Blau syndrome: Difference between revisions
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==Overview== | ==Overview== | ||
'''Blau syndrome''' is characterized by | '''Blau syndrome''' is characterized by the [[Triad (anatomy)|triad]] of early-onset symmetric polyarticular [[synovitis]], [[skin rash]], and [[eye]] involvement with recurrent [[anterior uveitis]]. | ||
==Historical Perspective== | ==Historical Perspective== | ||
*Blau syndrome was first discovered by Dr. Edward B. Blau, in 1985 following observation of a four-generation family with a variety of [[symptoms]] including [[granulomatous]] [[arthritis]], [[iritis]], and [[skin rash]].<ref name="Blau1985">{{cite journal|last1=Blau|first1=Edward B.|title=Familial granulomatous arthritis, iritis, and rash|journal=The Journal of Pediatrics|volume=107|issue=5|year=1985|pages=689–693|issn=00223476|doi=10.1016/S0022-3476(85)80394-2}}</ref> | *Blau syndrome was first discovered by Dr. Edward B. Blau, in 1985 following observation of a four-generation family with a variety of [[symptoms]] including [[granulomatous]] [[arthritis]], [[iritis]], and [[skin rash]].<ref name="Blau1985">{{cite journal|last1=Blau|first1=Edward B.|title=Familial granulomatous arthritis, iritis, and rash|journal=The Journal of Pediatrics|volume=107|issue=5|year=1985|pages=689–693|issn=00223476|doi=10.1016/S0022-3476(85)80394-2}}</ref> | ||
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*The exact [[pathogenesis]] of Blau syndrome is not fully understood. However, it is [[Causes|caused]] by a NATCH domain of the [[NOD2]] / [[CARD15]] [[gene]].<ref name="Miceli-RichardLesage2001">{{cite journal|last1=Miceli-Richard|first1=Corinne|last2=Lesage|first2=Suzanne|last3=Rybojad|first3=Michel|last4=Prieur|first4=Anne-Marie|last5=Manouvrier-Hanu|first5=Sylvie|last6=Häfner|first6=Renate|last7=Chamaillard|first7=Mathias|last8=Zouali|first8=Habib|last9=Thomas|first9=Gilles|last10=Hugot|first10=Jean-Pierre|title=CARD15 mutations in Blau syndrome|journal=Nature Genetics|volume=29|issue=1|year=2001|pages=19–20|issn=1061-4036|doi=10.1038/ng720}}</ref> | *The exact [[pathogenesis]] of Blau syndrome is not fully understood. However, it is [[Causes|caused]] by a NATCH domain of the [[NOD2]] / [[CARD15]] [[gene]].<ref name="Miceli-RichardLesage2001">{{cite journal|last1=Miceli-Richard|first1=Corinne|last2=Lesage|first2=Suzanne|last3=Rybojad|first3=Michel|last4=Prieur|first4=Anne-Marie|last5=Manouvrier-Hanu|first5=Sylvie|last6=Häfner|first6=Renate|last7=Chamaillard|first7=Mathias|last8=Zouali|first8=Habib|last9=Thomas|first9=Gilles|last10=Hugot|first10=Jean-Pierre|title=CARD15 mutations in Blau syndrome|journal=Nature Genetics|volume=29|issue=1|year=2001|pages=19–20|issn=1061-4036|doi=10.1038/ng720}}</ref> | ||
*The [[disease]] is inherited in an [[autosomal dominant]] mode. | *The [[disease]] is inherited in an [[autosomal dominant]] mode. | ||
*This gene encodes a [[protein]] involving in the immune system.<ref name="OguraInohara2001">{{cite journal|last1=Ogura|first1=Yasunori|last2=Inohara|first2=Naohiro|last3=Benito|first3=Adalberto|last4=Chen|first4=Felicia F.|last5=Yamaoka|first5=Shoji|last6=Núñez|first6=Gabriel|title=Nod2, a Nod1/Apaf-1 Family Member That Is Restricted to Monocytes and Activates NF-κB|journal=Journal of Biological Chemistry|volume=276|issue=7|year=2001|pages=4812–4818|issn=0021-9258|doi=10.1074/jbc.M008072200}}</ref> | *This [[gene]] encodes a [[protein]] involving in the [[immune system]].<ref name="OguraInohara2001">{{cite journal|last1=Ogura|first1=Yasunori|last2=Inohara|first2=Naohiro|last3=Benito|first3=Adalberto|last4=Chen|first4=Felicia F.|last5=Yamaoka|first5=Shoji|last6=Núñez|first6=Gabriel|title=Nod2, a Nod1/Apaf-1 Family Member That Is Restricted to Monocytes and Activates NF-κB|journal=Journal of Biological Chemistry|volume=276|issue=7|year=2001|pages=4812–4818|issn=0021-9258|doi=10.1074/jbc.M008072200}}</ref> | ||
