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1.
Br J Dermatol ; 190(6): 895-903, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38123140

RESUMO

BACKGROUND: Concerns regarding contact allergies and intolerance reactions to dental materials are widespread among patients. Development of novel dental materials and less frequent amalgam use may alter sensitization profiles in patients with possible contact allergy. OBJECTIVES: To analyse current sensitization patterns to dental materials in patients with suspected contact allergy. METHODS: This retrospective, multicentre analysis from the Information Network of Departments of Dermatology (IVDK) selected participants from 169 834 people tested in 2005-2019 and registered with (i) an affected area of 'mouth' (and 'lips'/'perioral'), (ii) with the dental material in question belonging to one of three groups (dental filling materials, oral implants or dentures or equivalents) and (iii) with patch-testing done in parallel with the German baseline series, (dental) metal series and dental technician series. RESULTS: A total of 2730 of 169 834 tested patients met the inclusion criteria. The patients were predominantly women (81.2%) aged ≥ 40 years (92.8%). The sensitization rates with confirmed allergic contact stomatitis in women (n = 444) were highest for metals (nickel 28.6%, palladium 21.4%, amalgam 10.9%), (meth)acrylates [2-hydroxyethyl methacrylate (HEMA) 4.8%] and the substances propolis (6.8%) and 'balsam of Peru' (11.4%). The most relevant acrylates were HEMA, 2-hydroxypropyl methacrylate, methyl methacrylate, ethylene glycol dimethacrylate and pentaerythritol triacrylate. Few men were diagnosed with allergic contact stomatitis (n = 68); sensitization rates in men were highest for propolis (14.9%) and amalgam (13.6%). CONCLUSIONS: Allergic contact stomatitis to dental materials is rare. Patch testing should not only focus on metals such as nickel, palladium, amalgam and gold, but also (meth)acrylates and the natural substances propolis and 'balsam of Peru'.


Assuntos
Amálgama Dentário , Materiais Dentários , Dermatite Alérgica de Contato , Testes do Emplastro , Humanos , Feminino , Masculino , Estudos Retrospectivos , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/etiologia , Dermatite Alérgica de Contato/epidemiologia , Dermatite Alérgica de Contato/imunologia , Adulto , Pessoa de Meia-Idade , Materiais Dentários/efeitos adversos , Amálgama Dentário/efeitos adversos , Idoso , Adolescente , Adulto Jovem , Criança , Metacrilatos/efeitos adversos , Bálsamos/efeitos adversos , Implantes Dentários/efeitos adversos , Estomatite/epidemiologia , Estomatite/induzido quimicamente , Estomatite/imunologia , Estomatite/diagnóstico , Estomatite/etiologia , Própole/efeitos adversos , Dentaduras/efeitos adversos , Alemanha/epidemiologia , Alérgenos/efeitos adversos , Alérgenos/imunologia , Pré-Escolar
2.
J Dtsch Dermatol Ges ; 22(5): 730-747, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38679790

RESUMO

Sebaceous gland carcinomas are rare malignant cutaneous adnexal tumors with sebocytic differentiation. The typical predilection area is the head and neck region, where sebaceous gland carcinomas are the most common malignant adnexal tumors of the skin. According to their localization a distinction is made between periocular and extraocular sebaceous gland carcinomas. Muir-Torre syndrome (MTS) should always be ruled out if it is suspected. In terms of prognosis, sebaceous gland carcinomas are potentially aggressive tumors with a clear tendency to recur and metastasize. Only small extraocular sebaceous gland carcinomas that have been completely resected have a very good prognosis. Sebaceous gland carcinomas most frequently metastasize lymphogenously to regional or distant lymph nodes; organ metastasis occurs less frequently. Periocular sebaceous gland carcinomas have a higher metastasis rate (up to 15%) than extraocular sebaceous gland carcinomas (up to 2%). Complete micrographically controlled surgery (MCS) of the primary tumor is the therapy of first choice, regardless of periocular or extraocular localization. Adjuvant or therapeutic radiotherapy may be considered. There is currently no established standard therapy for advanced, inoperable, or metastatic sebaceous gland carcinomas. Local procedures and systemic therapies such as chemotherapy or immunotherapy can be considered. The procedure should be determined individually by an interdisciplinary tumor board. Close follow-up care is recommended for these potentially aggressive carcinomas.


