NOD2-associated pediatric granulomatous arthritis, an expanding phenotype

Study of an international registry and a national cohort in Spain

Carlos D. Rosé, Juan I. Aróstegui, Tammy M. Martin, Graciela Espada, Lisabeth Scalzi, Jordi Yagüe, James T. Rosenbaum, Consuelo Modesto, Maria Cristina Arnal, Rosa Merino, Julia García-Consuegra, María Antonia Carballo Silva, Carine H. Wouters

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Objective. To study the phenotype characteristics of the largest to date cohort of patients with pediatric granulomatous arthritis (PGA) and documented mutations in the NOD2 gene. Methods. We analyzed merged data from 2 prospective cohorts of PGA patients, the International PGA Registry and a Spanish cohort. A systematic review of the medical records of interest was performed to identify phenotype characteristics. Results. Forty-five patients with PGA (23 sporadic cases and 22 from familial pedigrees) and documented NOD2 mutations were identified and formed the basis of the study. Of these 45 patients, 18 had the R334W-encoding mutation, 18 had R334Q, 4 had E383K, 3 had R587C, 1 had C495Y, and 1 had W490L. The majority of patients manifested the typical triad of dermatitis, uveitis, and arthritis. In contrast, in 13 patients, the following "atypical" manifestations were noted: fever, sialadenitis, lymphadenopathy, erythema nodosum, leukocytoclastic vasculitis, transient neuropathy, granulomatous glomerular and interstitial nephritis, interstitial lung disease, arterial hypertension, hypertrophic cardiomyopathy, pericarditis, pulmonary embolism, hepatic granulomatous infiltration, splenic involvement, and chronic renal failure. In addition, 4 individuals who were asymptomatic carriers of a disease-causing mutation were documented. Conclusion. NOD2-associated PGA can be a multisystem disorder with significant visceral involvement. Treating physicians should be aware of the systemic nature of this condition, since some of these manifestations may entail long-term morbidity.

Original languageEnglish (US)
Pages (from-to)1797-1803
Number of pages7
JournalArthritis and rheumatism
Volume60
Issue number6
DOIs
StatePublished - Jun 1 2009

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Spain
Registries
Phenotype
Mutation
Sialadenitis
Erythema Nodosum
Interstitial Nephritis
Pericarditis
Hypertrophic Cardiomyopathy
Uveitis
Interstitial Lung Diseases
Dermatitis
Pedigree
Pulmonary Embolism
Chronic Kidney Failure
Arthritis
Medical Records
Blau syndrome
Fever
Hypertension

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

Rosé, Carlos D. ; Aróstegui, Juan I. ; Martin, Tammy M. ; Espada, Graciela ; Scalzi, Lisabeth ; Yagüe, Jordi ; Rosenbaum, James T. ; Modesto, Consuelo ; Arnal, Maria Cristina ; Merino, Rosa ; García-Consuegra, Julia ; Silva, María Antonia Carballo ; Wouters, Carine H. / NOD2-associated pediatric granulomatous arthritis, an expanding phenotype : Study of an international registry and a national cohort in Spain. In: Arthritis and rheumatism. 2009 ; Vol. 60, No. 6. pp. 1797-1803.
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abstract = "Objective. To study the phenotype characteristics of the largest to date cohort of patients with pediatric granulomatous arthritis (PGA) and documented mutations in the NOD2 gene. Methods. We analyzed merged data from 2 prospective cohorts of PGA patients, the International PGA Registry and a Spanish cohort. A systematic review of the medical records of interest was performed to identify phenotype characteristics. Results. Forty-five patients with PGA (23 sporadic cases and 22 from familial pedigrees) and documented NOD2 mutations were identified and formed the basis of the study. Of these 45 patients, 18 had the R334W-encoding mutation, 18 had R334Q, 4 had E383K, 3 had R587C, 1 had C495Y, and 1 had W490L. The majority of patients manifested the typical triad of dermatitis, uveitis, and arthritis. In contrast, in 13 patients, the following {"}atypical{"} manifestations were noted: fever, sialadenitis, lymphadenopathy, erythema nodosum, leukocytoclastic vasculitis, transient neuropathy, granulomatous glomerular and interstitial nephritis, interstitial lung disease, arterial hypertension, hypertrophic cardiomyopathy, pericarditis, pulmonary embolism, hepatic granulomatous infiltration, splenic involvement, and chronic renal failure. In addition, 4 individuals who were asymptomatic carriers of a disease-causing mutation were documented. Conclusion. NOD2-associated PGA can be a multisystem disorder with significant visceral involvement. Treating physicians should be aware of the systemic nature of this condition, since some of these manifestations may entail long-term morbidity.",
author = "Ros{\'e}, {Carlos D.} and Ar{\'o}stegui, {Juan I.} and Martin, {Tammy M.} and Graciela Espada and Lisabeth Scalzi and Jordi Yag{\"u}e and Rosenbaum, {James T.} and Consuelo Modesto and Arnal, {Maria Cristina} and Rosa Merino and Julia Garc{\'i}a-Consuegra and Silva, {Mar{\'i}a Antonia Carballo} and Wouters, {Carine H.}",
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Rosé, CD, Aróstegui, JI, Martin, TM, Espada, G, Scalzi, L, Yagüe, J, Rosenbaum, JT, Modesto, C, Arnal, MC, Merino, R, García-Consuegra, J, Silva, MAC & Wouters, CH 2009, 'NOD2-associated pediatric granulomatous arthritis, an expanding phenotype: Study of an international registry and a national cohort in Spain', Arthritis and rheumatism, vol. 60, no. 6, pp. 1797-1803. https://doi.org/10.1002/art.24533

