATIENTS.
• CLINICAL MANIFESTATIONS ARE LESS FREQUENT.
• ACTIVE HEPATIC INFLAMMATION MAY BE ASSOCIATED
WITH FEVER, TENDER HEPATOMEGALY , OR PRURITUS
THAT MAY MIMIC PRIMARY BILIARY CIRRHOSIS EXCEPT
THAT ANTIMITOCHONDRIAL ANTIBODIES ARE ABSENT.
• THE SERUM ALKALINE PHOSPHATASE AND Γ-
GLUTAMYLTRANSFERASE ARE ELEVATED
PROPORTIONATELY HIGHER THAN THE TRANSAMINASES
OR BILIRUBIN.
• ELEVATED SERUM LIVER FUNCTION FREQUENTLY
REVERTS TO NORMAL SPONTANEOUSLY OR AFTER
TREATMENT WITH CORTICOSTEROIDS.

39. GASTROINTESTINAL SARCOIDOSIS
• SARCOIDOSIS INVOLVEMENT OF THE
GASTROINTESTINAL TRACT IS RARE.
• DIRECT ESOPHAGEAL INVOLVEMENT MAY
CAUSE DYSPHAGIA, BUT MORE COMMONLY
THIS SYMPTOM MAY BE CAUSED BY EXTENSIVE
MEDIASTINAL LYMPHADENOPATHY THAT
IMPINGES ESOPHAGEAL MOTILITY.
• GASTRIC SARCOIDOSIS MAY MANIFEST AS
DYSPEPSIA, ABDOMINAL PAIN, OR GASTRIC
NODULE.

40. ABDOMINAL SARCOIDOSIS
• MANIFESTS WITH LIVER, SPLEEN & BONE
MARROW INVOLVEMENT WITH HYPERCALCEMIA
OR ABDOMINAL LYMPHADENOPATHY .
• CONSTITUTIONAL SYMPTOMS WITH FEVER
AND FATIGUE.

41. CARDIAC SARCOIDOSIS
• 5 % - 10 % OF PATIENTS.
• ARRHYTHMIAS, HEART BLOCK , OR SUDDEN
DEATH MAY BE THE INITIAL MANIFESTATION
DUE TO INVOLVEMENT OF THE CONDUCTION
SYSTEM.
• MANIFESTATIONS RESULT FROM INFILTRATION
OF THE HEART MUSCLE BY GRANULOMAS .
• MYOCARDIAL INFLAMMATION CAN LEAD TO
DILATED CARDIOMYOPATHY & CONGESTIVE
HEART FAILURE, OR ANEURYSMS.

42. • IF THE ATRIOVENTRICULAR (AV) NODE IS INFILTRATED, HEART
BLOCK CAN OCCUR.
• DETECTED BY ROUTINE ELECTROCARDIOGRAPHY.
• VENTRICULAR ARRHYTHMIAS AND SUDDEN DEATH DUE TO
VENTRICULAR TACHYCARDIA ARE COMMON CAUSES OF DEATH.
• ARRHYTHMIAS ARE BEST DETECTED USING 24-H AMBULATORY
MONITORING.
• BECAUSE VENTRICULAR ARRHYTHMIAS ARE USUALLY MULTIFOCAL
DUE TO PATCHY MULTIPLE GRANULOMAS IN THE HEART, ABLATION
THERAPY IS NOT USEFUL.
• PATIENTS WITH SIGNIFICANT VENTRICULAR ARRHYTHMIAS SHOULD
BE CONSIDERED FOR AN IMPLANTED DEFIBRILLATOR, WHICH
APPEARS TO HAVE REDUCED THE RATE OF DEATH IN CARDIAC
SARCOIDOSIS.

