Search

Dermatophytosis is a very common superficial mycosis, but there are few studies about the human immune response to dermatophytes. We aim to analyze the in situ expression of TNF-α and IL-10 in human dermatophytosis. Expression of TNF-α and IL-10 were evaluated in skin samples from 10 patients with dermatophytosis and 12 healthy subjects using an immunohistochemistry assay. TNF-α and IL-10 were significantly elevated in lesions from patients with dermatophytosis compared to healthy controls. These data illustrate the balance of pro- and anti-inflammatory cytokines suggesting Trichophyton rubrum infection could control the local immune response. [ABSTRACT FROM AUTHOR]

This article discusses a case of nivolumab-induced psoriasis successfully treated with risankizumab in a patient with metastatic clear cell renal carcinoma. The patient initially developed psoriasis after nivolumab treatment, but showed significant improvement with risankizumab. Risankizumab, an IL-23 inhibitor, was found to be safe and effective in managing psoriasis in this patient, highlighting its potential as an alternative therapy. Dermatologists and oncologists should be aware of adverse drug reactions like 'de novo' psoriasis under PD-1 inhibitors use, and consider IL-23 inhibitors as a treatment option. [Extracted from the article]

Copyright of Polish Journal of Allergology / Alergologia Polska is the property of Termedia Publishing House and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We present a 57-year-old woman with cutaneous lupus erythematosus (CLE), initially treated as acne. She noted blemishes, including nodules and facial swelling for nine months associated with discrete itching of the ears. Examination showed multiple malar nodules, comedones, pustules, atrophic scars, and hyperpigmentation. A biopsy was performed and revealed atrophic epidermis, discrete hyperkeratosis, vacuolar degeneration of basal layer, basal membrane zone with upper dermal lymphohistiocytic inflammatory infiltrate and deep perivascular and peri-adenexal lymphocytes, vascular ectasia, and mucin deposits. The acneiform presentation of CLE is commonly underdiagnosed due to the similarity with inflammatory acne. Histopathologic diagnostic in acneiform lupus is of extreme importance. This case emphasizes the relevance of knowing the notable variety of presentations of CLE and considering this diagnosis. [ABSTRACT FROM AUTHOR]

Since more than a century ago, there has been awareness of the connection between viral infections and the onset and exacerbation of urticaria. Our knowledge about the role of viral infection and vaccination in acute and chronic urticaria improved as a result of the COVID-19 pandemic but it has also highlighted knowledge gaps. Viral infections, especially respiratory tract infections like COVID-19, can trigger the onset of acute urticaria (AU) and the exacerbation of chronic urticaria (CU). Less frequently, vaccination against viruses including SARS-CoV-2 can also lead to new onset urticaria as well as worsening of CU in minority. Here, with a particular focus on COVID-19, we review what is known about the role of viral infections and vaccinations as triggers and causes of acute and chronic urticaria. We also discuss possible mechanistic pathways and outline the unmet needs in our knowledge. Although the underlying mechanisms are not clearly understood, it is believed that viral signals, medications, and stress can activate skin mast cells (MCs). Further studies are needed to fully understand the relevance of viral infections and vaccinations in acute and chronic urticaria and to better clarify causal pathways. [ABSTRACT FROM AUTHOR]

Objective and design: The discovery of new inflammatory pathways and the mechanism of action of inflammatory, autoimmune, genetic, and neoplastic diseases led to the development of immunologically driven drugs. We aimed to perform a narrative review regarding the rising of a new class of drugs capable of blocking important and specific intracellular signals in the maintenance of these pathologies: the small molecules. Materials/methods: A total of 114 scientific papers were enrolled in this narrative review. Results: We describe in detail the families of protein kinases—Janus Kinase (JAK), Src kinase, Syk tyrosine kinase, Mitogen-Activated Protein Kinase (MAPK), and Bruton Tyrosine Kinase (BTK)—their physiologic function and new drugs that block these pathways of intracellular signaling. We also detail the involved cytokines and the main metabolic and clinical implications of these new medications in the field of dermatology. Conclusions: Despite having lower specificity compared to specific immunobiological therapies, these new drugs are effective in a wide variety of dermatological diseases, especially diseases that had few therapeutic options, such as psoriasis, psoriatic arthritis, atopic dermatitis, alopecia areata, and vitiligo. [ABSTRACT FROM AUTHOR]

