Favourable effect of TNF-alpha inhibitor (infliximab) on Blau syndrome in monozygotic twins with a de novo CARD15 mutation

TY - JOUR

T1 - Favourable effect of TNF-alpha inhibitor (infliximab) on Blau syndrome in monozygotic twins with a de novo CARD15 mutation

AU - Milman, Nils

AU - Andersen, Claus B

AU - Hansen, Annette

AU - van Overeem Hansen, Thomas

AU - Nielsen, Finn C

AU - Fledelius, Hans

AU - Ahrens, Peter

AU - Nielsen, Ole Haagen

PY - 2006/12

Y1 - 2006/12

N2 - Blau syndrome is a hereditary granulomatous disease caused by mutations in the CARD15 gene that is diagnosed in children of young age with exanthema/erythema, arthritis/periarthritis and/or uveitis. We report two cases of Blau syndrome in Danish Caucasian monozygotic male twins, exhibiting a heterozygous de novo R334W mutation in codon 334 of CARD15. The patients were initially diagnosed as having sarcoidosis. In both twins, symptoms (exanthema, arthritis/periarthritis) started at 1 year of age, and were followed by uveitis at 7-10 years of age. There was no involvement of the lungs or other organs. An initial course of standard antituberculous treatment had no effect on the symptoms. Hydroxychloroquine and cyclosporine A were also ineffective, and the latter caused impaired renal function. Partial symptomatic relief was obtained with prednisolone and increased benefit was observed in combination with methotrexate. Subsequent introduction of the TNF-alpha inhibitor eternacept did not discernibly benefit the clinical condition, but was associated with recurrent infections. In contrast, a trial of infliximab therapy demonstrated clinical efficacy and eliminated all symptoms, restoring a high quality of life. At follow up at 20 years of age (after 2-5 years of infliximab treatment) the twins had an almost normal physical appearance and a normal psychomotoric development, indicating a favourable short-term prognosis of the disease. Blau syndrome has pathologic, clinical and therapeutic features in common with sarcoidosis, but rarely involves the lungs or other parenchymatous organs. In children, discrimination between early onset sarcoidosis and Blau syndrome should include a CARD15 mutation analysis.

AB - Blau syndrome is a hereditary granulomatous disease caused by mutations in the CARD15 gene that is diagnosed in children of young age with exanthema/erythema, arthritis/periarthritis and/or uveitis. We report two cases of Blau syndrome in Danish Caucasian monozygotic male twins, exhibiting a heterozygous de novo R334W mutation in codon 334 of CARD15. The patients were initially diagnosed as having sarcoidosis. In both twins, symptoms (exanthema, arthritis/periarthritis) started at 1 year of age, and were followed by uveitis at 7-10 years of age. There was no involvement of the lungs or other organs. An initial course of standard antituberculous treatment had no effect on the symptoms. Hydroxychloroquine and cyclosporine A were also ineffective, and the latter caused impaired renal function. Partial symptomatic relief was obtained with prednisolone and increased benefit was observed in combination with methotrexate. Subsequent introduction of the TNF-alpha inhibitor eternacept did not discernibly benefit the clinical condition, but was associated with recurrent infections. In contrast, a trial of infliximab therapy demonstrated clinical efficacy and eliminated all symptoms, restoring a high quality of life. At follow up at 20 years of age (after 2-5 years of infliximab treatment) the twins had an almost normal physical appearance and a normal psychomotoric development, indicating a favourable short-term prognosis of the disease. Blau syndrome has pathologic, clinical and therapeutic features in common with sarcoidosis, but rarely involves the lungs or other parenchymatous organs. In children, discrimination between early onset sarcoidosis and Blau syndrome should include a CARD15 mutation analysis.

KW - Adult

KW - Anti-Inflammatory Agents

KW - Antibodies, Monoclonal

KW - Arthritis

KW - DNA

KW - Diseases in Twins

KW - Exanthema

KW - Humans

KW - Infliximab

KW - Male

KW - Nod2 Signaling Adaptor Protein

KW - Polymerase Chain Reaction

KW - Polymorphism, Single Nucleotide

KW - Syndrome

KW - Twins, Monozygotic

KW - Uveitis

KW - Case Reports

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1111/j.1600-0463.2006.apm_522.x

DO - 10.1111/j.1600-0463.2006.apm_522.x

M3 - Journal article

C2 - 17207093

SN - 0903-4641

VL - 114

SP - 912

EP - 919

JO - APMIS : acta pathologica, microbiologica, et immunologica Scandinavica

JF - APMIS : acta pathologica, microbiologica, et immunologica Scandinavica

IS - 12

ER -