Mixed connective tissue disease pathophysiology: Difference between revisions
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{{CMG}}; {{AE}} {{SHH}} | {{CMG}}; {{AE}} {{SHH}} | ||
==Overview== | ==Overview== | ||
MCTD is a [[Systemic autoimmune diseases|systemic autoimmune disease]] that is characterized by overlapping symptoms of 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 pathogenesis in MCTD include [[vasculopathy]] leading to tissue [[ischemia]], [[Immunology|immunological]] and [[Inflammation|inflammatory]] processes and [[fibrosis]] caused by excessive synthesis of [[collagen]] and other [[Matrix protein|proteins of matrix]]. In MCTD associated conditions include secondary [[Sjögren's syndrome|Sjogren’s syndrome]] and [[trigeminal neuralgia]]. A significant association between U1RNP disease and [[HLA-DR4]] and DR154-61 is detected. [[Gross pathology]] of skin may include photo-distributed erythematosus annular lesions, [[papulosquamous lesions]], [[Telangiectasia]], and [[Sclerodactyly]] and the skin [[Histopathology|histopathological]] findings include poor and [[Lichen|lichenoid]] interface [[dermatitis]] and suprabasilar [[exocytosis]] around [[Necrosis|necrotic]] [[Keratinocyte|keratinocytes]]. | |||
==Pathophysiology== | ==Pathophysiology== | ||
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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 autoimmune diseases|systemic autoimmune disease]] that characterized by | * MCTD is a [[Systemic autoimmune diseases|systemic autoimmune disease]] that is characterized by: | ||
* MCTD is characterized by clinical | ** Overlapping symptoms of two or more [[systemic autoimmune diseases]] | ||
* | ** Presence of [[antibodies]] against the U1 small nuclear ribonucleoprotein autoantigen (U1snRNP) | ||
** [[Vasculopathy]] | * MCTD is characterized by clinical symptoms seen in [[Systemic lupus erythematosus|systemic lupus erythematosus (SLE)]], [[Rheumatoid arthritis|rheumatoid arthritis (RA)]], [[Dermatomyositis|dermatomyositis (DM)]], [[polymyositis]], and [[scleroderma]]. | ||
** [[Immunology| | * Primary pathogenesis in MCTD include: | ||
** | ** [[Vasculopathy]] leading to tissue [[ischemia]] | ||
*In MCTD, | ** [[Autoimmunity]] causes [[Immunology|immunological]] and [[Inflammation|inflammatory]] | ||
** [[fibrosis]] caused by excessive synthesis of [[collagen]] and other [[Matrix protein|proteins of matrix]] | |||
*In MCTD, U1-snRNP components play an important role for triggering [[Immune system|immune responses]]. | |||
*Two [[Complication (medicine)|complications]] of [[pulmonary hypertension]] and [[interstitial lung disease]] are the most frequent causes of death. | |||
==Genetics== | ==Genetics== | ||
*In MCTD, the frequency of [[HLA-DR4]] is increased compared with healthy | *In MCTD, the frequency of [[HLA-DR4]] is increased compared with healthy individuals in worldwide 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 | *A significant association between U1RNP disease and [[HLA-DR4]] and DR154-61 is detected. | ||
==Associated Conditions== | ==Associated Conditions== | ||
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*[[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><ref name="pmid23756459">{{cite journal |vauthors=Dabiri G, Falanga V |title=Connective tissue ulcers |journal=J Tissue Viability |volume=22 |issue=4 |pages=92–102 |date=November 2013 |pmid=23756459 |pmc=3930159 |doi=10.1016/j.jtv.2013.04.003 |url=}}</ref> | ||
**Photo-distributed erythematosus annular lesions | **Photo-distributed erythematosus annular lesions | ||
**[[Papulosquamous lesions]] | **[[Papulosquamous lesions]] | ||
** [[Telangiectasia]] | |||
** [[Sclerodactyly]] | |||
==Microscopic Pathology== | ==Microscopic Pathology== | ||
*In MCTD, [[Histopathology|histopathological]] | *In MCTD, [[Histopathology|histopathological]] features of [[interstitial lung disease]] are similar to [[Idiopathic pulmonary fibrosis|idiopathic pulmonary fibrosis (IPF)]]. The findings 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> | ||
