RESUMO
We presented the case of an adult patient with hyper-IgE syndrome (HIES) who was admitted acutely with a large hydropneumothorax from lung consolidation, a bronchopleural fistula and pleural infection. He has had recurrent pulmonary and skin infections since childhood and longstanding pneumatoceles. He was treated with systemic antibiotics and chest tube drainage. Administration of two doses of low-dose intrapleural therapy (1 mg tissue plasminogen activator and 5 mg deoxyribonuclease) allowed complete evacuation of his residual loculated pleural fluid, aided resolution of his infection without provoking a significant air leak and avoided the need for surgery.
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With the advent of next-generation sequencing (NGS), monogenic forms of common variable immunodeficiency (CVID) have been increasingly described. Our study aimed to identify disease-causing variants in a Western Australian CVID cohort using a novel targeted NGS panel. Targeted amplicon NGS was performed on 22 unrelated subjects who met the formal European Society for Immunodeficiencies-Pan-American Group for Immunodeficiency diagnostic criteria for CVID and had at least one of the following additional criteria: disease onset at age <18 years, autoimmunity, low memory B lymphocytes, family history, and/or history of lymphoproliferation. Candidate variants were assessed by in silico predictions of deleteriousness, comparison to the literature, and classified according to the American College of Medical Genetics and Genomics-Association for Molecular Pathology criteria. All detected genetic variants were verified independently by an external laboratory, and additional functional studies were performed if required. Pathogenic or likely pathogenic variants were detected in 6 of 22 (27%) patients. Monoallelic variants of uncertain significance were also identified in a further 4 of 22 patients (18%). Pathogenic variants, likely pathogenic variants, or variants of uncertain significance were found in TNFRSF13B, TNFRSF13C, ICOS, AICDA, IL21R, NFKB2, and CD40LG, including novel variants and variants with unexpected inheritance pattern. Targeted amplicon NGS is an effective tool to identify monogenic disease-causing variants in CVID, and is comparable or superior to other NGS methods. Moreover, targeted amplicon NGS identified patients who may benefit from targeted therapeutic strategies and had important implications for family members.
Assuntos
Imunodeficiência de Variável Comum , Adolescente , Austrália , Estudos de Coortes , Imunodeficiência de Variável Comum/diagnóstico , Imunodeficiência de Variável Comum/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , MutaçãoAssuntos
Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/congênito , Diarreia/sangue , Doenças Genéticas Ligadas ao Cromossomo X/sangue , Doenças do Sistema Imunitário/congênito , Síndrome de Isaacs/sangue , Canais de Potássio de Abertura Dependente da Tensão da Membrana/imunologia , Adolescente , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/terapia , Diarreia/genética , Diarreia/imunologia , Diarreia/terapia , Fatores de Transcrição Forkhead/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Transplante de Células-Tronco Hematopoéticas , Humanos , Doenças do Sistema Imunitário/sangue , Doenças do Sistema Imunitário/genética , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/terapia , Recém-Nascido , Síndrome de Isaacs/genética , Síndrome de Isaacs/imunologia , Síndrome de Isaacs/terapia , Masculino , MutaçãoRESUMO
BACKGROUND: Calculated globulin fraction is derived from the liver function tests by subtracting albumin from the total protein. Since immunoglobulins comprise the largest component of the serum globulin concentration, increased or decreased calculated globulins and may identify patients with hypogammaglobulinaemia or hypergammaglobulinaemia, respectively. METHODS: A retrospective study of laboratory data over 2.5 years from inpatients at three tertiary hospitals was performed. Patients with paired calculated globulins and immunoglobulin results were identified and clinical details reviewed. The results of serum electrophoresis testing were also assessed where available. RESULTS: A total of 4035 patients had paired laboratory data available. A calculated globulin ≤20 g/L (<2nd percentile) had a low sensitivity (5.8%) but good positive predictive value (82.5%) for hypogammaglobulinaemia (IgG ≤5.7 g/L), with a positive predictive value of 37.5% for severe hypogammaglobulinaemia (IgG ≤3 g/L). Paraproteins were identified in 123/291 (42.3%) of patients with increased calculated globulins (≥42 g/L) who also had a serum electrophoresis performed. Significantly elevated calculated globulin ≥50 g/L (>4th percentile) were seen in patients with either liver disease (37%), haematological malignancy (36%), autoimmune disease (13%) or infections (9%). CONCLUSIONS: Calculated globulin is an inexpensive and easily available test that assists in the identification of hypogammaglobulinaemia or hypergammaglobulinaemia which may prompt further investigation and reduce diagnostic delays.
