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{{Sarcoidosis}}
{{Sarcoidosis}}
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{{CMG}} {{AE}}Roshan Dinparasti Saleh M.D.
 
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==Overview==
==Overview==
==Pathophysiology==
[[Sarcoidosis]] is a multisystem disorder of unknown etiology characterized by [[noncaseating granuloma]]s 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]].  
No direct cause of sarcoidosis has been identified, although there have been reports of cell wall deficient [[bacteria]] that may be possible pathogens.<ref>Almenoff PL, Johnson A, Lesser M, Mattman LH. ''Growth of acid fast L forms from the blood of patients with sarcoidosis.'' Thorax 1996;51:530-3. PMID 8711683.</ref> These bacteria are not identified in standard laboratory analysis. It has been thought that there may be a hereditary factor because some families have multiple members with sarcoidosis. To date, no reliable genetic markers have been identified, and an alternate hypothesis is that family members share similar exposures to environmental pathogens. There have also been reports of transmission of sarcoidosis via [[organ transplant]]s.<ref>Padilla ML, Schilero GJ, Teirstein AS. ''Donor-acquired sarcoidosis.'' Sarcoidosis Vasc Diffuse Lung Dis 2002;19:18-24. PMID 12002380.</ref>
 
Sarcoid granulomas are suggested to have formed with HLA-mediated processing of antigens by macrophages.<ref>Goldman's Cecil Medicine,24th Edition.</ref>. The process is driven by CD4+ helper T cells. There is increased levels of T cell–derived TH1 cytokines such as IL-2 and IFN-γ, resulting in T-cell expansion and macrophage activation, respectively. Increased levels of several cytokines in the local environment (IL-8, TNF, macrophage inflammatory protein 1α) that favor recruitment of additional T cells and monocytes and contribute to the formation of granulomas. TNF in particular is released at high levels by activated alveolar macrophages.<ref>Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition, 8th ed.</ref><ref name="pmid21750528">{{cite journal| author=Chen ES, Moller DR, Medscape| title=Sarcoidosis--scientific progress and clinical challenges. | journal=Nat Rev Rheumatol | year= 2011 | volume= 7 | issue= 8 | pages= 457-67 | pmid=21750528 | doi=10.1038/nrrheum.2011.93 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21750528  }} </ref>
 
Sarcoidosis frequently causes a dysregulation of [[vitamin D]] production with an increase in extrarenal (outside the kidney) production.<ref>Barbour GL, Coburn JW, Slatopolsky E, Norman AW, Horst RL. ''Hypercalcemia in an anephric patient with sarcoidosis: evidence for extrarenal generation of 1,25-dihydroxyvitamin D.'' N Engl J Med 1981;305:440-3. PMID 6894783.</ref> Specifically, [[macrophages]] inside the granulomas convert vitamin D to its active form, resulting in elevated levels of the hormone 1,25-dihydroxyvitamin D and symptoms of [[hypervitaminosis D]] that may include [[fatigue (physical)|fatigue]], [[lack of strength]] or energy, [[irritability]], [[metallic taste]], temporary [[memory loss]] or cognitive problems. Physiological compensatory responses (e.g. suppression of the [[parathyroid hormone]] levels) may mean the patient does not develop frank [[hypercalcemia]].
 
Sarcoidosis has been associated with [[celiac disease]]. Celiac disease is a condition in which there is a chronic reaction to certain protein chains, commonly referred to as glutens, found in some cereal grains. This reaction causes destruction of the villi in the small intestine, with resulting malabsorption of nutrients.


While disputed, some cases have been determined to be caused by inhalation of the dust from the collapse of the World Trade Center after the September 11, 2001 attacks.<ref>[http://www.nytimes.com/2007/05/24/nyregion/24dust.html ''New York Times'' article, May 24, 2007]</ref> ''See [[Health effects arising from the September 11, 2001 attacks]] for more information.''
==Pathophysiology==
[[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 [[granuloma]]s. 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]] <ref>Iannuzzi MC, Rybicki BA, Teirstein AS: Sarcoidosis. N Engl J Med 357:2153–2165, 2007.</ref>.
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]]<ref>Zissel G: Cellular activation in the immune response of sarcoidosis. Semin Respir Crit Care Med 35:307–315, 2014.</ref>.


Gallium-67 citrate is useful for diagnosing suspected sarcoidosis and evaluation of treatment response. It is more sensitive than radiographic images on diagnosis of Sarcoidosis.


==Histopathological Findings==
==Histopathological Findings==
[[Granulomatous inlammation]] is necessary/but not sufficient to establish a diagnosis of [[sarcoidosis]] in most cases<ref>Statement on sarcoidosis: Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med
160:736–755, 1999.</ref>. 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)<ref>Rosen Y: Pathology of sarcoidosis. Semin Respir Crit Care Med 28(1):36–52, 2007.</ref>


The first histopathological finding in the lung is a [[CD4+ T cell]] [[alveolitis]], followed by the development of [[noncaseating granuloma]]<ref>Thomas PD, Hunninghake GW: Current concepts of the pathogenesis of sarcoidosis. The American review of respiratory disease 1987, 135(3):747-760.</ref>
[http://www.peir.net Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
[http://www.peir.net Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]


