Abstract Background: There are few epidemiological studies of urticaria, published in the indexed literature (PubMed/Medline). Objective: The study aimed to evaluate the epidemiological and clinical data among patients with urticaria/angioedema attending a reference clinic in Brazil. Methods: Two hundred sixty-seven patients were evaluated retrospectively considering demographic data, time course of the disease, triggering symptoms, the presence of angioedema, complementary laboratory tests including total blood count, reactive-C protein, erythrocyte sedimentation rate, IgE serum levels, and other, as necessary. Results: The most commonly diagnosed type of urticaria was chronic spontaneous urticaria (56.93%). Angioedema was associated with chronic urticaria in 108 patients (40.08%). Study limitations: Unicentered and retrospective. Conclusion: Some relevant findings in this study are the observation of a female prevalence of cases (4-females: 1-man), a result more elevated than demonstrated in previous studies in Europe and Asia, the median age was 43-years old and the delay of time between the diagnosis of urticaria and the admission for treatment in a specialized center was approximately 2-years. Other multicenter studies can better establish these differences in Brazilian patients.

Abstract Vasculitis is a group of several clinical conditions in which the main histopathological finding is fibrinoid necrosis in the walls of blood vessels. This article assesses the main dermatological aspects relevant to the clinical and laboratory diagnosis of small- and medium-vessel cutaneous and systemic vasculitis syndromes. The most important aspects of treatment are also discussed.

Abstract The term vasculitis refers to the inflammation of vessel walls. It may range in severity from a self-limited disorder in one single organ to a life-threatening disease due to multiple organ failure. It has many causes, although they result in only a few histological patterns of vascular inflammation. Vessels of any type and in any organ can be affected, a fact that results in a broad variety of signs and symptoms. Different vasculitides with indistinguishable clinical presentations have quite different prognosis and treatments. This condition presents many challenges to physicians in terms of classification, diagnosis, appropriate laboratory workup, and treatment. Moreover, it compels a careful follow-up. This article reviews the Chapel-Hill 2012 classification, etiology, recent insights in pathophysiology, some important dermatological clues for the diagnosis and summarizes treatment of some of these complex vasculitis syndromes.

Abstract: Background: Urticarias are frequent diseases, with 15% to 20% of the population presenting at least one acute episode in their lifetime. Urticaria are classified in acute ( ≤ 6 weeks) or chronic (> 6 weeks). They may be induced or spontaneous. Objectives: To verify the diagnostic and therapeutic recommendations in chronic spontaneous urticaria (CSU), according to the experience of Brazilian experts, regarding the available guidelines (international and US). Methods: A questionnaire was sent to Brazilian experts, with questions concerning diagnostic and therapeutic recommendations for CSU in adults. Results: Sixteen Brazilian experts answered the questionnaire related to diagnosis and therapy of CSU in adults and data were analyzed. Final text was written, considering the available guidelines (International and US), adapted to the medical practices in Brazil. Diagnostic work up in CSU is rarely necessary. Biopsy of skin lesion and histopathology may be indicated to rule out other diseases, such as, urticarial vasculitis. Other laboratory tests, such as complete blood count, CRP, ESR and thyroid screening. Treatment of CSU includes second-generation anti-histamines (sgAH) at licensed doses, sgAH two, three to fourfold doses (non-licensed) and omalizumab. Other drugs, such as, cyclosporine, immunomodulatory drugs and immunosuppressants may be indicated (non-licensed and with limited scientific evidence). Conclusions: Most of the Brazilian experts in this study partially agreed with the diagnostic and therapeutic recommendations of the International and US guidelines. They agreed with the use of sgAH at licensed doses. Increase in the dose to fourfold of sgAH may be suggested with restrictions, due to its non-licensed dose. Sedating anti-histamines, as suggested by the US guideline, are indicated by some of the Brazilian experts, due to its availability. Adaptations are mandatory in the treatment of CSU, due to scarce or lack of other therapeutic resources in the public health system in Brazil, such as omalizumab or cyclosporine.

