Sarcoidosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief:

Sarcoidosis, also called sarcoid (from the Greek ‘sark’ and ‘oid’ meaning “flesh-like”) or Besnier-Boeck disease, is an immune system disorder characterised by non-caseating granulomas (small inflammatory nodules) that most commonly arises in young adults. The cause of the disease is still unknown. Virtually any organ can be affected; however, granulomas most often appear in the lungs (D86.0) or the lymph nodes (D86.1). Symptoms can occasionally appear suddenly but usually appear gradually. The clinical course varies and ranges from asymptomatic disease that resolves spontaneously to a debilitating chronic condition that may lead to death.^[1]

• [Disease name] was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event].
• In [year], [gene] mutations were first identified in the pathogenesis of [disease name].
• In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name].

• [Disease name] may be classified according to [classification method] into [number] subtypes/groups:

• [group1]
• [group2]
• [group3]

• Other variants of [disease name] include [disease subtype 1], [disease subtype 2], and [disease subtype 3].

• The pathogenesis of [disease name] is characterized by [feature1], [feature2], and [feature3].
• The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
• On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
• On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

• [Disease name] may be caused by either [cause1], [cause2], or [cause3].
• [Disease name] is caused by a mutation in the [gene1], [gene2], or [gene3] gene[s].
• There are no established causes for [disease name].

• [Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:

• [Differential dx1]
• [Differential dx2]
• [Differential dx3]

• The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
• In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].

• Patients of all age groups may develop [disease name].

• [Disease name] is more commonly observed among patients aged [age range] years old.
• [Disease name] is more commonly observed among [elderly patients/young patients/children].

• [Disease name] affects men and women equally.

• [Gender 1] are more commonly affected with [disease name] than [gender 2].
• The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

• There is no racial predilection for [disease name].

• [Disease name] usually affects individuals of the [race 1] race.
• [Race 2] individuals are less likely to develop [disease name].

• Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

• The majority of patients with [disease name] remain asymptomatic for [duration/years].
• Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
• If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
• Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
• Prognosis is generally [excellent/good/poor], and the [1/5/10­year mortality/survival rate] of patients with [disease name] is approximately [#%].

• The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:

• [criterion 1]
• [criterion 2]
• [criterion 3]
• [criterion 4]

• [Disease name] is usually asymptomatic.
• Symptoms of [disease name] may include the following:

• [symptom 1]
• [symptom 2]
• [symptom 3]
• [symptom 4]
• [symptom 5]
• [symptom 6]

• Patients with [disease name] usually appear [general appearance].
• Physical examination may be remarkable for:

• [finding 1]
• [finding 2]
• [finding 3]
• [finding 4]
• [finding 5]
• [finding 6]

• There are no specific laboratory findings associated with [disease name].

• A [positive/negative] [test name] is diagnostic of [disease name].
• An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
• Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

• There are no [imaging study] findings associated with [disease name].

• [Imaging study 1] is the imaging modality of choice for [disease name].
• On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
• [Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

• [Disease name] may also be diagnosed using [diagnostic study name].
• Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

• There is no treatment for [disease name]; the mainstay of therapy is supportive care.

• The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
• [Medical therapy 1] acts by [mechanism of action 1].
• Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

• Surgery is the mainstay of therapy for [disease name].
• [Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
• [Surgical procedure] can only be performed for patients with [disease stage] [disease name].

• There are no primary preventive measures available for [disease name].

• Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

• Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Roshan Dinparasti Saleh, M.D.

The word “sarcoidosis” comes from the Greek word “sarcoid”, meaning “one having flesh or tissue,” and the Greek suffix “-osis,” meaning “condition.” which refers to the skin involvement of various body parts.

