Sarcoidosis is a chronic inflammatory disease characterized by the formation of non-caseating granulomas in multiple organs, most commonly affecting the lungs. It has unknown causes but is thought to involve genetic and environmental factors. Historically, it was first described in the skin in 1899 and was later found to also affect the lungs and lymph nodes. It presents variably from being asymptomatic to causing respiratory symptoms or lesions in other organs. Diagnosis involves clinical features, chest imaging typically showing bilateral hilar lymphadenopathy, and biopsy demonstrating granulomas. Treatment involves observation of asymptomatic cases but corticosteroids for symptomatic or progressive disease. Prognosis is generally good with many cases resolving spontaneously but advanced lung fibrosis can occasionally occur

1. Kursk State Medical University
Department of Internal Disease N 1
Sarcoidosis
Student: Gustavo Duarte Viana
Group: 17
Course: 6th
year 2nd
semester

2. Sarcoidosis (or Bersier Boeck-
Schaumann disease)
• Chronic multisystemic inflammatory disorder of
unknown etiology that lead to non ceseous
granuloma formation, it most commonly affects
the lungs, but can also affect other organs mainly
the eyes, skin and bones.
• The name sarcoidosis is derived from a
misunderstanding, because doctor in the ninth
century thought that it was a benign form of
extreme aggressive neoplasm.

3. History of sarcoidosis
• In 1899, the pioneering Norwegian
dermatologist Caesar Boeck describe skin
nodules characterized by compact,
sharply defined foci of "epithelioid cells
with large pale nuclei and also a few giant
cells .
• Thinking this resembled sarcoma, he
called the condition "multiple benign
sarcoid of the skin.

4. Epidemiology
It is a worldwide disease, but there are some
prevalence in Scandinavian countries. But it may
affect all ethnic groups.
•It has a biphasic peak: Mostly in the ages around 20-
40, but it also appears around the 60.
•M-F ratio 2:1.
•Affects siblings of first- or second- degree relatives in
15% of patients with sarcoidosis.
•It is known that US black people have more severe
cases of pulmonary and skin sarcoidosis, but Japonese
have more cases of eyes sarcoidosis.

5. Etiology and Pathogenesis
• Cause is unknown, although both genetic and environmental
factors suspected.
• Theory that disease develops in genetically predetermined hosts
who are exposed to certain environmental agents that trigger an
exaggerated inflammatory immune response leading to
granuloma formation, specially because the organs most affects
(lungs, skin and eyes) are in direct exposure to the triggers.
• The trigger may be some insecticides, fungi, firefighting chemical,
wood-burning stoves, tree pollen, heavy metals, some dusts or
even bacteria such as Propionibacterium acnes (its DNA was
detected by PCR in the granulomas).
• Dust, miners or civil workers are more affected, there was a
break out of sarcoidosis in the workers helping in the 11-09-2001

6. • Hallmark is non caseaous granulomasn formation, composed
of a compact core of macrophages and around it a layer
oflymphocytes T CD+4 and lesser quantity lymphocytes B,
sometimes the macrophages can even fuse together forming
a multinucleated giant cell. There are a surrounding group of
macrophages forming the epithelioid histocytes.
• It is made in the porpose to surround and protect the
organism of a still unknown trigger.
• If the inflammatory process is persistent, it realease
chemiotaxis to fibroblasts which circumscribe the granuloma
and lead to formation of fibrotic tissue (scar) of granuloma
and surrounding tissue. It may lead to abnormalities in
normal architecture of the organ and further dysfunction.

7. T cells, Macrophages
Chemoattractants
Growth Factors
Cellular proliferation
Granuloma
Fibrosis
Pathogenesis

9. Curiosities
 In severe cases of AIDS, there is a very low account of T lymphocytes T CD4+, It lead to sarcoidosis
“spontaneous remission”, but when patient starts properly the antiretroviral therapy, sarcoidosis return
as the level of CD4+ raise up to normal level, it is one of the phenomenon of the IMMUNE
RECONSTITUTION SYNDROME.
 Kveim Siltzbach test: if positive, it is considered of diagnostic value, for rarely done due to difficulties in
the method and standardization of the method itself. It consists of injection a known homogenized
sarcoidosis tissue to the subcutaneous tissue of the patient, if after 4-6 weeks appear a papule, it is
considered positive. Mechanism is due to the Kveim Siltzbach reaction. It differs from a hypersensitivity
reaction because it only occurs after 4-6 weeks.
 It is possible to find markers of other disease, which my difficult at first the diagnosis, markers such as
Rheumatoid factor, antinuclear antibodies, anti T lymphocyte antibodies.
 As long as the disease persists untreated, more likely is to develop secondary organ disfunction.