Assuntos
Neoplasias das Glândulas Sebáceas , Neoplasias das Glândulas Sebáceas/patologia , Neoplasias das Glândulas Sebáceas/terapia , Neoplasias das Glândulas Sebáceas/diagnóstico , Humanos , Síndrome de Muir-Torre/patologia , Síndrome de Muir-Torre/diagnóstico , Síndrome de Muir-Torre/terapia , Prognóstico , Adenocarcinoma Sebáceo/patologia , Adenocarcinoma Sebáceo/terapia , Adenocarcinoma Sebáceo/diagnóstico , Dermatologia/normas , Alemanha , Cirurgia de Mohs , Guias de Prática Clínica como Assunto
3.
Allergy ; 78(6): 1615-1627, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36479710

RESUMO

BACKGROUND: Drugs are a frequent cause of severe anaphylactic reactions. Here, we analyze a large dataset on drug induced anaphylaxis regarding elicitors, risk factors, symptoms, and treatment. METHODS: Data from the European Anaphylaxis Registry (2007-2019) with 1815 reported cases of drug-induced anaphylaxis were studied accordingly. RESULTS: Drugs are the third most frequent cause of anaphylaxis reported in the Anaphylaxis Registry. Among the eliciting groups of drugs analgesics and antibiotics were far most often reported. Female and senior patients were more frequently affected, while the number of children with DIA was low. DIA patients had symptoms affecting the skin and mucous membranes (n = 1525, 84.02%), the respiratory (n = 1300, 71.63%), the cardiovascular (n = 1251, 68.93%) and the gastrointestinal system (n = 549, 30.25%). Drugs caused significant more severe reactions, occurred more often in medical facilities and led to increased hospitalization rates in comparison to food and insect venom induced anaphylaxis. Adrenaline was used more often in patients with DIA than in anaphylaxis due to other causes. Patients with skin symptoms received more antihistamines and corticosteroids in the acute treatment, while gastrointestinal symptoms led to less adrenaline use. CONCLUSION: The study contributes to a better understanding of DIA, with a large number of cases from Europe supporting previous data, e.g., analgesics and antibiotics being the most frequent culprits for DIA. Female gender and higher age are relevant risk factors and despite clear recommendations, the emergency treatment of DIA is not administered according to the guidelines.


Assuntos
Anafilaxia , Hipersensibilidade a Drogas , Humanos , Feminino , Anafilaxia/diagnóstico , Hipersensibilidade a Drogas/diagnóstico , Epinefrina/uso terapêutico , Sistema de Registros , Fenótipo , Antibacterianos/uso terapêutico
4.
Am J Dermatopathol ; 45(2): 86-89, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36669070

RESUMO

ABSTRACT: Injection site reactions are defined as skin reactions at the injection site to drugs administered subcutaneously. Pathophysiologically, these reactions are based on different immunological mechanisms. We report the case of a 49-year-old patient with type 1 diabetes mellitus (first diagnosis in 1994 at the age of 23 years). Continuous subcutaneous insulin infusion using an insulin pump has been used for many years. The patient presented to the department of dermatology with progressive symptoms in the area of the insulin injection sites on the lower abdomen, accompanied by pain, burning, erythema, tenderness, and the formation of subcutaneous nodules. Previous attempts to use different insulins and to change the injection sites did not improve his symptoms. Furthermore, the symptoms appeared within hours after the insulin pump was attached, so that the injection site has to be changed as soon as every 48 hours. No anaphylactic shock was reported at any time. Multiple histological specimens were obtained from an older lesion on the abdomen as well as from test sites after standard allergological tests (prick and intradermal tests) of various insulins. Histologically, these biopsies showed the image of an extensive deep-reaching small vessel vasculitis with the aspect of an urticarial vasculitis and confirmed the diagnosis of an injection-site reaction that can be characterized as a type III hypersensitivity reaction.


Assuntos
Diabetes Mellitus Tipo 1 , Hipersensibilidade a Drogas , Doenças do Complexo Imune , Urticária , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 1/tratamento farmacológico , Reação no Local da Injeção/etiologia , Insulina/efeitos adversos , Urticária/induzido quimicamente
5.
J Dtsch Dermatol Ges ; 21(3): 305-320, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36929552

