Potential interactions of SARS-CoV-2 with human cell receptors in the skin: Understanding the enigma for a lower frequency of skin lesions compared to other tissues.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a new public health problem, with a total of 10.577.263 documented COVID-19 cases worldwide and 513.441 deaths up to the present date. Few cases of disease-related cutaneous manifestations have been reported in the literature, and such manifestations are scarce. Integumentary manifestations from COVID-19 include exanthemas and papular dermatoses, urticarial eruptions, atopic dermatitis, vesiculobullous lesions and skin signs of hypercoagulable states, such as acral ischaemia, livedo and retiform purpura. Most common extracutaneous manifestations from the disease include headache, cough, anosmia, ageusia, fever, dyspnoea, nausea, diarrhoea and cardiovascular events. The objectives of this review were to discuss the role of human cell receptors described as interaction targets of SARS-CoV-2, as well to understand the current state of knowledge on skin expression of these receptors, in order to substantiate future research. The authors present a thorough literature review on SARS-CoV-2 and its possible interaction with cell receptors and human tissues including the skin. They discuss a molecular hypothesis to explain the lower prevalence of dermatological manifestations from direct SARS-CoV-2 infection. Distinct human cell receptors binding the virus appear to be less expressed in the skin compared to other organs. Additionally, the presence of resolvins and the disintegrin metalloprotease ADAM17 provide a putative protection to the skin, explaining the majority of COVID-19 manifestations to be extracutaneous. This review represents an excellent opportunity for future studies using skin biopsies from COVID-19 patients to investigate molecular expression in the pathophysiology of cutaneous manifestations of the disease.

What the physicians should know about mast cells, dendritic cells, urticaria, and omalizumab during COVID-19 or asymptomatic infections due to SARS-CoV-2?

Coronavirus disease (COVID-19) pandemic presents several dermatological manifestations described in the present indexed literature, with around 700 cases reported until May 2020, some described as urticaria or urticarial rashes. Urticaria is constituted by evanescent erythematous-edematous lesions (wheals and flare), which does not persist in the same site for more than 24 to 48 hours and appears in other topographic localization, resolving without residual hyper pigmentation. During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, some cytokines are synthesized, including Interferon (IFN) type I, TNF-α, and chemokines which may induce mast cells (MCs) and basophils degranulation by mechanisms similar to the autoinflammatory monogenic or polygenic diseases. In this article, we discuss the spectrum of the urticaria and urticarial-like lesions in the COVID-19's era, besides other aspects related to innate and adaptative immune response to viral infections, interactions between dermal dendritic cells and MCs, and degranulation of MCs by different stimuli. Plasmacytoid dendritic cells share, in allergic patients, expression of the high-affinity IgE receptors on cell membranes and demonstrated a low pattern of type I IFN secretion in viral infections. We discuss the previous descriptions of the effects of omalizumab, a monoclonal antibody directed to IgE and high-affinity IgE receptors, to improve the IFN responses and enhance their antiviral effects.

Prurigo: review of its pathogenesis, diagnosis, and treatment.

Prurigo is a reactive, hyperplastic skin condition characterized by pruritic papules, plaques, and/or nodules. The temporal classification includes acute/subacute and chronic disease (≥ 6 weeks), with different clinical variants, synonymies, and underlying etiological factors. The immunology of chronic prurigo shows similarities with atopic dermatitis due to the involvement of IL-4 and IL-13, IL-22, and IL-31. Treatment includes antihistamines, topical steroids, dupilumab, and JAK inhibitors. Several conditions manifest clinically as prurigo-like lesions, and the correct clinical diagnosis must precede correct treatment. Furthermore, chronic prurigos represent a recalcitrant and distressing dermatosis, and at least 50% of these patients have atopic diathesis, the treatment of which may induce adverse effects, especially in the elderly. The quality of life is significantly compromised, and topical treatments are often unable to control symptoms and skin lesions. Systemic immunosuppressants, immunobiologicals, and JAK inhibitors, despite the cost and potential adverse effects, may be necessary to achieve clinical improvement and quality of life. This manuscript reviews the main types of prurigo, associated diseases, their immunological bases, diagnosis, and treatment.

Patient-Reported Outcome Measures in Atopic Dermatitis and Chronic Urticaria Are Underused in Clinical Practice.