10. Clinical Presentation
• One third have non-specific symptoms of fever, fatigue, weight
loss and malaise.
• It may be very difficult to diagnose sarcoidosis due to lack of
specific symptoms, in average it takes 1 year to diagnosis if
disease affects mostly the lungs and 6 months if affects mostly
the skin.
Forms: asymptomatic
Acute
Chronic

11.  Asymptomatic: 30-50% of patients and are diagnosed on routine CXR, usually with the classical SYMMETRICAL
BILATERAL HILAR ADENOPATHY with or without infiltrate.
 Acute: with evolution within few weeks with generalized symptoms as fever, severe asthenia and anorexia and
symptoms of pulmonary affection as dyspnea, cough and chest discomfort.
there are two acute syndromes distinguished separately in acute sarcoidosis
Loefgren syndrome, it is mostly frequent in Scandinavian women, from inland and Puerto Rico.
1- Uveitis
2- Erythema Nodosum
3- X-ray finding of symmetrical bilateral hilar adenopathy or parabrachial.
4- acute peripheral arthritis or poliarthralgia.
Heerfordt Walderstrom syndrome or AKA eveoparotid fever
1- Fever
2- parotid enlargement
3- anterior uveitis
4- facial paralysis.
 Chronic: insidious form lasting for months, strongly linked with respiratory symptoms and in lesser stand with
generalized symptoms, it lead to permanent irreversible organ changes, in specially lungs.

14. Specific organ involvement
✕ Lungs: more than 90% of patients with sarcoidosis will evolve to abnormalities shown in the X-ray, in very early stages
where interstitial pneumonia is present before formation of the granulomas. The infiltrate is usually in the upper lobes (in
contrary to other non infectious pneumopathy).
One third of the patients shows restrictive pneumopathy in pulmonary function test and one third of the patients show
criteria of obstructive pneumopathy.
There is the classical symmetrical bilateral hilar adenopathy which is very suggestive, but not pathognomonic because it
may be also present in fungic infections and neoplasia like bronchogenic carcinoma.
The main symptoms are dyspnea, dry cough and retrosternal dysconfort, others symptoms are seldom seen as pleural
involvement, pleural infusion, hemoptesis.
✕ Upper air ways: 20% of patients has involvement of the nasal mucosa leading to nasal obstruction, but all naso-oral
mucosa may be involved leading to high dyspnea, wheezing and hoarseness (Laryngeal sarcoidosis).
✕ Lymph-nodes: intrathoracic are enlarged in more than 90% of the patients with the classic symmetrical bilateral hilar
adenopathy, other lymph- nodes may be also involved as cervical chain, axillary and inguinal and they are painless,
mobile and non ulcerative and usually not perceived by the patient.

15. ✕ Skin: about one third of patients which
• Erythema nodosum: they are erythematous painful nodules in the anterior surface of the legs, they
represent a subcutaneous vasculitis.
• Maculopapulous eruptions: they are due to granulomas itself and may be up to 3cm with a plateau
surface and of wax appearance, they may be found all over the body.
• Dischromias: usually painless and of a violate tin.
• Subcutanous nodules: in trunk and extrimities
• Lupus pernio: it forms complex of shining cyanotic harden lessions around the nose, libs, checks and
ears, it may erode to bones and cartilages around.
• It may develop over surgical scars and tattoo.

