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1.
BMC Med Genet ; 20(1): 114, 2019 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-31242861

RESUMO

BACKGROUND: Dedicator of cytokinesis 8 (DOCK8) deficiency (MIM #243700) is a rare disease, leads to a combined primary immunodeficiency (PID), and accounts for the autosomal recessive-hyper immunoglobulin E syndrome (AR-HIES). DOCK8 deficiency status characterizes by recurrent infections, atopy, and risk of cancer. Lymphoproliferative disease complicating PID, is difficult to diagnose. Our aim is to present a rare case of PID, and to the best of our knowledge, she is the first case of DOCK8 deficiency from Iraq. The genetic diagnosis was carried out in Japan using dried blood spot-based DNA transfer and whole-exome sequencing. CASE PRESENTATION: An 11-year-old Iraqi girl, of double first-cousin-parents, had a history of severe eczema, food allergy, and repeated infections. She presented with a jaw mass, bilateral cervical and axillary lymphadenopathy, and immunoglobulin (Ig) assays of 20, 3.3 and 1.7-fold above maximum normal level for age of IgE, IgA and IgG, respectively, along with a low IgM, eosinophilia and lymphopenia. Based on the jaw mass biopsy, non-Hodgkin lymphoma was suggested in Iraq, whereas histopathological re-evaluation in Japan revealed the diagnosis of a polyclonal reactive proliferation spectrum of lymphoproliferative disorders/plasmacytic hyperplasia, complicating PID. Whole-exome sequencing supported the diagnosis of PID by identifying a homozygous DOCK8 mutation with previously reported pathogenicity (NM_203447:c.3332delT, p.Phe1113Leufs*2), that may be attributed to consanguinity. CONCLUSIONS: International collaboration using an effective DNA transportation technique and next-generation sequencing was the key to pinpoint the diagnosis of DOCK8 deficiency. Our case asserted that careful pathogenetic evaluation, in an advanced setting, was crucial for ruling out the neoplastic process. Pediatricians in areas with a high prevalence of consanguinity marriage should have a high index of suspicion of DOCK8 deficiency in patients with recalcitrant eczema, and frequent respiratory and skin infectious episodes.


Assuntos
Sequenciamento do Exoma/métodos , Estudos de Associação Genética , Predisposição Genética para Doença , Fatores de Troca do Nucleotídeo Guanina/genética , Síndrome de Job/genética , Mutação , Anticorpos/sangue , Criança , Consanguinidade , DNA/sangue , Eosinofilia/imunologia , Feminino , Homozigoto , Humanos , Iraque , Japão , Arcada Osseodentária/patologia , Síndrome de Job/diagnóstico por imagem , Síndrome de Job/imunologia , Síndrome de Job/patologia , Linfopenia/imunologia , Transtornos Linfoproliferativos/genética , Linhagem
2.
J Allergy Clin Immunol Pract ; 7(6): 1986-1995.e3, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30878710

RESUMO

BACKGROUND: Autosomal-dominant signal transducer and activator of transcription 3 (STAT3) deficiency predisposes to recurrent bacterial pneumonia, complicated by bronchiectasis and cavitations. Aspergillosis is a major cause of morbidity in these patients. However, its diagnosis, classification, and treatment are challenging. OBJECTIVE: We aimed to assess the prevalence and describe the clinical, mycological, and radiological presentation and related therapy and outcome of Aspergillus infections of the respiratory tract in the STAT3-deficient patients of the National French cohort. METHODS: We performed a retrospective study of all pulmonary aspergillosis cases in STAT3-deficient patients (n = 74). Clinical and mycological data were collected up to October 2015 and imaging was centralized. RESULTS: Twenty-one episodes of pulmonary aspergillosis in 13 (17.5%) STAT3-deficient patients were identified. The median age at first episode was 13 years (interquartile range, 10-26 years). Ninety percent of patients had previous bronchiectasis or cavitations. Infections were classified as follows: 5 single aspergilloma, 9 chronic cavity pulmonary aspergillosis, 5 allergic bronchopulmonary aspergillosis-like disease, and 2 mixed forms of concomitant allergic bronchopulmonary aspergillosis-like disease and chronic cavity pulmonary aspergillosis. No invasive aspergillosis cases were identified. Aspergillus species were isolated in 71% of episodes and anti-Aspergillus antibodies in 93%. Eleven episodes were breakthrough infections. Antifungal treatment was prolonged, with a median of 13 months, and 6 patients (7 episodes) required surgery, with a high rate of postsurgical complications. One patient died and 6 had a relapse. CONCLUSIONS: Chronic and allergic forms of aspergillosis occurred in 17.5% of STAT3-deficient patients, mostly in lung cavities. Almost half had recurrences, despite prolonged antifungal treatment and/or surgery.


