1. Sarcoidosis & OrphanSarcoidosis & Orphan
Lung DiseasesLung Diseases
Iman Galal , MDIman Galal , MD
Pulmonary Medicine DepartmentPulmonary Medicine Department
Ain Shams UniversityAin Shams University

2.  Page 2
At The End Of This Lecture You Should Know
 Who discovered Sarcoidosis?
 Epidemiology of Sarcoidosis
 Epidemiology of Sarcoidosis
 Pathology of Sarcoidosis
 Pathophysiology of Sarcoidosis
 Organ involvement in Sarcoidosis
 Staging of Sarcoidosis
 How to diagnose Sarcoidosis?
 How to treat Sarcoidosis?
 Recommended clinical evaluation of Sarcoidosis
 How to assess the activity of Sarcoidosis?

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Historical Perspective
 In 1887, Sir Jonathan
Hutchinson was the first
to describe a case of
cutaneous sarcoid
disease. He named the
condition "Mortimer's
Malady" after the patient.
 In 1899, Caesar Boeck
called this condition
'sarcoid' as he thought it
resembles sarcoma. It was
called "Boeck's Sarcoid"
in his honour.
Sir Jonathan HutchinsonSir Jonathan Hutchinson Caesar BoeckCaesar Boeck

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Epidemiology
 Non-infectious multisystem granulomatous
disorder of unknown origin.
 Female > Male.
 Black > White.
 3rd
& 4th
decade with 2nd
peak at 6th
decade.
 Prevalence rate: 10-40 cases per 100,000.
 Mortality rate: 1-5 %.

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Etiology
 Disease of unknown cause.
 Possible infectious & transmissible cause in
genetically susceptible individuals.
 Possible environmental exposure cause.
 Possible genetic-environmental interactions.
 Possible autoimmune cause.

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Pathophysiology of Sarcoidosis

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Pathophysiology of Sarcoidosis
 T-helper cells to T-suppressor cells ratio is
increased in BAL but decreased in
peripheral blood.
 Exaggerated T-cell activity indicates an altered
immune response.
 Hyper globulinemia (Ig A & Ig G).
 Mass effect of granulomas damages the tissues.

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Pathology of Sarcoidosis

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Pathophysiology of Sarcoidosis
 Non-caseating epithelioid cell granuloma is the
characteristic lesion of sarcoidosis.
 It occurs along perivascular, peribronchial & septal region
areas rich in lymphatic vessels.
 Granuloma consists of a central collection of modified
mononuclear phagocytes called epithelioid cells.
 Epithelioid cells are mature macrophages that gain
secretory & bactericidal capabilities but lose some
phagocytic capability.

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Pathophysiology of Sarcoidosis
 Epithelioid cells are large, polygonal and have an
elliptical nucleus which contains fine chromatin & 1-2
nucleoli.
 Conglomeration of epithelioid cells with multiple
peripherally arranged nuclei forms giant cells in the
central part of the granuloma.
 The central epithelioid & giant cells are surrounded by a
rim of small, oval, basophilic T-lymphocytes.

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Pathology of Sarcoidosis

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Pathology of Sarcoidosis

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Inclusion Bodies in Sarcoidosis
Schaumann’s Bodies (Conchoidal Bodies) &
Birefringent Crystals:
Large, concentrically lamellated, calcified structures that
are present within the cytoplasm of giant cells in 88% of
cases of sarcoidosis.
The majority of Schaumann’s bodies have birefringent
crystals composed of calcium oxalate.
Birefringent crystals may serve as a nidus for their
formation.

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Pathology of Sarcoidosis

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Inclusion Bodies in Sarcoidosis
Asteroid Bodies:
Intracytoplasmic stellate inclusions within giant cells
exhibiting 30 or more rays radiating from a central core.
They probably represent functionally obsolescent cell
organelles.
Reported in 2 – 9 % of sarcoidosis.