[[Image:Sarcoidosis lymph node case 001.jpg|left|thumb|400px|This is a low-power photomicrograph of a lymph node. Note the rather pale-pink color of the tissue with dark-staining cells found in only a few scattered areas. These darker cells represent the original lymphocytes of this lymphoid organ.]]
[[Image:Sarcoidosis lymph node case 001.jpg|left|thumb|400px|This is a low-power photomicrograph of a lymph node. Note the rather pale-pink color of the tissue with dark-staining cells found in only a few scattered areas. These darker cells represent the original lymphocytes of this lymphoid organ.]]
<br clear="left"/>
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[[Image:Sarcoidosis lymph node case 002.jpg|left|thumb|400px|This photomicrograph of lymph node tissue illustrates a paucity of lymphocytes as well as numerous small, pale-staining nodules (arrows) throughout the tissue.]]
[[Image:Sarcoidosis lymph node case 002.jpg|left|thumb|400px|This photomicrograph of lymph node tissue illustrates a paucity of lymphocytes as well as numerous small, pale-staining nodules (arrows) throughout the tissue.]]
<br clear="left"/>
<br clear="left" />


[[Image:Sarcoidosis lymph node case 003.jpg|left|thumb|400px|This is a photomicrograph of the small nodules (arrows) seen in the previous image. Close examination reveals that they are composed of large macrophages (epithelioid macrophages). These small granulomas form multiple series of reaction centers throughout the lymph node. Note the remaining lymphocytes surrounding the granulomas.]]
[[Image:Sarcoidosis lymph node case 003.jpg|left|thumb|400px|This is a photomicrograph of the small nodules (arrows) seen in the previous image. Close examination reveals that they are composed of large macrophages (epithelioid macrophages). These small granulomas form multiple series of reaction centers throughout the lymph node. Note the remaining lymphocytes surrounding the granulomas.]]
<br clear="left"/>
<br clear="left" />


[[Image:Sarcoidosis lymph node case 004.jpg|left|thumb|400px|This photomicrograph of a single granuloma illustrates the individual macrophages (arrows) which make up the bulk of this tissue. There is an absence of necrosis in the center of the lesions in this case.]]
[[Image:Sarcoidosis lymph node case 004.jpg|left|thumb|400px|This photomicrograph of a single granuloma illustrates the individual macrophages (arrows) which make up the bulk of this tissue. There is an absence of necrosis in the center of the lesions in this case.]]
<br clear="left"/>
<br clear="left" />


[[Image:Sarcoidosis lymph node case 005.jpg|left|thumb|400px|This is a photomicrograph of a multinucleated giant cell (1). In the center of this foreign body-containing giant cell there is a small asteroid body (2). There is no functional significance to this asteroid body.]]
[[Image:Sarcoidosis lymph node case 005.jpg|left|thumb|400px|This is a photomicrograph of a multinucleated giant cell (1). In the center of this foreign body-containing giant cell there is a small asteroid body (2). There is no functional significance to this asteroid body.]]
<br clear="left"/>
<br clear="left" />


[[Image:Sarcoidosis lymph node case 006.jpg|left|thumb|400px|This is a higher-power photomicrograph of an asteroid body (arrow) inside of a multinucleated giant cell.]]
[[Image:Sarcoidosis lymph node case 006.jpg|left|thumb|400px|This is a higher-power photomicrograph of an asteroid body (arrow) inside of a multinucleated giant cell.]]
<br clear="left"/>
<br clear="left" />


==References==
==References==
{{Reflist|2}}


{{Reflist|2}}
[[Category:Needs content]]
[[Category:Ailments of unknown etiology]]
[[Category:Pulmonology]]
[[Category:Pulmonology]]
[[Category:Abdominal pain]]
[[Category:Rheumatology]]
[[Category:Rheumatology]]


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Latest revision as of 21:48, 14 May 2018

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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.

Overview

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.

Pathophysiology

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].


Histopathological Findings

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

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

This is a low-power photomicrograph of a lymph node. Note the rather pale-pink color of the tissue with dark-staining cells found in only a few scattered areas. These darker cells represent the original lymphocytes of this lymphoid organ.


This photomicrograph of lymph node tissue illustrates a paucity of lymphocytes as well as numerous small, pale-staining nodules (arrows) throughout the tissue.


This is a photomicrograph of the small nodules (arrows) seen in the previous image. Close examination reveals that they are composed of large macrophages (epithelioid macrophages). These small granulomas form multiple series of reaction centers throughout the lymph node. Note the remaining lymphocytes surrounding the granulomas.


This photomicrograph of a single granuloma illustrates the individual macrophages (arrows) which make up the bulk of this tissue. There is an absence of necrosis in the center of the lesions in this case.


This is a photomicrograph of a multinucleated giant cell (1). In the center of this foreign body-containing giant cell there is a small asteroid body (2). There is no functional significance to this asteroid body.


This is a higher-power photomicrograph of an asteroid body (arrow) inside of a multinucleated giant cell.


References

  1. Iannuzzi MC, Rybicki BA, Teirstein AS: Sarcoidosis. N Engl J Med 357:2153–2165, 2007.
  2. Zissel G: Cellular activation in the immune response of sarcoidosis. Semin Respir Crit Care Med 35:307–315, 2014.
  3. Statement on sarcoidosis: Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med 160:736–755, 1999.
  4. Rosen Y: Pathology of sarcoidosis. Semin Respir Crit Care Med 28(1):36–52, 2007.
  5. Thomas PD, Hunninghake GW: Current concepts of the pathogenesis of sarcoidosis. The American review of respiratory disease 1987, 135(3):747-760.

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