Mixed connective tissue disease pathophysiology: Difference between revisions
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===Pathogenesis=== | ===Pathogenesis=== | ||
The pathogenesis of mixed connective tissue disease is as follows:<ref name="pmid24461387">{{cite journal |vauthors=Tani C, Carli L, Vagnani S, Talarico R, Baldini C, Mosca M, Bombardieri S |title=The diagnosis and classification of mixed connective tissue disease |journal=J. Autoimmun. |volume=48-49 |issue= |pages=46–9 |date=2014 |pmid=24461387 |doi=10.1016/j.jaut.2014.01.008 |url=}}</ref><ref name="pmid26245523">{{cite journal |vauthors=Thongpooswan S, Tushabe R, Song J, Kim P, Abrudescu A |title=Mixed Connective Tissue Disease and Papillary Thyroid Cancer: A Case Report |journal=Am J Case Rep |volume=16 |issue= |pages=517–9 |date=August 2015 |pmid=26245523 |pmc=4530986 |doi=10.12659/AJCR.894176 |url=}}</ref><ref name="pmid243534962">{{cite journal |vauthors=Latuśkiewicz-Potemska J, Zygmunt A, Biernacka-Zielińska M, Stańczyk J, Smolewska E |title=Mixed connective tissue disease presenting with progressive scleroderma symptoms in a 10-year-old girl |journal=Postepy Dermatol Alergol |volume=30 |issue=5 |pages=329–36 |date=October 2013 |pmid=24353496 |pmc=3858664 |doi=10.5114/pdia.2013.38365 |url=}}</ref><ref name="pmid27436003">{{cite journal |vauthors=Ciang NC, Pereira N, Isenberg DA |title=Mixed connective tissue disease-enigma variations? |journal=Rheumatology (Oxford) |volume=56 |issue=3 |pages=326–333 |date=March 2017 |pmid=27436003 |doi=10.1093/rheumatology/kew265 |url=}}</ref> | The [[pathogenesis]] of mixed connective tissue disease is as follows:<ref name="pmid24461387">{{cite journal |vauthors=Tani C, Carli L, Vagnani S, Talarico R, Baldini C, Mosca M, Bombardieri S |title=The diagnosis and classification of mixed connective tissue disease |journal=J. Autoimmun. |volume=48-49 |issue= |pages=46–9 |date=2014 |pmid=24461387 |doi=10.1016/j.jaut.2014.01.008 |url=}}</ref><ref name="pmid26245523">{{cite journal |vauthors=Thongpooswan S, Tushabe R, Song J, Kim P, Abrudescu A |title=Mixed Connective Tissue Disease and Papillary Thyroid Cancer: A Case Report |journal=Am J Case Rep |volume=16 |issue= |pages=517–9 |date=August 2015 |pmid=26245523 |pmc=4530986 |doi=10.12659/AJCR.894176 |url=}}</ref><ref name="pmid243534962">{{cite journal |vauthors=Latuśkiewicz-Potemska J, Zygmunt A, Biernacka-Zielińska M, Stańczyk J, Smolewska E |title=Mixed connective tissue disease presenting with progressive scleroderma symptoms in a 10-year-old girl |journal=Postepy Dermatol Alergol |volume=30 |issue=5 |pages=329–36 |date=October 2013 |pmid=24353496 |pmc=3858664 |doi=10.5114/pdia.2013.38365 |url=}}</ref><ref name="pmid27436003">{{cite journal |vauthors=Ciang NC, Pereira N, Isenberg DA |title=Mixed connective tissue disease-enigma variations? |journal=Rheumatology (Oxford) |volume=56 |issue=3 |pages=326–333 |date=March 2017 |pmid=27436003 |doi=10.1093/rheumatology/kew265 |url=}}</ref> | ||
* MCTD is a systemic | * MCTD is a [[Systemic autoimmune diseases|systemic autoimmune disease]] that characterized by overlapping features between two or more [[systemic autoimmune diseases]] and the presence of [[antibodies]] against the U1 small nuclear ribonucleoprotein autoantigen (U1snRNP). | ||
* MCTD is characterized by clinical features seen in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), dermatomyositis (DM), polymyositis, and scleroderma. | * MCTD is characterized by clinical features seen in [[Systemic lupus erythematosus|systemic lupus erythematosus (SLE)]], [[Rheumatoid arthritis|rheumatoid arthritis (RA)]], [[Dermatomyositis|dermatomyositis (DM)]], [[polymyositis]], and [[scleroderma]]. | ||