RESUMO

Merkel cell carcinoma (MCC, ICD-O M8247/3) is a rare, malignant, primary skin tumor with epithelial and neuroendocrine differentiation. The tumor cells share many morphologic, immunohistochemical, and ultrastructural features with cutaneous Merkel cells. Nevertheless, the cell of origin of MCC is unclear. MCC appears clinically as a reddish to purple spherical tumor with a smooth, shiny surface and a soft to turgid, elastic consistency, usually showing rapid growth. Spontaneous and often complete regressions of the tumor are observed. These likely immunologically-mediated regressions explain the cases in which only lymph node or distant metastases are found at the time of initial diagnosis and why the tumor responds very well to immunomodulatory therapies even at advanced stages. Due to its aggressiveness, the usually given indication for sentinel lymph node biopsy, the indication of adjuvant therapies to be evaluated, as well as the complexity of the necessary diagnostics, clinical management should already be determined by an interdisciplinary tumor board at the time of initial diagnosis.


Assuntos
Carcinoma de Célula de Merkel , Carcinoma Neuroendócrino , Neoplasias Cutâneas , Humanos , Carcinoma de Célula de Merkel/diagnóstico , Carcinoma de Célula de Merkel/terapia , Carcinoma de Célula de Merkel/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/patologia , Pele/patologia , Biópsia de Linfonodo Sentinela
6.
Acta Derm Venereol ; 102: adv00695, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35199180

RESUMO

Most patients with advanced basal cell carcinomas (BCCs) may not benefit sufficiently from standard treatment comprising surgery and radiation. Vismodegib, an oral selective hedgehog pathway inhibitor, is approved for treatment of patients with locally advanced BCC inappropriate for surgery or radiotherapy, or for patients with symptomatic metastatic BCC. In order to enhance understanding of the effectiveness, safety and utilization of vismodegib in clinical practice in Germany, a non-interventional study, JONAS, was conducted. A total of 53 patients with locally advanced BCC who initiated treatment with vismodegib between 2016 and 2018 were included in the study, which was embedded in the German ADOReg skin cancer registry. Duration of response, the primary endpoint, was 12.4 months, progression-free survival 32.2 months and overall response rate 77.4%. Most adverse events were mild to moderate. Overall, results confirmed previous findings, demonstrating favourable responses and manageable safety of vismodegib in patients with locally advanced BCC in clinical practice.


Assuntos
Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutâneas , Anilidas/efeitos adversos , Antineoplásicos/efeitos adversos , Carcinoma Basocelular/tratamento farmacológico , Carcinoma Basocelular/patologia , Estudos de Coortes , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/uso terapêutico , Humanos , Piridinas , Neoplasias Cutâneas/patologia
7.
J Allergy Clin Immunol ; 147(2): 653-662.e9, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32585173

RESUMO

BACKGROUND: Venom-induced anaphylaxis (VIA) is a common, potentially life-threatening hypersensitivity reaction associated with (1) a specific symptom profile, 2) specific cofactors, and 3) specific management. Identifying the differences in phenotypes of anaphylaxis is crucial for future management guidelines and development of a personalized medicine approach. OBJECTIVE: This study aimed to evaluate the phenotype and risk factors of VIA. METHODS: Using data from the European Anaphylaxis Registry (12,874 cases), we identified 3,612 patients with VIA and analyzed their cases in comparison with sex- and age-matched anaphylaxis cases triggered by other elicitors (non-VIA cases [n = 3,605]). RESULTS: VIA more frequently involved more than 3 organ systems and was associated with cardiovascular symptoms. The absence of skin symptoms during anaphylaxis was correlated with baseline serum tryptase level and was associated with an increased risk of a severe reaction. Intramuscular or intravenous epinephrine was administered significantly less often in VIA, in particular, in patients without a history of anaphylaxis. A baseline serum tryptase level within the upper normal range (8-11.5 ng/mL) was more frequently associated with severe anaphylaxis. CONCLUSION: Using a large cohort of VIA cases, we have validated that patients with intermediate baseline serum tryptase levels (8-11 ng/mL) and without skin involvement have a higher risk of severe VIA. Patients receiving ß-blockers or angiotensin-converting enzyme inhibitors had a higher risk of developing severe cardiovascular symptoms (including cardiac arrest) in VIA and non-VIA cases. Patients experiencing VIA received epinephrine less frequently than did cases with non-VIA.


