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01-02-2016 | Case Report

Successful treatment with adalimumab for severe multifocal choroiditis and panuveitis in presumed (early-onset) ocular sarcoidosis

Authors: Marino Achille, Pagnini Ilaria, Giani Teresa, Caputo Roberto, Arapi Ilir, Neri Piergiorgio, Cimaz Rolando, Simonini Gabriele

Published in: International Ophthalmology | Issue 1/2016

Abstract

Early-onset sarcoidosis (EOS) and Blau syndrome are rare auto-inflammatory diseases characterized by a triad of skin rash, granulomatous uveitis, and symmetrical polyarthritis occurring in early childhood. In this paper, we describe a case report very interesting for the multidisciplinary management (pediatric rheumatologist and ophthalmologist), the challenging diagnosis and the difficult choice of the best treatment. We describe a case report of an 8-year old with recurrent episodes of acute uveitis that developed bilateral granulomatous panuveitis initially treated with topical and systemic steroids. Genetic testing for NOD2/CARD15 revealed a heterozygous mutation on exon 4 in the NBD domain (P268S/SNP5). Therefore, an incomplete EOS was suspected. Because uveitis worsening with multifocal chorioretinitis aggravation, intravenous boluses of methylprednisolone were administered. During the steroids tapering, she flared again, and methotrexate was started along with corticosteroids pulse therapy. However, new ocular granuloma appeared, macular oedema with poor visual outcome occurred, and therefore, adalimumab was added to MTX and steroids. After 6 months since the new therapy started, she had a complete visual recovery, and she was able to stop steroid treatment. At 2 years of follow-up, she is still in remission on treatment, and her visual acuity is normal. No side effects were observed. In our patient, we found a heterozygous mutation on exon 4 in the NBD domain (P268S/SNP5) of NOD2/CARD15 gene and an incomplete EOS was hypothesized. The role of this variant is currently under study. Adalimumab use dramatically changed the course of eye disease, prompting to stop steroid treatment and preserving visual acuity.

Cunningham ET Jr (2000) Uveitis in children. Ocul Immunol Inflamm 8(4):251–261PubMedCrossRef

Reiff A, Kadayifcilar S, Özen S (2013) Rheumatic inflammatory eye diseases of childhood. Rheum Dis Clin N Am 39(4):801–832CrossRef

Punzi L, Furlan A, Podswiadek M et al (2009) Clinical and genetic aspects of Blau syndrome: a 25-year follow-up of one family and a literature review. Autoimmun Rev 8(3):228–232PubMedCrossRef

Blau EB (1985) Familial granulomatous arthritis, iritis, and rash. J Pediatr 107(5):689–693PubMedCrossRef

Miceli-Richard C, Lesage S, Rybojad M et al (2001) CARD15 mutations in Blau syndrome. Nat Genet 29(1):19–20PubMedCrossRef

Kanazawa N, Okafuji I, Kambe N et al (2005) Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-kappaB activation: common genetic etiology with (Blau syndrome). Blood 105(3):1195–1197 Epub 2004 Sep 30 PubMedCrossRef

Girardin SE, Boneca IG, Viala J et al (2003) Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem 278(11):8869–8872 (Epub 2003 Jan 13) PubMedCrossRef

Cimaz R, Ansell BM (2002) Sarcoidosis in the pediatric age. Clin Exp Rheumatol 20(2):231–237PubMed

Rosé CD, Aróstegui JI, Martin TM et al (2009) NOD2-associated pediatric granulomatous arthritis, an expanding phenotype: study of an international registry and a national cohort in Spain. Arthritis Rheum 60(6):1797–1803PubMedPubMedCentralCrossRef

10.

Sharma SM, Martin TM, Rosé CD et al (2011) Distinguishing between the innate immune response due to ocular inflammation and infection in a child with juvenile systemic granulomatous disease treated with anti-TNF-α monoclonal antibodies. Rheumatology 50:990–992PubMedPubMedCentralCrossRef

11.

Cunningham ET Jr, Demetrius R, Frieden IJ et al (1995) Vogt–Koyanagi–Harada syndrome in a 4-year old child. Am J Ophthalmol 120(5):675–677PubMedCrossRef

12.

Kim YG, Kamada N, Shaw MH et al (2011) The Nod2 sensor promotes intestinal pathogen eradication via the chemokine CCL2-dependent recruitment of inflammatory monocytes. Immunity 34(5):769–780PubMedPubMedCentralCrossRef

13.