Assuntos
Agamaglobulinemia/diagnóstico , Paraproteínas/análise , Soroglobulinas/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Hospitalização , Humanos , Hipergamaglobulinemia/diagnóstico , Imunoglobulina G/sangue , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Adulto JovemRESUMO
This consensus document outlines the recommendations from the Australasian Society of Clinical Immunology and Allergy Transplantation and Primary Immunodeficiency group for the diagnosis and management of patients with severe combined immunodeficiency. It also provides a proposed framework for the early investigation, management and supportive care prior to haematopoietic stem cell transplantation.
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Transplante de Células-Tronco Hematopoéticas , Síndromes de Imunodeficiência , Imunodeficiência Combinada Severa , Austrália , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/terapia , Nova Zelândia , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/terapiaRESUMO
Coeliac disease (CD) diagnosis is based on clinical assessment, detection of specific autoantibodies and histological examination of small intestinal biopsies. The European Society of Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines have recently been updated and recommend CD may be diagnosed without a biopsy or HLA typing in symptomatic patients with high titre IgA tissue transglutaminase antibodies (aTTG) and positive endomysial antibodies (EMA). However, the need for EMA in patients with high level aTTG has been questioned. We aimed to determine the diagnostic benefit of HLA typing, EMA and IgG antibodies to deamidated gliadin (DGP) in children with high level aTTG. We prospectively evaluated children presenting for assessment of possible CD. All patients underwent small bowel biopsy, serological testing and HLA typing. Results were analysed and correlated with histopathological diagnosis. A total of 209 children were assessed; 61.5% were found to have CD and 29% could have avoided biopsy as per 2020 ESPGHAN guidelines. Titres of aTTG ≥60 U/mL or DGP ≥28 U/mL gave 100% specificity and 100% positive predictive value (PPV) for CD. HLA typing and EMA did not improve the PPV of patients with aTTG ≥60 U/mL, but addition of DGP ≥28 U/mL improved diagnostic sensitivity whilst retaining 100% specificity. Addition of HLA and EMA testing in patients with high titre aTTG antibodies does not improve diagnostic performance and may possibly be omitted from the serological workup in these patients. Our data support combining aTTG and DGP testing and optimising cut-offs to maximise specificity as an alternative biopsy-free diagnostic approach.
Assuntos
Autoanticorpos , Doença Celíaca/diagnóstico , Imunoglobulina A/imunologia , Guias de Prática Clínica como Assunto , Adolescente , Austrália , Doença Celíaca/imunologia , Criança , Pré-Escolar , Endoscopia , Gastroenterologia , Gliadina/imunologia , Humanos , Lactente , Sensibilidade e EspecificidadeRESUMO
A 41-year-old male patient presented with isolated right lower limb swelling. An ultrasound scan showed right external iliac and femoral vein deep vein thrombosis due to extrinsic compression by an aneurysm of the right common iliac artery. Investigations including imaging and a tissue biopsy of right and left femoral arteries confirmed a rare clinical presentation of fibromuscular dysplasia involving iliac, coeliac, renal and pulmonary vessels. The common iliac artery aneurysm was successfully treated with endovascular repair. Six months later, he developed coronary artery involvement with spontaneous dissection of left anterior descending artery diagnosed on coronary angiogram which was managed conservatively. At 6-year follow-up, he remains clinically asymptomatic and continues with regular surveillance imaging. Iliac arterial fibromuscular dysplasia is uncommon and clinical presentation with a complication such as a deep vein thrombosis is atypical.
