Deferasirox-induced urticarial vasculitis in a patient with myelodysplastic syndrome

Abstract Deferasirox is an iron chelator agent used in the treatment of diseases with iron overload, such as thalassemia and myelodysplastic syndrome. Although the majority of adverse reactions of deferasirox involve gastrointestinal symptoms and increase in serum creatinine and transaminases, skin rashes, such as maculopapular and urticarial eruptions, have also been reported. This study reports a case of myelodysplastic syndrome with urticarial vasculitis due to deferasirox therapy. Drug eruption was been confirmed by means of a challenge test, together with histopathological and clinical findings. To the best of our knowledge, we report the first case of deferasirox-induced urticarial vasculitis. Physicians should be aware of the possibility of urticarial vasculitis on deferasirox therapy and the fact that the discontinuation of the drug generally results in improvement.

A Case of Recurrent Urticaria Due to Formaldehyde Release from Root-Canal Disinfectant

Although formaldehyde is well known to cause type 4 hypersensitivity, immunoglobulin E (IgE)-mediated hypersensitivity to formaldehyde is rare. Here, we report a case of recurrent generalized urticaria after endodontic treatment using a para-formaldehyde (PFA)-containing root canal sealant and present a review of previous studies describing cases of immediate hypersensitivity reactions to formaldehyde. A 50-year-old man visited our allergy clinic for recurrent generalized urticaria several hours after endodontic treatment. Prick tests to latex, lidocaine, and formaldehyde showed negative reactions. However, swelling and redness at the prick site continued for several days. The level of formaldehyde-specific IgE was high (class 4). Thus, the patient was deemed to have experienced an IgE-mediated hypersensitivity reaction caused by the PFA used in the root canal disinfectant. Accordingly, we suggest that physicians should pay attention to type I hypersensitivity reactions to root canal disinfectants, even if the symptoms occur several hours after exposure.

Serum Specific IgE to Thyroid Peroxidase Activates Basophils in Aspirin Intolerant Urticaria

Thyroid antibodies are frequently observed in urticaria patients, but their roles in urticaria are not clearly elucidated. We investigated the role of serum specific IgE to thyroid peroxidase (TPO) in patients with aspirin intolerant acute urticaria (AIAU) and aspirin intolerant chronic urticaria (AICU). We recruited 59 AIAU and 96 AICU patients with 69 normal controls (NC). Serum specific IgE to TPO was measured by manual direct ELISA, and CD203c expressions on basophil with additions of TPO were measured to prove a direct role of TPO in effector cells. The prevalences of serum specific IgE to TPO were significantly higher in AIAU (15.2%) and AICU groups (7.5%) compared to NC (0%, P=0.018: P=0.013, respectively). Flow cytometry showed CD203c induction in a dose dependent manner with serial additions of TPO in some AIAU and AICU patients having high specific IgE to TPO. Our findings show that the prevalence of serum specific IgE to TPO was significantly higher in both AIAU and AICU patients than in NC. It is suggested that specific IgE to TPO play a pathogenic role in AIAU and AICU.

Does Maintaining a Bottle of Adhesive Without the Lid Significantly Reduce the Solvent Content?

This study aimed to evaluate the effect of maintaining a bottle of adhesive without its lid on the solvent loss of the etch-and-rinse adhesive systems. Three 2-step etch-and-rinse adhesives with different solvents (acetone, ethanol or butanol) were used in this study. Drops of each adhesive were placed on an analytical balance and the adhesive mass was recorded until equilibrium was achieved (no significant mass alteration within time). The solvent content of each adhesive and evaporation rate of solvents were measured (n=3). Two bottles of each adhesive were weighted. The bottles were maintained without their lids for 8 h in a stove at 37 ºC, after which the mass loss was measured. Based on mass alteration of drops, acetone-based adhesive showed the highest solvent content (46.5%, CI 95%: 35.8-54.7) and evaporation rate (1.11 %/s, CI95%: 0.63-1.60), whereas ethanol-based adhesive had the lowest values (10.1%, CI95%: 4.3-16.0; 0.03 %/s CI95%: 0.01-0.05). However, none of the adhesives bottles exhibited significant mass loss after sitting for 8 h without their lids (% from initial content; acetone - 96.5, CI 95%: 91.8-101.5; ethanol - 99.4, CI 95%: 98.4-100.4; and butanol - 99.3, CI 95%: 98.1-100.5). In conclusion, maintaining the adhesive bottle without lid did not induce significant solvent loss, irrespective the concentration and evaporation rate of solvent.