43. NEUROSARCOIDOSIS
• 5%- 10 % OF PATIENTS .
• COMMON MANIFESTATIONS ARE CRANIAL
NEUROPATHIES WITH BILATERAL OR UNILATERAL
SEVENTH NERVE (BELL’S) PALSY .
• SPINAL CORD INVOLVEMENT IS RARE BUT CAN CAUSE
PARAPARESIS , HEMIPARESIS, BACK AND LEG PAINS
EITHER FROM A TRANSVERSE MYELITIS , OR TUMOR
LIKE GRANULOMATOUS INVOLVEMENT .
• PERIPHERAL NEUROPATHIES ACCOUNT FOR ABOUT
15% OF CASES OF NEUROSARCOIDOSIS, PRESENTING
AS MONONEURITIS MULTIPLEX OR A PREDOMINANT
SENSORY DEFICIT.

44. HEMATOLOGIC SARCOIDOSIS
• PERSISTENT, BULKY, PAINFUL, IS SEEN IN < 5 %
OF PATIENTS, MOSTLY INVOLVING THE
CERVICAL, SUPRACLAVICULAR , AXILLARY , OR
EPITROCHLEAR LYMPH NODES .
• SPLENOMEGALY OCCURS IN < 10% OF
PATIENTS, AND MAY BE MASSIVE AND
ASSOCIATED WITH HYPERSPLENISM.
• PERIPHERAL BLOOD LYMPHOPENIA IS
COMMON.

45. JOINT AND MUSCULOSKELETAL
SARCOIDOSIS
• A SHORT LIVED POLYARTHRITIS IS TYPICAL OF
ACUTE SARCOIDOSIS , USUALLY ASSOCIATED
WITH ERYTHEMA NODOSUM.
• CHRONIC JOINT DISEASE IS FOUND IN < 5% OF
PATIENTS.
• JOINT CARTILAGINOUS EROSION IS RARE, BUT
“PUNCHED OUT” BONY LESIONS WITH CYSTIC
CHANGES AND LOSS OF BONY TRABECULAE
MAY BE SEEN IN SUBCHONDRAL LOCATIONS.

46. EXOCRINE GLAND SARCOIDOSIS
• GRANULOMATOUS INFLAMMATION OF SALIVARY, PAROTID, AND LACRIMAL
GLANDS RESULTS IN ENLARGED, TENDER GLANDS, AND/OR SICCA
SYNDROME WITH DRY MOUTH AND DRY EYES IN < 5% OF PATIENTS WITH
SARCOIDOSIS.
• FEVER
• +
• PAROTID ENLARGEMENT
• +
• FACIAL PALSY
• +
• UVEITIS
• +
• BILATERAL HILAR ADENOPATHY.
UVEOPAROTID
FEVER
or
HEERFORDT SYNDROME

47. ENDOCRINE SARCOIDOSIS
• ABNORMAL CALCIUM METABOLISM IS FOUND IN
SARCOIDOSIS
• HYPERCALCIURIA IS MORE FREQUENT THAN
HYPERCALCEMIA.
• HYPOTHALAMIC / PITUITARY INSUFFICIENCY
MAY BE A MANIFESTATION OF
NEUROSARCOIDOSIS.

48. RENAL SARCOIDOSIS
• KIDNEY STONES ARE THE MOST FREQUENT
MANIFESTATION OF RENAL SARCOIDOSIS ,
USUALLY RELATED TO ABNORMAL CALCIUM
METABOLISM.
• RENAL FAILURE DUE TO NEPHROCALCINOSIS
MAY RESULT FROM CHRONIC ASYMPTOMATIC
HYPERCALCEMIA OR HYPERCALCIURIA .

49. AUTOIMMUNE DISORDERS
• SARCOIDOSIS IS ASSOCIATED WITH A VARIETY OF
DISORDERS OF THE IMMUNE SYSTEM
• CROHN’S DISEASE
• ULCERATIVE COLITIS
• PRIMARY BILIARY CIRRHOSIS
• SCLERODERMA
• SJ¨OGREN’S SYNDROME
• AUTOIMMUNE HEMOLYTIC ANEMIA
• AUTOIMMUNE ENDOCRINOPATHIES

50. GENITOURINARY SARCOIDOSIS
• < 1 % OF PATIENTS .
• IN MEN TESTICULAR MASSES & ACUTE
EPIDIDYMIS - ORCHIDITIS.
• IN WOMEN UTERINE OR OVARIAN
INVOLVEMENT THAT MAY CAUSE
DYSMENORRHEA OR MIMIC MALIGNANCY OR
FIBROIDS.

