RESUMEN
BACKGROUND: Cryopyrin-associated periodic syndrome (CAPS), a rare genetic autoimmune disease, is composed of familial cold autoinflammatory syndrome (FCAs), Muckle-Wells syndrome (MWS), and neonatal onset multisystem inflammatory disease (NOMID). MWS is caused by dominantly inherited or de novo gain-of-function mutations in the NOD-like receptor 3 (NLRP3) gene. At present, there is no report about the variation of R262W in China. CASE PRESENTATION: We reported a 3-year-old Chinese boy who had recurrent fever without obvious inducement, bilateral conjunctival congestion, and urticarial-like rash. Laboratory examination showed elevation in leukocyte count, neutrophil count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) and serum amyloid protein (SAA) levels. Whole exome sequencing identified a missense variation c.784-786delinsTGG (p.R262W) in the coding region of the NLRP3 gene. CONCLUSION: A classical variant of the NLRP3 gene in a patient with MWS was first reported in China.
Asunto(s)
Síndromes Periódicos Asociados a Criopirina , Preescolar , Humanos , Recién Nacido , Masculino , Síndromes Periódicos Asociados a Criopirina/diagnóstico , Síndromes Periódicos Asociados a Criopirina/genética , Mutación , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteínas NLR/genética , Enfermedades RarasRESUMEN
Cryopyrin-associated periodic syndrome (CAPS) is a rare inherited autoinflammatory disease caused by gain-of-function mutations in the NLRP3 gene, with a genotype-phenotype correlation. The clinical presentation of each mutation has been previously studied. However, very few studies have reported on the clinical characteristics and treatment effectiveness across different generations within a family with the same mutation. A detailed investigation of family members of patients with CAPS may help in the appropriate diagnosis and treatment of undiagnosed CAPS. Herein, we report a 2-year-old boy (proband), his father, and his grandmother who presented with several symptoms of CAPS, such as persistently positive inflammatory reactions and hearing impairment. All three patients had the same pathogenic mutation in the NLRP3 gene (c.1049C > T (p.Thr350Met) heterozygous mutation) and were diagnosed with CAPS. With canakinumab treatment, the laboratory data of all three patients improved, the proband and father's skin rash disappeared, and his grandmother's arthropathy improved. The proband's hearing also showed slight improvement but not in his father or grandmother. Among the various non-specific symptoms associated with CAPS, chronic ocular hyperaemia is a finding that can be easily identified by non-ophthalmologists. Diagnosis of CAPS should be considered when eye symptoms are present in a combination of hyperinflammatory response, arthropathy, or skin symptoms. Thorough family history records, physical examinations, and close collaboration between paediatricians and adult rheumatologists are important for prompt diagnosis and appropriate treatment of inherited autoinflammatory diseases.
Asunto(s)
Síndromes Periódicos Asociados a Criopirina , Síndromes Periódicos Asociados a Criopirina/diagnóstico , Síndromes Periódicos Asociados a Criopirina/tratamiento farmacológico , Síndromes Periódicos Asociados a Criopirina/genética , Humanos , Mutación , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Examen Físico , Resultado del TratamientoRESUMEN
BACKGROUND: Cryopyrin-Associated Periodic Syndrome (CAPS) is a variety of clinical variants of autoinflammatory diseases. The pathology is based on a mutation in the NLRP3 gene encoding the cryopyrin protein, which leads to the uncontrolled production of interleukin-1ß. Particular attention should be paid to the rarity of this disease and the lack of clinical knowledge about it in therapeutic and rheumatological practice, which leads to an erroneous diagnosis and the appointment of ineffective treatment for a long time, leading to the progression of the disease and disability of the patient. CASE PRESENTATION: This article describes a clinical case of this disease. The first manifestations of the disease in a woman appeared from the age of 2 years, in the form of a rash and fever. Since school age, there have been signs of arthritis. By the age of 24, sensorineural hearing loss and pain in the spine were evident. The disease occurred under the clinical manifestations of spondyloarthritis. Its treatment with anti-inflammatory therapy did not give a stable result. CONCLUSION: From the analysis, we can conclude that patient M. from early childhood suffers from a severe Neonatal-onset Multisystem Inflammatory Disease of a genetic nature. For a long time, the patient was diagnosed with ankylosing spondylitis, and appropriate treatment was carried out without significant success. The correct diagnosis of CAPS was made only in 2018. This patient has conditions of both CAPS and AS together, which is a very rare association in rheumatological practice. The only treatment method that could stop the manifestations of the disease and prevent life-threatening kidney damage (amyloidosis) is the use of genetically engineered biological drugs, i.e., IL-1ß inhibitors. The only drug of this group registered in Russia is canakinumab (Ilaris®). From the moment of diagnosis to the present day, the patient is treated with the genetically engineered drug canakinumab (Ilaris®) at a dose of 150 mg once every 8 weeks. 6 months after taking the drug, the patient went into complete clinical and laboratory remission.
Asunto(s)
Productos Biológicos , Síndromes Periódicos Asociados a Criopirina , Enfermedades Reumáticas , Espondilitis Anquilosante , Femenino , Recién Nacido , Preescolar , Humanos , Síndromes Periódicos Asociados a Criopirina/complicaciones , Síndromes Periódicos Asociados a Criopirina/diagnóstico , Síndromes Periódicos Asociados a Criopirina/genética , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Interleucina-1beta , Espondilitis Anquilosante/complicaciones , Espondilitis Anquilosante/genética , Espondilitis Anquilosante/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Enfermedades Reumáticas/tratamiento farmacológicoRESUMEN
Background: Muckle-Wells syndrome (MWS) represents a moderate phenotype of cryopyrinopathies. Sensorineural hearing loss and AA amyloidosis belong to the most severe manifestations of uncontrolled disease. Simultaneous discovery of MWS in four generations of one large kindred has enabled us to document natural evolution of untreated disease and their response to targeted therapy. Methods: A retrospective case study, clinical assessment at the time of diagnosis and 2-year prospective follow-up using standardized disease assessments were combined. Results: Collaborative effort of primary care physicians and pediatric and adult specialists led to identification of 11 individuals with MWS within one family. Presence of p.Ala441Val mutation was confirmed. The mildest phenotype of young children suffering with recurrent rash surprised by normal blood tests and absence of fevers. Young adults all presented with fevers, rash, conjunctivitis, and arthralgia/arthritis with raised inflammatory markers. Two patients aged over 50 years suffered with hearing loss and AA amyloidosis. IL-1 blockade induced disease remission in all individuals while hearing mildly improved or remained stable in affected patients as did renal function in one surviving individual with amyloidosis. Conclusions: We have shown that severity of MWS symptoms gradually increased with age toward distinct generation-specific phenotypes. A uniform trajectory of disease evolution has encouraged us to postpone institution of IL-1 blockade in affected oligosymptomatic children. This report illustrates importance of close interdisciplinary collaboration.