https://doi.org/10.4081/reumatismo.2023.1578
Vasculitis associated with adenosine deaminase 2 deficiency: at the crossroads between Behçet’s disease and autoinflammation. A viewpoint
Submitted: 21 March 2023
Accepted: 28 June 2023
Published: 18 September 2023
Accepted: 28 June 2023
Abstract Views: 1298
PDF: 543
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Adenosine deaminase 2 deficiency (DADA2) is a rare monogenic vasculopathy caused by loss-of-function homozygous or compound heterozygous mutations in ADA2, formerly CECR1 (cat eye syndrome chromosome region 1) gene. The DADA2 phenotype is widely heterogeneous, and patients may present with fever, weight loss, livedo reticularis/racemosa, digital ischemia, cutaneous ulceration, peripheral neuropathy, abdominal pain, bowel perforation, and portal or nephrogenic hypertension. More specific manifestations include early-onset ischemic or hemorrhagic stroke, mild immunodeficiency and hypogammaglobinemia, cytopenia, and vision disturbances. Herein, we present the case of a young male with vasculitis associated with DADA2. The presence of HLA-B51 and the clinical features of this patient raised the question of similarities between ADA2 deficiency, Behçet’s disease, and NOD2-associated diseases. Treatment of this rare monogenic disease is challenging and based on small case series. The long-term experience of this patient proved the difficulties of prednisone tapering and the lack of satisfactory therapeutic strategies.
Navon Elkan P, Pierce SB, Segel R, Walsh T, Barash J, Padeh S, et al. Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. N Engl J Med 2014; 370: 921-31.
DOI: https://doi.org/10.1056/NEJMoa1307362
Keino D, Kondoh K, Kim Y, Sudo A, Ohyama R, Morimotoet M, et al. Successful treatment with cyclosporine and anti-tumour necrosis factor agent for deficiency of adenosine deaminase-2. Scand J Rheumatol 2021; 50: 243-5.
DOI: https://doi.org/10.1080/03009742.2020.1772868
Zhou Q, Yang D, Ombrello AK, Zavialov AV, Toro C, Zavialovet AV, et al. Early-onset Stroke and vasculopathy associated with mutations in ADA2. N Engl J Med 2014; 370: 911-20.
DOI: https://doi.org/10.1056/NEJMoa1307361
Tanatar A, Karadağ ŞG, Sözeri B, Sönmez HE, Çakan M, Demirkol YK, et al. ADA2 deficiency: case series of five patients with varying phenotypes. J Clin Immunol 2020; 40: 253-8.
DOI: https://doi.org/10.1007/s10875-019-00734-0
Conticini E, Sota J, Falsetti P, Lamberti A, Miracco C, Guarnieri A, et al. Biologic drugs in the treatment of polyarteritis nodosa and deficit of adenosine deaminase 2: a narrative review. Autoimmun Rev 2021; 20: 102784.
DOI: https://doi.org/10.1016/j.autrev.2021.102784
Demir S, Sag E, Dedeoglu F, Ozen S. Vasculitis in systemic autoinflammatory diseases. Front Pediatr 2018; 6: 377.
DOI: https://doi.org/10.3389/fped.2018.00377
Rios Scherrer AM, Barreto Rocha V, Campos Garcia L. Behçet's disease: review with emphasis on dermatological aspects. An Bras Dermatol 2014; 92: 452-64.
DOI: https://doi.org/10.1590/abd1806-4841.20177359
Skef W, Hamilton MJ, Arayssi T. Gastrointestinal Behçet’s disease: a review. World J Gastroenterol 2015; 21: 3801-12.
DOI: https://doi.org/10.3748/wjg.v21.i13.3801
van Well GTJ, Kant B, van Nistelrooij A, Ekmekci SS, Henriet SV, Hoppenreijset E, et al. Phenotypic variability including Behçet’s disease-like manifestations in DADA2 patients due to a homozygous c.973-2A>G splice site mutation. Clin Exp Rheumatol 2019; 37: 142-6.
Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al. 2012 revised international chapel hill consensus conference nomenclature of vasculitides. Arthritis Rheum 2013; 65: 1-11.
DOI: https://doi.org/10.1002/art.37715
Caso F, Galozzi P, Costa L, Sfriso P, Cantarini L, Punzi L. Autoinflammatory granulomatous diseases: from Blau syndrome and early-onset sarcoidosis to NOD2-mediated disease and Crohn’s disease. RMD Open 2015; 1: e000097.
DOI: https://doi.org/10.1136/rmdopen-2015-000097
Dziedzic M, Marjańska A, Babol-Pokora K, Urbańczyk A, Grześk E, Młynarski W, et al. Co-existence of Blau syndrome and NAID? Diagnostic challenges associated with presence of multiple pathogenic variants in NOD2 gene: a case report. Pediatr Rheumatol 2017; 15: 57.
