Skip to main content
Key Specialties
Anesthesiology Cardiology Dermatology Diabetology Endocrinology Gastroenterology General Medicine Geriatrics Hematology Infectious Diseases Internal Medicine Nephrology Neurology Obstetrics and Gynecology Oncology Pediatrics Psychiatry Radiology Respiratory Medicine Rheumatology Surgery Urology
Congress Coverage
2024 ERS Congress 2024 EASD Congress 2024 ESC Congress 2024 EAN Congress 2024 ASCO Annual Meeting 2024 ACC Congress
Clinical Collections
Advances in Alzheimer’s

ERS Congress 2024

Keep up to date on the latest news from the annual European Respiratory Society conference.
ADVANCED SEARCH
Log in
Top
European Journal of Pediatrics
Published in:

22-09-2023 | Uveitis | REVIEW

Management of Blau syndrome: review and proposal of a treatment algorithm

Authors: Hanene Lassoued Ferjani, Lobna Kharrat, Dorra Ben Nessib, Dhia Kaffel, Kaouther Maatallah, Wafa Hamdi

Published in: European Journal of Pediatrics | Issue 1/2024

Login to get access

Abstract

Blau syndrome is a rare genetic granulomatosis affecting children. It could be responsible for vision-threatening complications and articular deformation. Due to the rarity of this disease, there are no standardized guidelines for its management. This work aimed to provide an updated overview of the different therapeutic options for Blau syndrome. We conducted research in the PubMed database for the different treatments used in Blau syndrome patients, and we proposed a therapeutic algorithm for disease management. High doses of corticosteroids are considered as a bridging therapy in Blau syndrome. Methotrexate should be initiated if the patient has articular or ocular involvement. An anti-tumor necrosis factor α should be added for patients with uveitis or residual arthritis. If the patient remains symptomatic, a switch to another anti-tumor necrosis factor α is the best option. In non-responders to the first- and second-line biotherapies, a switch to an anti-interleukin 1, an anti-interleukin 6, or tofacitinib is necessary.
Conclusion: This article suggested an algorithm for the treatment of Blau syndrome. Other studies are necessary to confirm the efficacy of these treatments.
What is Known:
• Blau syndrome is a rare but severe granulomatosis that could be responsible for vision-threatening complications and articular deformation.
• Blau syndrome seems to be refractory to treatments.
What is New:
• High doses of corticosteroids are usually insufficient and should be considered only as a bridging therapy.
• Blau syndrome could be considered as a poor factor for uveitis, thus, an anti-tumor necrosis factor α should be initiated for patients with uveitis or with residual arthritis.
Literature
1.
2.
Takada S, Saito MK, Kambe N (2020) Blau syndrome: NOD2-related systemic autoinflammatory granulomatosis. G Ital Dermatol Venereol 155(5):537–541PubMedCrossRef
3.
Chiu B, Chan J, Das S, Alshamma Z, Sergi C (2019) Pediatric sarcoidosis: a review with emphasis on early onset and high-risk sarcoidosis and diagnostic challenges. Diagnostics (Basel) 9(4):160PubMedCrossRef
4.
Sfriso P, Caso F, Tognon S, Galozzi P, Gava A, Punzi L (2012) Blau syndrome, clinical and genetic aspects. Autoimmun Rev 12(1):44–51PubMedCrossRef
5.
6.
Okazaki F, Wakiguchi H, Korenaga Y, Nakamura T, Yasudo H, Uchi S et al (2021) A novel mutation in early-onset sarcoidosis/Blau syndrome: an association with Propionibacterium acnes. Pediatr Rheumatol Online J 19(1):18PubMedPubMedCentralCrossRef
