RESUMO
An 8-year old boy with generalized pustular psoriasis unresponsive to several topical and systemic treatments responded dramatically with long-lasting remission to infliximab in combination with methotrexate. Combined therapy might offer a new therapeutic strategy yielding long-term remission.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Quimioterapia Combinada/métodos , Metotrexato/uso terapêutico , Psoríase/tratamento farmacológico , Anticorpos Monoclonais/administração & dosagem , Criança , Fármacos Dermatológicos/administração & dosagem , Humanos , Infliximab , Metotrexato/administração & dosagem , Indução de Remissão/métodos , Resultado do TratamentoRESUMO
OBJECTIVE: To assess the efficacy of golimumab (GLM) as a treatment option for juvenile idiopathic arthritis (JIA)-associated uveitis refractory to adalimumab (ADA). METHODS: Retrospective single-centre study including patients with JIA receiving GLM for active uveitis after failing ADA. JIA- and uveitis-related data, including intraocular inflammation, best-corrected visual acuity, corticosteroid-sparing potential, and ocular complications were evaluated at start of GLM treatment, at 1 month and 3 months, and every 3 months thereafter during GLM administration. We further investigated the association of response to GLM with primary and secondary failure of ADA treatment. RESULTS: Ten patients were studied, all female (17 affected eyes, mean age 14.3 + 6.7 yrs., mean follow-up 25.2 + 21.7 mos). Two patients were switched to GLM because of primary non-response to ADA. Eight were switched because of loss of response (LOR). In 5 of the latter LOR was associated with neutralizing anti-ADA-antibodies. Response to GLM was observed in all 8 patients with LOR, while the 2 patients with primary non-response to ADA also did not respond to GLM. Three of the 8 responders experienced LOR. At the end of follow-up 4 of the 5 remaining responders had achieved complete response. One had achieved partial response. CONCLUSION: GLM is an efficacious therapeutic option in patients who experience LOR to ADA. Our data indicate that patients without primary response to ADA should be rather switched to a biologic agent with a different mode of action instead of further blocking the TNF-alpha pathway.
Assuntos
Adalimumab , Anticorpos Monoclonais/administração & dosagem , Artrite Juvenil/tratamento farmacológico , Substituição de Medicamentos/métodos , Uveíte , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Adolescente , Artrite Juvenil/diagnóstico , Artrite Juvenil/epidemiologia , Artrite Juvenil/imunologia , Áustria/epidemiologia , Produtos Biológicos/administração & dosagem , Biomarcadores Farmacológicos , Criança , Monitoramento de Medicamentos/métodos , Duração da Terapia , Feminino , Humanos , Testes Imunológicos/métodos , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Estudos Retrospectivos , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Uveíte/etiologiaRESUMO
BACKGROUND: To compare clinical presentation, diagnostic and treatment strategies, and outcome between pediatric and adult patients with chronic non-bacterial osteomyelitis (CNO). METHODS: Retrospective single-centre comparative study of pediatric and adult patients diagnosed with chronic recurrent multifocal osteomyelitis (CRMO)/CNO or synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome treated at the Medical University of Graz. RESULTS: 24 pediatric patients diagnosed with CRMO/CNO and 10 adult patients diagnosed with SAPHO syndrome were compared. Median age at diagnosis was 12.3 years (range 7.9-18.9) in the pediatric group and 32.5 years (range 22-56) in the adult group. Median time to diagnosis was shorter in children than in adults (0.3 vs. 1.0 years). Initial clinical presentation, laboratory and histopathological findings were similar in children and adults. Mean numbers of bone lesions were comparable between pediatric and adult patients (3.1 vs. 3.0), as were rates of skin involvement (33% vs. 30%). Sternal involvement was more frequent in adults whereas involvement of clavicle and long bones was more frequent in children (41.7% vs.10, 33% vs. 10%). Computerized tomography (CT) was used more often in adults, whereas whole-body magnetic resonance imaging (MRI) was used only in children. Bisphosphonates were applied more often in children and outcome was better in children than in adults (62.5% vs.30%). CONCLUSION: Results of our study suggest that CNO/CRMO and SAPHO syndrome in children and adults might represent a single clinical syndrome that needs a similar diagnostic and therapeutic approach.