Este estudo avaliou o efeito da manutenção do frasco do adesivo sem sua tampa na perda de solvente de sistemas adesivos convencionais. Três adesivos convencionais de 2 passos com diferentes solventes (acetona, etanol ou butanol) foram usados neste estudo. Gotas de cada adesivo foram colocadas em uma balança analítica e a massa dos adesivos foi registrada até a obtenção do equilíbrio (nenhuma alteração significativa com o tempo). O conteúdo de solvente de cada adesivo e a taxa de evaporação dos solventes foram mensurados (n=3). Dois frascos de cada adesivo foram pesados. Os frascos foram mantidos sem suas tampas por 8 h em uma estufa a 37 ºC, seguido pela mensuração da pera de massa. Baseado na alteração de massa das gotas, o adesivo a base de acetona demonstrou o maior conteúdo de solvente (46,5%, IC 95%: 35,8-54,7) e de taxa de evaporação (1,11 %/s, IC95%: 0,63-1,60), enquanto que o adesivo à base de etanol teve os menores valores (10,1%, IC95%: 4,3-16,0; 0,03 %/s IC95%: 0,01-0,05). Entretanto, nenhum dos frascos dos adesivos exibiu perda significante de massa após ficar por 8 h sem suas tampas (% do conteúdo inicial; acetona - 96,5, IC95%: 91,8-101,5; etanol - 99,4, IC95%: 98,4-100,4; e butanol - 99,3, IC95%: 98,1-100,5). Em conclusão, a manutenção do frasco do adesivo sem tampa não induziu perda significante de solvente independente da concentração e da taxa de evaporação do solvente.

Immunologic Evaluation of Immediate Hypersensitivity to Cefaclor

PURPOSE: Cefaclor is widely prescribed for various infectious diseases. As its consumption increases, the number of hypersensitivity reactions to cefaclor has increased. This study aimed to evaluate the immunologic findings of immediate hypersensitivity to cefaclor. MATERIALS AND METHODS: We enrolled 47 patients with immediate hypersensitivity to cefaclor from Ajou University Hospital and Asan Medical Center. Serum specific IgE, IgG1, and IgG4 antibodies to cefaclor-human serum albumin (HSA) conjugate were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The most common phenotype was anaphylaxis (Group I, 78.7%), followed by urticaria (Group II, 21.3%). The detection of specific IgE, IgG1, and IgG4 to cefaclor-HSA conjugate by ELISA tended to be higher in Group I (40.5%, 41.7%, 21.6%) than in Group II (20.0%, 20.0%, 0%) with no statistical significance. Significant associations were found between specific IgE and IgG1 or IgG4 (p<0.001, p=0.019). ELISA inhibition tests showed significant inhibitions by both free cefaclor and cefaclor-HSA conjugate. For basophil activation tests in patients having no specific IgE antibody, the CD63 expression level on basophils increased with incubations of free cefaclor. CONCLUSION: The most common manifestation of immediate hypersensitivity to cefaclor was anaphylaxis, most of which was mediated by IgE; however, a non-IgE mediated direct basophil activation mechanism was suggested in a subset of anaphylaxis patients.