Assuntos
Anafilaxia/etiologia , Anafilaxia/fisiopatologia , Anafilaxia/terapia , Venenos de Artrópodes/efeitos adversos , Mordeduras e Picadas de Insetos/complicações , Adulto , Estudos de Casos e Controles , Criança , Estudos de Coortes , Europa (Continente) , Feminino , Humanos , Masculino , Fenótipo , Sistema de Registros , Fatores de Risco
8.
J Autoimmun ; 123: 102705, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34325306

RESUMO

BACKGROUND: Pemphigus is a group of bullous diseases characterized by acantholysis and skin blisters. As for other autoimmune diseases, the strongest genetic associations found so far for pemphigus foliaceus (PF) and vulgaris (PV) are with alleles of HLA genes. However, apart from protein-coding genes, the MHC region includes a set of poorly explored long non-coding RNA (lncRNA) genes, the HLA complex group (HCG). OBJECTIVES: To investigate if HCG lncRNA alleles are associated with pemphigus susceptibility. METHODS AND RESULTS: We analyzed SNPs in 13 HCG lncRNA genes, both in PV (Germany: 241 patients; 1,188 controls) and endemic PF (Brazil: 227 patients; 194 controls), applying multivariate logistic regression. We found 55 associations with PV (pcorr < 0.01) and nine with endemic PF (pcorr < 0.05), the majority located in TSBP1-AS1 (which includes HCG23) and HCG27 lncRNA genes, independently of HLA alleles previously associated with pemphigus. The association of TSBP1-AS1 rs3129949*A allele was further replicated in sporadic PF (p = 0.027, OR = 0.054; 75 patients and 150 controls, all from Germany). Next, we evaluated the expression levels of TSBP1-AS1, TSBP1, HCG23, and HCG27 in blood mononuclear cells of Brazilian patients and controls. HCG27 was upregulated in endemic PF (p = 0.035, log2 FC = 1.3), while TSBP1-AS1 was downregulated in PV (p = 0.029, log2 FC = -1.29). The same expression patterns were also seen in cultured keratinocytes stimulated with IgG antibodies from patients and controls from Germany. TSBP1 mRNA levels were also decreased in endemic PF blood cells (p = 0.042, log2 FC = -2.14). TSBP1-AS1 and HCG27 were also observed downregulated in CD19+ cells of endemic PF (p < 0.01, log2 FC = -0.226 and -0.46 respectively). CONCLUSIONS: HCG lncRNAs are associated with susceptibility to pemphigus, being TSBP1-AS1 and HCG27 also differentially expressed in distinct cell populations. These results suggest a role for HCG lncRNAs in pemphigus autoimmunity.


Assuntos
Antígenos HLA/genética , Pênfigo/genética , Pênfigo/imunologia , RNA Longo não Codificante/fisiologia , Humanos , Queratinócitos/imunologia , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único
9.
Exp Dermatol ; 30(6): 831-840, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33394553

RESUMO

Pemphigus foliaceus (PF) is an autoimmune blistering disease of the skin, clinically characterized by erosions and, histopathologically, by acantholysis. PF is endemic in the Brazilian Central-Western region. Numerous single nucleotide polymorphisms (SNPs) have been shown to affect the susceptibility for PF, including SNPs at long non-coding RNA (lncRNA) genes, which are known to participate in many physiological and pathogenic processes, such as autoimmunity. Here, we investigated whether the genetic variation of immune-related lncRNA genes affects the risk for endemic and sporadic forms of PF. We analysed 692 novel SNPs for PF from 135 immune-related lncRNA genes in 227 endemic PF patients and 194 controls. The SNPs were genotyped by Illumina microarray and analysed by applying logistic regression at additive model, with correction for sex and population structure. Six associated SNPs were also evaluated in an independent German cohort of 76 sporadic PF patients and 150 controls. Further, we measured the expression levels of two associated lncRNA genes (LINC-PINT and LY86-AS1) by quantitative PCR, stratified by genotypes, in peripheral blood mononuclear cells of healthy subjects. We found 27 SNPs in 11 lncRNA genes associated with endemic PF (p < .05 without overlapping with protein-coding genes). Among them, the LINC-PINT SNP rs10228040*A (OR = 1.47, p = .012) was also associated with increased susceptibility for sporadic PF (OR = 2.28, p = .002). Moreover, the A+ carriers of LY86-AS1*rs12192707 mark lowest LY86-AS1 RNA levels, which might be associated with a decreasing autoimmune response. Our results suggest a critical role of lncRNA variants in immunopathogenesis of both PF endemic and sporadic forms.