*NOD2 mutation leads to | *[[NOD2]] [[mutation]] leads to over activation of [[NF-kB]] which may explain an exaggerated [[inflammatory response]] observed in these [[patients]]. | ||
==Causes== | ==Causes== | ||
*Blau syndrome may be [[Causes|caused]] by a [[mutation]] in the [[NOD2]] [[gene]].<ref name="Miceli-RichardLesage2001">{{cite journal|last1=Miceli-Richard|first1=Corinne|last2=Lesage|first2=Suzanne|last3=Rybojad|first3=Michel|last4=Prieur|first4=Anne-Marie|last5=Manouvrier-Hanu|first5=Sylvie|last6=Häfner|first6=Renate|last7=Chamaillard|first7=Mathias|last8=Zouali|first8=Habib|last9=Thomas|first9=Gilles|last10=Hugot|first10=Jean-Pierre|title=CARD15 mutations in Blau syndrome|journal=Nature Genetics|volume=29|issue=1|year=2001|pages=19–20|issn=1061-4036|doi=10.1038/ng720}}</ref> | *Blau syndrome may be [[Causes|caused]] by a [[mutation]] in the [[NOD2]] [[gene]].<ref name="Miceli-RichardLesage2001">{{cite journal|last1=Miceli-Richard|first1=Corinne|last2=Lesage|first2=Suzanne|last3=Rybojad|first3=Michel|last4=Prieur|first4=Anne-Marie|last5=Manouvrier-Hanu|first5=Sylvie|last6=Häfner|first6=Renate|last7=Chamaillard|first7=Mathias|last8=Zouali|first8=Habib|last9=Thomas|first9=Gilles|last10=Hugot|first10=Jean-Pierre|title=CARD15 mutations in Blau syndrome|journal=Nature Genetics|volume=29|issue=1|year=2001|pages=19–20|issn=1061-4036|doi=10.1038/ng720}}</ref> | ||
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===Diagnostic Study of Choice=== | ===Diagnostic Study of Choice=== | ||
*There are no established criteria for the [[diagnosis]] of Blau syndrome. However, it usually manifests with a triad consist of:<ref name="ImayoshiOgata2018">{{cite journal|last1=Imayoshi|first1=Miyoko|last2=Ogata|first2=Yoshiyasu|last3=Yamamoto|first3=Shuichi|title=A Case of Sporadic Blau Syndrome with an Uncommon Clinical Course|journal=Case Reports in Rheumatology|volume=2018|year=2018|pages=1–5|issn=2090-6889|doi=10.1155/2018/6292308}}</ref> | *There are no established criteria for the [[diagnosis]] of Blau syndrome. However, it usually manifests with a triad consist of:<ref name="ImayoshiOgata2018">{{cite journal|last1=Imayoshi|first1=Miyoko|last2=Ogata|first2=Yoshiyasu|last3=Yamamoto|first3=Shuichi|title=A Case of Sporadic Blau Syndrome with an Uncommon Clinical Course|journal=Case Reports in Rheumatology|volume=2018|year=2018|pages=1–5|issn=2090-6889|doi=10.1155/2018/6292308}}</ref> | ||
** | **Symmetric early-onset of polyarticular [[synovitis]] | ||
**Skin rash | **[[Skin rash]] | ||
**Eye involvement with recurrent anterior uveitis | **Eye involvement with recurrent [[anterior uveitis]] | ||
*It is notable that some patients may present with signs/symptoms other than the aforementioned, which make the clinical diagnosis more challenging. Therefore, the genetic analysis is the diagnostic study of choice for Blau syndrome. | *It is notable that some [[patients]] may present with [[signs]]/[[symptoms]] other than the aforementioned, which make the clinical [[diagnosis]] more challenging. Therefore, the [[genetic analysis]] is the [[diagnostic]] study of choice for Blau syndrome. | ||
===History and Symptoms=== | ===History and Symptoms=== | ||
*Blau syndrome first presents with a scaly [[rash]] often by 4 months of age. [[Fever]], [[arthritis]], [[abdominal pain]], and other [[Symptom|symptoms]] may present later by 4 years of age.<ref name="RoséAróstegui2009">{{cite journal|last1=Rosé|first1=Carlos D.|last2=Aróstegui|first2=Juan I.|last3=Martin|first3=Tammy M.|last4=Espada|first4=Graciela|last5=Scalzi|first5=Lisabeth|last6=Yagüe|first6=Jordi|last7=Rosenbaum|first7=James T.|last8=Modesto|first8=Consuelo|last9=Cristina Arnal|first9=Maria|last10=Merino|first10=Rosa|last11=García-Consuegra|first11=Julia|last12=Carballo Silva|first12=María Antonia|last13=Wouters|first13=Carine H.