• In 1877, british physician Jonathan Hutchinson(1828–1913) first described dermatologic manifestations of sarcoidosis as ” a case of livid papillary psoriasis” ^[1].
• in 1889, Besnier described a patient with lupus pernio(a variant of cutaneous sarcoidosis) ^[2].
• in 1899, Caesar Boeck(1845-1917) reported 24 cases of “benign military lupoids. He observed epithelioid cells with large pale nuclei and giant cells which resembled sarcoma, and named this condition “multiple benign sarcoid of the skin^[3].
• Christian Heerfordt(1871–1953) was an ophthalmologist who explained uveoparotid fever characterized by anterior uveitis and parotid gland enlargement in 1909.^[4].
• in 1936, swedish dermatologist Jorgen Schaumann(1879–1953), introduced sarcoidosis as a multisystem disease for the first time and called it “lymphogranuloma benigna” to differentiate it from Hodgkin lymphoma^[5].
• in 1939, french dermatologist Lucien-Marie Pautrier(1876–1959) wrote a textbook on sarcoidosis and regarded sarcoidosis as a reticuloendothelial disease^[6].
• in 1941, Ansgar Kveim(1892–1966) observed that intradermal inoculation of sarcoid lymph node tissues in sarcoidosis patients, gave rise to sarcoid papules but injection of tuberculin and Frei antigen did not produce papules and he served to distinguish sarcoidosis from tuberculosis by this test^[7].
• in 1953, Sven Lofgren(1910–1978) did studies on primary pulmonary sarcoidosis and the combination of hilar adenopathy and erythema nodosum became famous as Lofgren syndrome^[8]. Lofgren attended the first world congress on sarcoidosis in London in 1958 and proposed a viral cause for sarcoidosis^[6].
• in 1961, Nils Svanborg(1920-1997) published the first monograph about cardiopulmonary function abnormalities in sarcoidosis^[9].
• in 1967, Guy Scadding published Sarcoidosis book and collaborated with Sheila Sherlock on liver biopsy for diagnosis of sarcoidosis^[6].
• in 1984, italian pulmonologist Gianfranco Rizzato established a journal devoted to sarcoidosis and founded WASOG(World Congress of Sarcoidosis and Other Granulomatous Disorders) in 1987.^[6].

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Roshan Dinparasti Saleh M.D.

There is no universally accepted classification system for sarcoidosis according to our knowledge, but in some references sarcoidosis is classified regarding the organ system involved. The lung is involved in 90% of patients diagnosed with sarcoidosis, thus sarcoidosis is generally classified into pulmonary sarcoidosis and extra-pulmonary sarcoidosis.

Scadding proposed a scoring system regarding the chest radiograph for pulmonary sarcoidosis in 1961.

stage 1: Hilar adenopathy alone

stage 2: Hilar adenopathy plus lung infiltrates

stage 3: Lung infiltrates alone

stage 4: Fibrosis^[1]

Scadding‘s classification correlates with prognosis. Individuals with stage 1 disease, have a 80% chance of resolution of hilar adenopathy and those with stage 3 disease, have less than 30% chance of CXR resolution. The limitations of Scadding‘s scoring system include: 1. It does not characterize extra-pulmonary sarcoidosis 2. There is a significant variability in staging even among experienced radiologists^[2].

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Roshan Dinparasti Saleh M.D.

Sarcoidosis is a multisystem disorder of unknown etiology characterized by noncaseating granulomas in involved tissues. The lungs are affected most commonly, and pulmonary disease accounts for the majority of the morbidity and mortality associated with this disease. Other tissues commonly involved include the skin, eyes, and lymph nodes.

Granuloma formation is a hallmark of sarcoidosis disease. The underlying immunologic events include (1) exposure to antigens, (2) activation of antigen-presenting cells (macrophages and/or dendritic cells), (3) a T cell response in an effort to eliminate the antigen, and (4) granuloma formation. macrophages differentiate into epithelioid cells, which gain secretory capability, lose phagocytic capacity, and fuse to form multinucleated giant cells which are cellular basis of granulomas. Th2 cells also contribute to granuloma formation. These cells secrete fibronectin and CCL18, which finally lead to macrophage-mediated collagen formation and fibrosis in 25% of patients with sarcoidosis ^[1]. It is estimaed that two possible immunologic scenarios play role in sarcoidosis: an intense immune reaction in patients with active disease, finally resulting in antigen clearance, or chronic disease with less inflammation but the inability to eradicate the antigen and chronic stimulation of the immune response, resulting in organ damage such as lung fibrosis^[2].

Granulomatous inlammation is necessary/but not sufficient to establish a diagnosis of sarcoidosis in most cases^[3]. Histologic features that suggest sarcoidosis:

• Compact (organized) collection of mononuclear phagocytes (macrophages and epithelioid cells)
• No necrosis within the sarcoid granuloma
• Inclusions may be present within the sarcoid granuloma, including asteroid bodies, Schaumann bodies, birefringent crystals, and Hamazaki-Wesenberg bodies(neither specific nor diagnostic)
• Granulomatous inlammation in at least two organs(although not routinely performed)^[4]

The first histopathological finding in the lung is a CD4+ T cell alveolitis, followed by the development of noncaseating granuloma^[5] Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Roshan Dinparasti Saleh M.D.