18. ✕ Eyes: 25% of patients
Anterior uveitis: photophobia, epiphora and blurred vision.
Sicca keroconjutivitis
Blindness
✕ Bone marrow: 40% of patients, but lead only to a mild lymphopenia, very rare hematological
alterations.
✕ Spleen: 10%, but rarely lead to hiper-splenism syndrome.
✕ Liver: 50% reveals granulomas during autopsy, but rarely lead to hepatogram abnormalities, usually
only alkaline phosphatase is increased.
✕ Pancreas and intestine are rare affects, only granulomas at autopsy.
✕ Kidney: rare formation of granuloma, but sarcoidosis indirectly may lead to renal morbidity due to
increasing of active D vitamin (Granuloma has 25-hydroxivitamin D), which leads to hyperkalemia and
therefor nephrocalcinosis and repeated nephrolithiasis. All patients with sarcoidosis must routinely
check urine level of calcium and in blood analysis.
✕ Central and peripheral nervous system or neurosarcoidosis: A) cranial nerve paralysis B)
migraines C) ataxia D) cognitive dysfunction E) Asthenia F) seizures G) mononeuropathy or even
polyneuropathies of peripheral nerves leading to sensorial loss or paresthesy H) Incidious lymphocytic
meningitis (sarcoidosis meningitis) I) Diabetes insipidus due to granulomatous lesion to hypothalamus.
✕ Endocrine glands: 10% involving the parotid gland (Heerfordt syndrome) and rarely suprarenal cortex
insufficiency.

22. ✕ Heart: 25% reveal granulomas in cardiac tissue, but only 5% will have symptoms, except Japoneses
where one forth of them will have heart sarcoidosis affection.
it may lead to: cardiac blocks, arrhythmias, angina, aneurisms, pericardial effusion, chronic cardiac
insufficiency. Cor pumonale is rare, but has association to pulmonary fibrosis in advanced sarcoidosis.
✕ Bones: affects mostly the phalanges, metacarpus and metatarsus leading to deformities in fingers and
nails. May lead to osteoporosis and cist formation
✕ Joints: arthritis or polyarthritis of big joints as ankles, knees, wrists and elbow. Patients with gout may
have worsening of the clinical picture because the granuloma itself produces purines.
✕ Muscles: acute myositis and chronic myopathy.
✕ Breats
✕ Tests
✕ Ovaries
✕ Stomach
✕ Others

26. Common Clinical Features

27. Erythema Nodosum

28. Lupus Pernio

30. X-ray manifestations
✕Nodules on X-ray may be isolated or multiples which may suggest
tumor, or they may be even miliar suggesting TB.
✕Hilar or mediastinal lymph-nodes may have the EGG SHELL
appearance of calcifications suggesting as differential diagnosis
silicosis.
✕May have bullae formation or true cavities with mycetoma inside.
✕Lobar atelectasia by endobronchic granulomas
✕Pleural infusion

31. 4 Stages of Pulmonary Sarcoidosis
I Bilateral hilar lymphadenopathy
and paratracheal adenopathy
55-90%
remission
II Mediastinal adenopathy with
pulmonary parenchymal
involvements
40-70%
III Pulmonary parenchymal without
adenopathy
10-20%
IV Pulmonary fibrosis with
honeycombing
0-5%

32. Stages

33. Laboratory Studies
Routine lab evaluation often is unrevealing.
Blood and biochemical blood analysis
Increased erythrocyte sedimentation rate (except in
Loefgren syndrome)
Lymphopenia
Hyperglobulinemia
Hypercalcemia or hypercalciuria. Hypercalcemia is seen in
about 10-13% of patients, whereas hypercalciuria is 3 times
more common.
Elevated alkaline phosphatase level suggests hepatic
involvement.
Angiotensin converting enzyme may be elevated.
Lumbar Puncture
Liqueur may have pleocytosis due to lymphocytes, elevated
protein and normal glucose (aseptic lymphocytic meningitis)

34. Biopsy specimen
• A biopsy specimen should be obtained from the
involved organ that is most easily accessed, such
as the skin, peripheral LN. (not in erythema
nodosum)
• Eyes, lacrimal glands and gums only if they are
affected.
• If diagnosis requires pulmonary tissue, trans-
bronchial biopsy by means of bronchoscopy has a
diagnostic yield of at least 85% when multiple lung
segments are sampled. It may also be obtained by
mediastinoscopy or thoracothomy.

35. The central histologic finding is the presence of
NCGs with special stains negative for fungus
and mycobacteria.

36. Diagnosis
Consists of 3 main points
•Clinical manifestations
•Chest X-ray showing typical picture
• biopsy showing non caseating granuloma
Differential diagnosis
•TB
•Fungal infections
•Lymphoma
•Epithelioid tumors of the breast
•Lung cancer

37. Treatment
60% has remission spontaneously
10-20% has remission by corticosteroids
The main goal is to prevent fibrosis (ocular and
pulmonary)
•Observation
•Initiating corticosteroid therapy when
appropriate
•Monitoring response to therapy
•Discontinuing corticosteroids when clinically or
physiologically indicated.