|title=NOD2-Associated pediatric granulomatous arthritis, an expanding phenotype: Study of an international registry and a national cohort in spain|journal=Arthritis & Rheumatism|volume=60|issue=6|year=2009|pages=1797–1803|issn=00043591|doi=10.1002/art.24533}}</ref> | *Blau syndrome first presents with a scaly [[rash]] often by 4 months of age. [[Fever]], [[arthritis]], [[abdominal pain]], and other [[Symptom|symptoms]] may present later by 4 years of age.<ref name="RoséAróstegui2009">{{cite journal|last1=Rosé|first1=Carlos D.|last2=Aróstegui|first2=Juan I.|last3=Martin|first3=Tammy M.|last4=Espada|first4=Graciela|last5=Scalzi|first5=Lisabeth|last6=Yagüe|first6=Jordi|last7=Rosenbaum|first7=James T.|last8=Modesto|first8=Consuelo|last9=Cristina Arnal|first9=Maria|last10=Merino|first10=Rosa|last11=García-Consuegra|first11=Julia|last12=Carballo Silva|first12=María Antonia|last13=Wouters|first13=Carine H.|title=NOD2-Associated pediatric granulomatous arthritis, an expanding phenotype: Study of an international registry and a national cohort in spain|journal=Arthritis & Rheumatism|volume=60|issue=6|year=2009|pages=1797–1803|issn=00043591|doi=10.1002/art.24533}}</ref> | ||
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|[[File:Blau syndrome.jpg|thumb|none|300px|Multiple, reddish-brown papules coalescing over the right arm in a boy with Blau syndrome, Image courtesy of Donald A Glass II MD, PhD, Jennifer Maender MD, Denise Metry M]] | |[[File:Blau syndrome.jpg|thumb|none|300px|Multiple, reddish-brown papules coalescing over the right arm in a boy with Blau syndrome, Image courtesy of Donald A Glass II MD, PhD, Jennifer Maender MD, Denise Metry M]] | ||
|} | |} | ||
*Common physical examination findings of Blau syndrome include [[fever]], scaly [[rash]], and [[arthritis]].<ref name="RoséAróstegui2009">{{cite journal|last1=Rosé|first1=Carlos D.|last2=Aróstegui|first2=Juan I.|last3=Martin|first3=Tammy M.|last4=Espada|first4=Graciela|last5=Scalzi|first5=Lisabeth|last6=Yagüe|first6=Jordi|last7=Rosenbaum|first7=James T.|last8=Modesto|first8=Consuelo|last9=Cristina Arnal|first9=Maria|last10=Merino|first10=Rosa|last11=García-Consuegra|first11=Julia|last12=Carballo Silva|first12=María Antonia|last13=Wouters|first13=Carine H.|title=NOD2-Associated pediatric granulomatous arthritis, an expanding phenotype: Study of an international registry and a national cohort in spain|journal=Arthritis & Rheumatism|volume=60|issue=6|year=2009|pages=1797–1803|issn=00043591|doi=10.1002/art.24533}}</ref> | *Common [[physical examination]] findings of Blau syndrome include [[fever]], scaly [[rash]], and [[arthritis]].<ref name="RoséAróstegui2009">{{cite journal|last1=Rosé|first1=Carlos D.|last2=Aróstegui|first2=Juan I.|last3=Martin|first3=Tammy M.|last4=Espada|first4=Graciela|last5=Scalzi|first5=Lisabeth|last6=Yagüe|first6=Jordi|last7=Rosenbaum|first7=James T.|last8=Modesto|first8=Consuelo|last9=Cristina Arnal|first9=Maria|last10=Merino|first10=Rosa|last11=García-Consuegra|first11=Julia|last12=Carballo Silva|first12=María Antonia|last13=Wouters|first13=Carine H.|title=NOD2-Associated pediatric granulomatous arthritis, an expanding phenotype: Study of an international registry and a national cohort in spain|journal=Arthritis & Rheumatism|volume=60|issue=6|year=2009|pages=1797–1803|issn=00043591|doi=10.1002/art.24533}}</ref> | ||
*Other possible findings include: | *Other possible findings include: | ||
**[[Cranial nerve]] involvement | **[[Cranial nerve]] involvement | ||
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===X-ray=== | ===X-ray=== | ||
