Severe pericarditis as the first manifestation of a combination of genetic autoinflammatory disease and genetic anemia. Case report
Abstract
Pericarditis is one of the most common pericardial diseases. The activation of the NLRP3 (nucleotide-binding andoligomerization (NOD) like receptor (NLR) containing pyrin domain (NLRP) 3) inflammasome is central in the genesis of autoinflammatory pericarditis. Cryopyrin-associated periodic syndrome (CAPS) is a rare, heterogeneous disease associated with NLRP3 gene pathogenic variants and increased interleukin-1 (IL-1) secretion. Glucose-6-phosphate dehydrogenase (G6PD) deficiency in erythrocytes causes acute haemolytic anaemia during distress or chronic non responsive to iron anemia X-linked. We present the case of a male 1-year-9-months-old patient, with pericarditis and hemolytic anemia, diagnosed as inherited X-linked Glucose 6 Phosphate Dehydrogenase Deficiency p.[Val68Met;Asn126Asp] haplotype, and a heterozygous pathogenic variant in the NLRP3 gene: c.1315G>A/p.Ala439Thr compatible with Autosomal Dominant Cryopyrin Associated Periodic Syndrome. This is the first Paraguayan patient with a “de novo” autoinflammatory condition coexisting with a glucose 6-phosphate dehydrogenase deficiency.
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(1) Shahid R, Jin J, Hope K, Tunuguntla H, Amdani S. Pediatric Pericarditis: Update. Curr Cardiol Rep. 2023 Mar;25(3):157-170. doi: https://doi.org/10.1007/s11886-023-01839-0.
(2) Kontzias A, Barkhodari A, Yao Q. Pericarditis in Systemic Rheumatologic Diseases. Curr Cardiol Rep. 2020 Sep 10;22(11):142. doi: https://doi.org/10.1007/s11886-020-01415-w.
(3) Lopalco G, Rigante D, Cantarini L, Imazio M, Lopalco A, Emmi G, et al. The autoinflammatory side of recurrent pericarditis: Enlightening the pathogenesis for a more rational treatment. Trends Cardiovasc Med. 2021 Jul;31(5):265-274. doi: https://doi.org/10.1016/j.tcm.2020.04.006.
(4) Vecchié A, Del Buono MG, Chiabrando GJ, Dentali F, Abbate A, Bonaventura A. Interleukin-1 and the NLRP3 Inflammasome in Pericardial Disease. Curr Cardiol Rep. 2021 Oct 1;23(11):157. doi: https://doi.org/10.1007/s11886-021-01589-x.
(5) Peet CJ, Rowczenio D, Omoyinmi E, Papadopoulou C, Mapalo BRR, Wood MR, et al. Pericarditis and Autoinflammation: A Clinical and Genetic Analysis of Patients With Idiopathic Recurrent Pericarditis and Monogenic Autoinflammatory Diseases at a National Referral Center. J Am Heart Assoc. 2022 Jun 7;11(11):e024931. doi: https://doi.org/10.1161/JAHA.121.024931.
(6) Bizzi E, Trotta L, Pancrazi M, Nivuori M, Giosia V, Matteucci L, et al. Autoimmune and Autoinflammatory Pericarditis: Definitions and New Treatments. Curr Cardiol Rep. 2021 Jul 28;23(9):128. doi: https://doi.org/10.1007/s11886-021-01549-5.
(7) Kuemmerle-Deschner JB, Ozen S, Tyrrell PN, Kone-Paut I, Goldbach-Mansky R, Lachmann H, et al. Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS). Ann Rheum Dis. 2017 Jun;76(6):942-947. doi: https://doi.org/10.1136/annrheumdis-2016-209686.
(8) Booshehri LM, Hoffman HM. CAPS and NLRP3. J Clin Immunol. 2019 Apr;39(3):277-286. doi: https://doi.org/10.1007/s10875-019-00638-z.
(9) Moltrasio C, Romagnuolo M, Marzano AV. NLRP3 inflammasome and NLRP3-related autoinflammatory diseases: From cryopyrin function to targeted therapies. Front Immunol. 2022 Oct 6;13:1007705. doi: https://doi.org/10.3389/fimmu.2022.1007705.
(10) Jamwal M, Sharma P, Das R. Laboratory Approach to Hemolytic Anemia. Indian J Pediatr. 2020 Jan;87(1):66-74. doi: https://doi.org/10.1007/s12098-019-03119-8.
(11) Nannelli C, Bosman A, Cunningham J, Dugué PA, Luzzatto L. Genetic variants causing G6PD deficiency: Clinical and biochemical data support new WHO classification. Br J Haematol. 2023 Sep;202(5):1024-1032. doi: https://doi.org/10.1111/bjh.18943.
