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1.
Artigo em Inglês | MEDLINE | ID: mdl-37937715

RESUMO

BACKGROUND AND OBJECTIVE: The safety profile of venom immunotherapy (VIT) is a relevant issue and considerable differences in safety and efficacy of VIT have been reported. The primary aim of this study was to evaluate the safety of ACE inhibitors and beta-blockers during VIT, which has already been published. For a second analysis, data concerning premedication and venom preparations in relation to systemic adverse events (AE) during the up-dosing phase and the first year of the maintenance phase were evaluated as well as the outcome of field stings and sting challenges. METHODS: The study was conducted as an open, prospective, observational, multicenter study. In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. RESULTS: Premedication with oral antihistamines was taken by 52.1% of patients during the up-dosing and 19.7% of patients during the maintenance phase. Taking antihistamines had no effect on the frequency of systemic AE (p=0.11) but large local reactions (LLR) were less frequently seen (OR: 0.74; 95% CI: 0.58-0.96; p=0.02). Aqueous preparations were preferentially used for up-dosing (73.0%) and depot preparations for the maintenance phase (64.5%). The type of venom preparation neither had an influence on the frequency of systemic AE nor on the effectiveness of VIT (p=0.26 and p=0.80, respectively), while LLR were less frequently seen when depot preparations were used (p<0.001). CONCLUSION: Pretreatment with oral antihistamines during VIT significantly reduces the frequency of LLR but not systemic AE. All venom preparations used were equally effective and did not differ in the frequency of systemic AE.

2.
Br J Dermatol ; 186(3): 429-439, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34608631

RESUMO

BACKGROUND: Pemphigus vulgaris and pemphigus foliaceus are potentially life-threatening autoimmune disorders triggered by IgG autoantibodies against mucosal and epidermal desmogleins. There is an unmet need for fast-acting drugs that enable patients to achieve early sustained remission with reduced corticosteroid reliance. OBJECTIVES: To investigate efgartigimod, an engineered Fc fragment that inhibits the activity of the neonatal Fc receptor, thereby reducing serum IgG levels, for treating pemphigus. METHODS: Thirty-four patients with mild-to-moderate pemphigus vulgaris or foliaceus were enrolled in an open-label phase II adaptive trial. In sequential cohorts, efgartigimod was dosed at 10 or 25 mg kg-1 intravenously with various dosing frequencies, as monotherapy or as add-on therapy to low-dose oral prednisone. Safety endpoints comprised the primary outcome. The study is registered at ClinicalTrials.gov (identifier NCT03334058). RESULTS: Adverse events were mostly mild and were reported by 16 of 19 (84%) patients receiving efgartigimod 10 mg kg-1 and 13 of 15 (87%) patients receiving 25 mg kg-1 , with similar adverse event profiles between dose groups. A major decrease in serum total IgG and anti-desmoglein autoantibodies was observed and correlated with improved Pemphigus Disease Area Index scores. Efgartigimod, as monotherapy or combined with prednisone, demonstrated early disease control in 28 of 31 (90%) patients after a median of 17 days. Optimized, prolonged treatment with efgartigimod in combination with a median dose of prednisone 0·26 mg kg-1 per day (range 0·06-0·48) led to complete clinical remission in 14 of 22 (64%) patients within 2-41 weeks. CONCLUSIONS: Efgartigimod was well tolerated and exhibited an early effect on disease activity and outcome parameters, providing support for further evaluation as a therapy for pemphigus.


Assuntos
Anticorpos Monoclonais Humanizados , Pênfigo , Anticorpos Monoclonais Humanizados/efeitos adversos , Autoanticorpos , Desmogleína 1 , Estudos de Viabilidade , Antígenos de Histocompatibilidade Classe I , Humanos , Imunoglobulina G , Recém-Nascido , Pênfigo/tratamento farmacológico , Prednisona/administração & dosagem , Receptores Fc
3.
Eur Ann Allergy Clin Immunol ; 50(5): 232-234, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29384114

RESUMO

Summary: Drone larvae are mostly considered a by-product of beekeeping, but have recently been advo-cated as a high-protein source of food. There are as yet no data concerning their allergenic potential. We report on a 29-year old bee keeper who experienced an anaphylactic reaction following the consumption of a freshly prepared beverage from raw drone larvae. Larvae-specific sensitization was confirmed by prick-to-prick and basophil activation testing. Bee stings and classical bee products including honey and royal jelly were tolerated. This is the hitherto first report on IgE-mediated allergy to drone larvae. We suggest that a certain awareness towards the allergenicity of bee larvae is required.


