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BACKGROUND: Immediate IgE-mediated hypersensitivity reactions to polyethylene glycol (PEG) are rare. Our understanding of PEG hypersensitivity is limited. OBJECTIVE: To evaluate the clinical characteristics and investigation outcomes of the largest cohort of patients with PEG allergy reported. METHODS: A total of 44 patients investigated for suspected PEG allergy across 4 United Kingdom tertiary allergy centers between October 2013 and December 2020 were studied. Clinical characteristics, index reaction, and approaches to and outcomes of allergy investigations were analyzed. RESULTS: PEG hypersensitivity was confirmed in 42 of 44 cases. Macrogol laxatives were the most common index drugs reported (23%), followed by depo-medroxyprogesterone (19%), oral penicillin V (10%), and depo-methylprednisolone (10%). In general, 61% experienced grade III anaphylaxis. Intradermal testing (IDT) increased the diagnostic sensitivity from 51% to 85%. Five patients experienced systemic reactions during IDT. Of the 5 patients, 2 were skin prick test positive to a high molecular weight PEG. Three patients with negative skin test results had positive drug provocation test results. Seven patients with PEG allergy reported tolerance to H1-antihistamines containing PEG. Administration of messenger RNA COVID-19 or Oxford/AstraZeneca COVID-19 vaccines was tolerated in all 16 patients to whom they were administered. CONCLUSION: PEG hypersensitivity is an uncommon cause of drug-induced anaphylaxis. Four index drugs accounted for two-thirds of the cases, and reactions to these drugs should prompt PEG hypersensitivity investigations. PEG IDT increases diagnostic yield. The role of skin prick test with higher molecular weight PEGs requires further attention. Further studies are required to understand PEG thresholds and PEG equivalent doses of various administration routes. COVID-19 vaccines were tolerated by all exposed.
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Hipersensibilidade a Drogas , Polietilenoglicóis , Humanos , Masculino , Polietilenoglicóis/efeitos adversos , Feminino , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/imunologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Idoso , Anafilaxia/diagnóstico , Testes Cutâneos , COVID-19/imunologia , COVID-19/diagnóstico , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Reino Unido , Imunoglobulina E/imunologia , Imunoglobulina E/sangue , SARS-CoV-2/imunologia , Testes IntradérmicosRESUMO
BACKGROUND: Vitamin B12 (Vit B12) deficiency affects approximately 20% of those above the age of 60 years in the United Kingdom and United States. If untreated, it leads to detrimental health outcomes. OBJECTIVE: To investigate a cohort of patients with Vit B12 hypersensitivity (VB12H) referred to 3 UK allergy centers and design a pathway for the investigation of VB12H. METHODS: A total of 29 patients seen between 2014 and 2022 underwent skin prick testing (1 mg/mL) with cyanocobalamin (CC) and hydroxycobalamin (HC) and intradermal testing (0.1 and 0.01 mg/mL). Patients with negative skin tests underwent a Vit B12 drug provocation test (DPT) with either the index or the alternative drug. RESULTS: Of 29 patients, 18 (62%) presented with immediate VB12H. Eight experienced anaphylaxis (4 to HC and 4 to CC) and had positive skin tests to the index drug. One patient reacted to oral and 7 patients to injectable Vit B12. Seven patients sensitized to one form of Vit B12-tolerated DPT with an alternative Vit B12. One patient with immediate VB12H reacted to polyethylene glycol (PEG) in oral cobalamin. Of 29 patients, 8 presented with delayed hypersensitivity reaction; 4 patients tolerated the intramuscular index formulation, whereas 2 patients tolerated the per oral formulation. One patient presented with symptoms consistent with symmetrical drug-related intertriginous and flexural exanthema. Three patients were referred because of cobalt allergy. CONCLUSION: Confirmed VB12H is rare. We propose a comprehensive evaluation protocol that includes Vit B12 skin tests and considers PEG allergy in patients presenting with VB12H.