DOI: https://doi.org/10.1186/s12969-017-0188-7
Kaczmarek-Ryś M, Hryhorowicz ST, Lis E, Banasiewicz T, Paszkowski J, Borejsza-Wysocki M, et al. Crohn’s disease susceptibility and onset are strongly related to three NOD2 gene haplotypes. J Clin Med 2021; 10: 3777.
DOI: https://doi.org/10.3390/jcm10173777
Berni Canani R, Scudiero O, Nigro E, Monaco ML, Polito R, Capasso M, et al. 802C>T NOD2/CARD15 SNP is associated to Crohn’s disease in italian patients. Hered Genet 2015; s7. DOI:10.4172/2161-1041.S7-005.
DOI: https://doi.org/10.4172/2161-1041.S7-005
Long WY, Chen L, Zhang CL, Nong RM, Jin MJ, Zhan LL, et al. Association between NOD2/CARD15 gene polymorphisms and Crohn’s disease in chinese zhuang patients. World J Gastroenterol 2014; 20: 4737-44.
DOI: https://doi.org/10.3748/wjg.v20.i16.4737
Pardeo M, Cortis E, Bracaglia C, Nicolai R, De Benedetti F, Insalaco A. PReS-FINAL-2201: A P268S NOD mutation in one Blau patient. Pediatr Rheumatol 2013; 11: P191.
DOI: https://doi.org/10.1186/1546-0096-11-S2-P191
Achille M, Ilaria P, Teresa G, Roberto C, Ilir A, Piergiorgio N, et al. Successful treatment with adalimumab for severe multifocal choroiditis and panuveitis in presumed (early-onset) ocular sarcoidosis. Int Ophthalmol 2016; 36: 129-35.
DOI: https://doi.org/10.1007/s10792-015-0135-x
Paç Kisaarslan A, Sözeri B, Şahin N, ÇİÇek SÖ, GÜndÜz Z, Demİrkaya E, et al. Blau syndrome and early-onset sarcoidosis: a six case series and review of the literature. Arch Rheumatol 2020; 35: 111-27.
DOI: https://doi.org/10.5606/ArchRheumatol.2020.7060
Zhong Z, Ding J, Su G, Liao W, Gao Y, Zhu Y, et al. Genetic and clinical features of Blau syndrome among chinese patients with uveitis. Ophthalmology 2022; 129: 821-8.
DOI: https://doi.org/10.1016/j.ophtha.2022.03.014
Mao L, Dhar A, Meng G, Fuss I, Montgomery-Recht K, Yang Z, et al. Blau syndrome NOD2 mutations result in loss of NOD2 cross-regulatory function. Front Immunol 2022; 13: 988862.
DOI: https://doi.org/10.3389/fimmu.2022.988862
Signa S, Bertoni A, Penco F, Caorsi R, Cafaro A, Cangemi G, et al. Adenosine deaminase 2 deficiency (DADA2): a crosstalk between innate and adaptive immunity. Front Immunol 2022; 13: 935957.
DOI: https://doi.org/10.3389/fimmu.2022.935957
Caorsi R, Penco F, Schena F, Gattorno M. Monogenic polyarteritis: the lesson of ADA2 deficiency. Pediatr Rheumatol 2016; 14: 51.
DOI: https://doi.org/10.1186/s12969-016-0111-7
Yap JY, Moens L, Lin MW, Kane A, Kelleher A, Toong C, et al. Intrinsic defects in B cell development and differentiation, T cell exhaustion and altered unconventional T cell generation characterize human adenosine deaminase type 2 deficiency. J Clin Immunol 2021; 41: 1915-35.
DOI: https://doi.org/10.1007/s10875-021-01141-0
Carmona-Rivera C, Khaznadar SS, Shwin KW, Irizarry-Caro JA, O'Neil LJ, Liu Y, et al. Deficiency of adenosine deaminase 2 triggers adenosine-mediated NETosis and TNF production in patients with DADA2. Blood 2019; 134: 395-406.
DOI: https://doi.org/10.1182/blood.2018892752
Meyts I, Aksentijevich I. Deficiency of adenosine deaminase 2 (DADA2): updates on the phenotype, genetics, pathogenesis, and treatment. J Clin Immunol 2018; 38: 569-78.
DOI: https://doi.org/10.1007/s10875-018-0525-8
Pinto B, Deo P, Sharma S, Syal A, Sharma A. Expanding spectrum of DADA2: a review of phenotypes, genetics, pathogenesis and treatment. Clin Rheumatol 2021; 40: 3883-96.
DOI: https://doi.org/10.1007/s10067-021-05711-w
Nanthapisal S, Murphy C, Omoyinmi E, Hong Y, Standing A, Berg S, et al. Deficiency of adenosine deaminase type 2: a description of phenotype and genotype in fifteen cases. Arthritis Rheumatol 2016; 68: 2314-22.