Assuntos
Anafilaxia/diagnóstico , Bebidas , Hipersensibilidade Alimentar/diagnóstico , Adulto , Alérgenos/imunologia , Anafilaxia/imunologia , Animais , Teste de Degranulação de Basófilos , Abelhas/fisiologia , Serviços Médicos de Emergência , Hipersensibilidade Alimentar/imunologia , Humanos , Imunoglobulina E/metabolismo , Proteínas de Insetos/imunologia , Larva , Masculino , Testes Cutâneos
4.
Clin Exp Allergy ; 46(1): 125-32, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26767493

RESUMO

BACKGROUND: Immunoglobulin E-mediated allergy to drugs and substances used during general anaesthesia as well as non-allergic drug hypersensitivity reactions may account for anaesthesia-induced anaphylaxis. As IgE-mediated anaphylaxis is a potentially life-threatening reaction, identification of the culprit allergen is essential to avoid anaphylaxis recurrence during subsequent general anaesthesia. OBJECTIVE: To study whether preventive recommendations derived from allergy testing after intraoperative anaphylaxis were followed in subsequent general anaesthesia. METHODS: Results of standardized allergy testing after anaesthesia-induced anaphylaxis and outcome of subsequent general anaesthesia were analysed retrospectively. RESULTS: Fifty-three of 107 patients were diagnosed with IgE-mediated allergy to a drug or substance used during general anaesthesia, and 54 patients were test negative. Twenty-eight of 29 allergy patients tolerated subsequent general anaesthesia uneventfully. One patient with cefazolin allergy suffered from anaphylaxis recurrence due to accidental reapplication of cefazolin. Twenty-two of 24 test-negative patients tolerated subsequent general anaesthesia, whereas two patients again developed anaphylaxis despite pre-medication regimens. CONCLUSION AND CLINICAL RELEVANCE: Our results confirm the practical impact of allergy testing in general anaesthesia-induced anaphylaxis. By identification of the allergen, it is possible to avoid allergic anaphylaxis during subsequent anaesthesia. In most cases, recommended pre-medication seems to prevent the recurrence of non-allergic drug hypersensitivity reactions.


Assuntos
Anafilaxia/etiologia , Anestesia Geral/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alérgenos/imunologia , Anafilaxia/diagnóstico , Anafilaxia/prevenção & controle , Especificidade de Anticorpos/imunologia , Basófilos/imunologia , Basófilos/metabolismo , Criança , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/imunologia , Feminino , Humanos , Imunização , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Testes Cutâneos , Triptases/sangue , Fluxo de Trabalho , Adulto Jovem
5.
Clin Exp Allergy ; 44(12): 1531-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25323308

RESUMO

BACKGROUND: The lymphocyte transformation test (LTT) has been promoted as in-vitro test for diagnosis of drug hypersensitivity. For determination of statistical LTT sensitivity, series of patients with clinically uniform reactions followed by complete drug hypersensitivity work-up are mandatory. Assessment of LTT specificity requires control patients who tolerated exposure to the drug studied. OBJECTIVE: To prospectively determine the diagnostic value of the LTT in a clinically and diagnostically well-defined series of patients. METHODS: Patients with exanthematous skin eruptions after ampicillin (AMP) intake were included in this study. After exclusion or confirmation of delayed-onset allergic AMP hypersensitivity by skin and provocation testing, two independent LTTs were performed: one standard LTT and a modified LTT with additional anti-CD3/anti-CD28 monoclonal antibody stimulation. RESULTS: By testing, delayed-onset allergic AMP hypersensitivity was diagnosed in 11 patients and definitely ruled out in 26. The standard LTT reached a diagnostic sensitivity of 54.5% while the modified LTT yielded 72.7%. However, the methodical test modification resulted in a decline of specificity from 92.3% (standard LTT) to 76.9%. CONCLUSIONS AND CLINICAL RELEVANCE: In cases of AMP-associated exanthems, the diagnostic value of the LTT compared with routine allergy testing is limited. When evaluating such exanthems, provocation testing remains the gold standard. Delayed reading of intradermal skin tests remains most useful to avoid positive provocation reactions.