*There are no [[x-ray]] findings associated with Blau syndrome. However, an [[x-ray]] may be helpful in the evaluation of [[arthritis]] associated with Blau syndrome, which may indicate the following findings:<ref name="RosePans2014">{{cite journal|last1=Rose|first1=C. D.|last2=Pans|first2=S.|last3=Casteels|first3=I.|last4=Anton|first4=J.|last5=Bader-Meunier|first5=B.|last6=Brissaud|first6=P.|last7=Cimaz|first7=R.|last8=Espada|first8=G.|last9=Fernandez-Martin|first9=J.|last10=Hachulla|first10=E.|last11=Harjacek|first11=M.|last12=Khubchandani|first12=R.|last13=Mackensen|first13=F.|last14=Merino|first14=R.|last15=Naranjo|first15=A.|last16=Oliveira-Knupp|first16=S.|last17=Pajot|first17=C.|last18=Russo|first18=R.|last19=Thomee|first19=C.|last20=Vastert|first20=S.|last21=Wulffraat|first21=N.|last22=Arostegui|first22=J. I.|last23=Foley|first23=K. P.|last24=Bertin|first24=J.|last25=Wouters|first25=C. H.|title=Blau syndrome: cross-sectional data from a multicentre study of clinical, radiological and functional outcomes|journal=Rheumatology|volume=54|issue=6|year=2014|pages=1008–1016|issn=1462-0324|doi=10.1093/rheumatology/keu437}}</ref> | *There are no [[x-ray]] findings associated with Blau syndrome. However, an [[x-ray]] may be helpful in the evaluation of [[arthritis]] associated with Blau syndrome, which may indicate the following findings:<ref name="RosePans2014">{{cite journal|last1=Rose|first1=C. D.|last2=Pans|first2=S.|last3=Casteels|first3=I.|last4=Anton|first4=J.|last5=Bader-Meunier|first5=B.|last6=Brissaud|first6=P.|last7=Cimaz|first7=R.|last8=Espada|first8=G.|last9=Fernandez-Martin|first9=J.|last10=Hachulla|first10=E.|last11=Harjacek|first11=M.|last12=Khubchandani|first12=R.|last13=Mackensen|first13=F.|last14=Merino|first14=R.|last15=Naranjo|first15=A.|last16=Oliveira-Knupp|first16=S.|last17=Pajot|first17=C.|last18=Russo|first18=R.|last19=Thomee|first19=C.|last20=Vastert|first20=S.|last21=Wulffraat|first21=N.|last22=Arostegui|first22=J. I.|last23=Foley|first23=K. P.|last24=Bertin|first24=J.|last25=Wouters|first25=C. H.|title=Blau syndrome: cross-sectional data from a multicentre study of clinical, radiological and functional outcomes|journal=Rheumatology|volume=54|issue=6|year=2014|pages=1008–1016|issn=1462-0324|doi=10.1093/rheumatology/keu437}}</ref> | ||
**Camptodactyly (flexion contracture in PIP joints) | **[[Camptodactyly]] ([[flexion]] [[contracture]] in [[Proximal interphalangeal joints|PIP]] [[joints]]) | ||
**Carpal dysplasia with carpal crowding (changes in shape and position affecting bones in the proximal carpal row) | **[[Carpal]] [[dysplasia]] with [[carpal]] crowding (changes in shape and position affecting [[bones]] in the proximal [[carpal]] row) | ||
**Abnormal distal radial epiphysis with a biconcave articular surface (prominent bony ridge is in contact with the scapholunate joint) | **Abnormal distal radial [[epiphysis]] with a biconcave articular surface (prominent bony ridge is in contact with the scapholunate [[joint]]) | ||
**Abnormal shape of the distal ulna (plump ulna) as well as a short ulna | **Abnormal shape of the distal [[ulna]] (plump [[ulna]]) as well as a short [[ulna]] | ||
**Abnormal shape of the second metacarpal bone (long small diaphysis) | **Abnormal shape of the second [[Metacarpal bones|metacarpal bone]] (long small [[diaphysis]]) | ||
===Echocardiography or Ultrasound=== | ===Echocardiography or Ultrasound=== | ||
*There are no [[echocardiography]] findings associated with Blau syndrome. However, [[pericarditis]] may be one of the possible [[complication]] of Blau syndrome.<ref name="RoséAróstegui2009">{{cite journal|last1=Rosé|first1=Carlos D.|last2=Aróstegui|first2=Juan I.|last3=Martin|first3=Tammy M.|last4=Espada|first4=Graciela|last5=Scalzi|first5=Lisabeth|last6=Yagüe|first6=Jordi|last7=Rosenbaum|first7=James T.|last8=Modesto|first8=Consuelo|last9=Cristina Arnal|first9=Maria|last10=Merino|first10=Rosa|last11=García-Consuegra|first11=Julia|last12=Carballo Silva|first12=María Antonia|last13=Wouters|first13=Carine H.