Immunoelectron microscopy study of superficial skin nerves in drug-induced acute urticaria / Estudo de microscopia imunoeletrônica dos nervos superficiais da pele na urticária aguda induzida por medicamentos

BACKGROUND: Few studies have evaluated the ultrastructure of the superficial skin nerves in urticaria. OBJECTIVE: The objective of this study was to describe findings in superficial skin nerves in cases of drug-induced acute urticaria. METHODS: Seven patients with drug-induced acute urticaria were included in the study. Skin biopsies were obtained from the urticarial lesion and from the apparently normal skin. The 14 fragments collected were processed for immunogold electron microscopy using single stains for antitryptase and anti-FXIIIa antibodies, as well as double immunogold labeling for both. RESULTS: Some sections showed mast cells in the process of degranulation. Following double immunogold staining, 10 nm (FXIIIa) and 15 nm (Tryptase) gold particles were found together throughout the granules in mast cells, indicating that tryptase and FXIIIa are located inside each one of the granules of these cells. Interestingly, we found strong evidence of the presence of tryptase and factor XIIIa in the superficial skin nerves of these patients, both in cases of urticarial lesions (wheals) and in the apparently normal skin. CONCLUSIONS: Tryptase and FXIIIa are present in the superficial nerves of the skin in drug-induced acute urticaria. This is the first report of tryptase and FXIIIa expression in the superficial skin nerves of patients with urticaria. Tryptase may be participating in neural activation in these patients, while FXIIIa may be present in the nerves to guarantee the functional integrity of structures.

FUNDAMENTOS: Poucos autores têm estudado a ultraestrutura dos nervos superficiais na urticária. OBJETIVO: Descrever os achados nos nervos cutâneos superficiais em casos de urticária aguda induzida por medicamentos. MÉTODOS: Sete pacientes com urticária aguda induzida por medicamentos foram incluídos no estudo. Foram obtidas biopsias da pele da lesão urticariforme e da pele aparentemente normal. Os 14 fragmentos coletados foram processados usando imunomarcação com ouro para anticorpos anti-triptase e anti-FXIIIa separadamente, além da dupla imunomarcação com ambos anticorpos. A seguir as amostras foram submetidas à análise por microscopia imunoeletrônica. RESULTADOS: Alguns cortes demonstraram mastócitos em processo de degranulação. Após a imunomarcação dupla, partículas de ouro de 10 nm (FXIIIa) e partículas de ouro de 15 nm (Triptase) apresentavam-se juntas em grânulos de mastócitos indicando que a triptase e o FXIIIa se localizam dentro de cada um dos grânulos dessas células. Curiosamente, foi encontrada uma forte evidência da presença da triptase e do fator XIIIa nos nervos superficiais dos pacientes avaliados, tanto em lesões urticadas, como na pele aparentemente normal. CONCLUSÕES: A triptase e o FXIIIa estão presentes nos nervos superficiais da pele na urticária aguda medicamentosa. Este é o primeiro relato da expressão de triptase e de FXIIIa nos nervos superficiais na urticária. A triptase poderia estar participando da ativação neural nos pacientes estudados. O FXIIIa poderia estar presente nos nervos, com a finalidade de manter a integridade funcional dessas estruturas.

Reacciones medicamentosas severas en piel / Severe skin drug reactions

Las drogas son sustancias químicas que pueden interferir con el sistema inmune y a veces conducen a reacciones inusuales y severas. Éstas pueden amenazar la vida, requerir hospitalizaciones prolongadas o dejar secuelas significativas. Cerca del 2 por ciento de las reacciones cutáneas inducidas por fármacos se consideran graves. Estas son el angioedema, el shock anafiláctico, el síndrome de Stevens-Johnson (SSJ), la necrolisis epidérmica tóxica (NET), y el síndrome de hipersensibilidad (DRESS), entre otros. Requieren atención especial ya que los síntomas clínicos son heterogéneos y pueden imitar diferentes enfermedades, lo que lleva a retardar el diagnóstico correcto.