Assuntos
Hipersensibilidade a Drogas/diagnóstico , Exantema/diagnóstico , Penicilinas/efeitos adversos , Adulto , Idoso , Anticorpos Monoclonais , Antígenos CD28/antagonistas & inibidores , Antígenos CD28/imunologia , Complexo CD3/imunologia , Hipersensibilidade a Drogas/imunologia , Exantema/imunologia , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Testes Cutâneos/métodos
6.
Clin Exp Allergy ; 44(5): 747-55, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24447144

RESUMO

BACKGROUND: There is an ongoing debate on whether angiotensin-converting enzyme inhibitors (ACEI) should be substituted prior to initiation of venom immunotherapy (VIT) for safety reasons. OBJECTIVE: We aimed to assess the influence of ACEI medication on the incidence of systemic reactions (SR) during the build-up phase of VIT in a large and homogeneous cohort of patients. METHODS: The frequency of SR during 775 consecutive cycles of VIT initiation was analyzed in relation to cardiovascular medication, age, sex, venom, reactivity in diagnostic tests, severity of preceding sting-induced anaphylaxis, comorbidities, latency before the initiation of VIT, and treatment protocols. ACEI were routinely maintained throughout VIT, beta-blockers replaced if appropriate. RESULTS: During VIT-initiation, 190 (24.5%) patients were on some kind of cardiovascular treatment, 90 (11.6%) on ACEI, 23 (3.0%) on beta-blockers. VIT-related SR rates were 11.7% (any documented reactions including subjective symptoms) and 3.0% (reactions fulfilling objective diagnostic criteria of anaphylaxis). Medication with ACEI (P = 0.097) or beta-blockers (P = 1.0) was not significantly related to the incidence of SR. A reduced rate of SR in patients taking cardiovascular drugs was not statistically significant in the final multivariate regression model. A prolonged latency before the initiation of VIT (P = 0.018, odds ratio = 1.010), and use of 5-day compared to 3-day rush protocols (P = 0.008, odds ratio = 3.522) increased the frequency of SR. CONCLUSIONS AND CLINICAL RELEVANCE: Study data do not provide evidence of an ACEI-mediated increase of VIT-related SR, supporting the continued use of these valuable and hard-to-replace substances throughout VIT.


Assuntos
Alérgenos/imunologia , Anafilaxia/imunologia , Anafilaxia/terapia , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Dessensibilização Imunológica , Himenópteros/imunologia , Peçonhas/imunologia , Adulto , Idoso , Anafilaxia/complicações , Anafilaxia/diagnóstico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/tratamento farmacológico , Dessensibilização Imunológica/efeitos adversos , Interações Medicamentosas , Feminino , Humanos , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Índice de Gravidade de Doença
7.
Dermatology ; 224(3): 224-7, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22678083

RESUMO

Elimination of pathogenic autoantibodies by immunoadsorption (IA) has been described as an effective adjuvant treatment in severe bullous autoimmune diseases, especially in pemphigus. There is much less experience in the treatment of bullous pemphigoid (BP). BP was diagnosed in a 62-year-old Caucasian woman presenting a pruritic rash with multiple tense blisters. Standard treatments with topical and oral corticosteroids, steroid-sparing agents including dapsone, azathioprine, mycophenolate mofetil (MMF) and intravenous immunoglobulins were ineffective or had to be discontinued due to adverse events. An immediate clinical response could be achieved by two treatment cycles of adjuvant protein A immunoadsorption (PA-IA) in addition to continued treatment with MMF (2 g/day) and prednisolone (1 mg/kg/day). Tolerance was excellent. Clinical improvement remained stable after discontinuation of IA and went along with sustained reduction of circulating autoantibodies. Our data demonstrate that PA-IA might be a safe and effective adjuvant treatment in severe and recalcitrant BP.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Técnicas de Imunoadsorção , Penfigoide Bolhoso/terapia , Desintoxicação por Sorção/métodos , Autoanticorpos/sangue , Autoanticorpos/imunologia , Autoantígenos/imunologia , Proteínas de Transporte , Proteínas do Citoesqueleto , Fármacos Dermatológicos/uso terapêutico , Quimioterapia Combinada , Distonina , Feminino , Humanos , Glicoproteínas de Membrana/imunologia , Pessoa de Meia-Idade , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Proteínas do Tecido Nervoso , Colágenos não Fibrilares/imunologia , Penfigoide Bolhoso/sangue , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Bolhoso/imunologia , Prednisolona/uso terapêutico , Índice de Gravidade de Doença , Proteína Estafilocócica A/imunologia , Resultado do Tratamento , Colágeno Tipo XVII
8.
Klin Padiatr ; 224(1): 8-11, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21969027