|title=NOD2-Associated pediatric granulomatous arthritis, an expanding phenotype: Study of an international registry and a national cohort in spain|journal=Arthritis & Rheumatism|volume=60|issue=6|year=2009|pages=1797–1803|issn=00043591|doi=10.1002/art.24533}}</ref> | *There are no [[echocardiography]] findings associated with Blau syndrome. However, [[pericarditis]] may be one of the possible [[complication]] of Blau syndrome.<ref name="RoséAróstegui2009">{{cite journal|last1=Rosé|first1=Carlos D.|last2=Aróstegui|first2=Juan I.|last3=Martin|first3=Tammy M.|last4=Espada|first4=Graciela|last5=Scalzi|first5=Lisabeth|last6=Yagüe|first6=Jordi|last7=Rosenbaum|first7=James T.|last8=Modesto|first8=Consuelo|last9=Cristina Arnal|first9=Maria|last10=Merino|first10=Rosa|last11=García-Consuegra|first11=Julia|last12=Carballo Silva|first12=María Antonia|last13=Wouters|first13=Carine H.|title=NOD2-Associated pediatric granulomatous arthritis, an expanding phenotype: Study of an international registry and a national cohort in spain|journal=Arthritis & Rheumatism|volume=60|issue=6|year=2009|pages=1797–1803|issn=00043591|doi=10.1002/art.24533}}</ref> | ||
*For more information on [[echocardiography]] finding of [[pericarditis]] please [[Pericarditis echocardiography|click here]] | *For more information on [[echocardiography]] finding of [[pericarditis]] please [[Pericarditis echocardiography|click here]] | ||
===CT scan=== | ===CT scan=== | ||
*[[CT scan]] findings may be helpful in the diagnosis of conditions associated with Blau syndrome. It may indicate findings associated with pneumonitis such as:<ref name="RoséAróstegui2009">{{cite journal|last1=Rosé|first1=Carlos D.|last2=Aróstegui|first2=Juan I.|last3=Martin|first3=Tammy M.|last4=Espada|first4=Graciela|last5=Scalzi|first5=Lisabeth|last6=Yagüe|first6=Jordi|last7=Rosenbaum|first7=James T.|last8=Modesto|first8=Consuelo|last9=Cristina Arnal|first9=Maria|last10=Merino|first10=Rosa|last11=García-Consuegra|first11=Julia|last12=Carballo Silva|first12=María Antonia|last13=Wouters|first13=Carine H.|title=NOD2-Associated pediatric granulomatous arthritis, an expanding phenotype: Study of an international registry and a national cohort in spain|journal=Arthritis & Rheumatism|volume=60|issue=6|year=2009|pages=1797–1803|issn=00043591|doi=10.1002/art.24533}}</ref> | *[[CT scan]] findings may be helpful in the diagnosis of conditions associated with Blau syndrome. It may indicate findings associated with [[pneumonitis]] such as:<ref name="RoséAróstegui2009">{{cite journal|last1=Rosé|first1=Carlos D.|last2=Aróstegui|first2=Juan I.|last3=Martin|first3=Tammy M.|last4=Espada|first4=Graciela|last5=Scalzi|first5=Lisabeth|last6=Yagüe|first6=Jordi|last7=Rosenbaum|first7=James T.|last8=Modesto|first8=Consuelo|last9=Cristina Arnal|first9=Maria|last10=Merino|first10=Rosa|last11=García-Consuegra|first11=Julia|last12=Carballo Silva|first12=María Antonia|last13=Wouters|first13=Carine H.|title=NOD2-Associated pediatric granulomatous arthritis, an expanding phenotype: Study of an international registry and a national cohort in spain|journal=Arthritis & Rheumatism|volume=60|issue=6|year=2009|pages=1797–1803|issn=00043591|doi=10.1002/art.24533}}</ref> | ||
**Mild upper mediastinal adenopathy | **Mild upper [[mediastinal]] [[adenopathy]] | ||
**Several small areas of ground glass opacity | **Several small areas of [[Ground glass opacification on CT|ground glass]] opacity | ||
===MRI=== | ===MRI=== | ||
*There are no [[MRI]] findings associated with Blau syndrome. | *There are no [[MRI]] findings associated with Blau syndrome. | ||
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===Medical Therapy=== | ===Medical Therapy=== | ||