DOI: https://doi.org/10.1002/art.39699
Garg N, Kasapcopur O, Foster JI, Barut K, Tekin A, Kızılkılıç O, et al. Novel adenosine deaminase 2 mutations in a child with a fatal vasculopathy. Eur J Pediatr 2014; 173: 827-30.
DOI: https://doi.org/10.1007/s00431-014-2320-8
Belot A, Wassmer E, Twilt M, Lega JC, Zeef LA, Oojageer A, et al. Mutations in CECR1 associated with a neutrophil signature in peripheral blood. Pediatr Rheumatol Online J 2014; 12: 44.
DOI: https://doi.org/10.1186/1546-0096-12-44
Cragg MS, Walshe CA, Ivanov AO, Glennie MJ. B Cell Trophic Factors and B cell antagonism in autoimmune disease. Curr Dir Autoimmun 2005; 8: 140-74.
DOI: https://doi.org/10.1159/000082102
Taylor RP, Lindorfer MA. Drug insight: the mechanism of action of rituximab in autoimmune disease - the immune complex decoy hypothesis. Nat Clin Pract Rheumatol 2007; 3: 86-95.
DOI: https://doi.org/10.1038/ncprheum0424
Hong Y, Casimir M, Houghton BC, Zhang F, Jensen B, Omoyinmi E, et al. Lentiviral mediated ADA2 gene transfer corrects the defects associated with deficiency of adenosine deaminase type 2. Front Immunol 2022; 13: 852830.
DOI: https://doi.org/10.3389/fimmu.2022.852830
How to Cite
Colangelo, A., Tromby, F., Cafaro, G., Gerli, R., Bartoloni, E., & Perricone, C. (2023). Vasculitis associated with adenosine deaminase 2 deficiency: at the crossroads between Behçet’s disease and autoinflammation. A viewpoint. Reumatismo, 75(3). https://doi.org/10.4081/reumatismo.2023.1578
Copyright (c) 2023 the Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
Similar Articles
- F.M. Perrotta, A. Scarno, A. Carboni, V. Bernardo, M. Montepaone, E. Lubrano, A. Spadaro, Assessment of subclinical atherosclerosis in ankylosing spondylitis: correlations with disease activity indices , Reumatismo: Vol. 65 No. 3 (2013)
- T. Borges, J. Vilaça, S. Ferreira, I. Chora, S. Silva, C. Dias, Systemic sclerosis sine scleroderma: a case report of anterior uveitis , Reumatismo: Vol. 67 No. 1 (2015)
- W. Häuser, F. Wolfe, Diagnosis and diagnostic tests for fibromyalgia (syndrome) , Reumatismo: Vol. 64 No. 4 (2012)
- V. Grosso, E. Boveri, L. Bogliolo, C. Montecucco, R. Caporali, Diffuse alveolar hemorrhage as a manifestation of Behçet disease , Reumatismo: Vol. 65 No. 3 (2013)
- M. Colaci, D. Giuggioli, M. Sebastiani, A. Manfredi, F. Lumetti, F. Luppi, S. Cerri, C. Ferri, Predictive value of isolated DLCO reduction in systemic sclerosis patients without cardio-pulmonary involvement at baseline , Reumatismo: Vol. 67 No. 4 (2015)
- E. Hansson, J. Manjer, H. Svensson, M. Åberg, B. Fagher, R. Ekman, H. Brorson, Neuropeptide levels in Dercum's disease (adiposis dolorosa) , Reumatismo: Vol. 64 No. 3 (2012)
- C. Caranfil, G. Lorenzon, B. Barberio, R. Ramonda, E.V. Savarino, F. Zingone, Inflammatory bowel diseases and spondyloarthritis: a focus on female patients , Reumatismo: Vol. 76 No. 3 (2024)
- D. Camellino, C. Dejaco, Update on treatment of polymyalgia rheumatica , Reumatismo: Vol. 70 No. 1 (2018): Monographic issue on Polymyalgia Rheumatica
- L. Cometi, P. Francesconi, B. Bellini, L. Turco, F. Voller, F. Nacci, S. Bellando-Randone, M. Matucci-Cerinic, S. Guiducci, Rheumatic diseases in migrant patients resident in Tuscany: epidemiological data analysis and single-center experience , Reumatismo: Vol. 76 No. 1 (2024)
- G. Biasi, V. Di Sabatino, A. Ghizzani, M. Galeazzi, Chronic pelvic pain: comorbidity between chronic musculoskeletal pain and vulvodynia , Reumatismo: Vol. 66 No. 1 (2014)
<< < 1 2 3 4 5 6 7 8 9 10 > >>
You may also start an advanced similarity search for this article.