RESUMO

BACKGROUND: Junctional epidermolysis bullosa with pyloric atresia (JEB-PA) is a rare autosomal recessive disease with blister formation within the lamina lucida due to mutations in the integrin ß4 (ITGB4) and α6 (ITGA6) genes. CASE REPORT: A female preterm infant, first child of healthy non-consanguineous parents, was born at 26 + 4 weeks of gestation by caesarean section, following polyhydramnion and abruption of placenta. She presented with extensive areas of denuded skin on both lateral sides of the head, neck and extremities. Auricles were hypoplastic. Abdominal ultrasound and X-ray were suggestive of pyloric atresia which was revised surgically on the 4th day of life. Further course was complicated by progressive skin detachment, sepsis, and renal insufficiency with fatal outcome at 18 days of age. Immunofluorescence mapping of cryopreserved skin showed junctional cleft formation with negative staining for integrin α6 and integrin ß4. Mutational analysis disclosed compound heterozygosity for two novel nonsense mutations in the ITGB4 gene: c.600dupC/p.F201fsX14 and c.2533C>T/p.Q845X. 2 subsequent pregnancies were terminated following prenatal diagnosis disclosing the same ITGB4 mutations, a 4th pregnancy was unaffected. CONCLUSION: We describe a case of lethal JEB-PA with negative immunoreactivity to integrin α6 and integrin ß4 predicting a poor outcome. Identification of compound heterozygosity for two novel ITGB4 mutations in the affected preterm infant permitted prenatal diagnosis and finally birth of a healthy sibling.


Assuntos
Aberrações Cromossômicas , Análise Mutacional de DNA , Displasia Ectodérmica/genética , Genes Recessivos/genética , Triagem de Portadores Genéticos , Doenças do Prematuro/genética , Integrina alfa6beta1/genética , Integrina beta4/genética , Orelha Externa/anormalidades , Orelha Externa/patologia , Displasia Ectodérmica/patologia , Evolução Fatal , Feminino , Imunofluorescência , Humanos , Recém-Nascido , Doenças do Prematuro/patologia , Gravidez , Pele/patologia
9.
Hautarzt ; 62(3): 215-8, 2011 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-20945055

RESUMO

Chelation therapy with (RS)-2,3-Bis(sulfonyl)propane-1-sulfonic acid (DMPS) after an occupational lead exposure led to the development of a severe bullous drug eruption. Skin tests and histology/immunohistology of the test reactions indicated a T-cell-mediated immune response against DMPS. Metal-binding thiol groups as in DMPS are chemically highly reactive and therefore effectively mediate the development of immunogenic hapten (DMPS)-protein complexes. Therefore, the pharmacological effects and sensitization potential of dithiols are tightly connected. Cross-reactivity of DMPS to other chelators like D-penicillamine is possible; the indications for chelation therapy should be weighed carefully.


Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Quelantes/toxicidade , Toxidermias/diagnóstico , Intoxicação por Chumbo/tratamento farmacológico , Doenças Profissionais/tratamento farmacológico , Dermatopatias Vesiculobolhosas/induzido quimicamente , Unitiol/toxicidade , Adulto , Apoptose/efeitos dos fármacos , Quelantes/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Toxidermias/patologia , Humanos , Queratinócitos/efeitos dos fármacos , Masculino , Microscopia de Fluorescência , Testes do Emplastro , Pele/efeitos dos fármacos , Pele/patologia , Dermatopatias Vesiculobolhosas/diagnóstico , Dermatopatias Vesiculobolhosas/patologia , Unitiol/uso terapêutico
12.
J Med Genet ; 45(3): 161-6, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17993581

RESUMO

Gap junctions are intercellular channels that mediate rapid intercellular communication. They consist of connexins, small transmembrane proteins that belong to a large family found throughout the animal kingdom. In the skin, several connexins are expressed and are involved in the regulation of epidermal growth and differentiation. One of the skin expressed gap junction genes is GJB2, which codes for connexin 26 and is associated with a wide variety of keratinisation disorders. Here, we report on a family with a novel GJB2 mutation (p.His73Arg) causing a syndrome of focal palmoplantar keratoderma with severe progressive sensorineural hearing impairment, a phenotype reminiscent of Vohwinkel syndrome. Using fluorescent connexin fusion proteins, we show that the mutation induces a transport defect similar to that found for the Vohwinkel syndrome mutation p.Asp66His. Co-transfection into cells expressing wild type connexin26 shows that the mutant has a dominant negative effect on connexin trafficking. We suggest that there may be a weak genotype-phenotype correlation for mutations in GJB2.