Although sarcoidosis was first introduced as a clinical entity 140 years ago, the main cause of the disease remains elusive. The contributory factors are believed to be a combination of: antigens(environment), genetic factors, and the immune system.

Environmental factors

Because sarcoidosis commonly involves lung, eyes, and skin, several environmental/occupational exposures are believed to be associated with the risk for sarcoidosis:

• Rural setting, emmisions from wood-burning stove & firplace, tree pollen^[1][2]
• Inorganic particles^[3]
• Pesticides^[4]
• Mold exposure^[5]
• Navy personnel^[6]
• Firefighters and first responders involved in World Trade Center disaster^{[7][8][9][10]}
• Metalworking (especially tittanium)^[5]
• Photocopier exposure^[11]
• Hairdressers^[12]
• Healthcare workers^[13]

• Propionibacterium acnes^[14]
• Mycobacteria^[15][16][17].
• Hepatitis C virus^[18]

Genetic factors

Sarcoidosis is the result of environmental triggers acting upon an immunogenetically susceptible host^[19]. The importance of genetic factors in pathophysiology of sarcoidosis is supported by familial clusters of sarcoidosis^[20][21].

• The first-degree relatives are belived to be have 5 fold increased risk of developing sarcoidosis^[22].
• HLA-DRB1*1101 is associated with cardiac sarcoidosis and hypercalcemia^[23].
• HLA-DRB1*01 and HLA-DRB1*04 are protective against sarcoidosis^[24].
• In patients diagnosed with Lofgren’s Syndrome, HLA-DRB1*03 is 4 times higher than normal individuals^[25].^[26][27].
• BTNL-2(butyrophilin-like 2) gene, is associated with 23% of sarcoidosis risk in German individuals^[28].

Immune System

Sarcoidosis is the result of environmental triggers acting upon an immunogenetically susceptible host^[19].

• Higher expression of serum amyloid A which originates from macrophages and giant cells, is observed in sarcoidosis granuloma^[29].
• Immune system exhaustion and failure of effective antigen clearence, is proposed as a contributing mechanism for the disease. NK T-cells are depleted in sarcoidosis^[30].

Drug side effect

• Adalimumab^[31]
• Etanercept^[32][33]

• Ipilimumab^[34]
• Infliximab^[35]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]Roshan Dinparasti Saleh M.D.

Sarcoidosis has many differentials, which can be classified depending on the organ involved, pathologic findings and laboratory findings.

Sarcoidosis has been defined as a multisystem granulomatous disorder of unknown cause^[1], but granulomatous inflammation alone is not sufficient for the diagnosis of sarcoidosis because alternative etiologies of granulomatous inflammation need to be excluded.

• Mycobacterium tuberculosis
• Mycoplasma
• Pneumocystis jiroveci
• Brucellosis
• Cat-scratch fever
• Atypical mycobacteria
• Toxoplasmosis
• Berylliosis
• Hard metal
• Zirconium
• Tattoo
• Hypersensitivity pneumonitis
• Medications (e.g., methotrexate)
• ANCA-associated vasculitis
• Necrotizing sarcoid granuloma
• Lymphoma
• Cancer
• Granulomatous lesions of unknown significance
• Crohn’s disease
• Lymphocytic interstitial pneumonia
• Behçet’s disease
• Rheumatoid nodules^[1]

1. Demographics
   1. U.S. African American
   2. Northern European
2. Medical history
   1. Non-smoker
   2. No symptoms (in patient with bilateral hilar adenopathy on CXR)
   3. Family history of sarcoidosis
   4. Symptoms involving more than two organs commonly involved by sarcoidosis
3. Laboratory data
   1. Elevated ACE level (especially if > 2× ULN)
   2. Elevated calcium level
   3. Elevated alkaline phosphatase level
   4. Elevated soluble IL-2 receptor
   5. Leukopenia
4. Radiographic findings
   1. CXR:
      1. bilateral hilar adenopathy especially if without symptoms
      2. Upper lobe disease
   2. HRCT:
      1. Disease along bronchovascular bundle
      2. Subpleural reticulonodular infiltrates
      3. Mediastinal adenopathy
      4. Peribronchial thickening
      5. Traction bronchiectasis of upper lobe
5. Skin lesions
   1. Lupus pernio
   2. Erythema nodosum
   3. Maculopapular lesions
6. Ocular disease
   1. Uveitis
   2. Optic neuritis
7. Neurological disease
   1. Seventh cranial nerve palsy
8. Renal disease
   1. Nephrocalcinosis
   2. Interstitial nephritis^[2]