*There is no treatment for Blau syndrome; the mainstay of therapy is supportive care.<ref name="DeSouzaShah2019">{{cite journal|last1=DeSouza|first1=Philip J.|last2=Shah|first2=Rajiv|title=Characterization of Blau syndrome panuveitis with wide-field fluorescein angiography|journal=American Journal of Ophthalmology Case Reports|volume=14|year=2019|pages=92–94|issn=24519936|doi=10.1016/j.ajoc.2019.03.006}}</ref> | *There is no treatment for Blau syndrome; the mainstay of therapy is supportive care.<ref name="DeSouzaShah2019">{{cite journal|last1=DeSouza|first1=Philip J.|last2=Shah|first2=Rajiv|title=Characterization of Blau syndrome panuveitis with wide-field fluorescein angiography|journal=American Journal of Ophthalmology Case Reports|volume=14|year=2019|pages=92–94|issn=24519936|doi=10.1016/j.ajoc.2019.03.006}}</ref> | ||
*Treatment options for mild clinical phenotype include: | *Treatment options for mild [[clinical]] phenotype include: | ||
**Topical steroid drops | **Topical [[steroid]] drops | ||
**NSAIDs | **[[NSAIDs]] | ||
**Methotrexate | **[[Methotrexate]] | ||
*Treatment options for severe clinical phenotype include: | *Treatment options for severe [[clinical]] phenotype include: | ||
**Systemic corticosteroids | **Systemic [[corticosteroids]] | ||
**Systemic immune suppression with biologic agents | **Systemic [[immune]] suppression with [[biologic]] agents | ||
***Biologic agents targeting TNF and IL-1 are especially beneficial in refractory uveitis.<ref name="RoseMartin2011">{{cite journal|last1=Rose|first1=Carlos D.|last2=Martin|first2=Tammy M.|last3=Wouters|first3=Carine H.|title=Blau syndrome revisited|journal=Current Opinion in Rheumatology|volume=23|issue=5|year=2011|pages=411–418|issn=1040-8711|doi=10.1097/BOR.0b013e328349c430}}</ref> | ***Biologic agents targeting [[TNF]] and [[IL-1]] are especially beneficial in refractory [[uveitis]].<ref name="RoseMartin2011">{{cite journal|last1=Rose|first1=Carlos D.|last2=Martin|first2=Tammy M.|last3=Wouters|first3=Carine H.|title=Blau syndrome revisited|journal=Current Opinion in Rheumatology|volume=23|issue=5|year=2011|pages=411–418|issn=1040-8711|doi=10.1097/BOR.0b013e328349c430}}</ref> | ||
===Surgery=== | ===Surgery=== | ||
*[[Surgical]] intervention is not recommended for the management of Blau syndrome. | *[[Surgical]] intervention is not recommended for the management of Blau syndrome. | ||
Revision as of 20:34, 26 July 2019
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]
Synonyms and keywords: Pediatric Granulomatous Arthritis (PGA), Juvenile Systemic Granulomatosis, Early Onset Sarcoidosis, Jabs Syndrome, NOD2-associated disease-Blau
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Overview
Blau syndrome is characterized by the triad of early-onset symmetric polyarticular synovitis, skin rash, and eye involvement with recurrent anterior uveitis.
Historical Perspective
- Blau syndrome was first discovered by Dr. Edward B. Blau, in 1985 following observation of a four-generation family with a variety of symptoms including granulomatous arthritis, iritis, and skin rash.[1]
- Jabs Syndrome was introduced in the same year (1985) by Dr. A. Douglas Jabs following visiting patients with polyarthritis, uveitis, and cranial neuropathy.[2]
- In 2001, NOD2 mutations were first implicated in the pathogenesis of Blau syndrome.[3]
Classification
- There is no established system for the classification of Blau syndrome.
Pathophysiology
- The exact pathogenesis of Blau syndrome is not fully understood. However, it is caused by a NATCH domain of the NOD2 / CARD15 gene.[3]
- The disease is inherited in an autosomal dominant mode.
- This gene encodes a protein involving in the immune system.[4]
- NOD2 mutation leads to over activation of NF-kB which may explain an exaggerated inflammatory response observed in these patients.
Causes
Differentiating Blau syndrome from Other Diseases
- Blau syndrome must be differentiated from other diseases that cause arthritis, skin rash, and ophthalmological involvement, such as Neonatal onset multisystem inflammatory disease (NOMID), cryopyrin-associated periodic syndrome (CAPS), and familial mediterranean fever.