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Aneurisma/complicações , Displasia Fibromuscular/diagnóstico , Trombose Venosa/complicações , Adulto , Aneurisma/cirurgia , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/patologia , Veia Femoral/diagnóstico por imagem , Veia Femoral/patologia , Humanos , Artéria Ilíaca/diagnóstico por imagem , Artéria Ilíaca/patologia , Veia Ilíaca/diagnóstico por imagem , Veia Ilíaca/patologia , Masculino , Stents , Ultrassonografia DopplerRESUMO
Muscular polyarteritis nodosa where disease is isolated to skeletal muscle is a rare and often poorly recognised clinical entity. Patients typically present with fever and severe muscle pain limiting ability to ambulate without rise in creatine kinase. Often there is a significant delay between presentation and diagnosis, which requires histological confirmation. Musculoskeletal MRI is a sensitive investigation that can lead to timely biopsy and improve diagnostic yield. Early diagnosis of this condition is essential as patients typically respond favourably to corticosteroid treatment. Here we report 4 cases of muscular polyarteritis nodosa and review the reported literature.
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Músculo Esquelético/patologia , Mialgia/etiologia , Poliarterite Nodosa/diagnóstico , Adulto , Idoso , Anti-Inflamatórios , Antirreumáticos/administração & dosagem , Feminino , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Extremidade Inferior/diagnóstico por imagem , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Poliarterite Nodosa/tratamento farmacológico , Poliarterite Nodosa/fisiopatologiaRESUMO
Variants in MAGT1 have been identified as the cause of an immune deficiency termed X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection and neoplasia (XMEN) disease. Here, we describe 2 cases of XMEN disease due to novel mutations in MAGT1, one of whom presented with classical features of XMEN disease and another who presented with a novel phenotype including probable CNS vasculitis, HHV-8 negative multicentric Castelman disease and severe molluscum contagiosum, thus highlighting the clinical diversity that may be seen in this condition. Peripheral blood immunophenotyping of these 2 patients, together with an additional 4 XMEN patients, revealed reduced NKG2D expression, impaired CD28 expression on CD8+ T cells, CD4+ T cell lymphopenia, an inverted CD4:CD8 ratio and decreased memory B cells. In addition, we showed for the first time alterations to the CD8+ T cell memory compartment, reduced CD56hi NK cells, MAIT and iNKT cells, as well as compromised differentiation of naïve CD4+ T cells into IL-21-producing Tfh-type cells in vitro. Both patients were treated with supplemental magnesium with limited benefit. However, one patient has undergone allogeneic haematopoietic stem cell transplant, with full donor chimerism and immune reconstitution. These results expand our understanding of the clinical and immunological phenotype in XMEN disease, adding to the current literature, which we further discuss here.
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Proteínas de Transporte de Cátions/genética , Infecções por Vírus Epstein-Barr/genética , Herpesvirus Humano 4/fisiologia , Leucócitos Mononucleares/imunologia , Neoplasias/genética , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/genética , Adulto , Diferenciação Celular , Criança , Quimerismo , Infecções por Vírus Epstein-Barr/imunologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Memória Imunológica , Imunofenotipagem , Linfopenia , Magnésio/metabolismo , Masculino , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Neoplasias/imunologia , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/imunologiaRESUMO
We report two cases of cryptococcosis, associated with anti-granulocyte-macrophage colony-stimulating factor antibodies. We review this recently identified acquired form of autoimmune immune deficiency and discuss the potential applications of granulocyte-macrophage colony-stimulating factor antibody testing by enzyme-linked immunosorbent assay.
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Autoanticorpos/imunologia , Criptococose/diagnóstico , Criptococose/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Adulto , Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Autoanticorpos/sangue , Encéfalo/diagnóstico por imagem , Criptococose/tratamento farmacológico , Cryptococcus neoformans , Ensaio de Imunoadsorção Enzimática , Humanos , Pneumopatias Fúngicas/diagnóstico por imagem , Pneumopatias Fúngicas/imunologia , Imageamento por Ressonância Magnética , Masculino , Meningite Criptocócica/diagnóstico por imagem , Meningite Criptocócica/imunologia , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The extra-intestinal manifestation of tracheobronchitis is a rare complication of ulcerative colitis (UC). Here, we present a case of UC-related tracheobronchitis wherein the positive clinical effects of infliximab are demonstrated. CASE PRESENTATION: We report the case of a 39-year old woman who presented with a chronic productive cough on a distant background of surgically managed ulcerative colitis (UC). Our patient failed to achieve a satisfactory clinical improvement despite treatment with high dose inhaled corticosteroids, oral corticosteroids and azathioprine. Infliximab therapy was commenced and was demonstrated to achieve macroscopic and symptomatic remission of disease. CONCLUSIONS: We present the first case report documenting the benefits of infliximab in UC-related tracheobronchitis.