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Inclusion Bodies in Sarcoidosis
Hamazaki-Wesenberg Bodies:
Also known as yellow-brown bodies, yellow bodies, spindle
bodies & chromogenic bodies & giant extracellular &
intracellular lysosomes.
Seen in lymph nodes.
They are 0.5 - 0.8 mm oval or spindle shaped, and often
exhibit a yellow-brown color.
Because they may exhibit an appearance similar to yeast like
budding they may be mistaken for fungal organisms.

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Pathology of Sarcoidosis

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Organ Involvement in Sarcoidosis
Organ System % of affection
Pulmonary > 90 %
Psychosocial 30-60 %
Ocular 20-30 %
Skin 20-30 %
Hematologic 20-30 %
Endocrine 10-30 %
Hepatic/Abdominal 10-20 %
Joints & Musculoskeletal 10-20 %
Exocrine gland 10-20 %
URT & Oral cavity 5-10 %
Cardiac 5-10 %
Neurological 5-10 %
Renal <5 %
Genitourinary <5 %

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Classification of Sarcoidosis
 Asymptomatic (2/3 of patients).
 Acute sarcoidosis ± erythema nodosum.
 Intermediate sarcoidosis with symptoms or signs of
pulmonary disease for < 2 years.
 Chronic pulmonary sarcoidosis of > 2 years.
 Dominant extrapulmonary sarcoidosis.

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Pulmonary Sarcoidosis
Scadding's Classification
Stage 0=normal (5-15%)
Stage 1=Hilar LDN alone (45-65%)
Stage 2=Hilar LDN + parenchymal
infiltrates (30-40%)
Stage 3=Parenchymal infiltrates alone
(10-15%)
Stage 4=Pulmonary fibrosis (5%)

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Endobronchial Sarcoidosis

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Cutaneous Sarcoidosis
Erythema NodosumErythema Nodosum

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Lofgren's Syndrome
 Bilateral hilar lymphadenopathy.
 Fever.
 Arthritis.
 ± Erythema nodosum.

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Cutaneous Sarcoidosis
Lupus PernioLupus Pernio

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Cutaneous Sarcoidosis
RAISED PLAQUESRAISED PLAQUES NODULAR LESIONSNODULAR LESIONS

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Ocular Sarcoidosis
 Unilateral or bilateral anterior & posterior uveitis
(commonest).
 Conjunctival Granuloma.
 Iris Granuloma.
 Optic neuritis.
 Chorioretinitis.

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Ocular Sarcoidosis
Iris GranulomaIris Granuloma
Conjunctival GranulomaConjunctival Granuloma
Punched-outchoroidoretinallesionsPunched-outchoroidoretinallesions
Anterior UveitisAnterior Uveitis

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URT & Oral Cavity Sarcoidosis
 Sinusitis.
 Nasal congestion.
 Intermittent epistaxis.
 Destruction of nasal septum & Saddle Nose.
 Upper airway obstruction, stridor & acute respiratory
failure.
 Hoarseness.

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URT & Oral Cavity Sarcoidosis
Saddle NoseSaddle Nose

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Exocrine Glands
Panda SignPanda Sign
Bilateral symmetrical gallium uptake by the lacrimal, parotid, and
submandibular glands with Sicca syndrome

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Exocrine Glands
Heerfordt SyndromeHeerfordt Syndrome
 Bilateral hilar lymphadenopathy.
 Fever.
 Facial palsy.
 Parotid enlargement.
 Uveitis.

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Joint & Musculoskeletal Sarcoidosis
 Phalanges in the hands & feet are most frequently affected.
 Multiple.
 Punched out lytic lesions, lacelike honeycomb appearance,
or extensive bone erosion with pathologic fractures.
 The articular spaces are usually intact
 Arthralgia & polyarthritis.
 Subcutaneous soft-tissue mass or tenosynovitis.
 Myopathy.