Assuntos
Síndrome de Hiperostose Adquirida/diagnóstico , Osteomielite/diagnóstico , Síndrome de Hiperostose Adquirida/tratamento farmacológico , Adolescente , Adulto , Idade de Início , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Osteomielite/tratamento farmacológico , Estudos Retrospectivos , Esteroides/uso terapêutico , Tempo para o Tratamento , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: Assessing influence of anti-adalimumab (ADA) antibodies (AAA) on serum trough ADA levels and uveitis activity in long-term ADA treatment of juvenile idiopathic arthritis (JIA)-associated uveitis. PATIENTS AND INTERVENTIONS: This prospective observational study included 20 patients from a single centre treated with ADA for active uveitis refractory to conventional disease-modifying antirheumatic drugs. AAA, serum ADA trough levels and uveitis activity were evaluated at regular intervals up to 6 years. RESULTS: AAA were detected in nine patients (45%). Permanent AAA in seven were associated with undetectable ADA trough levels and loss of response (LOR). Transient AAA were detected in four with measurable ADA trough levels and response of uveitis to treatment, followed in two by permanent AAA associated with LOR. Use of concomitant immunosuppression was significantly higher in patients without AAA (p<0.05). CONCLUSIONS: AAA-associated LOR frequently occurs in long-term treatment with ADA for JIA-associated uveitis. Concomitant immunosuppressive therapy significantly reduces the risk of LOR due to AAA.
Assuntos
Adalimumab/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Juvenil/tratamento farmacológico , Uveíte/tratamento farmacológico , Adalimumab/efeitos adversos , Adalimumab/imunologia , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/imunologia , Anticorpos/metabolismo , Antirreumáticos/efeitos adversos , Antirreumáticos/imunologia , Artrite Juvenil/fisiopatologia , Criança , Esquema de Medicação , Monitoramento de Medicamentos , Feminino , Humanos , Assistência de Longa Duração , Masculino , Estudos Prospectivos , Resultado do Tratamento , Uveíte/fisiopatologia , Acuidade Visual/fisiologiaRESUMO
OBJECTIVES: Coeliac disease (CD) and juvenile idiopathic arthritis (JIA) often coexist. This association warrants assessment for CD in patients with JIA. We evaluated the clinical relevance and cost-effectiveness of human leucocyte antigen (HLA) genotyping in first-line screening for development of CD in children with JIA. PATIENTS AND INTERVENTIONS: 95 patients with JIA were screened for CD using CD-specific antibodies. In case of positivity, a small intestinal biopsy was performed to confirm diagnosis. In addition, HLA genotyping was performed. 110 age-matched and sex-matched Caucasian children from the same geographical area served as controls. RESULTS: CD was diagnosed in 4 of 95 patients with JIA (4.2%), a rate significantly higher compared with controls (p<0.02) and 14 times higher than in the general population. Twenty-six patients (27.4%) had one of the variants of the risk genotypes. All four patients diagnosed with CD had a HLA-DQ2.5 genotype: one was homozygote, the remainder heterozygote. Twenty-two patients are, judging by their HLA genotypes, at risk of developing CD and require repeated serological screening. None of the 69 patients without HLA-DQ2/DQ8 genotypes had CD-specific antibodies. Screening with HLA genotyping becomes cheaper than screening without after the second determination. CONCLUSIONS: In our cohort of patients with JIA, lack of HLA-DQ2/DQ8 genotypes identified a majority not at risk of CD in whom repeated serological testing is unnecessary. Genotyping is nowadays the most efficient and cost-effective way to screen for CD risk in JIA.