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Anafilaxia , Hipersensibilidade a Drogas , Humanos , Pessoa de Meia-Idade , Anafilaxia/tratamento farmacológico , Hipersensibilidade a Drogas/etiologia , Testes Intradérmicos , Polietilenoglicóis , Testes Cutâneos/efeitos adversos , Vitamina B 12/uso terapêutico , Vitaminas , Estudos RetrospectivosRESUMO
Introduction: Giant cell arteritis (GCA) is a systemic granulomatous vasculitis affecting the large arteries. Abnormal lymphocyte function has been noted as a pathogenic factor in GCA. Mycophenolate mofetil (MMF) inhibits inosine monophosphate dehydrogenase and is therefore a highly lymphocyte-specific immunosuppressive therapy. We aimed to assess the efficacy of MMF for inducing remission in GCA. Methods: Seven patients (5 female, 2 male) with GCA under therapy with MMF and who were treated at the outpatient clinic for rare inflammatory systemic diseases at Hannover Medical School between 2010 and 2023 were retrospectively included in the study. All patients underwent duplex sonography, 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET), magnetic resonance imaging (MRI), and/or biopsy to confirm the diagnosis. The primary endpoints were the number of recurrences, CRP levels at 3-6 and 6-12 months, and the period of remission. Results: All patients in this case series showed inflammatory activity of the arterial vessels in at least one of the imaging modalities: duplex sonography (n = 5), 18F-FDG PET (n = 5), MRI (n = 6), and/or biopsy (n = 5). CRP levels of all patients decreased at the measurement time points 3-6 months, and 6-9 months after initiation of therapy with MMF compared with CRP levels before MMF therapy. All patients with GCA in this case series achieved disease remission. Discussion: The results of the present case series indicate that MMF is an effective therapy in controlling disease activity in GCA, which should be investigated in future randomized controlled trials.
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BACKGROUND: Approximately 300 million people worldwide suffer from a rare disease. An optimal treatment requires a successful diagnosis. This takes a particularly long time, especially for rare diseases. Digital diagnosis support systems could be important aids in accelerating a successful diagnosis in the future. OBJECTIVE: The current possibilities of digital diagnostic support systems in the diagnosis of rare diseases and questions that still need to be clarified are presented in relation to the parameters of ethics, economy and quality of life. MATERIAL AND METHODS: Current research results of the authors were compiled and discussed in the context of the current literature. A case study is used to illustrate the potential of digital diagnostic support systems. RESULTS: Digital diagnostic support systems and experts together can accelerate the successful diagnosis in patients with rare diseases. This could have a positive impact on patients' quality of life and lead to potential savings in direct and indirect costs in the healthcare system. CONCLUSION: Ensuring data security, legal certainty and functionality in the use of digital diagnostic support systems is of great importance in order to create trust among experts and patients. Continuous further development of the systems by means of artificial intelligence (AI) could also enable patients to accelerate diagnosis in the future.
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Inteligência Artificial , Doenças Raras , Humanos , Doenças Raras/diagnóstico , Qualidade de Vida , Renda , ConfiançaRESUMO
The concept of autoinflammation includes a heterogeneous group of monogenic and polygenic diseases. These are characterized by excessive activation of the innate immune system without antigen-specific T cells or autoantibodies. The diseases are characterized by periodic episodes of fever and increased inflammation parameters. Monogenic diseases include familial Mediterranean fever (FMF) and the newly described VEXAS (vacuoles, E1 enzyme, Xlinked, autoinflammatory, somatic) syndrome. Heterogeneous diseases include adult-onset Still's disease and Schnitzler syndrome. Treatment is aimed at preventing the excessive inflammatory reaction in order to avoid long-term damage, such as amyloid A (AA) amyloidosis.
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This case report describes a congenital cystic scalp nodule on a 2-week-old infant.