51. DIAGNOSTIC APPROACH

52. • THE DIAGNOSIS OF SARCOIDOSIS RESTS ON A
TRIAD OF CLINICAL , RADIOLOGIC &
HISTOLOGICAL CRITERIA & EXCLUSION OF
OTHER GRANULOMATOUS DISORDERS OF
KNOWN CAUSE.

53. PATHOLOGICAL DIFFERENTIAL DIAGNOSIS
OF SARCOIDOSIS

54. HISTOLOGICAL DIAGNOSIS
• BIOPSY IS INDICATED FOR ALL PATIENTS
SUSPECTED OF SARCOIDOSIS , EXCEPT THOSE
WITH L¨OFGREN SYNDROME.
• THE EASIEST ACCESSIBLE BIOPSY SITE IS USED
TO CONFIRM DIAGNOSIS OF SARCOIDOSIS.
• BIOPSY OF A SKIN OR CONJUNCTIVAL NODULE,
ENLARGED SUPERFICIAL LYMPH NODE, OR
LACRIMAL GLAND HELPS TO ESTABLISH A
DIAGNOSIS.
• BIOPSY BY FOB IS USUALLY PERFORMED
BECAUSE OF ITS HIGH YIELD AND RELATIVE
SAFETY.

55. • THE DIAGNOSTIC YIELD FROM
TRANSBRONCHIAL BIOPSY (TBB) RANGES
FROM 40% - 90% IF AT LEAST FOUR BIOPSIES
ARE TAKEN, AND IS HIGHER WHEN THERE ARE
PULMONARY INFILTRATES ON THE CHEST
RADIOGRAPH OR CHEST CT SCAN.
• TRANSBRONCHIAL LUNG BIOPSY IN ADVANCED
FIBROCYSTIC SARCOIDOSIS HAS A LOW YIELD,
OWING TO EXTENSIVE FIBROTIC CHANGES

56. • A DIAGNOSIS OF NEUROSARCOIDOSIS IS USUALLY
CONFIRMED BY BIOPSY OF A NON-CNS SITE .
• A DIAGNOSIS OF CARDIAC SARCOIDOSIS IS
USUALLY ESTABLISHED BY A NONCARDIAC BIOPSY
.
• ENDOMYOCARDIAL BIOPSY IS POSITIVE IN < 10%
TO 25 % OF CARDIAC SARCOIDOSIS OWING TO
SAMPLING INEFFICIENCIES & INFREQUENCY OF
RIGHT VENTRICULAR INVOLVEMENT.

57. BRONCHOALVEOLAR LAVAGE (BAL)
• ELEVATED BAL T CELL CD4:CD8 RATIO > 3.5
TO 4.0 SUPPORTS A DIAGNOSIS OF
SARCOIDOSIS WITH A TEST SPECIFICITY OF
APPROXIMATELY 95 % & SENSITIVITY OF >
50% .

58. KVEIM TEST
• THE KVEIM – SILTZBACH TEST IS PERFORMED USING
INTRADERMAL INJECTIONS OF HUMAN SARCOID TISSUE .
•
• 4 WEEKS LATER THE PAPULE THAT FORMS AT THE SITE
OF THE INJECTION IS BIOPSIED .
• RELIABLE TEST FOR THE DIAGNOSIS OF SARCOIDOSIS
WITH POSITIVITY UPTO 98 % .
• MECHANISM OF TEST NOT CLEARLY UNDERSTOOD .