Background: Cryptococcosis is a devastating opportunistic infection in immunocompromised individuals, primarily in people living with HIV/AIDS. This study evaluated a protocol for the early diagnosis of meningitis due to C. neoformans, utilizing established molecular techniques from serum and CSF samples. Methods: The 18S and 5.8S (rDNA-ITS) sequence-specific nested PCR assays were compared with direct India ink staining and the latex agglutination test for detection of C. neoformans in serum and cerebrospinal fluid (CSF) from 49 Brazilian suspected meningitis patients. Results were validated with samples obtained from 10 patients negative for cryptococcosis and HIV, and by analysis of standard C. neoformans strains. Principal findings: The 5.8S DNA-ITS PCR was more sensitive (89–100%) and specific (100%) than the 18S rDNA PCR and conventional tests (India ink staining and latex agglutination) for identification of C. neoformans. While the 18S PCR exhibited a sensitivity (72%) similar to that of the latex agglutination assay in serum samples, it was superior to the latex agglutination assay when testing CSF, with a sensitivity of 84%. However, the latex agglutination was superior to the 18SrDNA PCR in specificity in CSF (92%). The 5.8S DNA-ITS PCR yielded the highest levels of accuracy (96–100%) of any test for detection (serological and mycological) of C. neoformans in both serum and CSF. Conclusion: Use of the nested 5.8S PCR was superior to other techniques for the diagnosis of cryptococcosis. The possibility of using serum, a non-invasively collected material, in a targeted 5.8S PCR analysis to identify Cryptococcus spp. is recommended, especially in immunosuppressed patients. Our results indicate that nested 5.8S PCR can increase the diagnostic capability of cryptococcosis, and we suggest its use to monitor patients in the future. Author summary: Cryptococcal meningitis is an infectious disease of global importance with high morbidity and mortality, especially among individuals with HIV/AIDS. While there have been improvements in the last two decades in the diagnosis of Cryptococcus neoformans, the methods presently employed are problematic for public hospitals in Brazil and other locations due to their extreme cost. In this study, we present a low-cost option for detection and identification of C. neoformans in noninvasive serum sample in immunosuppressed individuals, including those with HIV/AIDS. A nested PCR (5.8SrDNA-ITS) associated with the latex agglutination test has high precision in detection of suspected Cryptococcus spp. [ABSTRACT FROM AUTHOR]

Objective and design: The hallmark of type 2 inflammation is eosinophilia and/or high IgE serum levels, mostly in atopic dermatitis. Nevertheless, many dermatoses may present similar findings. Our aim is to explore the biological and clinical spectrum of cutaneous manifestations involving tissue and/or systemic eosinophilia, and distinct serum levels of IgE, where atopic dermatitis or other primary allergic eczema, not always is the definitive diagnosis. Materials/methods: A total of 37 scientific papers were enrolled in this narrative review. Results: A diagnostic approach for patients with elevated serum IgE level and a list of conditions not related to atopic dermatitis that runs through inborn errors of immunity, inflammatory disorders, lung disorders, malignancy, infections/infestations are displayed. Regarding to peripheral eosinophilia, differential diagnosis is also explored and clinical patterns of skin diseases associated with tissue eosinophilia are listed, to facilitate our diagnosis. Conclusions: We should maintain a high level of suspicion about other differential diagnosis involving eosinophilia and IgE dysregulation, especially in patients very young (when innate errors of the immunity may present) and in middle to elderly patients classified as having atopic dermatitis, due to the possibility of cutaneous hematological malignancies, paraneoplasia or autoimmune blistering diseases. [ABSTRACT FROM AUTHOR]

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell–driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert‐guided and evidence‐based diagnostic and therapeutic approaches for the different subtypes of urticaria. [ABSTRACT FROM AUTHOR]

Background: The infection by coronavirus disease 2019 (COVID‐19) has been associated with multiple cutaneous manifestations, although characterization of them in Hispanic patients with darker skin phototypes is lacking. The objective of this study is to characterize the clinical dermatological manifestations associated with COVID‐19 infection in cases with few or without general symptoms in patients from Latin America. Methods: Cross‐sectional study using a questionnaire that was made for health professionals (physicians with a specialty in dermatology) to investigate dermatological lesions associated with COVID‐19 infection in patients from 25 countries of Latin America. The survey was active from June 9 to July 30, 2020. Results: In this study, information was collected from a total of 347 patients. We found a female gender predominance: 179/347 (51.6%). The mean age at presentation was 40.87 years. The most frequent dermatological manifestations were maculopapular rash and urticarial lesions, followed by papulovesicular lesions, vesicular lesions, chilblain‐like lesions, papular lesions, ecchymosis, petechial purpura, pityriasis rosea‐like lesions, pruritus, palmoplantar dysesthesias, transient livedo, acral necrosis, palpable purpura, livedo racemosa, and retiform purpura. As far as we know, there are no previous reports of pruritus and palmoplantar dysesthesias. Conclusions: This registry emphasizes skin manifestations as an important criterion for establishing the diagnosis of COVID‐19 infection in Latin American countries. This information will be useful for the early identification of suspected cases by health professionals (dermatologists and nondermatologists) and will allow contact tracing to mitigate the impact on health systems at different levels. [ABSTRACT FROM AUTHOR]