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Skeletal Sarcoidosis
PUNCHED OUT LYTIC LESIONSPUNCHED OUT LYTIC LESIONS
Focal osteolytic lesions in the fingers are mostFocal osteolytic lesions in the fingers are most
common abnormality.common abnormality.
LACY TRABECULAR PATTERNLACY TRABECULAR PATTERN
Osteolysis has left a lacy trabecular pattern inOsteolysis has left a lacy trabecular pattern in
this phalanx (arrow)this phalanx (arrow)

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Muscle Sarcoidosis

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Endocrine Sarcoidosis
 Involvement of the
hypothalamus  Diabetes
Insipidus
 Hyperintensity of the posterior
pituitary lobe caused by
intracellular nerosecretory
granules.

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Vitamin D in Sarcoidosis
 Extrarenal source of calcitriol in Sarcoidosis is Alveolar
Macrophage & Epithelioid cells that contains 1,α-
hydroxylase, which converts 25(OH) D3 to 1,25(OH)2 D3.
 PTH gene expression is up-regulated by TNF-α & IL-6
produced by sarcoid macrophages.
 Absence of feedback for hypercalcemia  no down-
regulation of 1,α-hydroxylase in response to high level of
calcitriol & PTH.

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Renal Sarcoidosis
Calcium metabolism inCalcium metabolism in Sarcoidosis
 First described by Harrel in 1939
 Clinical manifestations:
- Hypercalciuria 40-62% (>400 mg/24hr)
- Hypercalcemia – asymptomatic, 5%
- Nephrocalcinosis from chronic hypercalciuria +/- hypercalcemia
- Nephrolithiais 10%
- Main cause of chronic renal failure

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Renal Sarcoidosis

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Neurosarcoidosis
 Unilateral or bilateral Bell’s
palsy.
 Optic neuritis.
 Multiple or solitary
parenchymal mass.
 May have a ring-like
appearance.
 Mimic glioblastoma or
metastases.

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Neurosarcoidosis

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Hematologic Sarcoidosis
 Lymphadenopathy: cervical, axillary,
epitrochlear & supraclavicular.
 Splenomegly & hypersplenism.
 Peripheral blood lymphopenia.

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Hepatic Sarcoidosis
 Dysfunction of these organ is uncommon.
 Hepatosplenic Sarcodosis: minimal
organomegaly & coalescing granulomas.

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Liver & Spleen Sarcoidosis

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GIT Sarcoidosis
 Most common site: stomach dyspepsia &
abdominal pain.
 Gastric sarcoidosis has predilection for the
antrum.
 Diagnosis requires endoscopic biopsy

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Genital Sarcoidosis
 Testicular involvement can be associated with Epididymitis
and is typically Bilateral & Multiple.
 Does not affect fertility & does not increase the incidence
of fetal or obsterical complications.

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Cardiac Sarcoidosis
 Clinically evident cardiac sarcoidosis is uncommon, affectingClinically evident cardiac sarcoidosis is uncommon, affecting
2-7% of patients with sarcoidosis. However, occult2-7% of patients with sarcoidosis. However, occult
involvement is much higher (> 20%).involvement is much higher (> 20%).
 Cardiac involvement may occur at any point during the courseCardiac involvement may occur at any point during the course
of sarcoidosis, may occur in the absence of pulmonary orof sarcoidosis, may occur in the absence of pulmonary or
systemic involvement & may be a presenting feature.systemic involvement & may be a presenting feature.
 Sarcoidosis can involve any part of the heart, includingSarcoidosis can involve any part of the heart, including
myocardium, endocardium & pericardium.myocardium, endocardium & pericardium.
 Although the disease is often clinically silent, cardiacAlthough the disease is often clinically silent, cardiac
sarcoidosis is a leading cause of death among patients withsarcoidosis is a leading cause of death among patients with
sarcoidosis, with mortality rate of 50-85%.sarcoidosis, with mortality rate of 50-85%.