BACKGROUND: Patient-reported outcome measures (PROMs) are validated and standardized tools that complement physician evaluations and guide treatment decisions. They are crucial for monitoring atopic dermatitis (AD) and chronic urticaria (CU) in clinical practice, but there are unmet needs and knowledge gaps regarding their use in clinical practice. OBJECCTIVE: We investigated the global real-world use of AD and CU PROMs in allergology and dermatology clinics as well as their associated local and regional networks. METHODS: Across 72 specialized allergy and dermatology centers and their local and regional networks, 2,534 physicians in 73 countries completed a 53-item questionnaire on the use of PROMs for AD and CU. RESULTS: Of 2,534 physicians, 1,308 were aware of PROMs. Of these, 14% and 15% used PROMs for AD and CU, respectively. Half of physicians who use PROMs do so only rarely or sometimes. Use of AD and CU PROM is associated with being female, younger, and a dermatologist. The Patient-Oriented Scoring Atopic Dermatitis Index and Urticaria Activity Score were the most common PROMs for AD and CU, respectively. Monitoring disease control and activity are the main drivers of the use of PROMs. Time constraints were the primary obstacle to using PROMs, followed by the impression that patients dislike PROMs. Users of AD and CU PROM would like training in selecting the proper PROM. CONCLUSIONS: Although PROMs offer several benefits, their use in routine practice is suboptimal, and physicians perceive barriers to their use. It is essential to attain higher levels of PROM implementation in accordance with national and international standards.

What lessons can we learn? Clinical and epidemiological retrospective analysis of 267 patients with urticaria in a Brazilian tertiary center.

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.

Update on vasculitis: overview and relevant dermatological aspects for the clinical and histopathological diagnosis - Part II.

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.

Update on vasculitis: an overview and dermatological clues for clinical and histopathological diagnosis - part I.

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.

The usage, quality and relevance of information and communications technologies in patients with chronic urticaria: A UCARE study.

BACKGROUND: Chronic urticaria (CU) is characterized by itchy recurrent wheals, angioedema, or both for 6 weeks or longer. CU can greatly impact patients' physical and emotional quality of life. Patients with chronic conditions are increasingly seeking information from information and communications technologies (ICTs) to manage their health. The objective of this study was to assess the frequency of usage and preference of ICTs from the perspective of patients with CU. METHODS: In this cross-sectional study, 1800 patients were recruited from primary healthcare centers, university hospitals or specialized clinics that form part of the UCARE (Urticaria Centers of Reference and Excellence) network throughout 16 countries. Patients were >12 years old and had physician-diagnosed chronic spontaneous urticaria (CSU) or chronic inducible urticaria (CIndU). Patients completed a 23-item questionnaire containing questions about ICT usage, including the type, frequency, preference, and quality, answers to which were recorded in a standardized database at each center. For analysis, ICTs were categorized into 3 groups as follows: one-to-one: SMS, WhatsApp, Skype, and email; one-to-many: YouTube, web browsers, and blogs or forums; many-to-many: Instagram, Twitter, Facebook, and LinkedIn. RESULTS: Overall, 99.6% of CU patients had access to ICT platforms and 96.7% had internet access. Daily, 85.4% patients used one-to-one ICT platforms most often, followed by one-to-many ICTs (75.5%) and many-to-many ICTs (59.2%). The daily ICT usage was highest for web browsers (72.7%) and WhatsApp (70.0%). The general usage of ICT platforms increased in patients with higher levels of education. One-to-many was the preferred ICT category for obtaining general health information (78.3%) and for CU-related information (75.4%). A web browser (77.6%) was by far the most commonly used ICT to obtain general health information, followed by YouTube (25.8%) and Facebook (16.3%). Similarly, for CU-specific information, 3 out of 4 patients (74.6%) used a web browser, 20.9% used YouTube, and 13.6% used Facebook. One in 5 (21.6%) patients did not use any form of ICT for obtaining information on CU. The quality of the information obtained from one-to-many ICTs was rated much more often as very interesting and of good quality for general health information (53.5%) and CU-related information (51.5%) as compared to the other categories. CONCLUSIONS: Usage of ICTs for health and CU-specific information is extremely high in all countries analyzed, with web browsers being the preferred ICT platform.

Consensus on the diagnostic and therapeutic management of chronic spontaneous urticaria in adults - Brazilian Society of Dermatology.

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.

O omalizumabe no tratamento da urticária no contexto da pandemia de COVID-19 / Omalizumab as urticaria treatment in the context of the COVID-19 pandemic

O início da pandemia de COVID-19 foi marcado por incertezas diante do desconhecimento sobre a doença. Uma série de dúvidas relacionadas ao uso de imunobiológicos no contexto da pandemia foi levantada, inclusive em relação ao tratamento com omalizumabe em pacientes com urticária crônica (UC). Este estudo teve como objetivo analisar os dados relacionados à gravidade da COVID-19 e a evolução da urticária em pacientes em terapia com omalizumabe acompanhados por especialistas no Brasil. Foi realizada análise retrospectiva de dados de pacientes com UC tratados com omalizumabe entre julho/2020 e junho/2021 que apresentaram COVID-19. Foram avaliados dados relacionados às características clínicas dos pacientes e evolução da urticária durante a infecção pelo SARS-CoV2. Foram incluídos 28 pacientes em tratamento com omalizumabe, sendo 27 com urticária crônica espontânea (UCE), dos quais 25% tinham alguma urticária induzida associada. A maior parte dos pacientes (71%) estavam utilizando doses quadruplicadas de anti-histamínicos modernos de 2ª geração associados ao omalizumabe. Todos os pacientes estavam com os sintomas controlados. Entre os sintomas apresentados durante a COVID-19, os mais frequentes foram: febre (43%), cefaleia (36%), mal-estar (32%), hipo/anosmia (29%) e tosse (21%). Quatro pacientes foram hospitalizados, um deles em unidade de terapia intensiva. Um paciente relatou piora dos sintomas da UC durante a COVID-19. Cinco (18%) pacientes apresentaram piora dos sintomas da UC após a resolução da COVID-19. Todos os pacientes se recuperaram da COVID-19 sem sequelas graves. O OMA não pareceu aumentar o risco de COVID-19 grave e poderia ser usado com segurança em pacientes com UC.