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Displasia Ectodérmica , Encefalocele , Humanos , Encefalocele/complicações , Encefalocele/diagnóstico , Displasia Ectodérmica/complicações , Displasia Ectodérmica/diagnóstico , Couro CabeludoRESUMO
BACKGROUND: Patients with rare diseases usually go through years of diagnostic odysseys. The large number of rare diseases and the associated lack of expertise pose a major challenge to physicians. There are few physicians dealing with patients with rare diseases and they usually work in a limited number of specialized centers. The aim of this study was to evaluate the diagnostic efficiency of an expert center. METHODS: The diagnostic pathway of 78 patients of the outpatient clinic for rare inflammatory systemic diseases with renal involvement was analyzed retrospectively. For this purpose, each examination day was documented with the corresponding examinations performed from the onset of initial symptoms. Three time points were considered: The time when patients first visited a physician with symptoms, the time when patients consulted an expert, and the time when they received the correct diagnosis. In addition, it was documented whether the diagnosis could be made without the expert, or only with the help of the expert. The examinations that confirmed the diagnosis were also documented for each patient. RESULTS: A correct diagnosis was made without the help of the expert in only 21% of cases. Each patient visited an average of 6 physicians before consulting the expert. Targeted diagnostics enabled the expert to make the correct diagnosis with an average of seven visits, or one inpatient stay. However, referral to the expert took an average of 4 years. CONCLUSION: The data show that rapid and targeted diagnostics were possible in the expert center due to the available expertise and the interdisciplinary exchange. Early diagnosis is of great importance for many patients, as an early and correct therapy can be decisive for the course of the disease.
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Instituições de Assistência Ambulatorial , Doenças Raras , Humanos , Doenças Raras/diagnóstico , Doenças Raras/terapia , Estudos Retrospectivos , Exame Físico , Encaminhamento e ConsultaRESUMO
The concept of autoinflammation includes a heterogeneous group of monogenic and polygenic diseases. These are characterized by excessive activation of the innate immune system without antigen-specific T cells or autoantibodies. The diseases are characterized by periodic episodes of fever and increased inflammation parameters. Monogenic diseases include familial Mediterranean fever (FMF) and the newly described VEXAS (vacuoles, E1 enzyme, Xlinked, autoinflammatory, somatic) syndrome. Heterogeneous diseases include adult-onset Still's disease and Schnitzler syndrome. Treatment is aimed at preventing the excessive inflammatory reaction in order to avoid long-term damage, such as amyloid A (AA) amyloidosis.
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Febre Familiar do Mediterrâneo , Doenças Hereditárias Autoinflamatórias , Humanos , Adulto , Doenças Hereditárias Autoinflamatórias/diagnóstico , Febre/terapia , InflamaçãoRESUMO
OBJECTIVE: To describe the clinical and laboratory outcomes of infants with subcutaneous fat necrosis of the newborn (SCFN) and propose a care algorithm. METHODS: This single-center, retrospective study of infants diagnosed with SCFN at Ann & Robert H. Lurie Children's Hospital of Chicago from 2009 to 2019. RESULTS: Of 32 infants who met inclusion criteria, most were born full-term (84%), born via cesarean section (58%), had normal weight for gestational age (69%), and experienced delivery complications (53%). Twenty-nine infants (91%) had calcium drawn, and all had hypercalcemia. Three infants developed clinical symptoms of hypercalcemia, two required hospital admission, two developed nephrocalcinosis, and one developed acute kidney injury. The majority of infants (62%) had a peak ionized calcium between 1.5 and 1.6 mmol/L. No infants with peak ionized calcium less than 1.5 mmol/L developed complications of hypercalcemia. Most patients were diagnosed with hypercalcemia (86%) and demonstrated peak ionized calcium levels (59%) within the first 28 days of life. No patients developed hypercalcemia after 3 months of age. CONCLUSION: Hypercalcemia occurred in 100% of infants who had laboratory monitoring. We recommend obtaining an initial ionized calcium level when SCFN is suspected, and monitoring for the first 3 months of life if hypercalcemia has not been detected. In patients with asymptomatic hypercalcemia less than 1.5 mmol/L, there appears to be low likelihood of related complications. For symptomatic, markedly elevated (>1.6 mmol/L), or persistently elevated levels (>6 months) we suggest coordinated care with endocrinology or nephrology, consider hospitalization, and urinary system ultrasound.