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Clinical Manifestations of Cardiac Sarcoidosis
 Asymptomatic granulomata.
 Conduction defects (e.g., bundle branch blocks; complete
heart block).
 Atrial arrhythmias.
 Mitral insufficiency.
 Ventricular aneurysms.
 Pericardial effusions; fibrosis.
 Tachyarrhythmias (ventricular > atrial).
 Congestive heart failure.

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Cardiac Sarcoidosis
Guidelines for Diagnosis of Cardiac Sarcoidosis from Japanese Ministry of Health & Welfare:
Cardiac sarcoidosis is diagnosed when histologic analysis of operative or endomyocardial
biopsy specimens demonstrates epithelioid granuloma without caseating granuloma
 Clinical diagnosis group:
In patients with histologic diagnosis of extracardiac sarcoidosis, cardiac sarcoidosis is
diagnosed when (a) and 1 or more of (b–e) are present.
(a) Complete right bundle branch block, left-axis deviation, atrioventricular block, ventricular
tachycardia, premature ventricular contraction (>grade 2 in Lown’s classification), or abnormal
Q or ST–T change on electrocardiogram or Holter electrocardiogram
(b) Abnormal wall motion, regional wall thinning or thickening, or dilatation of LV on
echocardiogram
(c) Perfusion defect in 201Tl myocardial scintigram or abnormal accumulation in 67Ga-citrate
or 99mTc-pyrophosphate myocardial scintigram
(d) Abnormal intracardiac pressure, low cardiac output, or abnormal wall motion or depressed
ejection fraction of LV
(e) Interstitial fibrosis or cellular infiltration over moderate grade in endomyocardial biopsy even
if findings are nonspecific

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Diagnosis
 Clinical.
 Radiological (Chest radiograph & Gallium scan).
 Functional (Spirometry, DLCO & Lung Volumes).
 Laboratory (CBC with differential count & SACE).
 Skin tests.
 Biopsy.
 ECG.
 Opthalmological examination.
 Organ-specific investigations.

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Radiological Staging of Sarcoidosis
Scadding's Classification
Stage 0=normal
Stage 1=Hilar LDN alone
Stage 2=Hilar LDN+parenchymal
infiltrates
Stage 3=Parenchymal infiltrates alone
Stage 4=Pulmonary fibrosis
Strong predilection for theStrong predilection for the
Upper LungUpper Lung

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Gallium 67 Scan
 Lung gallium scan is a type of nuclear scan involving
radioactive gallium (Ga.).
 The test helps determine whether a patient has
inflammation in the lungs.
 Gallium is injected IV.
 The scan will be taken 6-24 hrs after the gallium is
injected. (time depends on whether the condition is acute
or chronic ).
 During the test, you lie on a table that moves underneath a
scanner called a gamma camera. The camera detects the
rays emitted by the gallium.

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Gallium 67 Scan

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Serum Angiotensin Converting Enzyme
(SACE)
 SACE is the most widely used test in the follow-up of
sarcoidosis patients.
 It is a membrane bound glycoprotein found in Activated
Alveolar Macrophages & at the surface of
Epithelioid cells & consequently may reflect development
& extent of granulomas.
 It may be normal in early & acute disease reflecting the
small number of granulomas present at this stage.
 It is poorly correlated with pulmonary function & variably
related with radiographic stage.
 It correlates with the degree of extrapulmonary lesions.

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Serum Angiotensin Converting Enzyme
(SACE)
 ACE is secreted by granulomas and may be present in
serum, CSF & BAL washings.
 Steroids decrease SACE with a delay after onset of treatment.
A minimum dose of prednisone is required to normalized
SACE. After discontinuing steroids, a transient increase in
SACE may occur before final normalization.
 In spontaneous recovery of sarcoidosis without steroids, even
previously persistently elevated SACE levels may normalize.
 It is positive in 60% of sarcoidosis patients.
 SACE is neither sensitive nor specific in diagnosing
sarcoidosis.