Assuntos
Antígenos de Superfície/genética , Pênfigo/genética , Polimorfismo de Nucleotídeo Único/genética , RNA Longo não Codificante/genética , Antígenos de Superfície/imunologia , Predisposição Genética para Doença , Humanos , Pênfigo/imunologia , Polimorfismo de Nucleotídeo Único/imunologia , RNA Longo não Codificante/imunologia
10.
J Dtsch Dermatol Ges ; 19(8): 1145-1157, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34390159

RESUMO

Nodal inclusions of ectopic tissue within lymph nodes are seen comparatively often in dermatopathology and general pathology. Glandular and nonglandular epithelium, as well as melanocytic nevi can be observed within lymph nodes and represent mostly incidental findings without any relevance. The main challenge in reporting these morphologic features is to differentiate such benign inclusions from metastatic settlements of distinct organ tumors. As sentinel node biopsy and lymph node dissection have become standard procedure in clinical oncology and have an immense clinical impact, the correct evaluation of these nodal inclusions is indispensable to avoid undertreatment or overtreatment of patients. In addition, the genesis of these inclusions has not yet been satisfactorily clarified. Two concepts have been laid out: the theory of benign metastases and the migration arrest theory. However, neither theory has so far been able to answer the following questions: Why do we find more nodal nevi in patients with melanoma who had a sentinel node biopsy than in patients without melanoma, and why do we not find nodal nevi in deep visceral lymph nodes? We present a comprehensive review of the current knowledge on nodal inclusions, proposing a concept for the pathogenesis of nodal nevi, to answer these questions.


Assuntos
Nevo Pigmentado , Nevo , Neoplasias Cutâneas , Biomarcadores Tumorais/análise , Humanos , Linfonodos , Metástase Linfática , Nevo Pigmentado/cirurgia , Biópsia de Linfonodo Sentinela
11.
Allergy ; 75(4): 901-910, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31584692

RESUMO

BACKGROUND: Patients with a history of anaphylaxis are at risk of future anaphylactic reactions. Thus, secondary prevention measures are recommended for these patients to prevent or attenuate the next reaction. METHODS: Data from the Anaphylaxis Registry were analyzed to identify secondary prevention measures offered to patients who experienced anaphylaxis. Our analysis included 7788 cases from 10 European countries and Brazil. RESULTS: The secondary prevention measures offered varied across the elicitors. A remarkable discrepancy was observed between prevention measures offered in specialized allergy centers (84% of patients were prescribed adrenaline autoinjectors following EAACI guidelines) and outside the centers: Here, EAACI guideline adherence was only 37%. In the multivariate analysis, the elicitor of the reaction, age of the patient, mastocytosis as comorbidity, severity of the reaction, and reimbursement/availability of the autoinjector influence physician's decision to prescribe one. CONCLUSIONS: Based on the low implementation of guidelines concerning secondary prevention measures outside of specialized allergy centers, our findings highlight the importance of these specialized centers and the requirement of better education for primary healthcare and emergency physicians.


Assuntos
Anafilaxia , Prevenção Secundária , Anafilaxia/epidemiologia , Anafilaxia/etiologia , Anafilaxia/prevenção & controle , Brasil , Epinefrina , Europa (Continente)/epidemiologia , Humanos , Sistema de Registros
12.
Contact Dermatitis ; 81(5): 341-353, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31173644

RESUMO

BACKGROUND: Contact urticaria (CU) is an infrequent, mostly occupational disease that may be life-threatening (CU syndrome stage 4). OBJECTIVES: To identify the current frequency, elicitors and cofactors of CU. PATIENTS: Three cohorts were retrospectively analysed for CU: (a) patients from the Information Network of Departments of Dermatology (IVDK) database (2000-2014; n = 159 947); (b) patients from an allergy unit (Department of Dermatology, University Hospital Erlangen, 2000-2015; n = 4741); and (c) patients from the Anaphylaxis Registry (2007-2015: 6365 reported cases, including 2473 patients with Ring and Messmer grade III-IV reactions) for severe cases with skin/mucosal manifestations occurring at the workplace vs cases not occurring at the workplace (n = 68 vs n = 1821). RESULTS: Four hundred and forty-eight CU patients (0.28%) were diagnosed in the IVDK cohort, and 16 (0.34%) (10 of immunological aetiology, and 6 of non-immunological aetiology) in the Erlangen cohort. The most frequent elicitors in the IVDK cohort were cosmetics, creams, sun protection agents (although these were less frequent in CU patients than in controls without CU; 26.8% vs 35.6%, P < .0001), and gloves (significantly more frequent in CU patients than in controls; 18.1% vs 6.5%, P < .0001). The most frequent elicitors in the Erlangen cohort were natural rubber latex and sorbic acid. Among the MOAHLFA index characteristics, in both cohorts occupational disease was more common in CU patients than in patients without CU. CU was significantly associated with allergic rhinitis and allergic asthma. Wet work was a relevant cofactor. In the Anaphylaxis Registry, 19 cases (0.3%) were identified with severe reactions including skin symptoms at the workplace linked to common occupational elicitors. CONCLUSIONS: CU is a rare occupational skin manifestation with a frequency of <0.4% in the examined patients; it may, however, progress to anaphylaxis. Preventive measures are important, and should take into account the identified elicitors and cofactors.