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Bronquite/tratamento farmacológico , Bronquite/etiologia , Colite Ulcerativa/complicações , Fármacos Gastrointestinais/uso terapêutico , Infliximab/uso terapêutico , Traqueíte/tratamento farmacológico , Traqueíte/etiologia , Adulto , Colite Ulcerativa/tratamento farmacológico , Feminino , Humanos , Indução de Remissão , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
AIM: The primary aim of the present study was to determine if it is cost effective to use human leukocyte antigen (HLA) typing as a first-line screening test for celiac disease (CD) in children with type 1 diabetes (T1D), as recommended by the European Society of Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN). The second aim was to investigate whether anti-tissue transglutaminase IgA (anti-tTGA) antibodies can be used to diagnose CD without the need for a confirmatory duodenal biopsy in T1D. METHODS: Data for all T1D patients aged <18 years, who attended the diabetes clinics in Western Australia up to June 2017, were extracted from the Western Australian Children's Diabetes Database (WACDD) and analyzed for their demographic data and CD permissive HLA alleles (DQ2, DQ8, and DQ7). For T1D patients already diagnosed with CD, the mode of diagnosis of CD, anti-tTGA titers, and CD permissive HLA alleles were analyzed. RESULTS: Of the 936 eligible T1D patients identified, HLA-DQ typing was available for 551 (59%). Of these 551 patients, 504 (91.2%) were positive for celiac permissive HLA alleles. Eight percent (n = 75) of the T1D patients had a co-diagnosis of CD. High anti-tTGA titers were observed in those who were diagnosed with a positive duodenal biopsy. CONCLUSION: HLA-DQ typing is not cost effective as a first-line screening test for CD in T1D patients because of over-representation of CD permissive HLA alleles in this group. Anti-tTGA titers may be useful in diagnosing CD in T1D without duodenal biopsy, as high levels were found to be strongly predictive of CD.
Assuntos
Doença Celíaca/diagnóstico , Diabetes Mellitus Tipo 1/complicações , Antígenos HLA-DQ/sangue , Teste de Histocompatibilidade/economia , Doença Celíaca/complicações , Doença Celíaca/imunologia , Criança , Estudos de Coortes , Feminino , Proteínas de Ligação ao GTP/imunologia , Humanos , Masculino , Proteína 2 Glutamina gama-Glutamiltransferase , Transglutaminases/imunologia , Austrália OcidentalAssuntos
Imunodeficiência de Variável Comum/diagnóstico , Vírus JC/fisiologia , Neurônios/fisiologia , Infecções por Polyomavirus/diagnóstico , Feminino , Humanos , Mefloquina/uso terapêutico , Pessoa de Meia-Idade , Mirtazapina/uso terapêutico , Neurônios/virologia , Resultado do Tratamento , Ativação Viral , Latência ViralRESUMO
Plasma cell mucositis (PCM) is a rare non-neoplastic plasma cell proliferative disorder of the mucous membranes, which typically presents as soft tissue lesions involving oral, upper airway or genital mucosa. Laryngeal involvement resulting in stridor has been reported in four other cases previously, with three requiring tracheostomy. We present a case of supraglottic stenosis in a 53-year-old woman presenting with dysphonia and stridor, requiring surgical resection on three occasions accompanied by tracheostomy on two occasions; biopsy was consistent with PCM. Due to relapsing disease activity, high-dose prednisolone and mycophenolate mofetil were commenced with prednisolone eventually being ceased. After 2 years of mycophenolate mofetil therapy, the patient's disease has been controlled without need for further surgical intervention. This is the first reported case of prolonged symptomatic improvement with the use of systemic immunosuppressive therapy with mycophenolate mofetil in PCM.
