RESUMEN
Urticaria is an inflammatory skin disorder that may occur in isolation or associated with angioedema and/or anaphylaxis. Clinically, it is characterized by the presence of smooth, erythematous or blanching, itchy swelling, called wheals or hives, which greatly vary in size and shape and last less than 24 h before fading to leave normal skin. Urticaria is the consequence of mast-cell degranulation that can be caused by immunological or non-immunological mechanisms. From a clinical point of view, many skin conditions can mimic urticaria and their recognition is mandatory for a correct management and therapeutic approach. We have reviewed all of the main relevant studies which addressed differential diagnosis of urticarial, published until December 2022. The National Library of Medicine PubMed database was used for the electronic research. The present review offers a clinical narrative overview, based on the available literature, of the principal skin disorders that can be misdiagnosed as urticaria (mainly autoinflammatory or autoimmune disorders, drug-induced reactions, and hyperproliferative diseases). The aim of this review is to provide clinicians a useful tool for correctly suspecting and identifying all of these conditions.
RESUMEN
Auto-inflammatory syndromes are rare diseases characterized by arthritis and joint destruction, symptoms similar to but distinct from rheumatoid arthritis (RA). Therapeutic targets have not been well characterized for auto-inflammatory syndromes, although the E3 ligase Synoviolin was previously shown to be a novel therapeutic target for RA. Here, we show that Synoviolin loss has little impact on a model of auto-inflammatory diseases. We previously established such a model, the hIL-1 cTg mouse, in which IL-1 signaling was constitutively activated, and animals exhibit symptoms recapitulating auto-inflammatory syndromes such as major joint dominant arthritis. Here, we crossed hIL-1 cTg with Synoviolin flox'd mice to yield hIL-1 cTg/Synoviolin cKO mice. Synoviolin gene expression was ablated in adult hIL-1 cTg/Synoviolin cKO mice by injection of pIpC to activate Mx1 promoter-driven Cre recombinase. However, symptoms seen in hIL-1 cTg mice such as arthritis and joint destruction were not alleviated by targeting Synoviolin, ruling out Synoviolin as a therapeutic target for auto-inflammatory disease. Our results indicate that although similar, RA and auto-inflammatory diseases are different diseases, and treatment strategies should differ accordingly.
Asunto(s)
Enfermedades Autoinmunes/etiología , Inflamación/etiología , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Artritis Experimental/etiología , Artritis Experimental/genética , Artritis Experimental/metabolismo , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/metabolismo , Citocinas/metabolismo , Humanos , Inflamación/genética , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Interleucina-1/genética , Interleucina-1/metabolismo , Articulaciones/metabolismo , Articulaciones/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Ubiquitina-Proteína Ligasas/deficiencia , Ubiquitina-Proteína Ligasas/genética , Factores de Virulencia/deficiencia , Factores de Virulencia/genética , Factores de Virulencia/metabolismoRESUMEN
Our aim was to report our experiences of pediatric macrophage activation syndrome (MAS) patients treated with anakinra and to review previous studies reporting anakinra treatment in pediatric MAS patients associated with systemic juvenile idiopathic arthritis (sJIA) or autoinflammatory diseases (AIDs). The study group consisted of pediatric MAS patients due to sJIA or AIDs, followed up in the Pediatric Rheumatology Unit of Hacettepe University between January 2015 and January 2017 and treated with anakinra (anti-IL1). We conducted a systematic review of the published literature involving pediatric MAS patients associated with sJIA or AIDs, treated with anakinra. Thirteen sJIA patients and two AIDs patients were included the study. Nineteen MAS episodes were observed in 15 patients. Anakinra (2 mg/kg/day) was started in with a median 1 day after admission. Clinical symptoms resolved, and laboratory findings normalized within median (minimum-maximum) 2 (1-4) and 6 (4-9) days, respectively after the introduction of anakinra. Steroid treatment was stopped in a median of 10 (4-13) weeks after the initiation of anakinra treatment. Patients were followed up for a median of 13 (6-24) months. Two patients developed recurrent MAS episodes when the anakinra dose was reduced, while the other patients achieved remission. In the literature review, we identified nine articles, describing 35 pediatric MAS patients associated with sJIA or AIDs and treated with anakinra. Except for two, all the patients reached remission. Our study and systematic literature review may help to improve the knowledge on the role of anakinra treatment in the management of MAS.