59. Kveim biopsy
showing typical
sarcoid
granuloma.

60. • VALIDATED GOOD ANTIGEN IS NOT AVAILABLE .
• REQUIRES 4- 6 WEEKS AFTER INTRADERMAL
INJECTION OF THE ANTIGEN BEFORE A POSITIVE
REACTION IS OBTAINED.
• LONG PERIOD TO WAIT IN HOSPITALIZED
PATIENTS.
• FREQUENCY OF POSITIVITY DEPENDS UPON THE
DISEASE – DURATION.
• RISK OF TRANSMISSION OF THE ETIOLOGICAL
AGENT
DISADVANTAGES OF TEST

61. SERUM ANGIOTENSIN CONVERTING ENZYME
(SACE)
• ACE IS PRODUCED BY THE EPITHELIOID CELLS & MACROPHAGES OF SARCOID
GRANULOMA .
• ELEVATED IN 30% - 80 % OF PATIENTS WITH CLINICALLY ACTIVE DISEASE .
• ELEVATED LEVELS OF SACE ARE SEEN IN
INFECTIOUS GRANULOMATOUS DISEASES
LYMPHOMA
HEPATITIS
DIABETES
THYROID DISEASE
CHRONIC RENAL DISEASE
• SACE IS NOT RECOMMENDED AS A DIAGNOSTIC TOOL.

62. IMAGING TECHNIQUES
• GALLIUM 67 SCANS DEMONSTRATES INFLAMMATION
THROUGHOUT THE BODY.
• UPTAKE IN THE :-
BILATERAL HILAR & RIGHT PARATRACHEAL NODE REGION
LAMBDA SIGN .
PAROTID, SALIVARY & LACRIMAL GLAND REGION PANDA
SIGN IS PATHOGNOMIC FOR SARCOIDOSIS.

63. • F - FLUORODEOXY GLUCOSE POSITRON
EMISSION TOMOGRAPHY (FDG-PET) UPTAKE IS
FOUND IN UPTO 2/3RD OF PATIENTS WITH
STAGE 2 & 3 DISEASE WHEREAS NEGATIVE
UPTAKE IS ASSOCIATED WITH STAGE 0 , 1 & 4
DISEASE .

64. • PET SCANNING IS REPLACING GALLIUM
SCANNING AS THE PREFERRED METHOD TO
DETECT ACTIVE INFLAMMATORY SITES AS THE
TEST HAS MUCH LESS RADIATION EXPOSURE
AND GREATER RESOLUTION.

65. CLINICAL COURSE AND PROGNOSIS
• ORGAN INVOLVEMENT USUALLY DEFINES ITSELF
EARLY IN THE DISEASE .
• PATIENTS WHO UNDERGO REMISSION USUALLY
DO SO WITHIN THE FIRST 2 TO 3 YEARS .
• PATIENTS WITH CHRONIC SARCOIDOSIS
COMPRISE 30 % - 50 % OF ALL KNOWN
SARCOIDOSIS CASES & HAVE PROGRESSIVE,
UNREMITTING ORGAN IMPAIRMENT.
• PROGNOSIS IN SARCOIDOSIS IS STRONGLY
INFLUENCED BY THE INITIAL MANIFESTATIONS OF
DISEASE.

67. • SACE LEVELS CORRELATE WITH THE EXTENT OF
GRANULOMATOUS INFLAMMATION THROUGHOUT THE
BODY & DECREASE IN RESPONSE TO CORTICOSTEROIDS
OR WITH DISEASE REMISSION, BUT THE TEST IS HIGHLY
VARIABLE AND HAS NO PROGNOSTIC VALUE.
• MONITORING FOR AT LEAST 3 YEARS FOLLOWING “DISEASE
REMISSION” IS RECOMMENDED
• LONGER PERIODS OF OBSERVATION ARE INDICATED FOR
PATIENTS WITH SERIOUS PULMONARY OR EXTRA
PULMONARY MANIFESTATIONS.