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Necrose Gordurosa , Hipercalcemia , Gravidez , Recém-Nascido , Criança , Humanos , Feminino , Hipercalcemia/complicações , Cálcio , Estudos Retrospectivos , Cesárea , Gordura Subcutânea , Necrose Gordurosa/complicaçõesRESUMO
Getting access to specialists for autoinflammatory diseases (AID) can be challenging. Therefore, an increasing number of patients and healthcare professionals are seeking information on AID via the Internet, using the video platform YouTube, for example. However, the quality of such videos has not yet been evaluated. A YouTube search was conducted to assess videos about AID to evaluate the quality and usefulness from both the patient's and healthcare professional´s perspectives. Video duration, number of views, likes, dislikes, comments, and uploading source on various AID were extracted. Video quality was evaluated by the modified global quality scale (GQS). The reliability was assessed by the modified five-point DISCERN score. In total, 140 videos were screened of which 105 videos met the inclusion criteria for further analysis. Based on the GQS, the overall quality of videos for patients was found to be low in 64.8%, intermediate in 27.6%, and high in 7.6% of videos. The quality of videos for professionals was similar (54.3% low, 23.8% intermediate, and 21.9% of high quality). Videos were more often targeting medical professionals (65.7%) and less often patients (34.3%). This analysis demonstrates that the majority of videos regarding AIDs are of limited quality. Available videos more often address users with a professional medical background. Only a small proportion of existing videos provide understandable and useful information for AID patients. Thus, there is a strong need to develop high-quality and audience-oriented videos in the context of educational campaigns for these rare disease groups.
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Doenças Hereditárias Autoinflamatórias , Mídias Sociais , Humanos , Reprodutibilidade dos Testes , Gravação em Vídeo , Disseminação de InformaçãoRESUMO
BACKGROUND: The beta-lactam antibiotic amoxicillin and the beta-lactamase inhibitor clavulanic acid in combination with amoxicillin are known to cause both immediate- and nonimmediate-type hypersensitivity. OBJECTIVE: To characterize a large cohort of patients with a history of amoxicillin or amoxicillin-clavulanic acid hypersensitivity. METHODS: A retrospective analysis was conducted of the demographics, presentation, investigation, and management of 331 patients presenting to 1 allergy center with a history of hypersensitivity to amoxicillin or amoxicillin-clavulanic acid. RESULTS: Hypersensitivity was confirmed in 37 of 221 patients (17%) who took amoxicillin and 47 of 110 patients (43%) who took amoxicillin-clavulanic acid as the index drug. In immediate hypersensitivity, skin test results confirmed the diagnosis in 66 of 139 patients (47%). Penicillin cross-reactivity was observed in 16 of 36 patients (44%). Of the 16 patients who were cross-reactive, 13 (81%) reacted to amoxicillin-clavulanic acid as the index drug. All patients who had negative skin test results (73/139) underwent drug provocation. The negative predictive value of skin tests was 89%. In nonimmediate hypersensitivity, delayed intradermal tests confirmed diagnosis in 12 of 170 patients (7%). Of the 12 patients whose skin test results were positive, 8 (67%) presented with drug reaction with eosinophilia and systemic symptoms. All patients with a negative skin test result (158/170) underwent drug provocation. The negative predictive value of skin tests was 95%. Penicillin cross-reactivity was observed in 3 of 12 patients (25%). Ten patients were diagnosed with hypersensitivity to clavulanic acid. CONCLUSION: The negative predictive value of skin tests in both immediate and nonimmediate hypersensitivity reactions is excellent and excludes severe allergy. Nonimmediate hypersensitivity is rare. Confirmed hypersensitivity is more likely if amoxicillin-clavulanic acid is the index drug. Cross-reactivity was more common in patients presenting with immediate hypersensitivity, typically involving benzylpenicillin. A minority of patients were allergic to clavulanic acid.