* Main pathogenetic mechanisms in mixed connective tissue disease include: | * Main pathogenetic mechanisms in mixed connective tissue disease include: | ||
** Vasculopathy which leads to tissue ischemia | ** [[Vasculopathy]] which leads to tissue [[ischemia]] | ||
** Immunological and inflammatory processes deriving from autoimmunity | ** [[Immunology|Immunological]] and [[Inflammation|inflammatory]] processes deriving from [[autoimmunity]] | ||
** Excessive fibrosis caused by redundant synthesis of collagen and other matrix proteins | ** Excessive [[fibrosis]] caused by redundant synthesis of [[collagen]] and other [[Matrix protein|matrix proteins]] | ||
*In MCTD, components of U1-snRNP are important for triggering immune responses. Anti-RNP has a central pathogenic role and may contribute to disease manifestations. | *In MCTD, components of U1-snRNP are important for triggering [[Immune system|immune responses]]. Anti-RNP has a central [[Pathogenicity|pathogenic]] role and may contribute to disease manifestations. | ||
*Development of pulmonary hypertension and interstitial lung disease are the most frequent cause of death. | *Development of [[pulmonary hypertension]] and [[interstitial lung disease]] are the most frequent cause of death. | ||
==Genetics== | ==Genetics== | ||
*In MCTD, the frequency of HLA-DR4 is increased compared with healthy controls in worldwide population-based studies.<ref name="pmid27436003">{{cite journal |vauthors=Ciang NC, Pereira N, Isenberg DA |title=Mixed connective tissue disease-enigma variations? |journal=Rheumatology (Oxford) |volume=56 |issue=3 |pages=326–333 |date=March 2017 |pmid=27436003 |doi=10.1093/rheumatology/kew265 |url=}}</ref> | *In MCTD, the frequency of [[HLA-DR4]] is increased compared with healthy controls in worldwide population-based studies.<ref name="pmid27436003">{{cite journal |vauthors=Ciang NC, Pereira N, Isenberg DA |title=Mixed connective tissue disease-enigma variations? |journal=Rheumatology (Oxford) |volume=56 |issue=3 |pages=326–333 |date=March 2017 |pmid=27436003 |doi=10.1093/rheumatology/kew265 |url=}}</ref> | ||
*A significant association of U1RNP disease with HLA-DR4 and DR154-61 is noted. | *A significant association of U1RNP disease with [[HLA-DR4]] and DR154-61 is noted. | ||
==Associated Conditions== | ==Associated Conditions== | ||
In MCTD associated conditions include:<ref name="pmid243534962">{{cite journal |vauthors=Latuśkiewicz-Potemska J, Zygmunt A, Biernacka-Zielińska M, Stańczyk J, Smolewska E |title=Mixed connective tissue disease presenting with progressive scleroderma symptoms in a 10-year-old girl |journal=Postepy Dermatol Alergol |volume=30 |issue=5 |pages=329–36 |date=October 2013 |pmid=24353496 |pmc=3858664 |doi=10.5114/pdia.2013.38365 |url=}}</ref> | In MCTD associated conditions include:<ref name="pmid243534962">{{cite journal |vauthors=Latuśkiewicz-Potemska J, Zygmunt A, Biernacka-Zielińska M, Stańczyk J, Smolewska E |title=Mixed connective tissue disease presenting with progressive scleroderma symptoms in a 10-year-old girl |journal=Postepy Dermatol Alergol |volume=30 |issue=5 |pages=329–36 |date=October 2013 |pmid=24353496 |pmc=3858664 |doi=10.5114/pdia.2013.38365 |url=}}</ref> | ||
*Secondary Sjogren’s syndrome | *Secondary [[Sjögren's syndrome|Sjogren’s syndrome]] | ||
*Trigeminal neuralgia | *[[Trigeminal neuralgia]] | ||
==Gross Pathology== | ==Gross Pathology== | ||