**[[ | **Infiltration of [[Lymphocyte|lymphocytes]] and [[Plasma cell|plasma cells]] in [[Alveolus|alveolar]] [[Septum|septum]] | ||
**Deposition of [[Type-III collagen|type III collagen]] | **Deposition of [[Type-III collagen|type III collagen]] | ||
*In MCTD, [[Histopathology|histopathological]] | *In MCTD, skin [[Histopathology|histopathological]] characteristics are similar to [[Subacute cutaneous lupus erythematosus|subacute cutaneous lupus erythematosus (SCLE)]]. The findings 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 [[Lichen|lichenoid]] interface [[dermatitis]] | **Poor and [[Lichen|lichenoid]] interface [[dermatitis]] | ||
**Suprabasilar [[exocytosis]] around [[Necrosis|necrotic]] [[Keratinocyte|keratinocytes]] | **Suprabasilar [[exocytosis]] around [[Necrosis|necrotic]] [[Keratinocyte|keratinocytes]] | ||
==References== | ==References== | ||
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{{WH}} | {{WH}} | ||
{{WS}} | {{WS}} | ||
[[Category: | [[Category:Medicine]] | ||
[[Category:Up-To-Date]] | |||
[[Category:Rheumatology]] | |||
Latest revision as of 14:03, 7 May 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
MCTD is a systemic autoimmune disease that is characterized by overlapping symptoms of two or more systemic autoimmune diseases (SLE, RA, DM, polymyositis, and scleroderma) and the presence of antibodies against U1snRNP. Primary pathogenesis in MCTD include vasculopathy leading to tissue ischemia, immunological and inflammatory processes and fibrosis caused by excessive synthesis of collagen and other proteins of matrix. In MCTD associated conditions include secondary Sjogren’s syndrome and trigeminal neuralgia. A significant association between U1RNP disease and HLA-DR4 and DR154-61 is detected. Gross pathology of skin may include photo-distributed erythematosus annular lesions, papulosquamous lesions, Telangiectasia, and Sclerodactyly and the skin histopathological findings 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 symptoms of two or more systemic autoimmune diseases
- Presence of antibodies against the U1 small nuclear ribonucleoprotein autoantigen (U1snRNP)
- MCTD is characterized by clinical symptoms seen in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), dermatomyositis (DM), polymyositis, and scleroderma.
- Primary pathogenesis in MCTD include:
- Vasculopathy leading to tissue ischemia
- Autoimmunity causes immunological and inflammatory
- fibrosis caused by excessive synthesis of collagen and other proteins of matrix
- In MCTD, U1-snRNP components play an important role for triggering immune responses.
- Two complications of pulmonary hypertension and interstitial lung disease are the most frequent causes of death.
Genetics
- In MCTD, the frequency of HLA-DR4 is increased compared with healthy individuals in worldwide studies.[4]
- A significant association between U1RNP disease and HLA-DR4 and DR154-61 is detected.
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][6]
- Photo-distributed erythematosus annular lesions
- Papulosquamous lesions
- Telangiectasia
- Sclerodactyly
Microscopic Pathology
- In MCTD, histopathological features of interstitial lung disease are similar to idiopathic pulmonary fibrosis (IPF). The findings including:[7]
- Infiltration of lymphocytes and plasma cells in alveolar septum
- Deposition of type III collagen
- In MCTD, skin histopathological characteristics are similar to subacute cutaneous lupus erythematosus (SCLE). The findings include:[5]
- Poor and lichenoid interface dermatitis
- Suprabasilar exocytosis around necrotic keratinocytes
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.
- ↑ Dabiri G, Falanga V (November 2013). "Connective tissue ulcers". J Tissue Viability. 22 (4): 92–102. doi:10.1016/j.jtv.2013.04.003. PMC 3930159. PMID 23756459.
- ↑ 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.