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Hipersensibilidade a Drogas , Hipersensibilidade Imediata , Amoxicilina/efeitos adversos , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos , Antibacterianos/efeitos adversos , Ácido Clavulânico/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Humanos , Monobactamas , Penicilina G , Penicilinas/efeitos adversos , Estudos Retrospectivos , Testes Cutâneos , Inibidores de beta-Lactamases/efeitos adversosRESUMO
In this work, two vintages (2019 and 2020) of red-fleshed 'Weirouge' apples were processed with the innovative spiral filter press technology to investigate juice production in an oxygen-reduced atmosphere. After pressing, a more brilliant red color and appreciably higher amounts of oxidation-sensitive constituents (ascorbic acid, anthocyanins, and colorless (poly)phenols) were seen in spiral filter pressed juices compared to those produced with conventional systems (horizontal filter press and decanter). In a subsequent stability study (24 weeks storage at 4, 20, and 37 °C), the color and phenolic compounds were monitored and differences in the juices produced with the different pressing-systems were widely maintained during the storage period. The analyses of the anthocyanins and colorless (poly)phenols were conducted by UHPLC-DAD-ESI-QTOF-HR-MS/MS and UHPLC-DAD. The spiral filter press emerged as a promising technology for the production of juices with a more attractive color and a better retention of oxidation-sensitive constituents during processing and storage compared to conventional juices.
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Malus , Antocianinas , Frutas/química , Fenóis/análise , Espectrometria de Massas em TandemRESUMO
BACKGROUND/OBJECTIVES: The principal environmental risk factor for conventional nevi and melanomas is ultraviolet exposure. However, little is known about genetic or environmental risk factors for developing Spitz tumors. This study investigates risk factors associated with Spitz neoplasms. METHODS: Patients with Spitz tumors seen at Northwestern Memorial Hospital and Lurie Children's Hospital were surveyed with a 16-item questionnaire about environmental and inherited factors. Spitz tumor patients were compared to a pediatric control cohort from a similar clinical setting. This was supplemented with a meta-analysis of genetic and environmental causes of Spitz neoplasms. RESULTS: One hundred and six Spitz and 58 control surveys were obtained and no statistically significant differences in genetic or environmental risk factors were found between Spitz and control groups. CONCLUSION: Our data and meta-analysis suggest that typical risk factors associated with melanoma are not significantly associated with Spitz tumors. Identification of relevant genetic or environmental risk factors will likely require larger and population-based studies.
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Melanoma , Nevo de Células Epitelioides e Fusiformes , Nevo , Neoplasias Cutâneas , Criança , Diagnóstico Diferencial , Humanos , Melanoma/etiologia , Melanoma/genética , Nevo de Células Epitelioides e Fusiformes/epidemiologia , Nevo de Células Epitelioides e Fusiformes/genética , Fatores de Risco , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/genéticaRESUMO
INTRODUCTION: The aim of this study was to evaluate toxicity, oncological and functional outcome, and quality of life after salvage radiotherapy for recurrent prostate cancer after high-intensity focused ultrasound (HIFU) therapy. METHODS: A total of 13 patients undergoing salvage radiotherapy for biopsy-proven prostate cancer recurrence after HIFU therapy were included and followed up every 3 months. Oncological outcome (by PSA measurements), toxicity (according to CTCAE criteria), and functional outcome were evaluated. Quality of life was assessed by standardized questionnaires (QLQ-C30 and QLQ-PR25) at baseline, 3 months, and 12 months after salvage treatment. RESULTS: Median age of patients was 80 years (interquartile range [IQR] 75-82). Patients underwent normofractionated salvage radiotherapy with median 73.6 Gy. PSA nadir was reached at 6 months and was 0.2 ng/mL. Median follow-up was 76 months (IQR 55-96). Biochemical recurrence occurred in 3 patients (23.1%) at a median of 36.4 months. No gastrointestinal (GI) or genitourinary (GU) toxicity ≥ grade 3 was noted during follow-up. Early and late grade II GI toxicity occurred in 1 patient (7.7%), respectively. GU toxicity grade II was noted in up to 53.8% at 3 months and 61.5% at 12 months. In terms of health-related quality of life, there was no statistically significant difference at 3 and 12 months compared to the baseline. Only differences were seen in sexual functioning (3 and 12 months) and in diarrhea (3 months), affecting patients' wellbeing. DISCUSSION/CONCLUSION: Salvage radiotherapy after HIFU treatment can be performed safely, thereby providing acceptable recurrence-free survival without severe impact on post-interventional quality of life.