(12) Pepper RJ, Lachmann HJ. Autoinflammatory Syndromes in Children. Indian J Pediatr. 2016 Mar;83(3):242-7. doi: https://doi.org/10.1007/s12098-015-1985-y.
(13) Gattorno M, Hofer M, Federici S, Vanoni F, Bovis F, Aksentijevich I, et al. Classification criteria for autoinflammatory recurrent fevers. Ann Rheum Dis. 2019 Aug;78(8):1025-1032. doi: https://doi.org/10.1136/annrheumdis-2019-215048.
(14) Levy R, Gérard L, Kuemmerle-Deschner J, Lachmann HJ, Koné-Paut I, Cantarini L, et al. Phenotypic and genotypic characteristics of cryopyrin-associated periodic syndrome: a series of 136 patients from the Eurofever Registry. Ann Rheum Dis. 2015 Nov;74(11):2043-9. doi: https://doi.org/10.1136/annrheumdis-2013-204991.
(15) Papa R, Doglio M, Lachmann HJ, Ozen S, Frenkel J, Simon A, et al. A web-based collection of genotype-phenotype associations in hereditary recurrent fevers from the Eurofever registry. Orphanet J Rare Dis. 2017 Oct 18;12(1):167. doi: https://doi.org/10.1186/s13023-017-0720-3.
(16) Cuisset L, Jeru I, Dumont B, Fabre A, Cochet E, Le Bozec J, et al. Mutations in the autoinflammatory cryopyrin-associated periodic syndrome gene: epidemiological study and lessons from eight years of genetic analysis in France. Ann Rheum Dis. 2011 Mar;70(3):495-9. doi: https://doi.org/10.1136/ard.2010.138420.
(17) Ozen S, Frenkel J, Ruperto N, Gattorno M. The Eurofever project: towards better care for autoinflammatory diseases. Eur J Pediatr. 2011;170:445–52.
(18) AIDA Network. Autoinflammatory and Inflammatory Eye Diseases. Available in: https://aidanetwork.org/en/
(19) Infevers. The registry of Hereditary Auto-inflammatory Disorders Mutations. Available in: https://infevers.umai-montpellier.fr/
(20) Gaggiano C, Vitale A, Tufan A, Ragab G, Aragona E, Wiesik-Szewczyk E, et al. The Autoinflammatory Diseases Alliance Registry of monogenic autoinflammatory diseases. Front Med (Lausanne). 2022 Sep 9;9:980679. doi: https://doi.org/10.3389/fmed.2022.980679.
(21) Mitsui-Sekinaka K, Sekinaka Y, Endo A, Imai K, Nonoyama S. The Primary Immunodeficiency Database in Japan. Front Immunol. 2022 Jan 10;12:805766. doi: https://doi.org/10.3389/fimmu.2021.805766.
(22) Sönmez HE, Bayındır Y, Batu ED. Cardiovascular manifestations of monogenic periodic fever syndromes. Clin Rheumatol. 2023 Oct;42(10):2717-2732. doi: https://doi.org/10.1007/s10067-023-06504-z.
(23) Imazio M, Andreis A, De Ferrari GM, Cremer PC, Mardigyan V, Maestroni S, et al. Anakinra for corticosteroid-dependent and colchicine-resistant pericarditis: The IRAP (International Registry of Anakinra for Pericarditis) study. Eur J Prev Cardiol. 2020 Jun;27(9):956-964. doi: https://doi.org/10.1177/2047487319879534.
(24) Romano M, Arici ZS, Piskin D, Alehashemi S, Aletaha D, Barron KS, et al. The 2021 EULAR/American College of Rheumatology points to consider for diagnosis, management and monitoring of the interleukin-1 mediated autoinflammatory diseases: cryopyrin-associated periodic syndromes, tumour necrosis factor receptor-associated periodic syndrome, mevalonate kinase deficiency, and deficiency of the interleukin-1 receptor antagonist. Ann Rheum Dis. 2022 Jul;81(7):907-921. doi: https://doi.org/10.1136/annrheumdis-2021-221801.
(25) Landmann EC, Walker UA. Pharmacological treatment options for cryopyrin-associated periodic syndromes. Expert Rev Clin Pharmacol. 2017 Aug;10(8):855-864. doi: https://doi.org/10.1080/17512433.2017.1338946.
(26) Ter Haar N, Lachmann H, Özen S, Woo P, Uziel Y, Modesto C, et al. Treatment of autoinflammatory diseases: results from the Eurofever Registry and a literature review. Ann Rheum Dis. 2013 May;72(5):678-85. doi: https://doi.org/10.1136/annrheumdis-2011-201268.
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