Abstract BACKGROUND: Chronic urticaria is characterized by transient, pruritic lesions of varying sizes, with central pallor and well-defined edges, with disease duration longer than six weeks. Its cellular infiltrate consists of neutrophils, lymphocytes and eosinophils. There is a subgroup of patients with eosinophilic or neutrophilic urticaria, resistant to the treatment with antihistamines, but that respond to a combination of antihistamine with other drugs. OBJECTIVE: To evaluate the present infiltration in chronic urticaria biopsies and correlate it with the clinical disease activity and response to treatment. METHODS: Forty-one patients with chronic urticaria were classified according to the score of severity of the disease, response to treatment and type of perivascular infiltrate. Inflammatory infiltrates were divided in eosinophilic (46.30%), neutrophilic and mixed. RESULTS: An association was found between the eosinophilic infiltrate and clinical scores of greater severity (p = 0.002). CONCLUSION: This association shows that the eosinophilic inflammatory infiltrates denote high clinical activity, which means more severe and exuberant clinical pictures of the disease.

A síndrome Reação a Drogas com Eosinofilia e Sintomas Sistêmicos, também conhecida como Síndrome da Hipersensibilidade Induzida por Droga apresenta-se clinicamente como uma erupção cutâneomucosa extensa tipo exantemática, associada a febre, linfadenopatia, hepatite, anormalidades hematológicas com eosinofilia e linfócitos atípicos, e pode envolver outros órgãos, produzindo insuficiência renal, infiltrado eosinofílico cardíaco e pulmonar, além de pancreatite. O reconhecimento desta síndrome é de suma importância, uma vez que, a taxa de mortalidade é de cerca de 10% a 20% e uma terapia específica pode ser necessária. Sua etiopatogenia está relacionada a drogas específicas, principalmente os anticonvulsivantes aromáticos, alterações imunes, reativação sequencial de herpesvirus e associação com alelos do HLA. O pronto reconhecimento da síndrome e a retirada da droga desencadeante são os passos mais importantes e essenciais no tratamento dos doentes acometidos. Os corticosteróides são as medicações de escolha para o tratamento da síndrome, podendo ser associados imunoglobulina intravenosa e em, alguns casos selecionados, Ganciclovir. O artigo traz uma revisão dos conceitos atuais que envolvem essa importante manifestação de reação adversa a drogas.

The Drug Reaction with Eosinophilia and Systemic Symptoms syndrome, also known as Drug Induced Hypersensitivity Syndrome presents clinically as an extensive mucocutaneous rash, accompanied by fever, lymphadenopathy, hepatitis, hematologic abnormalities with eosinophilia and atypical lymphocytes, and may involve other organs with eosinophilic infiltration, causing damage to several systems, especially to the kidneys, heart, lungs, and pancreas. Recognition of this syndrome is of paramount importance, since the mortality rate is about 10% to 20%, and a specific therapy may be necessary. The pathogenesis is related to specific drugs, especially the aromatic anticonvulsants, altered immune response, sequential reactivation of herpes virus and association with HLA alleles. Early recognition of the syndrome and withdrawal of the offending drug are the most important and essential steps in the treatment of affected patients. Corticosteroids are the basis of the treatment of the syndrome, which may be associated with intravenous immunoglobulin and, in selected cases, Ganciclovir. The article reviews the current concepts involving this important manifestation of adverse drug reaction.

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.

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.

Descrevemos uma doente de 19 anos que nos procurou com quadro de intenso prurido há 2 semanas e demonstrando lesões eritêmato-pápulo-urticadas mais intensamente distribuídas nos membros superiores e inferiores. A anamnese detalhada excluiu causas internas e medicamentos como uma possível causa do prurigo. Após orientações quanto a dedetização do domicílio a doente retornou no consultório após 3 semanas sem lesões cutâneas e trazendo em um pote de vidro vários percevejos coletados após a dedetização.

This report describes a 19-year old female patient, who sought medical attention for severe itching of two weeks' duration. Erythematous papules and wheals were found, principally on her upper and lower limbs. Careful anamnesis excluded other etiologies of the pruritus, including those related to internal diseases and medication. Following counseling regarding the need to contract a domestic pest control company, the patient returned to the clinic three weeks later with no skin lesions and bearing a glass jar containing several bedbugs collected following pest control treatment.