Assuntos
Artrite Juvenil/genética , Doença Celíaca/genética , Antígenos HLA-DQ/genética , Adolescente , Idade de Início , Artrite Juvenil/economia , Artrite Juvenil/imunologia , Autoanticorpos/metabolismo , Doença Celíaca/diagnóstico , Doença Celíaca/economia , Doença Celíaca/imunologia , Criança , Pré-Escolar , Análise Custo-Benefício , Diagnóstico Precoce , Feminino , Genótipo , Técnicas de Genotipagem/economia , Técnicas de Genotipagem/métodos , Humanos , Lactente , Masculino , Estudos ProspectivosRESUMO
BACKGROUND: Loss-of-function CECR1 mutations cause polyarteritis nodosa (PAN) with childhood onset, an autoinflammatory disorder without significant signs of autoimmunity. Herein we describe the unusual presentation of an autoimmune phenotype with constitutive type I interferon activation in siblings with adenosine deaminase 2 (ADA2) deficiency. CASE PRESENTATION: We describe two siblings with early-onset recurrent strokes, arthritis, oral ulcers, discoid rash, peripheral vascular occlusive disease and high antinuclear antibody titers. Assessment of interferon signatures in blood revealed constitutive type I interferon activation. Aicardi-Goutières syndrome (AGS) was suspected, but no mutation in the known AGS genes were detected. Whole exome sequencing identified compound heterozygosity for a known and a novel mutation in the CECR1 gene. Functional consequences of the mutations were demonstrated by marked reduction in ADA2 catalytic activity. CONCLUSIONS: Our findings demonstrate that ADA2 deficiency can cause an unusual autoimmune phenotype extending the phenotypic spectrum of PAN. Constitutive interferon I activation in patient blood suggests a possible role of type I interferon in disease pathogenesis which may have therapeutic implications.
Assuntos
Adenosina Desaminase/deficiência , Agamaglobulinemia/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Interferon Tipo I/metabolismo , Poliarterite Nodosa/genética , Imunodeficiência Combinada Severa/genética , Adenosina Desaminase/genética , Agamaglobulinemia/complicações , Agamaglobulinemia/diagnóstico , Criança , Pré-Escolar , Humanos , Lactente , Interferon Tipo I/genética , Masculino , Mutação , Linhagem , Fenótipo , Poliarterite Nodosa/complicações , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/diagnósticoRESUMO
BACKGROUND: Inducible co-stimulator (ICOS) deficiency was the first monogenic defect reported to cause common variable immunodeficiency (CVID)-like disease in 2003. Since then, 16 patients have been reported worldwide with an increasing range of clinical phenotypes. OBJECTIVE: We sought to compare the clinical and immunological phenotype and provide clinical follow-up and therapeutic approaches for treating ICOS-deficient patients. METHODS: We describe the clinical and laboratory data of 15 patients with available clinical data. Previous publications and clinical assessment were used as data sources. RESULTS: The observed ICOS gene mutations were all deletions leading to undetectable protein expression. The clinical phenotype of ICOS deficiency is much broader than initially anticipated and includes not only CVID-like disease but an increased susceptibility to viral and opportunistic infections, as well as cancer. Impaired B-cell development led to decreased memory B-cells in all patients, and hypogammaglobulinemia in all but one patient. Circulating CXCR5+ CD4+ follicular T-helper-cell numbers were also reduced in all patients. Treatment included immunoglobulin replacement, regular antibiotic prophylaxis, corticosteroids, and steroid-sparing agents. Three patients underwent hematopoietic stem cell transplantation; one of them died due to capillary leak syndrome on day 5 posttransplantation. CONCLUSION: The disease spectrum of ICOS deficiency is expanding from solely B-cell to combined B- and T-cell immunodeficiency, suggesting genetic and environmental modifiers. Genetic diagnosis is the only tool to distinguish ICOS deficiency from other immunological defects. Patients with antibody deficiency, autoimmunity, and combined immunodeficiency should be screened for ICOS mutations.
RESUMO
The homozygous deletion of the inducible costimulator (ICOS), an activation-induced member of the CD28 family on T cells, causes an antibody deficiency syndrome in affected humans. The identification of a total of 9 ICOS-deficient patients revealed that this monogenic disease comprises the full clinical phenotype described for common variable immunodeficiency (CVID), including recurrent bacterial infections, adult as well as childhood onset, splenomegaly, autoimmune phenomena (autoimmune neutropenia), intestinal lymphoid hyperplasia, and malignancy (carcinoma of the vulva). All patients exhibited a profound hypogammaglobulinemia and a disturbed B-cell homeostasis. The severe reduction of class-switched memory B cells resulted from poor germinal center formation in the absence of ICOS. The additional decrease of naive B cells was associated with a partial inhibition of the early B-cell development at the pre-B-I stage. T-cell homeostasis seemed not to be affected, but low IL-10 production by ICOS-deficient T cells may contribute to the disturbed germinal center reaction. Human ICOS deficiency is indistinguishable from CVID and thus serves as a monogenic model for this complex syndrome.