1. Demographics
   1. Age< 18 years

1. Medical history
   1. Exposure to tuberculosis
   2. Exposure to organic bioaerosol
   3. Exposure to beryllium
   4. Intravenous drug abuse

1. Laboratory data
   1. Positive anti-neutrophil cytoplasm antibody (ANCA)

1. Radiographic findings
   1. CXR:
      1. Pleural effusion
   2. HRCT:
      1. Subpleural honeycombing

1. Ocular disease
   1. Episcleritis

1. Renal disease
   1. Glomerulonephritis ^[2]

Spirometry

Low FEV1/FVC ratio

Normal to high FEV1/FVC ratio

Obstructive Lung Disease

Restrictive Lung Disease

Bronchodilator therapy

DLCO

Increased FEV1

No change in FEV1

Normal DLCO

Decreased DLCO

Asthma

COPD

Chest wall disorders

Interstitial Lung Disease

Disease		Clinical manifestations											Diagnosis
		Symptoms				Physical exam							Lab findings	Imaging			Gold standard
		Cough	Dyspnea	Hemoptysis	Fever	History/Exposure	Cyanosis	Clubbing	JVD	Peripheral edema	Auscultation	Other prominent findings		CXR	CT	DLCco
Hypersensitivity Pneumonitis		+	+	–	+	History of allergen exposure	–	+	–	–	Diffuse fine bibasilar crackles	Constitutional symptoms Weight loss Anorexia Muscle weakness	Neutrophilia Elevated ESR Elevated CRP Elevated immunoglobulin No peripheral blood eosinophilia	Poorly defined micronodular or diffuse interstitial pattern In chronic form Fibrosis Loss of lung volume Coarse linear opacities	Ground-glass opacities or Diffusely increased radiodensities Diffuse micronodules Focal air trapping Mosaic perfusion Occasionaly thin-walled cysts Mild fibrotic changes	↓	Clinical diagnosis
Acute Respiratory Distress Syndrome (ARDS)		–	+	–	–	Trauma Sepsis Drug overdose Massive transfusion Acute pancreatitis Aspiration	+	–	–	–	Coarse breath sounds Rhonchi crackles Decreased breath sounds	Initially respiratory alkalosis transforming to respiratory acidosis	BNP level of less than 100 pg/mL PaO2 / FiO2 <300 Leukopenia Leukocytosis Thrombocytopenia	Bilateral pulmonary infiltrates Initially patchy peripheral Later diffuse bilateral Ground glass Frank alveolar infiltrate	Bronchial dilatation within areas of ground-glass opacification	↓	PaO2 / FiO2 <300
Bronchitis	Acute	+	–	+/-	+	–	–	–	–	–	Diffuse wheezes High-pitched continuous sounds The use of accessory muscles  Prolonged expiration Rhonchi Rales	Hoarseness	N/A	Normal	N/A	–	Clinical diagnosis
	Chronic	+	+	–	–	A positive history of chronic productive cough  Shortness of breath	+	–	+	+	Prolonged expiration; wheezing Diffusely decreased breath sound Coarse crackles with inspiration Coarse rhonchi	N/A	Chronic hypoxemia may lead to polycythemia  Increase in Neutrophils count Chronic respiratory acidosis.	Radiolucency Diaphragmatic flattening due to hyperinflation Increased retrosternal airspace on the lateral radiograph	N/A	↓	N/A
Pneumoconiosis[3]	SIlicosis[4][5]	+	+	+/-	–	Occupational history Sandblasting Bystanders Quartzite miller Tunnel workers Silica flour workers Workers in the scouring powder industry	+	+	+	–	Hyperresonant Fine crackles Rhonchi Bronchial breath sounds Expiratory wheezing Increased tactile fremitus. Loud P2	Increased susceptiblity to tuberculosis.	Respiratory acidosis Abnormal sputum Anemia Neutrophilia Elevated ESR Elevated CRP Elevated immunoglobulin	Small round opacities Symmetrically distributed Upper-zone predominance Diffuse interstitial pattern of fibrosis without the typical nodular opacities in chronic case	Nodular changes in lung parenchyma Progressive massive fibrosis Bullae, emphysema Pleural, mediastinal, and hilar changes	↓	Lung biopsy
	Asbestosis					Shipyard workers Pipe fitting Insulators						Lung cancer Mesothelioma		Predilection to lower lobes Fine and coarse linear, peripheral, reticular opacities	Subpleural linear opacities seen parallel to the pleura Basilar lung fibrosis Peribronchiolar, intralobular, and interlobular septal fibrosis; Honeycombing Pleural plaques.
	Berylliosis					Electronic manufactures						–		Hilar adenopathy Increased interstitial markings.	Ground glass opacification Parenchymal nodules Septal lines
	Byssinosis					Cotton wool workers						Increased susceptibility to Actinomyces and Aspergillus infection.		Diffuse air-space consolidation	Pulmonary fibrosis with honeycombing Peri bronchovascular distribution of nodules Ground-glass attenuations