7.
Arakawa A, Kambe N, Nishikomori R, Tanabe A, Ueda M, Nishigori C et al (2021) NOD2 mutation-associated case with Blau syndrome triggered by BCG vaccination. Children (Basel) 8(2):117PubMed
8.
Rosé CD, Pans S, Casteels I, Anton J, Bader-Meunier B, Brissaud P et al (2015) Blau syndrome: cross-sectional data from a multicentre study of clinical, radiological and functional outcomes. Rheumatology (Oxford) 54(6):1008–1016PubMedCrossRef
9.
Poline J, Bourrat E, Meinzer U (2020) Camptodactlyly in pediatric practice: Blau syndrome. J Pediatr 221:257–259PubMedCrossRef
10.
Poline J, Fogel O, Pajot C, Miceli-Richard C, Rybojad M, Galeotti C et al (2020) Early-onset granulomatous arthritis, uveitis and skin rash: characterization of skin involvement in Blau syndrome. J Eur Acad Dermatol Venereol 34(2):340–348PubMedCrossRef
11.
Maccora I, Marrani E, Mastrolia MV, Abu-Rumeileh S, Maniscalco V, Fusco E et al (2021) Ocular involvement in monogenic autoinflammatory disease. Autoimmun Rev 20(11):102944PubMedCrossRef
12.
Saini SK, Rose CD (1996) Liver involvement in familial granulomatous arthritis (Blau syndrome). J Rheumatol 23(2):396–399PubMed
13.
Ting SS, Ziegler J, Fischer E (1998) Familial granulomatous arthritis (Blau syndrome) with granulomatous renal lesions. J Pediatr 133(3):450–452PubMedCrossRef
14.
Jabs DA, Houk JL, Bias WB, Arnett FC (1985) Familial granulomatous synovitis, uveitis, and cranial neuropathies. Am J Med 78(5):801–804PubMedCrossRef
15.
Sinharay R, McKeown L, Phillips C, Li A, Duckworth A, Hall F et al (2021) First report of liver transplantation in Blau syndrome: the challenges faced in this rare granulomatous liver disease. Transpl Immunol 65:101378PubMedCrossRef
16.
Wu D, Shen M (2018) Two Chinese pedigrees of Blau syndrome with thirteen affected members. Clin Rheumatol 37(1):265–270PubMedCrossRef
17.
Su J, Liu D (2021) Blau syndrome with pulmonary nodule in a child. Australas J Dermatol 62(2):217–220PubMedCrossRef
18.
Sarens IL, Casteels I, Anton J, Bader-Meunier B, Brissaud P, Chédeville G et al (2018) Blau Syndrome-associated uveitis: preliminary results from an international prospective interventional case series. Am J Ophthalmol 187:158–166PubMedCrossRef
19.
Wu S, Zhong L, Sun Z, Zhu T, Song H, Sui R (2020) Ocular features in Chinese patients with Blau syndrome. Ocul Immunol Inflamm 28(1):79–85PubMedCrossRef
20.
21.
Jindal AK, Pilania RK, Suri D, Gupta A, Gattorno M, Ceccherini I et al (2021) A young female with early onset arthritis, uveitis, hepatic, and renal granulomas: a clinical tryst with Blau syndrome over 20 years and case-based review. Rheumatol Int 41(1):173–181PubMedCrossRef
22.
Matsuda T, Kambe N, Takimoto-Ito R, Ueki Y, Nakamizo S, Saito MK et al (2022) Potential benefits of TNF targeting therapy in Blau syndrome, a NOD2-associated systemic autoinflammatory granulomatosis. Front Immunol 13:895765PubMedPubMedCentralCrossRef
23.
Nascimento H, Sousa JM, Fernández DG, Salomão GHA, Sato EH, Muccioli C et al (2018) Blau-Jabs syndrome in a tertiary ophthalmologic center. Ophthalmic Surg Lasers Imaging Retina 49(1):70–75PubMedCrossRef
24.
Marín-Noriega MA, Muñoz-Ortiz J, Mosquera C, de-la-Torre A (2020) Ophthalmological treatment of early-onset sarcoidosis/Blau syndrome in a Colombian child: a case report. Am J Ophthalmol Case Rep 18:100714
25.
PaÇ Kisaarslan A, SÖzerİ B, Şahİn N, Özdemİr ÇİÇek S, GÜndÜz Z, Demİrkaya E et al (2020) Blau syndrome and early-onset sarcoidosis: a six case series and review of the literature. Arch Rheumatol 35(1):117–127