Assuntos
Dermatite Alérgica de Contato/epidemiologia , Dermatite Ocupacional/epidemiologia , Urticária/epidemiologia , Adulto , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/etiologia , Dermatite Ocupacional/diagnóstico , Dermatite Ocupacional/etiologia , Feminino , Alemanha/epidemiologia , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Urticária/diagnóstico , Urticária/etiologia
13.
J Allergy Clin Immunol ; 141(2): 638-649, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28751232

RESUMO

BACKGROUND: Omalizumab, a recombinant anti-IgE antibody, effectively treats chronic spontaneous urticaria. Evidence is lacking in patients with chronic inducible urticarias (CIndUs), which are frequently H1-antihistamine resistant. OBJECTIVE: From the current published literature, we aimed to determine the strength of evidence for omalizumab efficacy and safety in the treatment of CIndUs. METHODS: We performed a PubMed search to identify evidence on omalizumab use in the following 9 CIndU subtypes: symptomatic dermographism, cold urticaria, delayed-pressure urticaria, solar urticaria, heat urticaria, vibratory angioedema, cholinergic urticaria, contact urticaria, and aquagenic urticaria. RESULTS: Forty-three trials, case studies, case reports, and analyses were identified. Our review indicates that omalizumab has substantial benefits in patients with various CIndUs. The evidence is strongest for symptomatic dermographism, cold urticaria, and solar urticaria. Little/no evidence was available on vibratory angioedema and aquagenic and contact urticaria. Our review supports rapid onset of action demonstrated through early symptom control in most cases, sometimes within 24 hours. Many patients gained complete/partial symptom relief and substantially improved quality of life. Adverse events were generally low, with omalizumab being well tolerated by most patients, including children. CONCLUSIONS: A strong body of evidence supports the use of omalizumab in the treatment of patients with therapy-refractory CIndU. More data from randomized controlled studies are warranted.


Assuntos
Omalizumab/uso terapêutico , Urticária/tratamento farmacológico , Doença Crônica , Ensaios Clínicos como Assunto , Humanos , PubMed , Qualidade de Vida , Urticária/imunologia , Urticária/patologia
14.
J Dtsch Dermatol Ges ; 17(5): 562-576, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31056838

RESUMO

Merkel cell carcinoma (MCC, ICD-O M8247 / 3) is a rare malignant primary skin tumor with epithelial and neuroendocrine differentiation. The neoplastic cells share many morphological, immunohistochemical and ultrastructural characteristics with Merkel cells of the skin. The diagnosis of MCC is rarely made on clinical grounds. Histological and immunohistochemical studies are usually required to confirm the clinical suspicion. Given the frequent occurrence of occult lymph node metastasis, sentinel lymph node biopsy should be performed once distant metastasis has been ruled out by cross-sectional imaging. Primary tumors without evidence of organ metastases are treated with complete surgical excision with appropriate surgical margins. Radiation therapy should be considered at all stages of the disease. For advanced MCC that is no longer amenable to curative treatment by surgery or radiation therapy, there is currently no established systemic therapy for which an improvement in recurrence-free survival or overall survival has been demonstrated in a prospective randomized trial. However, immunotherapy using PD-1/PD-L1 blockade seems to be superior to chemotherapy. Various factors warrant that further diagnostic and therapeutic interventions be determined by an interdisciplinary tumor board. These factors include the tumor's aggressiveness, the frequent indication for sentinel lymph node biopsy along with the frequent occurrence in the head and neck region, the potential indication for adjuvant radiation therapy as well as the complexity of the required diagnostic workup.


