2. SARCOİDOSİS
• Sarcoidosis is a systemic granulomatous and
inflammatory disease of unknown cause.
• The most involved structures are intrathoracic
lymph nodes and lungs, but any organ can be
involved.
3. SARCOIDOSIS EPIDEMIOLOGY
• There is no clear information about the incidence and prevalence
of sarcoidosis.
• Sarcoidosis can be seen all over the world, in both sexes and in all
age groups.
• However, there are societies and age groups where it is more
common.
• Although it is seen in all age groups, it is mostly a disease of
young adults.
• The most common populations are Scandinavians and African
Americans.
• The course of the disease and the forms of involvement vary
according to races.
• 75% of the cases are non-smokers.
4. SARCOİDOSİS ETİOLOGY
• The cause of sarcoidosis is unknown.
• It is accepted that genetic predisposition plays a role in the
development of sarcoidosis.
• Regarding the genetics of sarcoidosis, a study was conducted on the
HLA Gene.
• Some genetic features have been associated with the frequency of
sarcoidosis, the mode of presentation or prognosis of sarcoidosis.
• It is accepted that environmental factors play a role in the
development of sarcoidosis.
• The most important of the environmental factors is the infectious
agents, Mycobacterium tuberculosis.
• The development of sarcoidosis has been reported in relation to
drugs that affect the immune system (such as interferon, anti-TNF
agents, “highly activated retroviral therapy” used in HIV+ patients...)
5. SARCOİDOSİS PATHOGENESİS
• The main event in the development of sarcoidosis is the development of granuloma.
• The antigen that triggers sarcoidosis is presented to CD4+ T lymphocytes by antigen-
presenting cells.
• Activated CD4+ T lymphocytes (Th0) transform into T helper type 1 (Th1) effector
cells with the effect of interleukin (IL) 12 and 18.
• Continuation of antigen presentation by alveolar macrophages to effector Th1 cells
and production of many cytokines, chemokines; It provides granuloma formation
through migration, collection and local proliferation of cells (especially T lymphocytes,
monocytes/macrophages).
• In later periods, in some cases, granulomas disappear with spontaneous resolution,
while in others they persist and go to chronic disease.
• In a very small group of patients, granulomas are replaced by fibrotic changes, and if
this is progressive, end-stage fibrosis may develop.
6. SARCOİDOSİS PATHOLOGY
• Typical histopathological lesion of sarcoidosis is compact epithelioid cell granulomas
without caseification necrosis.
• Granulomas contain epithelioid cells, giant cells and lymphocytes.
• Giant cells may contain cytoplasmic inclusions such as asteroid bodies and
Schaumann bodies.
• Occasionally, focal coagulation necrosis may be found in granulomas.
• In sarcoid granulomas, fibrotic changes may develop, starting from the periphery and
progressing to the centre, resulting in complete fibrosis and/or hyalinization.
• Granulomas may disappear or progress to fibrosis.
• Most of the granulomas in the lung are located in the connective tissue sheaths around
the bronchioles, in the subpleural or perilobular areas.
7. SARCOİDOSİS CLİNİC
• The manifestation of sarcoidosis is very variable.
• It may start with an acute noisy picture and
manifest itself with an insidious picture.
• Some patients with sarcoidosis present with non-
specific constitutional symptoms such as fever,
fatigue, fatigue, and weight loss.
• Weight loss is usually around 2-6 kg in the last 2-3
months.
• Weakness and fatigue are common
8. SARCOİDOSİS CLİNİC (LUNG SARCOİDOSİS)
• As the lungs are the most common site of involvement, respiratory system symptoms
are present in one third or half of the cases.
• In the ACCESS study, lung involvement was detected in 95% of the cases.
• The most common respiratory symptoms are shortness of breath, cough and chest
pain.
• Sarcoidosis is staged according to lung radiography.
• Stage 0: normal chest X-ray
• Stage 1: bilateral hilar lymphadenopathy
• Stage 2: bilateral hilar adenopathy and parenchymal infiltrates
• Stage 3: parenchymal infiltrates only
• Stage 4: fibrosis
9. SARCOİDOSİS CLİNİC (LUNG SARCOİDOSİS)
• The radiology of the vast majority of cases is compatible with stage 1 or 2.
• Stage 3 or 4 radiology was observed in only 15% of the cases in the
ACCESS study.
• Restrictive defects in pulmonary function tests are detected in more than 20-
30% of patients with sarcoidosis during the initial diagnosis period.
• There may be airway involvement in sarcoidosis, it is most commonly
observed as nodular swellings on the mucosa, and there may be the
appearance of a mass lesion from time to time.