- For more information on the differential diagnosis of Blau syndrome please click here.
Epidemiology and Demographics
- The prevalence of Blau syndrome has been reported less than 0.1 per 100,000 individuals worldwide.[5]
- Blau syndrome commonly affects individuals younger than 4 years of age.
- There is no racial predilection to Blau syndrome.
- Blau syndrome affects men and women equally.
Risk Factors
- There are no established risk factors for Blau syndrome.
Screening
There is insufficient evidence to recommend routine screening for Blau syndrome.
Natural History, Complications, and Prognosis
- If left untreated, patients with Blau syndrome may progress to develop blindness, vasculitis, and joint deformities.[6][7][8].
- Other possible complications include:
- Prognosis is generally poor if left untreated.
Diagnosis
Diagnostic Study of Choice
- There are no established criteria for the diagnosis of Blau syndrome. However, it usually manifests with a triad consist of:[9]
- Symmetric early-onset of polyarticular synovitis
- Skin rash
- Eye involvement with recurrent anterior uveitis
- It is notable that some patients may present with signs/symptoms other than the aforementioned, which make the clinical diagnosis more challenging. Therefore, the genetic analysis is the diagnostic study of choice for Blau syndrome.
History and Symptoms
- Blau syndrome first presents with a scaly rash often by 4 months of age. Fever, arthritis, abdominal pain, and other symptoms may present later by 4 years of age.[6]
- Rash spread follows a cephalocaudal order. It first appears on the face and then affects the trunk.
- Arthritis usually affects wrists, knees, and ankles and tends to be symmetrical and chronic.
Physical Examination
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- Common physical examination findings of Blau syndrome include fever, scaly rash, and arthritis.[6]
- Other possible findings include:
Laboratory Findings
- Common laboratory findings of Blau syndrome include:[7]
- Elevated acute phase reactant levels
- Hypercalcemia and hypercalciuria
- Elevated angiotensin converting enzyme (ACE) level
- Elevated immunoglobulins
- Leukopenia and eosinophilia
- Hematuria, proteinuria, pyuria
- Abnormal liver function tests
Electrocardiogram
- There are no ECG findings associated with Blau syndrome. However, pericarditis may be one of the possible complication of Blau syndrome.[6]
- For more information on ECG finding of pericarditis please click here
X-ray
- There are no x-ray findings associated with Blau syndrome. However, an x-ray may be helpful in the evaluation of arthritis associated with Blau syndrome, which may indicate the following findings:[10]
- Camptodactyly (flexion contracture in PIP joints)
- Carpal dysplasia with carpal crowding (changes in shape and position affecting bones in the proximal carpal row)
- Abnormal distal radial epiphysis with a biconcave articular surface (prominent bony ridge is in contact with the scapholunate joint)
- Abnormal shape of the distal ulna (plump ulna) as well as a short ulna
- Abnormal shape of the second metacarpal bone (long small diaphysis)
Echocardiography or Ultrasound
- There are no echocardiography findings associated with Blau syndrome. However, pericarditis may be one of the possible complication of Blau syndrome.[6]
- For more information on echocardiography finding of pericarditis please click here
CT scan
- CT scan findings may be helpful in the diagnosis of conditions associated with Blau syndrome. It may indicate findings associated with pneumonitis such as:[6]
- Mild upper mediastinal adenopathy
- Several small areas of ground glass opacity
MRI
- There are no MRI findings associated with Blau syndrome.
Other Imaging Findings
- There are no other imaging findings associated with Blau syndrome.
Other Diagnostic Studies
- There are no other diagnostic studies associated with Blau syndrome.
Treatment
Medical Therapy
- There is no treatment for Blau syndrome; the mainstay of therapy is supportive care.[11]
- Treatment options for mild clinical phenotype include:
- Topical steroid drops
- NSAIDs
- Methotrexate
- Treatment options for severe clinical phenotype include:
Surgery
- Surgical intervention is not recommended for the management of Blau syndrome.
Primary Prevention
- There are no established measures for the primary prevention of Blau syndrome.
Secondary Prevention
- There are no established measures for the secondary prevention of Blau syndrome.
References
- ↑ Blau, Edward B. (1985). "Familial granulomatous arthritis, iritis, and rash". The Journal of Pediatrics. 107 (5): 689–693. doi:10.1016/S0022-3476(85)80394-2. ISSN 0022-3476.