Bedbugs have been known as a human parasite for thousands of years, but scientific studies about this insect are recent and limited. Cimex lectularius, the common bedbug, was a well-known parasite in human dwellings until the end of the Second World War. Nowadays, bedbugs are considered uncommon in the industrialized world. Anecdotal reports suggest that bedbugs are getting more common in the United States, Canada, and United Kingdom. In Brazil, there are few reports about bedbug infestations in the literature. The aim of this article was to alert physicians, especially in Brazil, about this ectoparasitosis, including aspects of the bedbug biology, their parasitism in human host, treatment and prophylaxis.

Nós descrevemos um homem de 48 anos que procurou nossa clínica com múltiplas pápulas eritematosas e pruriginosas dois dias após uma viagem à Serra da Mantiqueira. O exame físico meticuloso com o dermatoscópio de epiluminescência demonstrou múltiplos carrapatos na fase de larva na pele.

We describe the case of a 48-year-old healthy man who sought for medical help in our clinic with multiple pruriginous erythematous papules after a 2-day trip to "Serra da Mantiqueira". (Mantiqueira Mountain). A meticulous physical exam with a portable epiluminescence microscopy showed several ticks on a larval form on the skin of the patient.

As drogas com ação anti-histamínica estão entre as medicações mais comumente prescritas na prática dermatológica diária, tanto em adultos como em crianças. Este artigo aborda os novos conceitos da função dos receptores de histamina (receptores H1) e discute os efeitos anti-inflamatórios dessas drogas. A segunda geração de anti-histamínicos difere da primeira geração devido a sua elevada especificidade e afinidade pelos receptores H1 periféricos e devido a seu menor efeito no sistema nervoso central, tendo como resultado menores efeitos sedativos. Embora a eficácia dos diferentes anti-histamínicos H1 (anti-H1) no tratamento de doentes alérgicos seja similar, mesmo quando se comparam anti-H1 de primeira e de segunda geração, eles são muito diferentes em termos de estrutura química, farmacologia e propriedades tóxicas. Consequentemente o conhecimento de suas características farmacocinéticas e farmacodinâmicas é importante para a melhor prática médica, especialmente em gestantes, crianças, idosos e doentes com comorbidades.

Drugs with antihistamine action are the most commonly prescribed medication in daily dermatologic practice, both to adults and children. This article addresses new concepts of the role of histamine receptors (H1 receptors) and discusses the anti-inflammatory effects of these drugs. Second generation antihistamines differs from first generation because of their high specificity and affinity for peripheral H1-receptors. Second generation antihistamines are also less likely to produce sedation because they have less effect on the central nervous system. Although the efficacy of the various H1-antihistamines in the treatment of allergic patients is similar, even when comparing first- and second-generation drugs, these drugs are still very different in terms of their chemical structure, pharmacology and toxic properties. Consequently, knowledge of their pharmacokinetic and pharmacodynamic characteristics is essential for a better medical care, especially that offered to pregnant women, children, the elderly, and patients with comorbidities.

A urticária apresenta-se com diversas formas clínicas e causas distintas. Constitui uma das dermatoses mais freqüentes: 15% a 20% da população têm pelo menos um episódio agudo da doença em sua vida, resultando em percentual que varia de um a 2% dos atendimentos nas especialidades de Dermatologia e Alergologia. A urticária é classificada do ponto de vista de duração da evolução temporal em aguda (inferior a seis semanas) ou crônica (superior a seis semanas). O tratamento da urticária pode compreender medidas não farmacológicas e intervenções medicamentosas, as quais são agrupadas em tratamentos de primeira (anti-histamínicos), segunda (corticosteróides e antileucotrienos) e terceira linha (medicamentos imunomoduladores). As medidas terapêuticas de segunda e terceira linha apresentam maiores efeitos adversos, devendo ser reservadas aos doentes que não apresentaram controle da doença com os de primeira linha, ou àqueles a respeito dos quais não é possível estabelecer uma etiologia, tal como nas urticárias auto-imunes.