Sarcoidosis		+	+	+	+	African Americans Autoimmune	–	–	–	–	Usually normal Occasional crackles	Dermatologic manifestations Ocular involvement Osseous involvement Heart failure from cardiomyopathy Lymphocytic meningitis Cranial nerve palsies	Hypercalcemia or hypercalciuria  Elevated 1, 25-dihydroxyvitamin D levels Elevated angiotensin-converting enzyme (ACE)	Bilateral hilar lymphadenopathy	High-resolution CT (HRCT) scanning of the chest may identify Active alveolitis Fibrosis	↓	Biopsy
Pleural Effusion		+	+	+/-	+/-	Transudate CHF Cirrhosis Exudate Parapneumonic causes  Malignancy	+/-	+/-	+/-	+/-	Decreased tactile fremitus  Diminished or inaudible breath sounds Pleural friction rub	Peripheral edema, distended neck veins, and S3 gallop suggest congestive heart failure. Edema may also be a manifestation of nephrotic syndrome, pericardial disease, or, when combined with yellow nailbeds, the yellow nail syndrome. Cutaneous changes and ascites suggest liver disease. Lymphadenopathy or a palpable mass suggests malignancy.	Thoracentesis  Exudate Transudate LDH, glucose, cytology Other specific labs of underlying etiology	Supine Blunting of the costophrenic angle Homogenous increase in density spread over the lower lung fields Lateral decubitus Free flowing effusion as layers	Thickened pleura Mild effusions can aslo be detected	↓	Thoracocentesis
Interstitial (Nonidiopathic) Pulmonary Fibrosis		+	++	+	–	Connective-tissue disorder Pneumoconiosis	+	+	+	+	Wheezing S3 P2 End-inspiratory rales	Increased A-a gradient	Elevated ESR Serologic testing for ANA, RF, ANCA & ASCA may be positive	Reticular and/or nodular opacities Honeycomb appearance (late finding)	Bilateral reticular and nodular interstitial infiltrates	↓	Video-assisted thoracoscopic lung biopsy
Lymphocytic Interstitial Pneumonia[6]		+	+	+	+	Autoimmune Lymphoproliferative disorders	–	+	–	–	Wheezing Rales	Increased A-a gradient	Polyclonal hypergammaglobulinemia Increased LDH	Bibasilar interstitial or micronodular infiltrates	Determines the degree of fibrosis Cysts (characterstic)	N	Open lung biopsy
Obesity[7][8]		+	+	–	–	Overweight Diabetes mellitus Asthma	–	–	–	+	Wheezing	–	Increased hematocrit	X ray findings are often limited due to body habitus	CT findings are variable and depends upon severity of obesity	N	Clinical
Pulmonary Eosinophilia[9]		+	+	+	+	Infections Parasitic Fungal Mycobacterial	+	–	+	+	Wheezing Rales	Increased A-a gradient	Leukocytosis with eosinophilia (> 250/µL)	Interstitial or diffuse nodular densities	Determines extent and distribution of the disease Interstitial infiltrates Cysts and nodules	↓	Biopsy of lesion (skin or lung)
Neuromuscular disease	Scoliosis	–	+	–	–	Postural abnormality	–	–	–	–	Decreased breath sounds	In severe scoliosis, the rib cage may press against the lungs making it more difficult to breathe.	R/0 genetic conditions Marfan’s syndrome Edward’s syndrome Total lymphocyte count (should be >1500/μL) Nutritional status must be assessed	Accurate depiction of the true magnitude of the spinal deformity can be assessed by supine anteroposterior (AP) and lateral spinal radiographs	N/A	N	Clinical Radiographs
	Muscular dystrophy	–	+	–	–	Proximal muscle weakness	–	–	–	–	Decreased breath sounds	Rash	Elevated CPK and aldolase +ANA +Anti-Jo abs Elevated ESR, CRP and RF	N/A	N/A	N	Muscle biopsy
	ALS	–	+	–	–	Muscle weakness Neurological deficit	–	–	–	–	Decreased breath sounds	Symptoms begin with limb involvement diue to muscle weakness and atrophy.  Cognitive or behavioral dysfunction Sensory nerves and the autonomic nervous system are generally unaffected	N/A	Not significant/diagnostic	Not significant/diagnostic	–	Clinical diagnosis Nerve conduction studies and needle electromyography (EMG)
	Myasthenia gravis	–	+	–	+	H/O of difficulty getting up from chair Combing Difficulty in swallowing	–	–	–	–	Decreased breath sounds	Extraocular, bulbar, or proximal limb muscles. Breathing as rapid and shallow Respiratory muscle weakness can lead to acute respiratory failure may require immediate intubation.	Anti–acetylcholine receptor (AChR) antibody (Ab) test +	Thymoma as an anterior mediastinal mass.	Thymoma as an anterior mediastinal mass.	N	Electromyography