Asunto(s)
Artritis Juvenil , Proteína Antagonista del Receptor de Interleucina 1 , Síndrome de Activación Macrofágica , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Artritis Juvenil/complicaciones , Artritis Juvenil/tratamiento farmacológico , Autoinmunidad , Inflamación , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Síndrome de Activación Macrofágica/complicaciones , Síndrome de Activación Macrofágica/tratamiento farmacológico , Seguridad del Paciente , Inducción de Remisión , Resultado del TratamientoRESUMEN
Background: The auto-inflammation and phospholipase Cγ2 (PLCγ2)-associated antibody deficiency and immune dysregulation (APLAID) syndrome is a rare primary immunodeficiency caused by a gain-of-function mutation S707Y in the PLCG2 gene previously described in two patients from one family. The APLAID patients presented with early-onset blistering skin lesions, posterior uveitis, inflammatory bowel disease (IBD) and recurrent sinopulmonary infections caused by a humoral defect, but lacked circulating autoantibodies and had no cold-induced urticaria, contrary to the patients with the related PLAID syndrome. Case: We describe a new APLAID patient who presented with vesiculopustular rash in the 1st weeks of life, followed by IBD, posterior uveitis, recurrent chest infections, interstitial pneumonitis, and also had sensorineural deafness and cutis laxa. Her disease has been refractory to most treatments, including IL1 blockers and a trial with ruxolitinib has been attempted. Results: In this patient, we found a unique de novo heterozygous missense L848P mutation in the PLCG2 gene, predicted to affect the PLCγ2 structure. Similarly to S707Y, the L848P mutation led to the increased basal and EGF-stimulated PLCγ2 activity in vitro. Whole blood assays showed reduced production of IFN-γ and IL-17 in response to polyclonal T-cell stimulation and reduced production of IL-10 and IL-1ß after LPS stimulation. Reduced IL-1ß levels and the lack of clinical response to treatment with IL-1 blockers argue against NLRP3 inflammasome hyperactivation being the main mechanism mediating the APLAID pathogenesis. Conclusion: Our findings indicate that L848P is novel a gain-of-function mutation that leads to PLCγ2 activation and suggest cutis laxa as a possible clinical manifestations of the APLAID syndrome.
Asunto(s)
Cutis Laxo/genética , Enfermedades Autoinflamatorias Hereditarias/genética , Síndromes de Inmunodeficiencia/genética , Mutación Missense , Fosfolipasa C gamma/genética , Secuencia de Aminoácidos , Secuencia de Bases , Cutis Laxo/complicaciones , Cutis Laxo/enzimología , Análisis Mutacional de ADN , Femenino , Enfermedades Autoinflamatorias Hereditarias/complicaciones , Enfermedades Autoinflamatorias Hereditarias/enzimología , Humanos , Síndromes de Inmunodeficiencia/complicaciones , Síndromes de Inmunodeficiencia/enzimología , Recién Nacido , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/genética , Masculino , Linaje , Fosfolipasa C gamma/química , Fosfolipasa C gamma/metabolismo , Homología de Secuencia de AminoácidoRESUMEN
INTRODUCTION: Interleukin-1 (IL-1) is the key molecule of a strong pro-inflammatory pathway in the innate immune system. The IL-1 family harbors components with pro- and anti-inflammatory effects essential for the regulation of the inflammation process. Auto-inflammatory diseases and systemic onset juvenile idiopathic arthritis (JIA) are examples of chronic inflammatory diseases that are IL-1 dependent. IL-1 blockade has proven to be very effective and has greatly improved the outcome of these disorders. AREAS COVERED: This review describes the components of the IL-1 family and the available IL-1 blocking agents for clinical practice. Among them, canakinumab was more recently introduced. Based on the published clinical trials one can conclude that the clinical efficacy in auto-inflammatory diseases is at least as good as other IL-1 blocking agents. The safety data are limited to those registration studies (Phase 2 and 3). In short term the adverse events described are not very different from the other IL-1 blockers. EXPERT OPINION: Longer term use in larger numbers of patients and adequate data collection using large-scale registries are necessary to provide us with a well-balanced overview of safety issues of canakinumab. Registration studies and open label extension studies show an acceptable safety profile so far.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Interleucina-1/antagonistas & inhibidores , Animales , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales Humanizados , Antirreumáticos/efectos adversos , Antirreumáticos/uso terapéutico , Artritis Juvenil/inmunología , Artritis Juvenil/fisiopatología , Ensayos Clínicos como Asunto , Humanos , Interleucina-1/inmunologíaRESUMEN
Type I interferonopathies are a group of Mendelian disorders characterized by a common physiopathology: the up-regulation of type I interferons. To date, interferonopathies include Aicardi-Goutières syndrome, familial chilblain lupus, spondyenchondromatosis, PRoteasome-associated auto-inflammatory syndrome (PRAAS) and Singleton-Merten syndrome. These diseases present phenotypic overlap including cutaneous features like chilblain lupus, that can be inaugural or present within the first months of life. This novel set of inborn errors of immunity is evolving rapidly, with recognition of new diseases and genes. Recent and improved understanding of the physiopathology of overexpression of type I interferons has allowed the development of targeted therapies, currently being evaluated, like Janus-kinases or reverse transcriptase inhibitors.