68. TREATMENT

69. INDICATIONS FOR TREATMENT OF SARCOIDOSIS
1. THREATENED ORGAN FAILURE—SEVERE OCULAR, CARDIAC, OR
NEUROLOGICAL DISEASE
2. PROGRESSIVE OR PERSISTENT PULMONARY DISEASE
3. UVEITIS UNRESPONSIVE TO TOPICAL CORTICOSTEROIDS
4. PERSISTENT HYPERCALCEMIA , RENAL OR HEPATIC
DYSFUNCTION
5. PALPABLE SPLENOMEGALY OR HYPERSPLENISM
6. SEVERE MYOPATHY
7. DISFIGURING SKIN DISEASE
8. PAINFUL LYMPHADENOPATHY
9. SEVERE FATIGUE AND WEIGHT LOSS

70. SYSTEMIC TREATMENT
CORTICOSTEROID THERAPY:-
• CORNERSTONE OF THERAPY .
• PROVIDE SYMPTOMATIC RELIEF AND REVERSE
ORGAN DYSFUNCTION IN PATIENTS WITH THE
DEGREE OF REVERSIBILITY DEPENDENT ON
THE EXTENT OF PREEXISTING FIBROSIS .
• INITIAL TREATMENT OF PULMONARY
SARCOIDOSIS 20 TO 40 MG/ DAY OF
PREDNISONE FOLLOWED BY A SLOW TAPER TO
A MAINTENANCE DOSE OF 5 TO 15 MG/DAY OF
PREDNISONE.

71. • TREATMENT IS CONTINUED FOR A MINIMUM OF
8 TO 12 MONTHS, SINCE PREMATURE
ATTEMPTS TO TAPER OFF STEROIDS ARE
LIKELY TO RESULT IN RELAPSE OF DISEASE .

72. ALTERNATIVE AGENTS
NONIMMUNOSUPPRESSIVE DRUGS:
• HYDROXYCHLOROQUINE IS EFFECTIVE IN PATIENTS
WITH
MUCOCUTANEOUS SARCOIDOSIS
HYPERCALCEMIA
• CHLOROQUINE IN
LUPUS PERNIO
SURT
SINUS DISEASE

73. • TETRACYCLINES, MINOCYCLINE , &
DOXYCYCLINE EFFECTIVE IN PATIENTS WITH
CUTANEOUS SARCOIDOSIS . (MILD ANTI-
INFLAMMATORY ACTION)

74. IMMUNOSUPPRESSIVE DRUGS :
• METHOTREXATE THE FIRST
IMMUNOSUPPRESSIVE THERAPY USED AS AN
ALTERNATIVE THERAPY FOR REFRACTORY
PULMONARY OR SYSTEMIC SARCOIDOSIS
{WHEN CORTICOSTEROID AND ANTIMALARIAL
THERAPIES ARE INEFFECTIVE OR POORLY
TOLERATED.}
• STUDIES SUGGEST METHOTREXATE IS
EFFECTIVE IN 50% TO 70 % OF PATIENTS
RESPONSES MAY TAKE LONGER THAN 6
MONTHS

75. • AZATHIOPRINE
• CYCLOPHOSPHAMIDE
• MYCOPHENOLATE MOFETIL SERIOUS
NEUROLOGIC, OCULAR, PULMONARY &
HEPATIC SARCOIDOSIS .

77. Antimalarial drugs

78. IMMUNOSUPPRESSIVE THERAPIES

79. WHEN TO TREAT PULMONARY SARCOIDOSIS ?
• ASYMPTOMATIC PATIENT WITH BILATERAL
HILAR LYMPHADENOPATHY (STAGE1) WITH OR
WITHOUT ERYTHEMA NODOSUM BUT WITHOUT
EXTRAPULMONARY INVOLVEMENT SHOULD BE
LEFT UNTREATED .
• PATIENTS WITH FEVER & JOINT PAINS
RESPOND TO NSAIDS . SHORT TERM COURSE
OF PREDNISONE 15 – 20 MG /DAY MAY BE
NEEDED TO CONTROL THE SYMPTOMS.
SYMPTOMS OF COUGH & DYSPNEA
ASSOCIATED WITH AIRWAY OBSTRUCTION
SHOULD BE TREATED WITH INHALED
CORTICOSTEROIDS .

83. REFERENCES:
FISHMAN PULMONARY DISEASE AND
DISSORDER 5TH EDITION.

84. THANK YOU