26.
Shetty AK, Gedalia A (1998) Sarcoidosis: a pediatric perspective. Clin Pediatr (Phila) 37(12):707–717PubMedCrossRef
27.
Millington GWM, Dobson J, Holden S, Waters G, Puvanachandra N, Close R et al (2019) Sporadic Blau syndrome treated with adalimumab. Clin Exp Dermatol 44(7):811–813PubMedCrossRef
28.
Kumrah R, Pilania RK, Menia NK, Rawat A, Sharma J, Gupta A et al (2022) Blau syndrome: lessons learned in a tertiary care centre at Chandigarh. North India Front Immunol 13:932919PubMedCrossRef
29.
Chen J, Luo Y, Zhao M, Wu D, Yang Y, Zhang W et al (2019) Effective treatment of TNFα inhibitors in Chinese patients with Blau syndrome. Arthritis Res Ther 21(1):236PubMedPubMedCentralCrossRef
30.
Yasui K, Yashiro M, Tsuge M, Manki A, Takemoto K, Yamamoto M et al (2010) Thalidomide dramatically improves the symptoms of early-onset sarcoidosis/Blau syndrome: its possible action and mechanism. Arthritis Rheum 62(1):250–257PubMedCrossRef
31.
Wang W, Wang W, Zhong LQ, Li WD, Wu SJ, Song HM (2022) Thalidomide may be an effective drug for Blau syndrome: a case report. Ann Palliat Med 11(7):2538–2543PubMedCrossRef
32.
Soper JR, Bonar SF, O’Sullivan DJ, McCredie J, Willert HG (2019) Thalidomide and neurotrophism. Skeletal Radiol 48(4):517–525PubMedCrossRef
33.
Lu L, Shen M, Jiang D, Li Y, Zheng X, Li Y et al (2018) Blau syndrome with good reponses to tocilizumab: a case report and focused literature review. Semin Arthritis Rheum 47(5):727–731PubMedCrossRef
34.
Nagakura T, Wakiguchi H, Kubota T, Yamatou T, Yamasaki Y, Nonaka Y et al (2017) Tumor necrosis factor inhibitors provide longterm clinical benefits in pediatric and young adult patients with Blau syndrome. J Rheumatol 44(4):536–538PubMedCrossRef
35.
Matsuda T, Kambe N, Ueki Y, Kanazawa N, Izawa K, Honda Y et al (2020) Clinical characteristics and treatment of 50 cases of Blau syndrome in Japan confirmed by genetic analysis of the NOD2 mutation. Ann Rheum Dis 79(11):1492–1499PubMedCrossRef
36.
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
37.
Bravo-Ljubetic L, Peralta-Calvo J, Noval S, Pastora-Salvador N, Abelairas-Gómez J, Merino R (2013) Adalimumab therapy for refractory childhood uveitis. J AAPOS 17(5):456–459PubMedCrossRef
38.
Simonini G, Xu Z, Caputo R, De Libero C, Pagnini I, Pascual V et al (2013) Clinical and transcriptional response to the long-acting interleukin-1 blocker canakinumab in Blau syndrome-related uveitis. Arthritis Rheum 65(2):513–518PubMedPubMedCentralCrossRef
39.
Caracseghi F, Izquierdo-Blasco J, Sanchez-Montanez A, Melendo-Perez S, Roig-Quilis M, Modesto C (2011) Etanercept-induced myelopathy in a pediatric case of blau syndrome. Case Rep Rheumatol 2011:134106PubMed
40.
Martin TM, Zhang Z, Kurz P, Rosé CD, Chen H, Lu H et al (2009) The NOD2 defect in Blau syndrome does not result in excess interleukin-1 activity. Arthritis Rheum 60(2):611–618PubMedPubMedCentralCrossRef
41.
Godfrey MS, Friedman LN (2019) Tuberculosis and biologic therapies: anti-tumor necrosis factor-α and beyond. Clin Chest Med 40(4):721–739PubMedCrossRef
42.
Barbati F, Marrani E, Volpi B, Ferrara G, Lodi L, Mastrolia MV et al (2022) Mycophenolate mofetil-induced hypogammaglobulinemia and infectious disease susceptibility in pediatric patients with chronic rheumatic disorders: a monocentric retrospective study. Eur J Pediatr 181(9):3439–3448PubMedCrossRef
43.