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Causes of Positive ACE
 Sarcoidosis
 Pulmonary
Berylliosis
Asbestosis
Gaucher's Disease
Hypersensitivity Pneumonitis
Miliary Tuberculosis
Coccidioidomycosis
Lymphoma
Silicosis
 Non-Pulmonary
Primary Biliary Cirrhosis
Diabetes Mellitus
Leprosy
Crohn's Disease
Hyperthyroidism .

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The Kveim-Siltzbach Test
 The test is based upon studies conducted by Dr. Morten Ansgar
Kveim, a Norwegian dermatologist in 1941 & was later studied by Dr.
Louis Siltzbach in New York.
 It is the only test that, if positive, is considered to be diagnostic of
sarcoidosis.
 It is both sensitive & specific.
 The test involves intradermal injection of a suspension of granuloma-
containing spleen or lymph node from a patient with sarcoidosis.
 A positive test is characterized by the formation of a papule at the site
of injection within 4-6 wks which, on microscopic examination,
exhibits non-necrotizing granulomas.

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The Kveim-Siltzbach Test
 Because of the difficulties involved in preparation,
standardization & validation of the test material as well as
significant variation in the sensitivity & specificity of test
suspensions obtained from different sources, the need for a
biopsy procedure & the wait of 4-6 weeks for a diagnosis,
the Kveim test has been largely replaced by TBLB for the
diagnosis of sarcoidosis.
 It may have a role in atypical cases where tissue is difficult
or impossible to obtain, such as in neurosarcoidosis.

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The Kveim-Siltzbach Test

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Lung Volumes & Capacities
Obstructive impairment is as common as restrictive
impairment

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DLCO

61.  Page 64
Biopsy
 Palpable lymph nodes
 Subcutaneous nodule
 Cutaneous lesion
 Enlarged parotid
 Lacrimal gland
 Transbronchial lung biopsy (TBLB)

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Cardiac Sarcoidosis
Diagnostic test Clinical feature
ECG
Non-specific ST & T wave changes; conduction disturbances;
arrhythmias
24-Holter monitor Arrhythmias (rest or exercise)
2-D echocardiography
Focal hypokinesis; ventricular thinning or hypertrophy; wall
motion abnormalities; depressed ejection fraction; papillary
muscle dysfunction; bright echos
Adenosine thallium201
radionuclide scan
Segmental defects; improve with exercise or adenosine
Gallium67 &
Technetium99 scans
Increased myocardial uptake
Positron emission
tomography (PET)
Increased myocardial uptake
MRI High-intensity lesions; thinning ventricular wall
Endomyocardial biopsies
Nonnecrotizing granulomata;
mononuclear cell infiltrates; fibrosis

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Treatment of Sarcoidosis
Corticosteroids:
 Glucocorticoids are very potent & effective drugs in
preventing & suppressing inflammation caused by
mechanical, chemical, infectious & immunological stimuli.
 They act mainly by repression of inflammatory genes, e.g.
interleukin (IL)-1 & tumour necrosis factor (TNF),
adhesion molecules & receptors & partly by induction of
anti-inflammatory genes e.g.,IL-1 receptor antagonist.
 In Sarcoidosis, corticosteroids have been shown to restore
the balance between locally produced type-1 & type-2 T-
helper cell cytokines.

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When To Treat?
Progressive or persistent symptomatic pulmonary disease
Threatened organ failure e.g., severe cardiac, neurological.
Asymptomatic pulmonary disease with persistent infiltrates
or progressive loss of lung function
Palpable splenomegly or hypersplenism
Severe myopathy, fatigue & weight loss.
Disfiguring skin lesion.
Uveitis unresponsive to topical corticosteroids.
Persistent hypercalcaemia, renal or hepatic dysfunction.