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Roshan Dinparasti Saleh M.D.

Sarcoidosis is a worldwide disease but there are some parts of the world and some ethnic groups which sarcoidosis is more common. Sarcoidosis is not common before adulthood. It is rarely diagnosed in patients younger than 10 years. In children the clinical picture is different from adult, mostly involving eyes(uveitis), skin and joints. Sarcoidosis is believed to be more common in women compared to men.

Sarcoidosis involves all ethnic groups over the world, but the incidence varies in different regions and/or ethnic groups^[1]. The annual incidence is highest in Northern Europe(5 to 40 cases per 100,000)^[2], whereas in Eastern Europe only 3.68 cases of sarcoidosis per 100,000 are reported^[3]. The global prevalence and incidence is difficult to calculate because of different diagnostic criteria and clinical heterogenicity. Many clinicians believe that the estimates of prevalence and incidence are lower than actual rates^[4].

• Sarcoidosis is not common before adulthood and in pediatric population it is usually diagnosed in patients older than 10 years with a peak of 13-15 year-old groups^[5]. In children there is a different clinical picture, involving mostly eyes(uveitis), joints and skin rather than lung and lung involvement is diagnosed incidentally by imaging studies^[6]. The most common finding in pediatric sarcoidosis is abnormal chest radiography^[7].
• The clinical scenario in juvenile-onset sarcoidosis is more similar to adult type^[8][9].
• In United States nearly half of the patients are older than 40 with a bimodal peaks of age of onset, 20-29 and 60-65^[1][10][11].

• Sarcoidosis is believed to be more common in women(57% of patients) compared to men^[12].
• Ocular and neurologic symptoms are more common in women^[13].

• The annual incidence of sarcoidosis in black americans compared to white americans is 3:1^[14][1].
• The prognosis is also more likely to be poor in black americans^[15].

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Roshan Dinparasti Saleh M.D.

Once thought rare, sarcoidosis is now known to be common and affects people worldwide. The disease can affect people of any age, race and gender. However, it is most common among adults between the ages of 20 and 40 and in certain ethnic groups.

• African americans^[1][2]
• People of Scandinavian descent^[3]
• Exposure to some dusty/moldy environments^[4][5]
• People between 25 and 40 years old^[6]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Roshan Dinparasti Saleh M.D.

According to the United States Preventive Services Task Force, screening for sarcoidosis is not recommended.

According to the United States Preventive Services Task Force, screening for sarcoidosis is not recommended.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Roshan Dinparasti Saleh M.D.

The overall mortality in sarcoidosis is low (about 5%), and many patients with spontaneous regression will never require treatment. Complications include pulmonary hypertension, fatigue, osteoporosis, aspergilloma, arrhythmias, and renal failure.

The overall mortality in sarcoidosis is low (about 5%), and many patients with spontaneous regression will never require treatment^[1]. In people who need treatment, important differences exist between African-American and white patients. African-American patients with sarcoidosis experience a more severe and systemic disease and 12 times higher mortality ^[2]

• SAPH: sarcoidosis-associated pulmonary hypertension^[3][4]
• Fatigue^[5]
• Osteoporosis^[6][7]
• Aspergilloma^[8][9][10]
• Ventricular arrhythmias^[11]
• Saddle nose defirmity
• Renal failure due to hypercalcemia and/or intersitial nephritis^[12]
• Lung fibrosis

• African-American patients with sarcoidosis experience a more severe and systemic disease and 12 times higher mortality ^[2]

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