Urticaria has diverse clinical presentations and causes. It is one of the most frequent dermatological conditions: 15% to 20% of population has at least one acute eruption during their lifetime, resulting in 1% to 2% of dermatological and allergological visits. Urticaria is classified based on its temporal evolution as acute (less than 6 weeks) or chronic (more than 6 weeks). Management strategies may involve non-pharmacological measures and drug interventions, which are grouped into first- (antihistamines), second- (corticosteroids and anti-leukotrienes) and third-line therapies (immunomodulators). Stronger, but potentially riskier, second- and third-line management may be justified for patients who do not respond to first-line therapy, or whenever a specific etiology cannot be determined, such as in autoimmune urticaria.

As reações cutâneas graves adversas à droga são as que geralmente necessitam de internação hospitalar, por vezes em unidade de terapia intensiva ou de queimados, com observação minuciosa dos sinais vitais e da função de órgãos internos. O objetivo é descrever estas reações facilitando o seu reconhecimento e tratamento. Fazem parte deste grupo a Síndrome de Hipersensibilidade à Droga (SHD), a Pustulose Exantemática Generalizada Aguda (PEGA), a Necrose Cutânea induzida por Anticoagulante, as Vasculites de Pequenos Vasos (VPV), a Vasculite de Hipersensibilidade ao Propiltiouracil (VHP) e as Reações tipo Doença do Soro (RDS). A SHD tem-se tornado de elevada relevância clínica devido ao uso amplo dos anticonvulsivantes aromáticos e da dapsona, utilizada no tratamento de doenças como a acne e a hanseníase. A PEGA é determinada principalmente pelos derivados beta-lactâmicos e tem como principal diagnóstico diferencial a psoríase pustulosa generalizada. As VPV tegumentares podem refletir uma doença multissistêmica subjacente, com danos graves em órgãos nobres, como os rins, pulmões e sistema hematológico, com morbidade elevada e possível letalidade. Abordamos as características clínicas e o tratamento destas reações adversas à droga.

Severe cutaneous adverse drug reactions generally require hospitalization, sometimes in intensive care or burns units, for observation of the vital signs and the visceral function. The objective was to describe these reactions in order to facilitate recognition and treatment. This group of drug reactions includes drug hypersensitivity syndrome (DHS), acute generalized exanthematous pustulosis (AGEP), anticoagulant-induced skin necrosis, small-vessel vasculitis (SVV), propylthiouracil hypersensitivity vasculitis and serum sickness disease. DHS has been most relevant due to universal prescription of aromatic anticonvulsant drugs and dapsone use in the treatment of some diseases such as acne and leprosy. AGEP is mostly induced by b-lactam related drugs and presents similar clinical characteristics as generalized pustular psoriasis, thus these must be differentiated. SVV can present an occult systemic illness, with impairment of relevant internal organs, such as kidneys, lungs and hematological system, with elevated morbidity and risk of death.

As reações cutâneas graves adversas a droga (RCGAD) são as que geralmente necessitam de internação hospitalar, por vezes em unidade de terapia intensiva ou de queimados, com observação minuciosa dos sinais vitais e da função de órgãos internos. O objetivo é descrever essas reações, facilitando seu reconhecimento e tratamento. Fazem parte desse grupo a anafilaxia, a síndrome de Stevens-Johnson (SSJ), a necrólise epidérmica tóxica (NET) e, dependendo do envolvimento sistêmico, as eritrodermias. Neste artigo, são abordados as características clínicas e o tratamento de algumas reações adversas a droga: anafilaxia, as eritrodermias, a síndrome de Stevens-Johnson (SSJ) e a necrólise epidérmica tóxica (NET).

Severe Cutaneous Adverse Reactions to drugs (SCARD) generally require hospitalization, and at times in the intensive therapy or burn care unit for observation of the vital signs and the viscera function. The aim of this study is to describe these reactions in order to facilitate recognition and treatment. This group of drug reactions includes anaphylaxis, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and, depending on the systemic involvement, erythroderma. In this article we approach the characteristics and treatment of some adverse reactions to drugs: anaphylaxis, erythroderma, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).