Mixed connective tissue disease pathophysiology: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
{{CMG}}; {{AE}} {{SHH}} | {{CMG}}; {{AE}} {{SHH}} | ||
==Overview== | ==Overview== | ||
MCTD is a [[Systemic autoimmune diseases|systemic autoimmune disease]] that characterized by overlapping features between two or more [[systemic autoimmune diseases]] ([[Systemic lupus erythematosus|systemic lupus erythematosus (SLE)]], [[Rheumatoid arthritis|rheumatoid arthritis (RA)]], [[Dermatomyositis|dermatomyositis (DM)]], [[polymyositis]], and [[scleroderma]]) and the presence of [[antibodies]] against U1snRNP. | MCTD is a [[Systemic autoimmune diseases|systemic autoimmune disease]] that is characterized by overlapping features between two or more [[systemic autoimmune diseases]] ([[Systemic lupus erythematosus|systemic lupus erythematosus (SLE)]], [[Rheumatoid arthritis|rheumatoid arthritis (RA)]], [[Dermatomyositis|dermatomyositis (DM)]], [[polymyositis]], and [[scleroderma]]) and the presence of [[antibodies]] against U1snRNP. Primary pathogenetic mechanisms in mixed connective tissue disease include [[vasculopathy]] leading to tissue [[ischemia]], [[Immunology|immunological]] and [[Inflammation|inflammatory]] processes and excessive [[fibrosis]] caused by redundant synthesis of [[collagen]] and other [[Matrix protein|matrix proteins]]. In MCTD associated conditions include secondary [[Sjögren's syndrome|Sjogren’s syndrome]] and [[trigeminal neuralgia]]. A significant association of U1RNP disease with [[HLA-DR4]] and DR154-61 is noted. Gross pathology of skin may include photo-distributed erythematosus annular lesions and [[papulosquamous lesions]] and the [[Histopathology|histopathological]] abnormalities of [[Skin lesion|skin lesions]] include poor and [[Lichen|lichenoid]] interface [[dermatitis]] and suprabasilar [[exocytosis]] around [[Necrosis|necrotic]] [[Keratinocyte|keratinocytes]]. | ||
==Pathophysiology== | ==Pathophysiology== | ||
| Line 10: | Line 10: | ||
===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 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 a [[Systemic autoimmune diseases|systemic autoimmune disease]] that is 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|systemic lupus erythematosus (SLE)]], [[Rheumatoid arthritis|rheumatoid arthritis (RA)]], [[Dermatomyositis|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]]. | ||
* | * Primary pathogenetic mechanisms in mixed connective tissue disease include: | ||
** [[Vasculopathy]] | ** [[Vasculopathy]] leading to tissue [[ischemia]] | ||
** [[Immunology|Immunological]] and [[Inflammation|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 protein|matrix proteins]] | ** Excessive [[fibrosis]] caused by redundant synthesis of [[collagen]] and other [[Matrix protein|matrix proteins]] | ||
Revision as of 15:33, 30 April 2018
|
Mixed connective tissue disease Microchapters |
|
Differentiating Mixed connective tissue disease from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Mixed connective tissue disease pathophysiology On the Web |
|
American Roentgen Ray Society Images of Mixed connective tissue disease pathophysiology |
|
Directions to Hospitals Treating Mixed connective tissue disease |
|
Risk calculators and risk factors for Mixed connective tissue disease pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shaghayegh Habibi, M.D.[2]
Overview
MCTD is a systemic autoimmune disease that is characterized by overlapping features between two or more systemic autoimmune diseases (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), dermatomyositis (DM), polymyositis, and scleroderma) and the presence of antibodies against U1snRNP. Primary pathogenetic mechanisms in mixed connective tissue disease include vasculopathy leading to tissue ischemia, immunological and inflammatory processes and excessive fibrosis caused by redundant synthesis of collagen and other matrix proteins. In MCTD associated conditions include secondary Sjogren’s syndrome and trigeminal neuralgia. A significant association of U1RNP disease with HLA-DR4 and DR154-61 is noted. Gross pathology of skin may include photo-distributed erythematosus annular lesions and papulosquamous lesions and the histopathological abnormalities of skin lesions include poor and lichenoid interface dermatitis and suprabasilar exocytosis around necrotic keratinocytes.
Pathophysiology
Pathogenesis
The pathogenesis of mixed connective tissue disease is as follows:[1][2][3][4]
- MCTD is a systemic autoimmune disease that is 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.
- Primary pathogenetic mechanisms in mixed connective tissue disease include:
- Vasculopathy leading 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.