Chromoblastomycosis (CMB) is a cutaneous fungal infection caused by dematiaceous fungi. According to the World Health Organization CMB has been elected as a tropical disease, and it is prevalent in tropical and subtropical regions. The lower extremities are the most affected areas, and the lesions progress with erythema, papules, nodules, verrucose plates and/or ulcerations. So far, few works have demonstrated neoplastic transformation in chronic CMB lesions, and it may be a consequence of prolonged inflammatory response. In the present case report, we described a neoplastic transformation from CMB lesion of a 55-year-old man, presenting lesions only in the left leg for 35 years. After treatment, a verrucous white plate with thick and irregular borders emerged in the ankle, which was identified as a sarcomatoid squamous cell carcinoma. The present case report highlights the importance of an early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Along the COVID-19 pandemic we have identified 11 case reports about COVID-19-associated cutaneous (Table S1)1-7and systemic vasculitis and 29 case reports on COVID-19 vaccine-associated cutaneous and systemic vasculitis on PubMed indexed literature (Table S2). We are adding a new case of cutaneous small-vessel vasculitis after COVID-19 immunization with the AstraZeneca vaccine. Keywords: COVID-19; cutaneous vasculitis; immunization; vaccine EN COVID-19 cutaneous vasculitis immunization vaccine 1 3 3 05/09/22 20220501 NES 220501 Dear Editor, The skin is often involved in primary and secondary vasculitis, and it may occur as single organ vasculitis limited to the skin. [Extracted from the article]

This study presents a single center experience with livedoid vasculopathy (LV). A rare disease that can lead to severe quality of life impairment. Characterize clinical data of LV patients at the Dermatology Division at the University of São Paulo. A retrospective and transversal study was conducted, from 1 January 2005 to 31 December 2019. About 75 patients diagnosed as LV and confirmed by skin biopsy were included. Epidemiology, clinical appearance, histopathology data, and treatment history were observed. There were 78.66% Caucasian women, with a mean age of 39.9 years. Frequent cutaneous manifestations were ulcers, atrophic blanche‐like scars, hyperpigmentation, purpuras, telangiectasias, and livedo racemosa. Pain, pruritus, and hypoesthesia were the main symptoms. After treatment, almost 40% of cases relapsed during spring and summer months. About 66% of cases had thrombophilia factors associated, such as high levels of lipoprotein(a). Frequent treatments included acetylsalicylic acid, pentoxifylline, and diosmin with hesperidin. Not being a prospective study. This research provides useful data on Latin American LV patients, indicating multifactorial conditions involved in LV pathogenesis. An extensive work‐up including autoimmune laboratory tests, thrombophilia factors, and other conditions associated with venous stasis should be part of LV investigation and controlled to improve treatment response. [ABSTRACT FROM AUTHOR]

Livedo racemosa is a cutaneous finding characterized by a persistent, erythematous, or violaceous discoloration of the skin, in a broken, branched, discontinuous, and irregular pattern. A retrospective review of 33 cases with clinical diagnosis of livedo racemosa over the past 6 years was evaluated in the dermatology department of a tertiary care hospital. We found predominance in Caucasian women (78.8%); age ranged from 8 to 81 years, with a mean age of 36 years. Livedo racemosa was described as generalized in 12 patients (36.4%), although the main localization was on lower limbs (42%). After laboratory testing and histopathological examinations, 12 patients (36.4%) were classified with idiopathic livedo racemosa; secondary diseases were diagnosis in 21 patients (63.6%), including Sneddon's syndrome, cutaneous polyarteritis nodosa, systemic lupus erythematosus, and others. Medical history of thrombotic events was described in 8 (24.2%) patients, and also 8 (24.2%) patients had abnormal results for 2 or more thrombophilia laboratory tests. Skin biopsy showed no histological abnormalities in 11 cases (33.3%), thrombosis of dermal blood vessels in 10 (30.3%), intimal/subintimal thickening in 7 (21.2%), and vasculitis in 5 (15.2%). In conclusion, livedo racemosa is a clinical feature that might be correlated to vascular disorders, such as thrombotic and/or hypercoagulable states, autoimmune diseases, and neoplastic diseases, or it can be secondary to specific medications. It is essential to establish a correct approach in cases of livedo racemosa, which includes anamnesis, physical examination, laboratory test, histological examination, and complementary examination according to clinical findings, in order to diagnosis underlying causes. [ABSTRACT FROM AUTHOR]