Assuntos
Terapia de Imunossupressão/métodos , Imunossupressores/administração & dosagem , Doenças da Laringe/tratamento farmacológico , Mucosite/tratamento farmacológico , Plasmócitos/imunologia , Esquema de Medicação , Feminino , Humanos , Doenças da Laringe/imunologia , Mucosa Laríngea/citologia , Mucosa Laríngea/imunologia , Pessoa de Meia-Idade , Mucosite/imunologia , Ácido Micofenólico/administração & dosagem , Prednisolona/administração & dosagem , Sons Respiratórios/etiologia , Tempo , Fatores de TempoRESUMO
Hyperplastic gingivitis is a rare manifestation of granulomatosis with polyangiitis (GPA). This gingivitis has a very distinctive clinical appearance (so-called Strawberry gingivitis) and when seen is virtually pathognomic for GPA. Gingivitis often precedes other organ involvement therefore making awareness of this manifestation particularly important to aid early diagnosis and treatment. Furthermore, histopathological findings of gingival specimens rarely reveal necrotizing granulomatous vasculitis, which is classically seen at other sites of involvement. As a result a delay in diagnosis is not uncommon. GPA if left untreated has a high mortality rate and early immunosuppressive treatment is associated with an improved prognosis. We present two cases of patients with GPA presenting with characteristic strawberry gingivitis and review the reported cases.
Assuntos
Gengivite/etiologia , Granulomatose com Poliangiite/complicações , Adulto , Feminino , Gengivite/tratamento farmacológico , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoAssuntos
Terapia Combinada/métodos , Imunoglobulina E/sangue , Leucemia Linfocítica Crônica de Células B , Linfonodos/patologia , Dermatopatias Vasculares , Vasculite , Adulto , Protocolos Antineoplásicos , Linfócitos B/imunologia , Biópsia/métodos , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/patologia , Leucemia Linfocítica Crônica de Células B/terapia , Tomografia por Emissão de Pósitrons/métodos , Dermatopatias Vasculares/diagnóstico , Dermatopatias Vasculares/etiologia , Dermatopatias Vasculares/fisiopatologia , Dermatopatias Vasculares/terapia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Vasculite/diagnóstico , Vasculite/etiologia , Vasculite/fisiopatologia , Vasculite/terapiaAssuntos
Glomérulos Renais/patologia , Síndrome Nefrótica/diagnóstico , Sífilis Congênita/complicações , Adulto , Antibacterianos/uso terapêutico , Biópsia , Diagnóstico Diferencial , Progressão da Doença , Feminino , Seguimentos , Humanos , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/etiologia , Recidiva , Sífilis Congênita/diagnóstico , Sífilis Congênita/tratamento farmacológicoRESUMO
Subcutaneous edema as a presenting feature of dermatomyositis has infrequently been described and is thought to signify a more aggressive disease course. We report a case involving a 38-year-old man who presented with significant subcutaneous edema involving his neck and upper body; he later developed clinical features and biopsy results consistent with dermatomyositis. Only sixteen previous cases of dermatomyositis with subcutaneous edema involving adults have been published in the literature and we aim to review disease progression, prognosis, and optimal treatment of the condition.
Assuntos
Dermatomiosite/complicações , Edema/etiologia , Corticosteroides/uso terapêutico , Adulto , Autoanticorpos/sangue , Terapia Combinada , Dermatomiosite/diagnóstico , Dermatomiosite/imunologia , Dermatomiosite/patologia , Progressão da Doença , Quimioterapia Combinada , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Masculino , Metotrexato/uso terapêutico , Debilidade Muscular/etiologia , Prognóstico , Respiração Artificial , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Tela Subcutânea , TraqueostomiaRESUMO
A 63-year-old man was admitted for investigation of blurred vision and multiple ring-enhancing lesions on cranial MRI. Histopathological examination of tissue obtained at brain biopsy showed multiple Toxoplasma gondii cysts. He was started on a combination of sulphadiazine and pyrimethamine for cerebral toxoplasmosis and was subsequently diagnosed with HIV-1 infection. He then developed acute renal failure and flank pain and was diagnosed with bilateral vesico-uretric calculi requiring bilateral stent insertion. The retrieved renal calculi were negative for the common stones that are routinely tested for in our laboratory and had the macroscopic characteristics of a sulphadiazine stone. His renal failure responded to cessation of the sulphadiazine.