Assuntos
Conexinas/genética , Conexinas/metabolismo , Perda Auditiva Neurossensorial/complicações , Perda Auditiva Neurossensorial/genética , Ceratodermia Palmar e Plantar/complicações , Ceratodermia Palmar e Plantar/genética , Mutação de Sentido Incorreto , Adulto , Sequência de Aminoácidos , Substituição de Aminoácidos , Sequência de Bases , Conexina 26 , Sequência Conservada , Primers do DNA/genética , DNA Complementar/genética , Feminino , Junções Comunicantes/metabolismo , Genótipo , Células HeLa , Perda Auditiva Neurossensorial/metabolismo , Perda Auditiva Neurossensorial/fisiopatologia , Humanos , Ceratodermia Palmar e Plantar/metabolismo , Ceratodermia Palmar e Plantar/patologia , Masculino , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Linhagem , Fenótipo , Transporte Proteico , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Homologia de Sequência de Aminoácidos , Síndrome , Transfecção
15.
J Bacteriol ; 183(8): 2570-5, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11274117

RESUMO

Neisseria meningitidis (the meningococcus) is a naturally competent bacterial species in which intra- and interspecific horizontal gene transfer is a major source of genetic diversity. In strains of the electrophoretic type 37 (ET-37) complex and of the A4 cluster, we identified genomic DNA coding for a novel restriction-modification system and for the tail of a previously unidentified prophage. Furthermore, a novel 7.2-kb DNA segment restricted to clones of the ET-37 complex and the A4 cluster was isolated and shown to occur both as a plasmid (pJS-B) and as a chromosomal integration. Neither the genomic loci nor pJS-B was present in ET-5 complex, lineage 3, or serogroup A meningococci. The differential distribution of the DNA segments described herein, as well as of opcA, porB, nmeAI, nmeBI, and nmeDI described previously, supports the concept of genetic isolation of hypervirulent lineages responsible for most cases of serogroup C disease worldwide.


Assuntos
Genoma Bacteriano , Neisseria meningitidis/genética , Bacteriófagos/genética , Mapeamento Cromossômico , Enzimas de Restrição-Modificação do DNA/metabolismo , Eletroforese/métodos , Enzimas/análise , Humanos , Dados de Sequência Molecular , Neisseria meningitidis/classificação , Neisseria meningitidis/virologia , Hibridização de Ácido Nucleico , Plasmídeos/genética , Análise de Sequência de DNA
16.
Epidemiol Infect ; 124(2): 337-40, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10813160

RESUMO

The distribution of the meningococcal insertion sequence IS1301 was analysed in 496 strains of different serogroups and clonal lineages of Neisseria meningitidis, and in 64 neisserial strains other than N. meningitidis. IS1301 was found in meningococci, but not in apathogenic Neisseria sp. and Neisseria gonorrhoeae. The copy numbers of IS1301 varied between 2 and 17 per genome. IS1301 positive strains were mostly found among the serogroups 29E, W135, X, and Y. Clonal lineages of serogroup A, B, and C meningococci associated with epidemic meningococcal disease were rarely positive for IS1301.


Assuntos
Elementos de DNA Transponíveis/genética , Neisseria meningitidis/genética , Neisseriaceae/genética , Southern Blotting , Células Clonais/química , Células Clonais/metabolismo , DNA Bacteriano/análise , DNA Bacteriano/genética , Dosagem de Genes , Frequência do Gene , Neisseria meningitidis/crescimento & desenvolvimento , Neisseria meningitidis/imunologia , Neisseria meningitidis/isolamento & purificação , Neisseria meningitidis/metabolismo , Neisseriaceae/crescimento & desenvolvimento , Neisseriaceae/imunologia , Neisseriaceae/isolamento & purificação , Neisseriaceae/metabolismo , Reação em Cadeia da Polimerase , Testes Sorológicos
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