• Pleural involvement is rare in sarcoidosis. Pleural fluid, pneumothorax,
pleural thickening and nodules, hydropneumorax, chylothorax may develop.
10. SARCOİDOSİS CLİNİC (SKİN SARCOİDOSİS)
• There is skin involvement in 25-35% of cases.
• Skin involvement may be in the form of specific lesions with granulomas on
biopsy or non-specific lesions without granulomatous inflammation on biopsy.
• Erythema nodosum is the most common, easily recognized non-specific
lesion.
• Some of the patients with sarcoidosis present with erythema nodosum,
fever, arthralgia, and bilateral hilar adenopathy (parenchymal infiltrates can
also be found) on chest X-ray.
• This picture, called Löfgren's syndrome, strongly suggests sarcoidosis,
• The prognosis of this group of patients is generally very good. Erythema
nodosum often resolves within 3 weeks.
• Another important skin involvement that is easily recognized in sarcoidosis
is lupus pernio.
• It is often a sign of chronic sarcoidosis, accompanying bone cysts and lung
fibrosis.
11. SARCOİDOSİS CLİNİC (EYE INVOLVEMENT)
• The frequency of eye involvement is reported to vary
between 10-80%.
• Every patient with sarcoidosis should be referred for
routine eye consultation.
• Although every layer of the eye can be involved,
uveitis is the most common.
• Chronic uveitis can lead to glaucoma, cataract and
blindness.
• Conjunctival follicles, retinal vasculitis, lacrimal gland
enlargement, dacryocystitis, keratoconjunctivitis sicca
can also be seen in sarcoidosis.
12. SARCOİDOSİS CLİNİC (MUSCULOSKELETAL INVOLVEMENT)
• Bone, muscle and joint involvement may occur in patients with sarcoidosis.
• Symptomatic muscle involvement is rare.
• When chronic myopathy is present, it is important to differentiate it from
corticosteroid-induced myopathy.
• The frequency of bone lesions due to sarcoidosis is between 3-13%, most
commonly the bones of the hands and feet are involved.
• Lytic lesions (bone cysts), reticular appearance, destructive changes may
occur in the bone.
• Acute sarcoid arthritis often accompanies Löfgren's syndrome and has a
good prognosis.
13. LİVER GASTROINTESTINAL SYSTEM INVOLVEMENT
• Granuloma can be detected frequently in liver biopsies; but most of the
patients do not have any complaints.
• Liver enzymes may be elevated in 10% of patients with sarcoidosis.
• Although hepatic sarcoidosis is often silent, itching, jaundice, liver failure
and portal hypertension may develop rarely due to liver involvement.
• Liver failure, hepatopulmonary syndrome, portal hypertension with varicose
bleeding is seen in less than 1% of cases.
• Gastrointestinal system involvement is very rare, gastric sarcoidosis can be
found in less than 10% of cases.
• Gastrointestinal involvement usually does not cause clinical symptoms.
14. SARCOİDOSİS CLİNİC ( HEART INVOLVEMENT)
• In sarcoidosis, the heart can be affected both by lung involvement and
directly by disease involvement.
• Clinically detected cardiac involvement is around 5%; however, higher
rates are reported in autopsy series.
• Cardiac sarcoidosis is a rare but life-threatening form of involvement.
• Sudden death may occur in cases with cardiac sarcoidosis if the diagnosis is
not considered.
• Cardiac involvement can occur at any time during the course of sarcoidosis,
before other organ involvement, simultaneously with others or after other
involvements.
• Sarcoid granulomas can affect every layer of the heart, myocardium is most
commonly affected.
• The clinical picture is related to the localization and prevalence of
granulomas.
• Major clinical findings occur with infiltration of myocardium and
conduction system.
• Benign arrhythmias, conduction delays, blocks, heart failure, and even
sudden cardiac death may occur with this infiltration.
• Diagnosis is difficult; Diagnostic difficulties and delayed diagnosis
negatively affect the prognosis.
• Endomyocardial biopsy, which is a definitive diagnostic method, is both
difficult and has low diagnostic value.
• Therefore, in a case with granulomas in a non-cardiac organ, a diagnosis of
cardiac sarcoidosis can be made by clinical signs and symptoms, ECG and
other non-invasive cardiac imaging methods.
• Electrocardiography, 24-hour Holter monitoring, echocardiography,
myocardial perfusion scintigraphy with thallium, gallium scintigraphy are
auxiliary tests in the diagnosis.
• In recent years, cardiac magnetic resonance imaging (MRI) and 18F-fluoro-
2-deoxyglucose positron emission tomography (FDG-PET) have been the
most emphasized methods in the diagnosis of cardiac sarcoidosis.