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Tratamento por Ondas de Choque Extracorpóreas , Neoplasias da Próstata , Idoso de 80 Anos ou mais , Humanos , Masculino , Recidiva Local de Neoplasia/terapia , Antígeno Prostático Específico , Neoplasias da Próstata/radioterapia , Qualidade de Vida , Terapia de Salvação/efeitos adversos , Resultado do TratamentoRESUMO
The development of vaccines against SARS-CoV2 brought about several challenges, including the management of hypersensitivity reactions to these formulations. The search for underlying mechanisms involved in these adverse events initially focused on excipients which may trigger mast cell activation responses via non-IgE pathways: polyethylene glycol and trometamol. We sought to determine whether these components, in their pure form, were capable of stimulating mast cells directly. To test this hypothesis, we used an in vitro model for non-IgE-mediated activation that has previously shown degranulation responses induced via MRGPRX2 with known drug agonists of the receptor. Human LAD2 mast cells were incubated with different concentrations (1, 10, 50 mg/ml) of trometamol and of purified polyethylene glycol/Macrogol (molecular weights: 2,000, 3,350, 4,000, and 6,000). Mast cell degranulation was assessed using a beta-hexosaminidase read-out. Interestingly, degranulation responses for all reagents tested showed no significant differences from those obtained from the negative control (basal degranulation). Receptor-silencing assays were therefore not conducted. In summary, purified PEG and trometamol did not induce mast cell degranulation in this in vitro model for the study of non-IgE mechanisms of drug hypersensitivity, previously shown to be useful in the investigation of MRGPRX2 ligands. Studies using complete vaccine formulations, lipid conjugates, and receptor gene variants are needed to further clarify mechanisms of vaccine hypersensitivity.
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A 32-year-old man presented with painless macrohaematuria. An endoscopic stone removal of the upper moiety of a left double kidney with ureter duplex was performed 4 years ago. The inserted ureteral catheter (DJ) was not removed although it was communicated to the patient and written in the discharge report. The DJ led to a large bladder stone, a total incrustation of the DJ, and a staghorn calculus of the upper moiety. Furthermore, renal function scintigraphy showed no clinically significant function of the upper moiety. Therefore, a heminephrectomy was performed with corresponding ureterectomy and sectio alta for bladder stone removal.
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Corpos Estranhos/cirurgia , Stents , Ureter , Obstrução Ureteral/cirurgia , Cateteres Urinários , Adulto , Corpos Estranhos/complicações , Humanos , Masculino , Medição de Risco , Obstrução Ureteral/etiologiaRESUMO
Periodic fever syndromes (PFS) are a group of rare autoinflammatory diseases, which are characterized by disorders of the innate immune reaction and life-long recurrent episodes of inflammatory symptoms. This article describes the diagnostic approach. In addition to the patient medical history, physical examination and laboratory determinations, gene tests are becoming increasingly more important. The panel diagnostics using high throughput sequencing or next generation sequencing (NGS) is the method of choice for the detection of a genetic cause of PFS. This article discusses the diagnostic decision support systems (DDSS) that can play a future role in the diagnosis of rare diseases, especially those with complex patterns of symptoms.