Assuntos
Carcinoma de Célula de Merkel/terapia , Neoplasias Cutâneas/terapia , Idoso , Antineoplásicos/uso terapêutico , Carcinoma de Célula de Merkel/diagnóstico , Transtornos Cognitivos/complicações , Humanos , Imunoterapia/métodos , Metástase Linfática , Terapia Neoadjuvante , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Neoplasias Cutâneas/diagnóstico
15.
Cancer Immunol Immunother ; 67(5): 825-834, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29487980

RESUMO

BACKGROUND: Ipilimumab and programmed death (PD) 1-antibodies are effective treatment options in metastatic melanoma. The safety and efficacy of ipilimumab in patients with pre-existing autoimmune disorders (AD) has only been evaluated in a selected number of patients. METHODS: We performed a retrospective analysis in 14 German skin cancer centers for patients with metastatic melanoma and pre-existing AD treated with ipilimumab. RESULTS: 41 patients with 44 pre-existing AD were treated with ipilimumab (thyroiditis n = 15, rheumatoid n = 11, dermatologic n = 10, Crohn's disease/ulcerative colitis n = 3, neurological n = 2, sarcoidosis n = 2, pancreatitis n = 1). 3 out of 41 patients had two AD, 11 patients required immunosuppressants at the time of induction of ipilimumab. 12 patients (29.2%) experienced a flare of their pre-existing AD, mainly patients with rheumatoid or dermatologic diseases. Additional immune-related adverse events (irAEs) occurred in 12 patients (29.2%). In 23 patients (56%) neither a change of their AD nor additional irAEs were observed. Objective responses were seen in five patients (one complete remission, four partial remissions, 12.1%). CONCLUSION: This is the largest series of patients with pre-existing AD and treatment with ipilimumab reported. Flares of pre-existing AD were observed but manageable. Response rates and occurrence of new irAEs were comparable to previous trials. Thus, in this patient subgroup, ipilimumab can be a treatment option after a thorough discussion of pros and cons and taking severity and activity of the preexisting AD into account.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Doenças Autoimunes/complicações , Ipilimumab/uso terapêutico , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Doenças Autoimunes/patologia , Feminino , Seguimentos , Humanos , Masculino , Melanoma/etiologia , Melanoma/secundário , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia , Resultado do Tratamento
17.
Transfus Med Hemother ; 44(6): 426-428, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29344020

RESUMO

BACKGROUND: Checkpoint blocking agents such as pembrolizumab or nivolumab may induce a diversity of mostly autoimmune-mediated side effects. These autoimmune phenomena mainly affect ductless glands such as the pituitary gland (hypophysitis), the thyroid gland (thyreoiditis), the skin (vitiligo and rash), the colon (colitis), and the lung (pneumonitis). Furthermore, many other organs or organ systems may be affected. CASE REPORT: This work describes a case of an immune thrombocytopenia that developed or rather became clinically significant shortly after initiation of a systemic therapy with first nivolumab and later pembrolizumab given due to metastatic melanoma. Platelet counts before this systemic therapy were slightly decreased with values around 110/nl (normal value 140-400/nl). Thrombocytopenia developed or became apparent rapidly within 10 days after the first intravenous application of nivolumab and worsened after changeover to pembrolizumab. Therapy had to be stopped due to disease progression and steady aggravation of thrombocytopenia. Immune hematology assays could prove an autoimmune mediated genesis of thrombocytopenia. CONCLUSION: Checkpoint inhibitors may induce a multiplicity of mostly autoimmune-mediated side effects. In contrast to chemotherapy-induced cytopenia that results from bone marrow toxicity, thrombocytopenia in melanoma patients treated with checkpoint inhibiting substances seems to result from autoimmune-mediated side effects in the majority of the cases. Thorough laboratory controls during these therapies are therefore required. In case of thrombocytopenia, immune hematology testing to diagnose or rule out immune thrombocytopenia is indispensable.

18.
J Dtsch Dermatol Ges ; 15(7): 695-700, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28598544

RESUMO

Tuberous sclerosis complex (TSC) is a genetic multisystem disorder with prominent skin involvement that frequently occurs in early childhood. Dermatologic manifestations include facial angiofibromas, hypomelanotic macules, fibrous cephalic plaques, shagreen patches, and ungual fibromas. The International TSC Consensus Conference in 2012 provided guidelines for standardized baseline evaluation and follow-up. Detailed clinical dermatological evaluation at the time of diagnosis and annual skin examination is recommended for both pediatric and adult populations. The onset of dermatological manifestations is clearly age-related. However, dermatologists also have to assess for clinical manifestations beyond their own specialty. With advances in genetics and the advent of mTORC1 inhibitors, new specific therapeutic options have become available for TSC patients with skin manifestations. Early intervention is commonly recommended for symptomatic, rapidly evolving, disfiguring, or debilitating lesions. The consensus guidelines recommend "treatment as appropriate for the lesion and clinical context" and suggest the use of surgical excision, laser therapy, or topical mTORC1 inhibitors. Topical mTORC1 inhibitors present a useful option for TSC-associated skin lesions, particularly in medically complex patients. They may prevent or reduce the risks of subsequent surgeries and permanent scarring.