Hugot JP, Chamaillard M, Zouali H et al (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 411(6837):599–603PubMedCrossRef

14.

Ogura Y, Bonen DK, Inohara N et al (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 411(6837):603–606PubMedCrossRef

15.

Lv C, Yang X, Zhang Y et al (2012) Confirmation of three inflammatory bowel disease susceptibility loci in a Chinese cohort. Int J Colorectal Dis 27(11):1465–1472PubMedCrossRef

16.

Hnatyszyn A, Szalata M, Stanczyk J et al (2010) Association of c.802C>T polymorphism of NOD2/CARD15 gene with the chronic gastritis and predisposition to cancer in H. pylori infected patients. Exp Mol Pathol 88(3):388–393PubMedCrossRef

17.

Aróstegui JI, Arnal C, Merino R et al (2007) NOD2 gene-associated pediatric granulomatous arthritis: clinical diversity, novel and recurrent mutations, and evidence of clinical improvement with interleukin-1 blockade in a Spanish cohort. Arthritis Rheum 56(11):3805–3813PubMedCrossRef

18.

Okafuji I, Nishikomori R, Kanazawa N et al (2009) Role of the NOD2 genotype in the clinical phenotype of Blau syndrome and early-onset sarcoidosis. Arthritis Rheum 60(1):242–250. doi:10.1002/art.24134 PubMedCrossRef

19.

Bhojwani R, Houtman AC, Stanga P et al (2009) Presumed early-onset sarcoidosis: a case of devastating ocular inflammation in an infant. J Pediatr Ophthalmol Strabismus 46(4):245–248PubMedCrossRef

20.

Sfriso P, Caso F, Tognon S et al (2012) Blau syndrome, clinical and genetic aspects. Autoimmun Rev 12:44–51PubMedCrossRef

21.

Saurenmann RK, Levin AV, Rose JB et al (2006) Tumour necrosis factor alpha inhibitors in the treatment of childhood uveitis. Rheumatology 45(8):982–989 (Epub 2006 Feb 3) PubMedCrossRef

22.

Simonini G, Taddio A, Cattalini M et al (2011) Prevention of flare recurrences in childhood-refractory chronic uveitis: an open-label comparative study of adalimumab versus infliximab. Arthritis Care Res 63(4):612–618CrossRef

23.

Simonini G, Zannin ME, Caputo R et al (2008) Loss of efficacy during long-term infliximab therapy for sight-threatening childhood uveitis. Rheumatology 47(10):1510–1514PubMedCrossRef

24.

La Torre F, Lapadula G, Cantarini L et al (2014) Early-onset sarcoidosis caused by a rare CARD15/NOD2 de novo mutation and responsive to infliximab: a case report with long-term follow-up and review of the literature. Clin Rheumatol 34(2):391–395PubMedCrossRef

25.

Milman N, Andersen CB, Hansen A et al (2006) Favourable effect of TNF-alpha inhibitor (infliximab) on Blau syndrome in monozygotic twins with a de novo CARD15 mutation. APMIS 114(12):912–919PubMedCrossRef

26.

Vitale A, Rigante D, Lucherini OM et al (2013) Biological treatments: new weapons in the management of monogenic autoinflammatory disorders. Mediat Inflamm 2013:939847

27.

Chauhan K, Michet C (2014) A case of Blau syndrome. Case Rep Rheumatol 2014:216056PubMedPubMedCentral

28.

Raiji VR, Miller MM, Jung LK (2011) Uveitis in Blau syndrome from a de novo mutation of the NOD2/CARD15 gene. J AAPOS 15(2):205–207PubMedCrossRef

Title: Successful treatment with adalimumab for severe multifocal choroiditis and panuveitis in presumed (early-onset) ocular sarcoidosis
Authors: Marino Achille
Pagnini Ilaria
Giani Teresa
Caputo Roberto
Arapi Ilir
Neri Piergiorgio
Cimaz Rolando
Simonini Gabriele
Publication date: 01-02-2016
Publisher: Springer Netherlands
Published in: International Ophthalmology / Issue 1/2016
Print ISSN: 0165-5701
Electronic ISSN: 1573-2630
DOI: https://doi.org/10.1007/s10792-015-0135-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Successful treatment with adalimumab for severe multifocal choroiditis and panuveitis in presumed (early-onset) ocular sarcoidosis

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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