Introduction: The COVID‐19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown. Aim: To understand how CU patients are affected by the COVID‐19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID‐19. Materials and Methods: Our cross‐sectional, international, questionnaire‐based, multicenter UCARE COVID‐CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences. Results: The COVID‐19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID‐19 patient care, which negatively impacted on the care of urticaria patients. The rate of face‐to‐face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID‐19, but COVID‐19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID‐19. Conclusions: The COVID‐19 pandemic brings major changes and challenges for CU patients and their physicians. The long‐term consequences of these changes, especially the increased use of remote consultations, require careful evaluation. [ABSTRACT FROM AUTHOR]

COVID‐19 generates a complex systemic inflammatory response that can lead to death due to wide macrophage activation, endothelial damage, and coagulation in critically ill patients. SARS‐CoV‐2‐induced lung injury due to inflammatory mediated thrombosis could be similar to the livedoid vasculopathy in the skin, supporting a translational comparison of these clinical settings. In this article, we discuss anticoagulation, suppression of inflammatory response, and hyperbaric oxygen therapy in the context of severe COVID‐19 and livedoid vasculopathy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: The SARS‐Cov‐2 is a single‐stranded RNA virus composed of 16 non‐structural proteins (NSP 1‐16) with specific roles in the replication of coronaviruses. NSP3 has the property to block host innate immune response and to promote cytokine expression. NSP5 can inhibit interferon (IFN) signalling and NSP16 prevents MAD5 recognition, depressing the innate immunity. Dendritic cells, monocytes, and macrophages are the first cell lineage against viruses' infections. The IFN type I is the danger signal for the human body during this clinical setting. Protective immune responses to viral infection are initiated by innate immune sensors that survey extracellular and intracellular space for foreign nucleic acids. In Covid‐19 the pathogenesis is not yet fully understood, but viral and host factors seem to play a key role. Important points in severe Covid‐19 are characterized by an upregulated innate immune response, hypercoagulopathy state, pulmonary tissue damage, neurological and/or gastrointestinal tract involvement, and fatal outcome in severe cases of macrophage activation syndrome, which produce a 'cytokine storm'. These systemic conditions share polymorphous cutaneous lesions where innate immune system is involved in the histopathological findings with acute respiratory distress syndrome, hypercoagulability, hyperferritinemia, increased serum levels of D‐dimer, lactic dehydrogenase, reactive‐C‐protein and serum A amyloid. It is described that several polymorphous cutaneous lesions similar to erythema pernio, urticarial rashes, diffuse or disseminated erythema, livedo racemosa, blue toe syndrome, retiform purpura, vesicles lesions, and purpuric exanthema or exanthema with clinical aspects of symmetrical drug‐related intertriginous and flexural exanthema. This review describes the complexity of Covid‐19, its pathophysiological and clinical aspects. [ABSTRACT FROM AUTHOR]

Background: SARS-Cov-2 is a single-stranded RNA virus, a Betacoronavirus, composed of 16 non-structural proteins, with specific roles in replication of coronaviruses. The pathogenesis of COVID-19 is not yet fully understood. The virus and host factors interplay among distinct outcomes of infected patients. Methods: Using MeSH (Medical Subject Headings) in PubMed, authors searched for articles cotaining information on COVID-19 and the skin. Results: The pathophysiology of the disease is multifactorial: association with innate immune response, hypercoagulability state, lung tissue damage, neurological and/or gastrointestinal tract involvement, monocytic/macrophage activation syndrome, culminating in exaggerated cytokine secretion, called "cytokine storm", which leads to worsening and death. These systemic conditions may be associated with cutaneous lesions, that have polymorphic aspects, where at histopathological level show involvement in different skin changes. These lesions may be associated with multisystemic manifestations that could occur due to angiotensin-converting enzyme 2 receptor and transmembrane serine protease action, allowing the pulmonary infection and possibly skin manifestation. Several reports in literature show cutaneous lesions similar to chilblain, urticarial eruptions, diffuse or disseminated erythema, livedo racemosa, blue toe syndrome, retiform purpura, vesicle trunk, purpuric exanthema or exanthema with clinical aspects of symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) and others. Conclusions: This review describes the complexity of Covid-19, pathophysiological and clinical aspects, dermatological finding and other dermatological conditions associated with SARS-CoV-2 infection or COVID-19. [ABSTRACT FROM AUTHOR]