Zhang S, Cai Z, Mo X, Zeng H (2021) Tofacitinib effectiveness in Blau syndrome: a case series of Chinese paediatric patients. Pediatr Rheumatol Online J 19(1):160PubMedPubMedCentralCrossRef
44.
Aróstegui JI, Arnal C, Merino R, Modesto C, Antonia Carballo M, Moreno P 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
45.
Lopalco G, Schiraldi S, Venerito V, Guerriero S, Iannone F (2020) Effectiveness and safety profile of anakinra in a HLA-B27 positive patient with multiple sclerosis-associated uveitis. Mult Scler Relat Disord 42:102152PubMedCrossRef
46.
Fabiani C, Vitale A, Emmi G, Lopalco G, Vannozzi L, Guerriero S et al (2017) Interleukin (IL)-1 inhibition with anakinra and canakinumab in Behçet’s disease-related uveitis: a multicenter retrospective observational study. Clin Rheumatol 36(1):191–197PubMedCrossRef
47.
Maccora I, Abu Rumeileh S, Curci F, de Libero C, Marrani E, Mastrolia MV et al (2022) Tocilizumab and abatacept for the treatment of childhood chronic uveitis: a monocentric comparison experience. Front Pediatr 10:851453PubMedPubMedCentralCrossRef
48.
Brunner HI, Wong R, Nys M, Kou TD, Dominique A, Martini A et al (2020) Abatacept: a review of the treatment of polyarticular-course juvenile idiopathic arthritis. Paediatr Drugs 22(6):653–672PubMedCrossRef
49.
Traves PG, Murray B, Campigotto F, Galien R, Meng A, Di Paolo JA (2021) JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib. Ann Rheum Dis 80(7):865–875PubMedCrossRef
50.
Álvarez-Reguera C, Prieto-Peña D, Herrero-Morant A, Sánchez-Bilbao L, Martín-Varillas JL, González-López E et al (2022) Clinical and immunological study of tofacitinib and baricitinib in refractory Blau syndrome: case report and literature review. Ther Adv Musculoskelet Dis 14:1759720X221093211
51.
Angeles-Han ST, Ringold S, Beukelman T, Lovell D, Cuello CA, Becker ML et al (2019) 2019 American College of Rheumatology/Arthritis Foundation guideline for the screening, monitoring, and treatment of juvenile idiopathic arthritis-associated uveitis. Arthritis Care Res (Hoboken) 71(6):703–716PubMedCrossRef
52.
Foeldvari I, Maccora I, Petrushkin H, Rahman N, Anton J, de Boer J et al (2023) New and updated recommendations for the treatment of juvenile idiopathic arthritis-associated uveitis and idiopathic chronic anterior uveitis. Arthritis Care Res (Hoboken) 75(5):975–982PubMedCrossRef
Metadata
Title
Management of Blau syndrome: review and proposal of a treatment algorithm
Authors
Hanene Lassoued Ferjani
Lobna Kharrat
Dorra Ben Nessib
Dhia Kaffel
Kaouther Maatallah
Wafa Hamdi
Publication date
22-09-2023
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Pediatrics / Issue 1/2024
Print ISSN: 0340-6199
Electronic ISSN: 1432-1076
DOI
https://doi.org/10.1007/s00431-023-05204-9

Other articles of this Issue 1/2024

European Journal of Pediatrics 1/2024 Go to the issue

RESEARCH

Relationship between hemodynamic type and syncopal symptoms in pediatric vasovagal syncope

RESEARCH

Association between aspirin dose and outcomes in patients with acute Kawasaki disease: a nationwide retrospective cohort study in Japan

RESEARCH

Shared decision-making between paediatric haematologists, children with sickle cell disease and their parents: an exploratory study

REVIEW

Personalized application of antimicrobial drugs in pediatric patients with augmented renal clearance: a review of literature

REVIEW

Cardiovascular anomalies in patients with Tessier syndrome: a systematic review

RESEARCH

Mediterranean diet adherence and glycemic control in children and adolescents with type 1 diabetes