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Treatment of Sarcoidosis
Decision to Treat with CORTICOSTEROIDS:
Patient Subgroup Decision:
1. Asymptomatic Pts → No treatment
2. Mild Pulmonary Dysfunction → Observation
3. Mild-Mod. Pulmonary Dysfunction → Observation Treat if→
no improvement after 6 months.
4. Severe Pulmonary Dysfunction → Treatment

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Corticosteroids in Systemic Sarcoidosis
DrugDrug DoseDose
CorticosteroidsCorticosteroids
 Prednisone 20-40 mg/d for 2 wk, 5 mg/2 wks tillPrednisone 20-40 mg/d for 2 wk, 5 mg/2 wks till
10-15 mg, then maintain for 8-12 ms, then taper10-15 mg, then maintain for 8-12 ms, then taper
2.5 mg/2-4 wks.2.5 mg/2-4 wks.
 Reinstitute if relapseReinstitute if relapse

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Alternative Drug Therapy
 Methotrexate 10-20 mg/wk + folate 1 mg/d
 Hydroxychloroquine 200 mg once or twice/day
 Chloroquine 500 mg/other day for 6 ms then 6 ms drug holiday
 Azathioprine 100-200 mg/day
 Doxycyclin, Minocyclin 100 mg twice/day

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Alternative Drug Therapy
 Corticosteroid resistance, however, has also been
described in Sarcoidosis patients & is characterised
by exaggerated TNF-release by alveolar
macrophages compared to that found in patients
showing favourable responses to steroids.
 Thus, steroid-refractory disease might benefit from
treatment with anti-TNF-antibody, i.e. infliximab.

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Alternative Drug Therapy
Infliximab & Etanercept:
 Infliximab is a “monoclonal antibody” that blocks the
action of TNFα by binding to it & preventing it from
signaling the receptors for TNFα on the surface of cells.
 TNFα is one of the key cytokines that triggers & sustains
the inflammation response.
 Infliximab neutralizes the biological activity of TNFα by
binding with high affinity to the soluble & transmembrane
forms of TNFα & inhibits or prevents the effective binding
of TNFα with its receptors.

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Alternative Drug Therapy
Infliximab & Etanercept:
 Treatment with infliximab has recently proved effective in
the treatment of refractory sarcoidosis.
 Etanercept, a soluble TNF receptor construct, was found
ineffective against pulmonary & chronic ocular sarcoidosis.
 Etanercept binds soluble TNF alone, whereas
infliximab also binds to the membrane-bound form.

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Potential Role for Antioxidants in Sarcoidosis
 Enhanced production of reactive oxygen species (ROS),
capable of reducing endogenous defense levels & enhancing
inflammation, is suggested to play a role in sarcoidosis.
 Antioxidant supplementation offers protection not only
against ROS-mediated damage but also by reducing
inflammation.
 A promising candidate for antioxidant supplementation is
the flavonoid quercetin.

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Recommended Clinical Evaluation In Sarcoidosis
Baseline:
•History taking, with emphasis on occupational & environmental exposure
•Physical examination, with emphasis on lung, skin, eye, liver, heart
•Biopsy to obtain histologic confirmation of non-caseating granulomas
•Chest radiography
•Pulmonary-function testing — spirometry + measurement of gas exchange
(e.g., DLCO (or) ABGs)
•Electrocardiography
•Ophthalmologic evaluation with slit-lamp examination
•Biochemical evaluation for hepatic & renal function+ measurement of s. Ca
•Tuberculin skin test
•Other tests depending on clinical presentation & suspicion of extrathoracic
disease; assessment of extent and severity of organ involvement
Follow-up:
•Monitoring for resolution or disease progression & for new organ involvement.
•Referral to subspecialists if there is evidence of disease progression or new
organ involvement.

