Abstract:Neonatal multisystem onset inflammatory disorder (NOMID) is a severe autoinflammatory syndrome that can have an initial presentation as infantile urticaria. Thus, an immediate recognition of the clinical symptoms is essential for obtaining a genetic diagnosis and initiation of early therapies to prevent morbidity and mortality. Herein, we describe a neonate presenting with urticaria and systemic inflammation within hours after birth who developed arthropathy and neurologic findings. Pathologic evaluation of th… Show more
“…Cryopyrin-associated periodic syndrome (CAPS) comprises a group of disorders with overlapping symptoms such as fever, urticarial rash, arthralgia, arthritis, and elevated acute-phase reactants (1)(2)(3). Previously, CAPS was classified into three subtypes according to distinct clinical characteristics.…”
Cryopyrin-associated periodic syndrome (CAPS) comprises a group of disorders characterized by recurrent bouts of systemic inflammation related to overactivation of inflammasome. So far, neither large cases of the correlation between genotype and phenotype nor treatment strategies have been clearly stated in China. Here, we studied the clinical and genetic characteristics and their correlation from 30 CAPS patients in China. We identified the pathogenesis for novel mutations by activating NLRP3 inflammasome for peripheral cells with ATP plus LPS, compared characteristics with other case series, and analyzed treatment outcomes of these patients. The patients harbored 19 substitutions in NLRP3, and 8 of them were novel mutations. Among these novel mutations, percentages of severe musculoskeletal, ophthalmologic, and neurological symptoms were higher compared with other case serials. The correlation of phenotypes and their variants seemed different in our cases, such as T350M, S333G/I/R, and F311V (somatic mosaicism). Ten patients received Canakinumab treatment, which proved effective at alleviating musculoskeletal, neurological, auditory, visual manifestations, fever, and rash for 10–20 months follow-up. Patients treated with prednisolone or prednisolone plus thalidomide or methotrexate, tocilizumab, TNF inhibiting agents, and sirolimus achieved only partial remission. Importantly, we firstly identified somatic mosaicism mutation of F311V, which was severe. Our study extended the spectrum of genotype and phenotype and characteristics of their correlations and provided detailed responses to different treatment strategies. These data provide guidance for future diagnosis and management for CAPS.
“…Cryopyrin-associated periodic syndrome (CAPS) comprises a group of disorders with overlapping symptoms such as fever, urticarial rash, arthralgia, arthritis, and elevated acute-phase reactants (1)(2)(3). Previously, CAPS was classified into three subtypes according to distinct clinical characteristics.…”
Cryopyrin-associated periodic syndrome (CAPS) comprises a group of disorders characterized by recurrent bouts of systemic inflammation related to overactivation of inflammasome. So far, neither large cases of the correlation between genotype and phenotype nor treatment strategies have been clearly stated in China. Here, we studied the clinical and genetic characteristics and their correlation from 30 CAPS patients in China. We identified the pathogenesis for novel mutations by activating NLRP3 inflammasome for peripheral cells with ATP plus LPS, compared characteristics with other case series, and analyzed treatment outcomes of these patients. The patients harbored 19 substitutions in NLRP3, and 8 of them were novel mutations. Among these novel mutations, percentages of severe musculoskeletal, ophthalmologic, and neurological symptoms were higher compared with other case serials. The correlation of phenotypes and their variants seemed different in our cases, such as T350M, S333G/I/R, and F311V (somatic mosaicism). Ten patients received Canakinumab treatment, which proved effective at alleviating musculoskeletal, neurological, auditory, visual manifestations, fever, and rash for 10–20 months follow-up. Patients treated with prednisolone or prednisolone plus thalidomide or methotrexate, tocilizumab, TNF inhibiting agents, and sirolimus achieved only partial remission. Importantly, we firstly identified somatic mosaicism mutation of F311V, which was severe. Our study extended the spectrum of genotype and phenotype and characteristics of their correlations and provided detailed responses to different treatment strategies. These data provide guidance for future diagnosis and management for CAPS.
“…Currently, the diagnostic awareness of CAPS is increasing, and there are reports of newborns and infants successfully diagnosed and treated (13)(14)(15). However, the rate of misdiagnosis before the results of genetic testing could be considerable (14).…”
Chronic infantile neurological cutaneous articular (CINCA) syndrome is an autoinflammatory disease encompassed in the group of cryopyrin-associated periodic syndromes (CAPS). Patients suffering from CINCA have an elevated risk of developing chronic sequelae, including deforming arthropathy, chronic meningitis, neurodevelopmental delay, and neurosensorial hearing loss. The diagnosis of CINCA presents several difficulties, as the clinical phenotype could be difficult to recognize, and almost half of the patients have negative genetic testing. In this paper, we describe the case of a patient presenting with the typical phenotype of neonatal-onset CINCA who resulted negative for NLRP3 mutations. Based on the clinical judgment, the patient underwent treatment with anti-interleukin-1 (IL-1) agents (anakinra and, later, canakinumab) resulting in a complete clinical and laboratory response that allowed confirmation of the diagnosis. Additional genetic investigations performed after the introduction of anti-IL-1 therapy revealed a pathogenic mosaicism in the NLRP3 gene. After a 12-year follow-up, the patient has not experienced chronic complications. Although genetics is rapidly progressing, this case highlights the importance of early diagnosis of CINCA patients when the clinical and laboratory picture is highly suggestive in order to start the appropriate anti-cytokine treatment even in the absence of a genetic confirmation.
“…On January 18, 2022, more than 50 cases of MIS-N have been described (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). As in older infants and children, the lack of a diagnostic test makes the clinical diagnosis challenging in non specific cases.…”
Section: Prompt Recognition Of Mis-nmentioning
confidence: 99%
“…Till January 18, 2022, more than 50 cases of MIS-N have been reported. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] As in older infants and children, the lack of a diagnostic test makes the clinical diagnosis challenging in non-specific cases. This may be specifically applicable to newborns and preterm ones as well, where there is a wide differential diagnosis of cases with acutely worsening conditions.…”
Section: Prompt Recognition Of Mis-nmentioning
confidence: 99%
“…Increase in the occurrence of multisystem inflammatory syndrome in neonates (MIS-N) has been reported within the last few months, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] including a recent case report describing a newborn with acute respiratory distress syndrome intubated on day 1 of life and diagnosed with possible MIS-N on day 4, treated with intravenous immunoglobulins (IVIGs) and steroids. The newborn also developed encephalopathy and severe endotheliitis of coronary arteries.…”
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