15. SARCOİDOSİS CLİNİC ( NEUROSARCOIDOSIS)
• Clinically detectable nervous system involvement is below 10%, but up to
25% nervous system involvement is reported in autopsies.
• Common forms of neurosarcoidosis are cranial nerve involvement,
especially facial paralysis, hypothalamic and hypopituitary lesions; Less
frequently, space-occupying masses, peripheral nerve involvement,
lymphocytic meningitis may be seen.
• Cranial nerve paralysis, headache, ataxia, cognitive dysfunction, loss of
strength and convulsions may be seen in the clinical picture.
• In 62-74% of patients with neurosarcoidosis, neurological symptoms are the
initial manifestations of the disease; in these cases, other systemic
manifestations occur later.
• The clinical picture can be acute, subacute or chronic, insidious.
• Angiotensin converting enzyme (ACE) level in cerebrospinal fluid (CSF)
and cranial MR are helpful in diagnosis.
• Paralysis of the seventh cranial pair may accompany uveo-parotid fever
(Herfort syndrome-uveitis, parotid swelling, 7th nerve paralysis).
16. SARCOİDOSİS CLİNİC ( HEMATOLOGICAL PROBLEMS)
• Not very serious anemia, leukopenia may be found.
• Hematological disorders may be related to splenomegaly or bone
marrow involvement.
• Leucomoid reaction, eosinophilia, thrombocytopenia are rare.
• Spleen enlargement is usually mild and asymptomatic; but
sometimes it can get too big and cause compression symptoms and
hyperseplenism.
• Hypercalcemia is found in 2-10% of cases, hypercalciuria is more
common; Detection and correction of hypercalcemia and
hypercalciuria may cause kidney stones, nephrocalcinosis, and kidney
failure.
• Therefore, blood calcium and 24-hour urine calcium should be
measured in all patients diagnosed with sarcoidosis.
• Endocrine findings such as diabetes insipidus, hypothyroidism,
hyperthyroidism, and adrenal suppression are very rare. There may be
swelling, painful enlargement of the parotid glands.
• Rarely, kidneys, reproductive organs, breast tissue may be involved.
• Involvement of oral cavity, larynx, tonsils, nasopharynx can be seen
rarely in sarcoidosis; hoarseness, sore throat, acute respiratory failure
and obstructive sleep apnea may develop.
17. SARCOİDOSİS DIAGNOSIS
• The diagnosis of sarcoidosis is made by excluding other causes that may cause these pictures in the presence of a compatible clinical,
radiological and histopathological picture.
• Presence of granuloma alone does not make the diagnosis of sarcoidosis.
• Tissue biopsy is required for histopathological demonstration of granulomas that do not contain caseification necrosis.
• However, in some cases, the patient may be considered sarcoidosis without a tissue diagnosis.
• These are bilateral hilar lymphadenopathy, Löfgren's syndrome, Heerford's syndrome, involvement of the lacrimal and parotid glands
on Gallium 67 scintigraphy (panda sign) and right paratracheal and bilateral hilar involvement (lambda sign) in an asymptomatic
patient.
• If the clinical picture is not so typical as to be called sarcoidosis without tissue diagnosis, biopsy should be performed.
• Other possibilities should be excluded when biopsy shows granulomatous inflammation..
18. SARCOİDOSİS DIAGNOSIS
• Detection of excess organ involvement is helpful in differential diagnosis.
• For example, sarcoidosis can be confused with lymphoma and tuberculosis; however, if uveitis is detected, it is an auxiliary finding in the
diagnosis of sarcoidosis, since uveitis is very rare in these diseases.
• Multiple sclerosis, like sarcoidosis, can cause optic neuritis and uveitis, but these patients do not have mediastinal, hilar lymphadenopathy.
• In the initial evaluation of sarcoidosis, after the history and physical examination, chest X-ray, pulmonary function tests (spirometry, diffusion
test), whole blood, complete urinalysis, all biochemistry (liver, kidney functions, angiotensin converting enzyme-ACE level), 24-hour urine calcium,
ECG, PPD should be done, all patients should be sent for routine eye consultation and fiberoptic bronchoscopy, bronchial mucosa and transbronchial
lung biopsy, BAL examination should be planned..
• Biopsy can be performed from any organ involved in the patient with sarcoidosis.
• Bronchoscopy can be performed to obtain bronchoalveolar lavage, bronchial mucosal biopsy, transbronchial needle aspiration, and transbronchial
biopsy.
19. SARCOİDOSİS DIAGNOSIS
• Although EBUS prolongs the bronchoscopy time a little, it greatly increases the chance of diagnosis.