Drugs are chemicals that can interfere with the immune system and may sometimes lead to unusual and severe reactions. These can be life threatening, requiring prolonged hospitalization or have significant sequelae. About 2 per cent of drug-induced skin reactions are considered serious. They are angioedema, anaphylactic shock, the Steven-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and hypersensitivity syndrome (DRESS), among others. They require special attention because clinical symptoms are heterogeneous and can mimic different diseases, leading to a delay in the correct diagnosis.

Reacciones adversas inmediatas en el uso de medios de contraste radiológicos no iónicos / Inmediate adverse reactions in the use of non ionic radiological contrast media

Las reacciones adversas a los medios de contraste utilizados en exámenes radiológicos son consideradas una de las variables que deben ser conocidas manejadas para evitar complicaciones y efectos nocivos en los pacientes. El objetivo de este trabajo fue establecer el comportamiento de las reacciones adversas al medio de contrate no iónico en los pacientes expuestos en el Hospital Regional de Concepción mediante un estudio de corte transversal en el que la muestra estuvo compuesta por 167 pacientes a los que se les inyectó un medio de contraste no iónico. En la recolección de datos se aplicó una encuesta y se observó su reacción. Resultados: Las reacciones adversas leves estuvieron presentes en un 16,2 por ciento (n=27), solo una de ellas fue moderada. Al analizar las variables estudiadas: edad, sexo, antecedentes alérgicos, volumen de medio contraste utilizado y exposición previa a medio de contraste anterior, no se encontraron diferencias estadísticamente significativas. Conclusiones: Llama la atención la cantidad de reacciones adversas, que para esta muestra resulta ser muy superior a cualquiera de las publicaciones encontradas. Esto alienta a proponer una nueva investigación en este ámbito considerando que se trata de identificar la realidad local y es un aporte para nuestra población , en cuanto al mejorar la calidad de la atención en base a un perfil nacional, incorporando para un próximo estudio variables del tipo estilo de vida, antecedentes de pueblos originarios y patología asociada, entre otros.

The adverse reactions to the contrast media used in radiological examinations are considered to be one of the variables that they muist be known and handled to avoid complications and harmful effcts in the exposed patients. The objective of this work was to establish the behavior of theadverse reactions to the way of nonionic contrast media in the patients exposed in the Regional Hospital Of Concepción by menas of a study of transverse cut in which the sample was composed by 167 patients to whom they there was injected a way of nonionic contrast media. In the compilation of information a survey was applied and the reaction was observed. Results: The adverse slight reactions were presents in 16,2 percent (n=27), only one them was moderate. When the studied variables analyzed age, sex, allergic precedents, volume of way of used differences. Conlusions: It is called the attention the quatity of adverse reactions, which for this samples turn out to be very superior to any of the opposing publications. This breathes to proposea new investigations in this area thinking that it tries of identifying the local reality and being a contribution for our population, as for improving the quality of the attention on the basis of a national profile, incorporating for a next study variables of the type way of life, precedents of original peoples and associate pathology, between others.

Chlorhexidine urticaria: A rare occurrence with a common mouthwash.

Chlorhexidine is a widely used antiseptic and disinfectant in medical and nonmedical environments. Compared to its ubiquitous use, allergic contact dermatitis from chlorhexidine has rarely been reported and so its sensitization rate seems to be low. The prevalence of contact urticaria and anaphylaxis due to chlorhexidine remains to be unknown. This case report presents a case of urticaria due to oral use of chlorhexidine. The adverse reaction was confirmed by skin prick test.

Comparative efficacy of levocetirizine, desloratidine and fexofenadine by histamine wheal suppression test.