- ↑ Jabs, Douglas A.; Houk, J.Lawrence; Bias, Wilma B.; Arnett, Frank C. (1985). "Familial granulomatous synovitis, uveitis, and cranial neuropathies". The American Journal of Medicine. 78 (5): 801–804. doi:10.1016/0002-9343(85)90286-4. ISSN 0002-9343.
- ↑ 3.0 3.1 3.2 Miceli-Richard, Corinne; Lesage, Suzanne; Rybojad, Michel; Prieur, Anne-Marie; Manouvrier-Hanu, Sylvie; Häfner, Renate; Chamaillard, Mathias; Zouali, Habib; Thomas, Gilles; Hugot, Jean-Pierre (2001). "CARD15 mutations in Blau syndrome". Nature Genetics. 29 (1): 19–20. doi:10.1038/ng720. ISSN 1061-4036.
- ↑ Ogura, Yasunori; Inohara, Naohiro; Benito, Adalberto; Chen, Felicia F.; Yamaoka, Shoji; Núñez, Gabriel (2001). "Nod2, a Nod1/Apaf-1 Family Member That Is Restricted to Monocytes and Activates NF-κB". Journal of Biological Chemistry. 276 (7): 4812–4818. doi:10.1074/jbc.M008072200. ISSN 0021-9258.
- ↑ Yi Yong, Cee; Mukhtyar, Chetan; Armon, Kate (2018). "65. Blau syndrome treated with sequential biologics". Rheumatology Advances in Practice. 2 (suppl_1). doi:10.1093/rap/rky034.028. ISSN 2514-1775.
- ↑ 6.0 6.1 6.2 6.3 6.4 6.5 Rosé, Carlos D.; Aróstegui, Juan I.; Martin, Tammy M.; Espada, Graciela; Scalzi, Lisabeth; Yagüe, Jordi; Rosenbaum, James T.; Modesto, Consuelo; Cristina Arnal, Maria; Merino, Rosa; García-Consuegra, Julia; Carballo Silva, María Antonia; Wouters, Carine H. (2009). "NOD2-Associated pediatric granulomatous arthritis, an expanding phenotype: Study of an international registry and a national cohort in spain". Arthritis & Rheumatism. 60 (6): 1797–1803. doi:10.1002/art.24533. ISSN 0004-3591.
- ↑ 7.0 7.1 Glass DA, Maender J, Metry D (December 2009). "Two pediatric cases of Blau syndrome". Dermatol. Online J. 15 (12): 5. PMID 20040255.
- ↑ Khubchandani, Raju P.; Hasija, Rachana; Touitou, Isabelle; Khemani, Chetna; Wouters, Carine H.; Rose, Carlos D. (2012). "Blau Arteritis Resembling Takayasu Disease with a Novel NOD2 Mutation". The Journal of Rheumatology. 39 (9): 1888–1892. doi:10.3899/jrheum.120156. ISSN 0315-162X.
- ↑ Imayoshi, Miyoko; Ogata, Yoshiyasu; Yamamoto, Shuichi (2018). "A Case of Sporadic Blau Syndrome with an Uncommon Clinical Course". Case Reports in Rheumatology. 2018: 1–5. doi:10.1155/2018/6292308. ISSN 2090-6889.
- ↑ Rose, C. D.; Pans, S.; Casteels, I.; Anton, J.; Bader-Meunier, B.; Brissaud, P.; Cimaz, R.; Espada, G.; Fernandez-Martin, J.; Hachulla, E.; Harjacek, M.; Khubchandani, R.; Mackensen, F.; Merino, R.; Naranjo, A.; Oliveira-Knupp, S.; Pajot, C.; Russo, R.; Thomee, C.; Vastert, S.; Wulffraat, N.; Arostegui, J. I.; Foley, K. P.; Bertin, J.; Wouters, C. H. (2014). "Blau syndrome: cross-sectional data from a multicentre study of clinical, radiological and functional outcomes". Rheumatology. 54 (6): 1008–1016. doi:10.1093/rheumatology/keu437. ISSN 1462-0324.
- ↑ DeSouza, Philip J.; Shah, Rajiv (2019). "Characterization of Blau syndrome panuveitis with wide-field fluorescein angiography". American Journal of Ophthalmology Case Reports. 14: 92–94. doi:10.1016/j.ajoc.2019.03.006. ISSN 2451-9936.
- ↑ Rose, Carlos D.; Martin, Tammy M.; Wouters, Carine H. (2011). "Blau syndrome revisited". Current Opinion in Rheumatology. 23 (5): 411–418. doi:10.1097/BOR.0b013e328349c430. ISSN 1040-8711.