Assuntos
Dermatopatias/diagnóstico , Neoplasias Cutâneas/diagnóstico , Esclerose Tuberosa/diagnóstico , Aberrações Cromossômicas , Genes Dominantes , Humanos , Dermatopatias/genética , Dermatopatias/terapia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapia , Esclerose Tuberosa/genética , Esclerose Tuberosa/terapia
19.
J Dtsch Dermatol Ges ; 15(2): 117-146, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28214316

RESUMO

Dermatosurgery occupies an exceptional position among all surgical disciplines. Above all, this includes the fact that, with very few exceptions, the vast majority of surgical interventions can be performed under local or regional anesthesia, usually in smaller procedure rooms that are spatially separated from larger operating suites. Thus, peri- and postinterventional patient monitoring is the responsibility of the dermatosurgeon and his team. Though inherently smaller, this team still has to observe numerous perioperative requirements that - in larger surgical specialties - would be attended to by a host of various specialists working in concert. Said requirements include hygienic aspects, knowledge concerning pre- and intraoperative patient monitoring, managing surgical site infections, adequate postsurgical pain management, as well as detailed pharmacological knowledge with respect to common local anesthetics and the toxic and allergic reactions associated therewith. Not only does this require interdisciplinary collaboration and shared responsibility for the patient. It also necessitates the development and implementation of quality-oriented and evidence-based guidelines that, in the dermatosurgical setting, usually extend far beyond the scope of the specialty per se. The objective of the present CME article is the condensed presentation of interdisciplinary aspects relating to the most important perioperative issues.


Assuntos
Anestesia Local/normas , Antibioticoprofilaxia/normas , Procedimentos Cirúrgicos Dermatológicos/normas , Assistência Perioperatória/normas , Guias de Prática Clínica como Assunto , Infecção da Ferida Cirúrgica/prevenção & controle , Procedimentos Cirúrgicos Dermatológicos/efeitos adversos , Desinfecção/normas , Medicina Baseada em Evidências , Alemanha , Remoção de Cabelo/normas , Humanos , Infecção da Ferida Cirúrgica/etiologia
20.
J Dtsch Dermatol Ges ; 15(2): 117-148, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28214321

RESUMO

Die Dermatochirurgie nimmt hinsichtlich vieler Punkte eine Sonderstellung unter den operativen Fächern ein. Hierzu gehört in erster Linie die Tatsache, dass bis auf wenige Ausnahmen fast alle Eingriffe traditionell in Lokal- bzw. Regionalanästhesie und oft auch in räumlich-infrastruktureller Trennung von den großen Zentral-Operationssälen stattfinden können. Die peri- und postoperative Überwachung obliegt dabei dem dermatochirurgischen Operationsteam. Das sui generis kleinere OP-Team hat somit eine ganze Reihe perioperativer Notwendigkeiten zu beachten, um die sich in den "großen" chirurgischen Fächern eine Vielzahl verschiedener beteiligter Fachgruppen gemeinsam kümmern. Hierzu gehören neben Hygieneaspekten, Kenntnissen in der Überwachung der Patienten sowie dem Aspekt der surgical site infections auch Fragen zur postoperativen Schmerztherapie sowie detailliertes pharmakologisches Wissen über die zur Anwendung kommenden Lokalanästhetika und das Handling der damit assoziierten toxischen und allergischen Reaktionen. Eine interdisziplinäre Zusammenarbeit und Verantwortung für den Patienten ist notwendig und erfordert die Erarbeitung und Umsetzung qualitätsorientierter und evidenzbasierter Handlungsanweisungen, die im dermatochirurgischen OP-Setting meist weit über das eigentliche Fach hinausgehen. Ziel dieses Weiterbildungsartikels soll die komprimierte Darstellung der genannten fachübergreifenden Standpunkte bezüglich der wichtigsten perioperativen Aspekte sein.

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