38. Treatment by X-stages
•Stage 1 – only observation, if worsening of clinical picture we should start
steroids.
•Stage 2 – Asymptomatic – observation for 6 months, if no improvement we should
treat.
Treatment only if symptomatic or Asymptomatic with elevated blood
ACE, alteration in relation CD4+CD8+ or enhanced absorption of gallium 67.
•Stage 3 – Treat
•Stage 4 – treat if there is still absorption of Gallium 67, if there is not absorption
that means that the fibrosis is already formed and disease is not active anymore,
so corticosteroids would be useless
If there is still absorption of Gallium 67, administer corticoids
Other organs sarcoidosis or extrapulmonary
We should always treat with corticoisteroid:
Vital organs as eyes, nervous system, heart, liver, kidney, spleen.
Affection of upper air ways, parotidis, thyroid, cutaneous, specially lupus pernio.
Severe forms of articular, bone or muscular sarcoidosis
Biochemical alterations such as hyperkalemia, elevated ACE.

39. Neurosarcoidosis: pulse metilprednisolone IV 500 mg every
second day or 1g every week for 4-6 weeks.
Ocular sarcoidosis: eyes drops for conjuctivitis or uveitis, but
if it is posterior uveitis systemic corticosteroids should be
administered.
Pulmonary sarcoidosis: inhaled
Upper air way sarcoidosis: inhaled
Cutaneous: with ointments, creams or local injections of
corticosteroids.

40. Treatment
• Topical therapy for cutaneous or ophthalmic
disease (eye drops).
• Systemic corticosteroids for patients with
unresponsive ophthalmic manifestations,
cardiac, neurologic and progressive pulmonary
involvement.
• Systemic therapy for patients with
hypercalcemia.

41. Treatment
• Prednisone, 20 to 60 mg/d in divided doses or
alternate-day dosing is used for organ
involvement that is not life threatening gradually
diminishing the dose until the matainence dose
of 5 – 10 mg daily or 10-20 alternate day.
• Higher dosage is used off-label for potentially life
threatening disease.
• High-dose inhaled corticosteroids may be useful
in patients with symptomatic pulmonary disease.

42. Treatment
• Clinical improvement should be assessed after 3
months of corticosteroids.
• If no improvement is found, further treatment is
unlikely to be beneficial.
• Long term adverse affects of therapy include
weight gain, mood swings, cataracts, GERD,
osteoporosis

43. Other drugs
they are not so useful as corticosteroids, but may help in association to it.
NSAIDS: if present erythema nodosum, polyarthritis or acute uveitis.
Hydroxichlorquine: chronic fibrotic lesions in lung or skin, 200mg in
alternate days for 9 months to avoid ocular toxicity and should be followed
by a ophthalmologist.
Metothrexate: Lupus pernio or chronic skin lesions, 10mg once per week
for 3 months.
Azathioprine (50mg 3x daily for 3 months), cyclophosphamide (50mg 1x
daily for 3 months) or chlorambucil (5mg 1x daily for 3 months) may be
also used to try to diminish corticosteroids intake.
Organ transplantation is a choice for whom have lost organs function
(pulmonary, liver or kidney), interesting fact is that after transplantation
there are formation of non caseating granuloma in the transplanted organ,
even in patients in immunosuppressive therapy.

44. Prognosis
Many patients do not require therapy, and their
conditions will spontaneously improve.
Markers for a poor prognosis include :
• Advanced CXR stage.
• Extrapulmonary disease (predominantly cardiac and
neurologic)
• Evidence of pulmonary hypertension.
• Multiple studies have demonstrated that the
most important marker for prognosis is the initial
CXR stage.

45. Remission
• 2/3 of patients with sarcoidosis generally have a
remission within a decade after diagnosis, with
few or no consequences; remission occurs for
more than half of patients within 3 years.
• Unfortunately, up to 1/3 of patients have
progressive disease, leading to clinically significant
organ impairment.
• A recurrence after 1 or more years of remission is
uncommon (affecting <5% of patients), but
recurrent disease may develop at any age and in
any organ.

46. Death
• Less than 5% of patients die from
sarcoidosis.
• death is usually the result of pulmonary
fibrosis with respiratory failure or of
cardiac or neurologic involvement.