BACKGROUND: Histamine is the major mediator of allergic reactions. Newer H1 antihistaminics like levocetirizine, fexofenadine, and desloratadine are used in the treatment of seasonal and perennial allergic rhinitis and urticaria. The ability to block the cutaneous response to intradermal histamine is used to evaluate the potential of antihistamines. AIMS: To compare the potency, onset, and duration of action of the commonly used antihistamines-levocetirizine, fexofenadine, and desloratadine. METHODS: Thirty volunteers were given three single doses of levocetirizine, fexofenadine and desloratadine at weekly intervals. A pretest was performed by using the intradermal histamine prick test. After administration of the drugs, the intradermal test was repeated at (1/2), 1, 2, 3, 6 and 24 h, and the sizes of the wheal were measured. The mean values were taken and were compared by using Levene's t-test. RESULTS: At 30 min, fexofenadine showed a statistically significant suppression of wheal size compared to levocetirizine and desloratadine. Two and three hours after administration, levocetirizine and fexofenadine showed statistically significant inhibition of wheal size while only levocetirizine had this effect after six hours when compared to desloratadine. Desloratadine showed greater inhibition of wheal size at the end of 24 h when compared to levocetirizine and fexofenadine but this was not statistically significant. CONCLUSIONS: Fexofenadine had the earliest onset of action while levocetirizine showed maximum inhibition of wheal response after three and six hours.

Adverse reactions of fluorescein angiography: a prospective study

PURPOSES: To determine both the incidence of adverse reactions in patients who underwent fluorescein angiography for the first time and to determine whether systemic arterial hypertension, diabetes or allergy history increases the chance of reaction to intravenous fluorescein. METHODS:Data collection was carried out between January 2001 and October 2002 in Recife, Brazil. Patients with prior fluorescein angiography history, pregnant patients or patients in use of corticosteroids, immunosuppressive or antihistamine drugs were excluded. RESULTS: Out of 1,500 enrolled patients, 1,039 (69.3 percent) underwent the test for the first time. The mean age was 58 ± 16 years and the median age was 60 years. Of these, 628 (60.4 percent) were women. Nausea occurred in 71 (6.83 percent) patients, vomiting in 14 (1.35 percent), urticaria in 11 (1.06 percent), bronchospasm in 4 (0.38 percent) and laryngeal edema in 1 (0.01 percent). Five patients presented more than one adverse reaction. Higher incidences of adverse reactions were observed in diabetic patients [p<0.002, RR=1.80 (CI=1.24-2.60)], patients with systemic arterial hypertension [p<0.002, RR=1.84 (CI=1.26-2.71)] and patients with allergy history [p<0.001, RR=3.90 (CI=2.70-5.63)]. CONCLUSIONS: A cumulative incidence of 9.72 percent adverse reactions was observed in patients who had undergone this test for the first time. The presence of the allergy history, diabetes or systemic arterial hypertension increased the incidence of adverse reactions to the dye.

OBJETIVO: Determinar a incidência de reações adversas em pacientes submetidos à angiofluoresceinografia pela primeira vez e determinar se hipertensão arterial sistêmica, diabetes ou história de alergia aumentam a chance de reações à fluoresceína intravenosa. MÉTODOS: Os dados foram coletados entre janeiro de 2001 e outubro de 2002 em Recife, Brasil. Pacientes com angiofluoresceinografia prévia, gestantes ou pacientes em uso de medicamentos corticosteróides, imunossupressores ou anti-histamínicos foram excluídos. RESULTADOS: Dos 1.500 pacientes iniciais, 1.039 (69,3 por cento) realizavam o exame pela primeira vez. A idade média foi de 58 ± 16 anos e a mediana de 60 anos. Dentre esses, 628 (60,4 por cento) pessoas eram do sexo feminino. Náusea ocorreu em 71 (6,83 por cento) pacientes, vômito em 14 (1,35 por cento), urticária em 11 (1,06 por cento), broncoespasmo em 4 (0,38 por cento) e edema de laringe em 1 (0,01 por cento). Cinco pacientes apresentaram mais de uma reação adversa. Maiores incidências de reações adversas foram observadas em diabéticos [p<0,002, RR=1,80 (IC=1,24-2,60)], hipertensos [p<0,002, RR=1,84 (IC=1,26-2,71)] e pacientes com história de alergia [p<0,001, RR=3,90 (IC=2,70-5,63)]. CONCLUSÕES: Uma incidência cumulativa de 9,72 por cento de reações adversas foi observada em pacientes submetidos à angiofluoresceinografia pela primeira vez. Presença de história de alergia, diabetes ou hipertensão arterial aumentou a incidência de reações adversas ao contraste.