Background/Aim: Non-melanoma skin cancer (NMSC) is the most prevalent type of cancer in adults. Surgery remains the golden-standard treatment for this disease. Mohs micrographic surgery (MMS), a surgical technique, is based on the three-dimensional histopathological examination of the margin and surgical bed, layer by layer, in the excised tissue allowing for the determination of the location of the residual tumor, for its complete excision, with high cure rates and preservation of the unaffected tissue. The aim of this study was to present the epidemiological characteristics of the population that was submitted to MMS, as well as, correlate these characteristics with the characteristics of the tumor itself and the surgical procedure. Patients and Methods: A retrospective cross-sectional study was conducted over a 10-year period with an analysis of patient medical records submitted for MMS at the Department of Dermatology of the ABC School of Medicine. Data were presented and evaluated by nonparametric and parametric analyses, using absolute and relative frequency values for the continuous variable, to which a Chi-square test was applied for the verification of power with a significance level of 5%. For the independent variables, the Student’s t-test was used to compare means, with a confidence interval (CI) ranging from 95 to 99%, and Friedman’s test was used to verify if there were significant differences in the variables of interest. Results: Female patients accounted for 67% of all enrolled patients (n=335). The mean age was 67 years (SD±12.04; median=68; range=25-93 years). The predominant skin phototype (Fitzpatrick's classification) was phototype II (n=228, 46%). All procedures were performed under local anesthesia. Flap reconstruction was the most predominant surgery type (n=17, 68%). The mean number of MMS’s stages was 1.6 (range=1-8). There was a mean of 3.8 fragments of skin tissue (range=1-29) per stage. The mean tumor size was 30 mm (92%). This was associated with female sex (p=0.03), H-zone area (p<0.001), flap reconstruction (p=0.004), tumor removal 7 to 12 months after diagnosis (p<0.001) and non-recurrence tumors (p=0.02). Conclusion: NMSCs were frequently observed in older women with skin phototypes II/III. Reconstruction of the primary defect was feasible under local anesthesia, even in tumors with a marked diameter, decreasing the morbidity of this surgery, providing very satisfactory functional and aesthetic results, reduction costs and ease of access to the surgical procedure. [ABSTRACT FROM AUTHOR]

Background: Erythrokeratodermas are a heterogeneous group of keratinization disorders. They are inherited in both autosomal dominant and autosomal recessive pattern. Erythrokeratoderma variabilis et progressive (EKVP) is a disorder caused by variations in genes that codify connexins (GJA1, GJB3, GJB4). The distinction between different phenotypes is not always simple. Age of presentation varies from birth to adulthood; stationary or migratory erythematous plaques associated with nonmigratory hyperkeratosis are characteristic of this disorder. Nails, hair, and teeth are not affected. Methods: In order to describe the clinical phenotypes and molecular findings in a large Brazilian pedigree affected by erythrokeratoderma, we performed a clinical evaluation of four patients with different presentations of erythrokeratoderma from the same family, in which there are 35 affected members distributed in six generations. Genomic DNA evaluation by Sanger sequencing of GJB3 and GJB4 was performed in two affected family members with different phenotypes. Results: Clinical heterogeneity in affected patients was remarkable. In patients investigated with genetic testing, a heterozygous pathogenic gene variant in the GJB4 (gap junction protein beta‐4) gene was found positive for GJB4:c.35G>A (rsrs80358211). One patient also presented a synonymous variant in GJB3:c.357C>T (rs41310442). Conclusion: Variants in GJB4 are classically associated with Erythrokeratodermia variabilis, but there is remarkable clinical heterogeneity. Our observation that the same variant caused different phenotypes within the same family corroborates clinical heterogeneity and suggests that other genes that compose the genetic background exert some influence on the disease phenotype. [ABSTRACT FROM AUTHOR]