*In MCTD, gross pathology of skin may include:<ref name="pmid9185904">{{cite journal |vauthors=Magro CM, Crowson AN, Regauer S |title=Mixed connective tissue disease. A clinical, histologic, and immunofluorescence study of eight cases |journal=Am J Dermatopathol |volume=19 |issue=3 |pages=206–13 |date=June 1997 |pmid=9185904 |doi= |url=}}</ref> | *In MCTD, gross pathology of skin may include:<ref name="pmid9185904">{{cite journal |vauthors=Magro CM, Crowson AN, Regauer S |title=Mixed connective tissue disease. A clinical, histologic, and immunofluorescence study of eight cases |journal=Am J Dermatopathol |volume=19 |issue=3 |pages=206–13 |date=June 1997 |pmid=9185904 |doi= |url=}}</ref> | ||
**Photo-distributed erythematosus annular | **Photo-distributed erythematosus annular lesions | ||
**Papulosquamous lesions | **[[Papulosquamous lesions]] | ||
==Microscopic Pathology== | ==Microscopic Pathology== | ||
*In MCTD, histopathological abnormalities of | *In MCTD, [[Histopathology|histopathological]] abnormalities of [[interstitial lung disease]] are similar to those seen in [[Idiopathic pulmonary fibrosis|idiopathic pulmonary fibrosis (IPF)]], including:<ref name="pmid15716315">{{cite journal |vauthors=Bodolay E, Szekanecz Z, Dévényi K, Galuska L, Csípo I, Vègh J, Garai I, Szegedi G |title=Evaluation of interstitial lung disease in mixed connective tissue disease (MCTD) |journal=Rheumatology (Oxford) |volume=44 |issue=5 |pages=656–61 |date=May 2005 |pmid=15716315 |doi=10.1093/rheumatology/keh575 |url=}}</ref> | ||
**Alveolar septal infiltration by lymphocytes and plasma cells | **[[Alveolus|Alveolar]] [[Septum|septal]] infiltration by [[Lymphocyte|lymphocytes]] and [[Plasma cell|plasma cells]] | ||
**Deposition of type III collagen | **Deposition of [[Type-III collagen|type III collagen]] | ||
*In MCTD, histopathological abnormalities of skin lesions are similar to that of subacute cutaneous lupus erythematosus (SCLE), include:<ref name="pmid9185904">{{cite journal |vauthors=Magro CM, Crowson AN, Regauer S |title=Mixed connective tissue disease. A clinical, histologic, and immunofluorescence study of eight cases |journal=Am J Dermatopathol |volume=19 |issue=3 |pages=206–13 |date=June 1997 |pmid=9185904 |doi= |url=}}</ref> | *In MCTD, [[Histopathology|histopathological]] abnormalities of [[Skin lesion|skin lesions]] are similar to that of [[Subacute cutaneous lupus erythematosus|subacute cutaneous lupus erythematosus (SCLE)]], include:<ref name="pmid9185904">{{cite journal |vauthors=Magro CM, Crowson AN, Regauer S |title=Mixed connective tissue disease. A clinical, histologic, and immunofluorescence study of eight cases |journal=Am J Dermatopathol |volume=19 |issue=3 |pages=206–13 |date=June 1997 |pmid=9185904 |doi= |url=}}</ref> | ||
**Poor and lichenoid interface dermatitis | **Poor and [[Lichen|lichenoid]] interface [[dermatitis]] | ||
**Suprabasilar exocytosis around necrotic keratinocytes (in the absence of deep periadnexal or perivascular extension or conspicuous follicular plugging) | **Suprabasilar [[exocytosis]] around [[Necrosis|necrotic]] [[Keratinocyte|keratinocytes]] (in the absence of deep periadnexal or [[Perivascular cell|perivascular]] extension or conspicuous follicular plugging) | ||
==References== | ==References== | ||
Revision as of 16:41, 12 April 2018
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shaghayegh Habibi, M.D.[2]
Overview
Pathophysiology
Pathogenesis
The pathogenesis of mixed connective tissue disease is as follows:[1][2][3][4]
- MCTD is a systemic autoimmune disease that characterized by overlapping features between two or more systemic autoimmune diseases and the presence of antibodies against the U1 small nuclear ribonucleoprotein autoantigen (U1snRNP).