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Doenças Hereditárias Autoinflamatórias , Febre/diagnóstico , Testes Genéticos , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , SíndromeRESUMO
In the last 20 years the clarification of monogenic periodic febrile diseases has led to the independent concept of autoinflammation. In this heterogeneous group polygenic complex diseases are also now included. The spectrum of symptoms is continuously growing. The main difference to autoimmunity is an excessive activation of the innate immune system without formation of autoantibodies or antigen-specific Tcells. The cardinal symptom is recurrent fever episodes accompanied by signs of inflammation, which in the periodic manifestations alternate with intervals of general well-being. The classical monogenic diseases are also known as hereditary recurrent fever (HRF). Examples are familial Mediterranean fever (FMF), cryopyrin-associated periodic syndrome (CAPS), tumor necrosis factor receptor 1associated periodic syndrome (TRAPS), adenosine deaminase 2 (ADA2) deficiency and mevalonate kinase deficiency (MKD, hyper-IgD syndrome). The polygenic diseases are also known as nonhereditary fever syndromes. These include adult-onset Still's disease (AoSD), Adamantiades-Behçet disease, the PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis) and gouty arthritis. All autoinflammatory fever syndromes are accompanied by a long-term risk of development of amyloid A amyloidosis, depending on the individual severity and treatment success. In some diseases severe complications can sometimes occur.
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Febre Familiar do Mediterrâneo , Doenças Hereditárias Autoinflamatórias , Amiloidose , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Febre Familiar do Mediterrâneo/genética , Febre , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/genética , Doenças Hereditárias Autoinflamatórias/terapia , Humanos , Proteína Amiloide A Sérica , SíndromeRESUMO
BACKGROUND: The U.K. 100,000 Genomes Project is in the process of investigating the role of genome sequencing in patients with undiagnosed rare diseases after usual care and the alignment of this research with health care implementation in the U.K. National Health Service. Other parts of this project focus on patients with cancer and infection. METHODS: We conducted a pilot study involving 4660 participants from 2183 families, among whom 161 disorders covering a broad spectrum of rare diseases were present. We collected data on clinical features with the use of Human Phenotype Ontology terms, undertook genome sequencing, applied automated variant prioritization on the basis of applied virtual gene panels and phenotypes, and identified novel pathogenic variants through research analysis. RESULTS: Diagnostic yields varied among family structures and were highest in family trios (both parents and a proband) and families with larger pedigrees. Diagnostic yields were much higher for disorders likely to have a monogenic cause (35%) than for disorders likely to have a complex cause (11%). Diagnostic yields for intellectual disability, hearing disorders, and vision disorders ranged from 40 to 55%. We made genetic diagnoses in 25% of the probands. A total of 14% of the diagnoses were made by means of the combination of research and automated approaches, which was critical for cases in which we found etiologic noncoding, structural, and mitochondrial genome variants and coding variants poorly covered by exome sequencing. Cohortwide burden testing across 57,000 genomes enabled the discovery of three new disease genes and 19 new associations. Of the genetic diagnoses that we made, 25% had immediate ramifications for clinical decision making for the patients or their relatives. CONCLUSIONS: Our pilot study of genome sequencing in a national health care system showed an increase in diagnostic yield across a range of rare diseases. (Funded by the National Institute for Health Research and others.).
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Genoma Humano , Doenças Raras/genética , Adolescente , Adulto , Criança , Pré-Escolar , Características da Família , Feminino , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Reação em Cadeia da Polimerase , Doenças Raras/diagnóstico , Sensibilidade e Especificidade , Medicina Estatal , Reino Unido , Sequenciamento Completo do Genoma , Adulto JovemRESUMO
BACKGROUND: Melkersson-Rosenthal syndrome is a rare disease characterized by the triad of recurrent orofacial swelling with facial paralysis and fissured dorsal tongue. Histologically, noncaseating granulomatous inflammation occurs that confirms the diagnosis. Overlaps between granulomatous diseases such as sarcoidosis and Crohn's disease are described. Systemic corticosteroid therapy is the treatment of choice for acute attacks. CASE PRESENTATION: We here present a case of a 59-year-old White woman suffering from Melkersson-Rosenthal syndrome with a past history of sarcoidosis on therapy with leflunomide in combination with low-dose tacrolimus successfully treated with the anti-leprosy drug clofazimine after failure of systemic steroid therapy. CONCLUSIONS: We propose clofazimine as an alternative treatment in steroid-refractory cases.