Association of beta2-Adrenergic Receptor Polymorphism with the Phenotype of Aspirin-Intolerant Acute Urticaria

The genetic mechanism of aspirin intolerant acute urticaria (AIAU) is unknown. To demonstrate an association between the beta2 adrenergic receptor (ADRB2) polymorphism and the phenotype of AIAU, one hundred fourteen patients with AIAU, 110 patients with aspirin intolerant chronic urticaria (AICU), and 498 normal healthy controls (NC) based on a Korean population were enrolled. The genotype of ADRB2 at 46 A > G was analyzed using a direct sequencing method. The ADRB2 polymorphism at 46 A > G showed a significant difference between AIAU and NC; the frequency of the major genotype was significantly higher in the AIAU group (p= 0.017 in recessive model), while no differences were noted in allele and genotype frequencies between AICU and NC. In conclusion, the ADRB2 (46 A > G) gene polymorphism may contribute to the development of the phenotype of AIAU.

[Urticarian vasculitis. a case report after sulfamethoxazole-trimethoprime ingestion]

Urticarian vasculitis [UV] is an anatomoclinical disorder characterized by the association of urticarian papules lasting for more than 24 hours with histological cutaneous vasculitis. Several etiologies are associated with the disease. We report the case of a 30-year-old woman with a-two-month history of urticarial purpuric and necrotic cutaneous lesions of the low limbs. These lesions occurred after oral sulfam‚thoxazole-trim‚thoprime ingestion, 2 weeks before the skin eruption. Histological examination revealed a leucocytoclasic vasculitis and direct immunofluorescence showed a perivascular IgG and C3 deposits. Immunological, allergological and radiological investigations were normal. The pharmacological enquiry confirmed the imputability of sulfam‚thoxazole-trim‚thoprime in the onset of skin eruption; Mild cutaneous improvement was observed after 3 months of treatment with prednisone 0,5 mg/Kg/day. Drug induced urticaria constitutes a rare etiology of UV. Sulfam‚thoxazole-trimethoprime imputability has not been reported before among the drug responsible for UV. Management of patients is difficult and improvement usually occurs after several months because of the resistance of the skin lesions

Polymorphisms of High-Affinity IgE Receptor and Histamine-Related Genes in Patients with ASA-Induced Urticaria/Angioedema

The pathogenic mechanism of ASA-induced urticaria/angioedema (AIU) is still poorly understood, but it has been known that histamine releasing by cutaneous mast cell activation is considered to be an important role. Considering the importance of histamine in AIU, we speculated that a genetic abnormality of histamine-related genes such as a high-affinity IgE receptor, a metabolic enzyme of histamines and histamine receptors, may be involved in the development of AIU. Enrolled in the study were 110 patients with AIU, 53 patients without ASA hypersensitivity who had various drug allergies presenting as exanthematous skin symptoms, and 99 normal healthy controls (NC). Eleven single nucleotide polymorphisms (SNPs) of the beta chain of the high-affinity IgE receptor (FCER1B) and three histamine-related genes-histamine N-methyltransferase (HNMT), histamine H1 receptor (HRH1), histamine H2 receptor (HRH2)-were screened using the SNP-IT assay based on a single base extension method. No significant differences were observed in allele and genotype frequencies, and haplotype frequencies of all the SNPs of FCER1B, HNMT, HRH1, and HRH2 among the three groups (p>0.05, respectively). These results suggest that the polymorphisms of FCER1B and the three histamine-related genes may not contribute to the development of AIU phenotype in the Korean population.