NOD2-associated pediatric granulomatous arthritis, an expanding phenotype : Study of an international registry and a national cohort in Spain. / Rosé, Carlos D.; Aróstegui, Juan I.; Martin, Tammy M.; Espada, Graciela; Scalzi, Lisabeth; Yagüe, Jordi; Rosenbaum, James T.; Modesto, Consuelo; Arnal, Maria Cristina; Merino, Rosa; García-Consuegra, Julia; Silva, María Antonia Carballo; Wouters, Carine H.

In: Arthritis and rheumatism, Vol. 60, No. 6, 01.06.2009, p. 1797-1803.

Research output: Contribution to journalArticle

TY - JOUR

T1 - NOD2-associated pediatric granulomatous arthritis, an expanding phenotype

T2 - Study of an international registry and a national cohort in Spain

AU - Rosé, Carlos D.

AU - Aróstegui, Juan I.

AU - Martin, Tammy M.

AU - Espada, Graciela

AU - Scalzi, Lisabeth

AU - Yagüe, Jordi

AU - Rosenbaum, James T.

AU - Modesto, Consuelo

AU - Arnal, Maria Cristina

AU - Merino, Rosa

AU - García-Consuegra, Julia

AU - Silva, María Antonia Carballo

AU - Wouters, Carine H.

PY - 2009/6/1

Y1 - 2009/6/1

N2 - Objective. To study the phenotype characteristics of the largest to date cohort of patients with pediatric granulomatous arthritis (PGA) and documented mutations in the NOD2 gene. Methods. We analyzed merged data from 2 prospective cohorts of PGA patients, the International PGA Registry and a Spanish cohort. A systematic review of the medical records of interest was performed to identify phenotype characteristics. Results. Forty-five patients with PGA (23 sporadic cases and 22 from familial pedigrees) and documented NOD2 mutations were identified and formed the basis of the study. Of these 45 patients, 18 had the R334W-encoding mutation, 18 had R334Q, 4 had E383K, 3 had R587C, 1 had C495Y, and 1 had W490L. The majority of patients manifested the typical triad of dermatitis, uveitis, and arthritis. In contrast, in 13 patients, the following "atypical" manifestations were noted: fever, sialadenitis, lymphadenopathy, erythema nodosum, leukocytoclastic vasculitis, transient neuropathy, granulomatous glomerular and interstitial nephritis, interstitial lung disease, arterial hypertension, hypertrophic cardiomyopathy, pericarditis, pulmonary embolism, hepatic granulomatous infiltration, splenic involvement, and chronic renal failure. In addition, 4 individuals who were asymptomatic carriers of a disease-causing mutation were documented. Conclusion. NOD2-associated PGA can be a multisystem disorder with significant visceral involvement. Treating physicians should be aware of the systemic nature of this condition, since some of these manifestations may entail long-term morbidity.

AB - Objective. To study the phenotype characteristics of the largest to date cohort of patients with pediatric granulomatous arthritis (PGA) and documented mutations in the NOD2 gene. Methods. We analyzed merged data from 2 prospective cohorts of PGA patients, the International PGA Registry and a Spanish cohort. A systematic review of the medical records of interest was performed to identify phenotype characteristics. Results. Forty-five patients with PGA (23 sporadic cases and 22 from familial pedigrees) and documented NOD2 mutations were identified and formed the basis of the study. Of these 45 patients, 18 had the R334W-encoding mutation, 18 had R334Q, 4 had E383K, 3 had R587C, 1 had C495Y, and 1 had W490L. The majority of patients manifested the typical triad of dermatitis, uveitis, and arthritis. In contrast, in 13 patients, the following "atypical" manifestations were noted: fever, sialadenitis, lymphadenopathy, erythema nodosum, leukocytoclastic vasculitis, transient neuropathy, granulomatous glomerular and interstitial nephritis, interstitial lung disease, arterial hypertension, hypertrophic cardiomyopathy, pericarditis, pulmonary embolism, hepatic granulomatous infiltration, splenic involvement, and chronic renal failure. In addition, 4 individuals who were asymptomatic carriers of a disease-causing mutation were documented. Conclusion. NOD2-associated PGA can be a multisystem disorder with significant visceral involvement. Treating physicians should be aware of the systemic nature of this condition, since some of these manifestations may entail long-term morbidity.

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