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Take Home Messages
 Therapy need not be given to all patients.
 Once initiated, at least 1 yr of treatment is required.
 Monitoring is mandatory if steriods discontinued.
 Steroid sparing agents useful for chronic patients.
 No long term benefit from corticosteroid therapy in
asymptomatic pts., regardless of CXR stage.
 Asymptomatic pts. with normal PFT should not be treated
because of radiographic abnormality alone.
 Neurologic, cardiac & ocular involvement warrants early
therapy.

74. Orphan LungOrphan Lung
DiseasesDiseases

75.  Page 78
Definition
 An ‘Orphan' disease is the name given to a
disease that is not widely researched and/or for
which there is no specific treatment, thus
making patients feel 'orphan' in the world of
healthcare.

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Orphan Lung Diseases
 Lymphangioleiomyomatosis (LAM).
 Pulmonary Langerhans’ Cell histiocytosis.
 Pulmonary Alveolar Proteinosis (PAP).
 Amyloidosis.
 Scleroderma.
 Idiopathic chronic eosinophilic pneumonia.

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Lymphangioleiomyomatosis
 Lymphangioleiomyomatosis (LAM) is a rare disorder of
unknown etiology characterized by proliferation of
atypical smooth muscle cell (LAM cell) in pulmonary
lymphatics, venules & small airways.
 The dominant clinical features are: ILD, chylous pleural
effusion & recurrent pneumothorax.
 It occurs in females during the childbearing period.

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Diagnosis of LAM
 Clinical.
 Radiological: chest radiograph.
 PFTs (combined obstructive & restrictive).
 Biopsy: TBLB.

79.  Page 82
Treatment of LAM
 Hormonal therapy e.g., progesterone &
tamoxifen.
 Hormonal manipulations e.g., oophorectomy.
 Lung transplantation.
 New experimental therapies e.g., Rapamycin,
Doxycycline & Octreotide.

80.  Page 83
Pulmonary Langerhans’ Cell Histiocytosis
Langerhans’ cell histiocytosis or Eosinophilic
granuloma of the lung.
Clinical: dry cough, dyspnea, chest pain rhinitis, fatigue,
fever, pneumothorax, hemoptysis, diabetes insipidus &
skeletal involvement with cystic bony lesions .
Examination: clubbing, cor pulmonale & crackles.
Langerhans’ cells are differentiated cells of monocyte–
macrophage lineage that function as APCs.
Common in young smokers.

81.  Page 84
Diagnosis of Langerhans’ Cell Histiocytosis
 Clinical.
 Radiological: chest radiograph.
 PFTs (normal, obstructive, restrictive or mixed).
 Biopsy: BAL & TBLB.

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Diagnosis of Langerhans’ Cell Histiocytosis

83.  Page 86
Diagnosis of Langerhans’ Cell Histiocytosis

84.  Page 87
 Corticosteroids & cytotoxic drugs no value.
 New experimental therapies e.g., gene therapy.
Treatment of Langerhans’ Cell Histiocytosis

85.  Page 88
Pulmonary Alveolar Proteinosis
 Pulmonary alveolar proteinosis (PAP) is a syndrome of
unknown etiology characterized by excessive
accumulation of surfactant phospholipids & apoproteins
within alveolar spaces.
 It can be primary (classic) or secondary
(pseudoproteinosis) due to environmental exposure,
drugs, infections & hematologic malignancies.
 More common in males between 30 & 50 yrs.

86.  Page 89
Diagnosis of PAP
 Clinical: dyspnea, dry cough, clubbing, cyanosis &
widespread crackles.
 Radiological: chest radiograph.
 PFTs restrictive pattern.
 ABGs.
 Laboratory LDH.
 Biopsy: FOB, BAL, TBLB & open lung biopsy
lipid laden macrophages.

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Diagnosis of PAP

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Diagnosis of PAP

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Treatment of PAP
 Therapeutic whole lung lavage under general
anesthesia using double lumen ETT (10-20 L
saline for every lung).

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