- MCTD is characterized by clinical features seen in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), dermatomyositis (DM), polymyositis, and scleroderma.
- Main pathogenetic mechanisms in mixed connective tissue disease include:
- Vasculopathy which leads to tissue ischemia
- Immunological and inflammatory processes deriving from autoimmunity
- Excessive fibrosis caused by redundant synthesis of collagen and other matrix proteins
- In MCTD, components of U1-snRNP are important for triggering immune responses. Anti-RNP has a central pathogenic role and may contribute to disease manifestations.
- Development of pulmonary hypertension and interstitial lung disease are the most frequent cause of death.
Genetics
- In MCTD, the frequency of HLA-DR4 is increased compared with healthy controls in worldwide population-based studies.[4]
- A significant association of U1RNP disease with HLA-DR4 and DR154-61 is noted.
Associated Conditions
In MCTD associated conditions include:[3]
- Secondary Sjogren’s syndrome
- Trigeminal neuralgia
Gross Pathology
- In MCTD, gross pathology of skin may include:[5]
- Photo-distributed erythematosus annular lesions
- Papulosquamous lesions
Microscopic Pathology
- In MCTD, histopathological abnormalities of interstitial lung disease are similar to those seen in idiopathic pulmonary fibrosis (IPF), including:[6]
- Alveolar septal infiltration by lymphocytes and plasma cells
- Deposition of type III collagen
- In MCTD, histopathological abnormalities of skin lesions are similar to that of subacute cutaneous lupus erythematosus (SCLE), include:[5]
- Poor and lichenoid interface dermatitis
- Suprabasilar exocytosis around necrotic keratinocytes (in the absence of deep periadnexal or perivascular extension or conspicuous follicular plugging)
References
- ↑ Tani C, Carli L, Vagnani S, Talarico R, Baldini C, Mosca M, Bombardieri S (2014). "The diagnosis and classification of mixed connective tissue disease". J. Autoimmun. 48-49: 46–9. doi:10.1016/j.jaut.2014.01.008. PMID 24461387.
- ↑ Thongpooswan S, Tushabe R, Song J, Kim P, Abrudescu A (August 2015). "Mixed Connective Tissue Disease and Papillary Thyroid Cancer: A Case Report". Am J Case Rep. 16: 517–9. doi:10.12659/AJCR.894176. PMC 4530986. PMID 26245523.
- ↑ 3.0 3.1 Latuśkiewicz-Potemska J, Zygmunt A, Biernacka-Zielińska M, Stańczyk J, Smolewska E (October 2013). "Mixed connective tissue disease presenting with progressive scleroderma symptoms in a 10-year-old girl". Postepy Dermatol Alergol. 30 (5): 329–36. doi:10.5114/pdia.2013.38365. PMC 3858664. PMID 24353496.
- ↑ 4.0 4.1 Ciang NC, Pereira N, Isenberg DA (March 2017). "Mixed connective tissue disease-enigma variations?". Rheumatology (Oxford). 56 (3): 326–333. doi:10.1093/rheumatology/kew265. PMID 27436003.
- ↑ 5.0 5.1 Magro CM, Crowson AN, Regauer S (June 1997). "Mixed connective tissue disease. A clinical, histologic, and immunofluorescence study of eight cases". Am J Dermatopathol. 19 (3): 206–13. PMID 9185904.
- ↑ Bodolay E, Szekanecz Z, Dévényi K, Galuska L, Csípo I, Vègh J, Garai I, Szegedi G (May 2005). "Evaluation of interstitial lung disease in mixed connective tissue disease (MCTD)". Rheumatology (Oxford). 44 (5): 656–61. doi:10.1093/rheumatology/keh575. PMID 15716315.