The beginning of the COVID-19 pandemic was marked by uncertainty due to lack of knowledge about the disease. Questions were raised about the use of immunobiologicals in the pandemic context, including omalizumab for patients with chronic urticaria (UC). This study assessed COVID-19 severity and the clinical course of urticaria in Brazilian patients on omalizumab therapy who were monitored by specialists. We retrospectively analyzed data from chronic urticaria patients treated with omalizumab between July, 2020 and June, 2021 who presented with COVID- 19. Clinical characteristics and the course of urticaria during SARS-CoV2 infection were analyzed. The sample consisted of 28 patients treated with omalizumab, 27 of whom had chronic spontaneous urticaria (UCE) and 25% of whom had associated chronic inducible urticaria. Most of the patients (71%) were using quadruple doses of second-generation antihistamines associated with omalizumab. The symptoms of all patients were controlled. The most frequent symptoms during COVID-19 were: fever (43%), headache (36%), malaise (32%), hypo/anosmia (29%) and cough (21%). Four patients were hospitalized, including 1 in intensive care. One patient reported worsening chronic urticaria symptoms while infected with COVID-19. Five (18%) patients experienced worsening chronic urticaria symptoms after recovery from COVID-19. All patients recovered from COVID-19 without serious sequelae. Omalizumab did not appear to increase the risk of severe COVID-19 and can be safely used in patients with chronic urticaria.

Urticária crônica espontânea nos adultos: diagnóstico e terapêutica no presente e futuro. Uma revisão narrativa / Chronic spontaneous urticaria in adults: diagnosis and therapy in the present and future. A narrative review

As urticárias são dermatoses frequentes, acometendo 15% a 20% da população, com pelo menos um episódio agudo da doença na vida. São classificadas em agudas (≤ 6 semanas) ou crônicas (> 6 semanas), de etiologia induzida ou espontânea. A urticária crônica espontânea tem prevalência estimada entre 1% e 2% da população mundial. Apresenta intenso comprometimento da qualidade de vida dos doentes, de forma que afeta várias esferas da vida como relacionamentos interpessoais, perdas laborais, interferência no estudo, perda de sono, entre outras, além de provocar transtornos psiquiátricos em 46% dos doentes pela imprevisibilidade das crises e peso monetário pela perda laboral e custo de tratamento contínuo. Atualmente os anti-histamínicos não sedantes (de segunda geração) constituem a pedra angular no tratamento da urticária crônica espontânea, em decorrência dos seus efeitos reduzidos sobre as atividades cognitivas e outras no sistema nervoso central e cardiovascular. A abordagem terapêutica se inicia com as doses licenciadas pelos fabricantes e é consenso internacional que os anti-histamínicos de segunda geração podem ser usados em doses duplicadas, triplicadas ou quadruplicadas, pois as doses padrão controlam apenas 39% dos doentes. Ainda assim, para grupo substancial dos doentes, torna-se necessária a segunda linha de tratamento, que é o omalizumabe, (um anticorpo monoclonal anti-imunoglobulina E [IgE] e anti-receptor de alta afinidade da IgE nos mastócitos e basófilos). Como terceira linha terapêutica, destaca-se a ciclosporina. Em raros casos refratários às medidas anteriores, há drogas com menor nível de evidência científica disponíveis, as quais são abordadas neste artigo de revisão.

Correlation between the histopathology of chronic urticaria and its clinical picture.

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.

What lessons can we learn? Clinical and epidemiological retrospective analysis of 267 patients with urticaria in a Brazilian tertiary center

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.

Update on vasculitis: an overview and dermatological clues for clinical and histopathological diagnosis - part I

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.

Update on vasculitis: overview and relevant dermatological aspects for the clinical and histopathological diagnosis - Part II

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.

Consensus on the diagnostic and therapeutic management of chronic spontaneous urticaria in adults - Brazilian Society of Dermatology

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.

Drug reaction with Eosinophilia and Systemic Symptoms (DRESS) / Drug-induced Hypersensitivity Syndrome (DIHS): a review of current concepts.

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.

Immunoelectron microscopy study of superficial skin nerves in drug-induced acute urticaria.

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.

Bedbugs (Heteroptera, Cimicidae): an etiology of pruritus to be remembered.

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.