Assuntos
Síndrome de Job , Aspergilose Pulmonar , Fator de Transcrição STAT3/deficiência , Adolescente , Adulto , Antifúngicos/uso terapêutico , Criança , Feminino , França/epidemiologia , Humanos , Síndrome de Job/diagnóstico por imagem , Síndrome de Job/tratamento farmacológico , Síndrome de Job/epidemiologia , Masculino , Aspergilose Pulmonar/diagnóstico por imagem , Aspergilose Pulmonar/tratamento farmacológico , Aspergilose Pulmonar/epidemiologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
4.
J Clin Immunol ; 37(7): 695-700, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28803389

RESUMO

OBJECTIVE: STAT 3 deficiency (autosomal dominant hyper immunoglobulin E syndrome (AD-HIES)) is a primary immunodeficiency disorder with multi-organ involvement caused by dominant negative signal transducer and activator of transcription gene 3 (STAT3) mutations. We sought to describe the gastrointestinal (GI) manifestations of this disease. METHODS: Seventy subjects aged five to 60 years with a molecular diagnosis of AD-HIES were evaluated at the National Institutes of Health (NIH). Data collection involved a GI symptom questionnaire and retrospective chart review. RESULTS: In our cohort of 70 subjects, we found that 60% had GI symptoms (42/70). The most common manifestations were gastroesophageal reflux disease (GERD) observed in 41%, dysphagia in 31%, and abdominal pain in 24%. The most serious complications were food impaction in 13% and colonic perforation in 6%. Diffuse esophageal wall thickening in 74%, solid stool in the right colon in 50% (12/24), and hiatal hernia in 26% were the most prevalent radiologic findings. Esophagogastroduodenoscopy (EGD) demonstrated esophageal tortuosity in 35% (8/23), esophageal ulceration in 17% (4/23), esophageal strictures requiring dilation in 9% (2/23), and gastric ulceration in 17% (4/23). Esophageal eosinophilic infiltration was an unexpected histologic finding seen in 65% (11/17). CONCLUSION: The majority of AD-HIES subjects develop GI manifestations as part of their disease. Most notable are the symptoms and radiologic findings of GI dysmotility, as well as significant eosinophilic infiltration, concerning for a secondary eosinophilic esophagitis. These findings suggest that the STAT3 pathway may be implicated in a new mechanism for the pathogenesis of several GI disorders.


Assuntos
Gastroenteropatias/etiologia , Síndrome de Job/complicações , Fator de Transcrição STAT3/deficiência , Adolescente , Adulto , Biópsia , Criança , Pré-Escolar , Colonoscopia , Eosinófilos/imunologia , Feminino , Gastroenteropatias/sangue , Gastroenteropatias/diagnóstico por imagem , Gastroenteropatias/patologia , Trato Gastrointestinal/diagnóstico por imagem , Trato Gastrointestinal/patologia , Trato Gastrointestinal/cirurgia , Humanos , Imunoglobulina E/sangue , Síndrome de Job/sangue , Síndrome de Job/diagnóstico por imagem , Síndrome de Job/patologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Tomografia Computadorizada por Raios X , Ultrassonografia , Adulto Jovem
5.
Spine (Phila Pa 1976) ; 31(14): E471-4, 2006 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-16778678

RESUMO

STUDY DESIGN: A case report of the hyperimmunoglobulin E syndrome (Job syndrome) presenting in the context of late postoperative infection after corrective surgery for scoliosis. OBJECTIVE: To describe the clinical presentation and treatment of a patient with Job syndrome, and its implications for spine surgeons. SUMMARY OF BACKGROUND DATA: Job syndrome classically presents with a triad of increased serum immunoglobulin E, multiple abscesses, and pneumonia with pneumatocele formation. In recent years nonimmunologic manifestations have been described, including scoliosis, joint hypermobility, eosinophilia, and atopy. METHODS: A 15-year-old female presented with local swelling and fever 2 years after anterior lumbar discectomy and fusion with spinal instrumentation involving T11-L3 levels. Computerized tomography revealed paravertebral, psoas, and pulmonary abscesses. The implants were removed and antibiotic therapy instituted. Further investigation revealed features of the hyperimmunoglobulin E syndrome (Job syndrome). RESULTS: The patient's symptoms resolved, as did markers of inflammation. CONCLUSIONS: Job syndrome is a primary immunodeficiency often associated with scoliosis. Given the implications for surgical outcome in immunodeficient patients, the diagnosis should be considered and, blood tests instituted in patients with scoliosis with any of the associated history and physical findings of Job syndrome.


Assuntos
Fixadores Internos , Síndrome de Job/complicações , Escoliose/complicações , Escoliose/cirurgia , Fusão Vertebral , Adolescente , Antibacterianos/uso terapêutico , Remoção de Dispositivo , Feminino , Humanos , Infecções/complicações , Infecções/tratamento farmacológico , Síndrome de Job/diagnóstico por imagem , Complicações Pós-Operatórias , Escoliose/diagnóstico por imagem , Tomografia Computadorizada por Raios X
8.
Artigo em Inglês | MEDLINE | ID: mdl-9823680

RESUMO

We report a 12-year-old girl with hyperimmunoglobulin E (HIE) syndrome who presented with genu vulgus of left knee, joint deformities involving both hands, and frequent fractures. She had had chronic eczema and recurrent skin and soft tissue infections since infancy, and was found to have a pneumatocele during admission. Immunologic abnormalities included extremely elevated serum IgE levels (18989 IU/ml) and cutaneous anergy to candida, purified protein derivative, and tetanus toxoid. The results of polymorphonuclear leukocyte function tests including the nitroblue tetrazolium test and chemotaxis were normal. A high index of suspicion for HIE syndrome should be given in patients with recurrent skin infections and orthopedic complaints. The physician should anticipate orthopedic problems in caring for patients with HIE syndrome, and optimal antibiotics prophylaxis should be used.


Assuntos
Artrografia , Doenças do Desenvolvimento Ósseo/diagnóstico por imagem , Osso e Ossos/diagnóstico por imagem , Síndrome de Job/diagnóstico por imagem , Criança , Feminino , Fraturas Espontâneas/diagnóstico por imagem , Humanos , Síndrome de Job/imunologia
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