• If chest X-ray findings are atypical, and if the chest X-ray is normal even though the disease is considered, CT, especially high-resolution CT (HRCT), is
helpful in the diagnosis.
• Generally, nodules with bronchovascular and subpleural distribution, thickening of the interlobular septum, structural deterioration, and conglomerate
masses are observed on CT.
• Sarcoidosis sometimes progresses with single or multiple nodules or mass lesions on chest X-ray and CT.
• Exclusion of malignant diseases is important in these cases, bronchoscopy and transbronchial biopsy are valuable in diagnosis.
• High serum ACE level is helpful in diagnosis, reflecting the total granuloma burden in sarcoidosis.
• Its sensitivity is low, therefore it is not diagnostic. Its sensitivity was found to be 57% and specificity around 90%.
• PPD is negative in approximately 85% of patients.
20. SARCOİDOSİS TREATMENT
• Spontaneous remission develops in a significant portion of patients with
sarcoidosis.
• Therefore, treatment should only be considered for symptomatic cases with
impaired organ functions.
• Steroids are used in treatment.
• In appropriate cases, treatment with local steroids should be tried.
• Steroid pomades in skin lesions, intralesional steroid injections, steroid eye
drops in eye involvement, steroid inhalers in cough complaints can control the
disease or symptoms.
• Nonsteroidal anti-inflammatories may be useful in acute conditions such as
erythema nodosum, arthralgia, and arthritis.
• Antimalarial drugs can be used instead of steroids in common skin lesions,
hypercalcemia, and hyperlaxia.
• Cardiac, neurological involvement, eye involvement that does not respond
to local treatment, severe hypercalcemia are absolute steroid treatment
indications.
21. SARCOİDOSİS TREATMENT
• In lung and other organ involvement, treatment decision should be made according to the patient's symptoms and organ functions.
• Stage 1, asymptomatic cases should be followed without treatment.
• If stage 2 or stage 3 cases have mild or moderate symptoms, the decision to treat can be left at the end of 6-12 months with a close follow-up.
• In these cases, it is appropriate to check every 2-3 months and to start treatment if the disease worsens.
• Symptomatic cases with impaired pulmonary function tests and diffuse infiltration should be treated.
• Only persistent radiological infiltrates and progressive loss of lung functions should bring up treatment in an asymptomatic patient ..
• Spontaneous remission is common in patients with acute sarcoidosis.
• Spontaneous remission usually occurs in the first 6 months, but it can last up to 2-5 years.
• Chronic cases usually have progressive or persistent disease that requires treatment.
• Patients whose disease lasts longer than two years and whose respiratory functions are found to be impaired in the last three months should be treated.
• Stage 4 cases may not respond to steroid/immunosuppressive therapy.
22. SARCOİDOSİS TREATMENT
• However, treatment may be attempted for a while to assess whether symptomatic or functional improvement will occur.
• This group of cases will require more supportive treatment.
• In cases requiring treatment, 20-40 mg of prednisone or its equivalent per day is started and a 12-24 month treatment is applied.
• Treatment may not be discontinued for a long time in a group of chronic cases.
• There are drugs that reduce the need for steroids in patients who need steroids for a long time:
• Methotrexate: 5-15mg once a week.
• 1mg/day folic acid is added to reduce the toxicity of methotrexate.
• Azathioprine: 50-200mg/day
• Leflunomide: 10-20mg/day Mycophenolate: 2-3x500mg
• Anti-TNF agents are recommended in chronic refractory cases..
23. SARCOİDOSİS RESOURCES
1-MD.. Özlem Özdemir Kumbasar Ankara University Faculty of Medicine Department of Chest Diseases
2- Musellim B, Kumbasar OO, Ongen G, Cetinkaya E, et al. Epidemiological features of Turkish patients with sarcoidosis. Respir Med 2009;
103:907-912.
3-de Boer S, Wilsher M. Sarcoidosis. Chronic Resp Dis 2010; 7:247-258.
4-Baughman RP, Teirstein AS, Judson MA, et al. Clinical Characteristics of Patients in a Case Control Study of Sarcoidosis. Am J Respir Crit Care
Med 2001;164: 1885-1889. 5-Grutter JC, Drent M, van den Bosch JMM. sarcoidosis. Eur Respir Mon 2009;46:126-154. 6- Judson MA.
Sarcoidosis: Clinical presentation, diagnosis and approach to treatment Am J Med Sci 2008; 335:26-33.
7--Ianuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis N Engl J Med 2007: 2153-65.
8- Lynch JP, Ma YL, Koss MN, White ES. pulmonary sarcoidosis. Semin Respir Crit Care Med 2007; 28:53-74.
