Monkeypox: What the Dermatologist Needs to Know.

Monkeypox, an endemic disease in some African countries, has provoked public health activeness on a global scale that even the World Health Organization (WHO), invoking international health regulations, declared it a public health emergency of international concern (PHEIC). The WHO called attention of member states to exert maximum surveillance over the disease, its patients, and contact persons in order to standardize control measures. A need was directed to provide complete knowledge about the disease, allowing the administration of prior diagnoses as well as isolation and more effective epidemiologic control measures. An updated review on monkeypox emphasized upon having the fundamental aspects of the lesions caused by the disease, and appropriate management of patients upon clinical and epidemiologic evaluation.

Consensus on the therapeutic management of atopic dermatitis ‒ Brazilian Society of Dermatology: an update on phototherapy and systemic therapy using e-Delphi technique.

This publication is an update of the "Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology" published in 2019, considering the novel, targeted-oriented systemic therapies for atopic dermatitis. The initial recommendations of the current consensus for systemic treatment of patients with atopic dermatitis were based on a recent review of scientific published data and a consensus was reached after voting. The Brazilian Society of Dermatology invited 31 experts from all regions of Brazil and 2 international experts on atopic dermatitis who fully contributed to the process. The methods included an e-Delphi study to avoid bias, a literature search and a final consensus meeting. The authors added novel approved drugs in Brazil and the indication for phototherapy and systemic therapy for AD. The therapeutical response to systemic treatment is hereby reported in a suitable form for clinical practice and is also part of this updated manuscript.

New small molecules in dermatology: for the autoimmunity, inflammation and beyond.

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.

Consensus on the therapeutic management of atopic dermatitis ‒ Brazilian Society of Dermatology: an update on phototherapy and systemic therapy using e-Delphi technique

Abstract This publication is an update of the "Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology" published in 2019, considering the novel, targeted-oriented systemic therapies for atopic dermatitis. The initial recommendations of the current consensus for systemic treatment of patients with atopic dermatitis were based on a recent review of scientific published data and a consensus was reached after voting. The Brazilian Society of Dermatology invited 31 experts from all regions of Brazil and 2 international experts on atopic dermatitis who fully contributed to the process. The methods included an e-Delphi study to avoid bias, a literature search and a final consensus meeting. The authors added novel approved drugs in Brazil and the indication for phototherapy and systemic therapy for AD. The therapeutical response to systemic treatment is hereby reported in a suitable form for clinical practice and is also part of this updated manuscript.

Cytokine Profiles Associated With Acute COVID-19 and Long COVID-19 Syndrome.

The duration and severity of COVID-19 are related to age, comorbidities, and cytokine synthesis. This study evaluated the impact of these factors on patients with clinical presentations of COVID-19 in a Brazilian cohort. A total of 317 patients diagnosed with COVID-19 were included; cases were distributed according to clinical status as severe (n=91), moderate (n=56) and mild (n=170). Of these patients, 92 had acute COVID-19 at sample collection, 90 had already recovered from COVID-19 without sequelae, and 135 had sequelae (long COVID syndrome). In the acute COVID-19 group, patients with the severe form had higher IL-6 levels (p=0.0260). In the post-COVID-19 group, there was no significant difference in cytokine levels between groups with different clinical conditions. In the acute COVID-19 group, younger patients had higher levels of TNF-α, and patients without comorbidities had higher levels of TNF-α, IL-4 and IL-2 (p<0.05). In contrast, patients over age 60 with comorbidities had higher levels of IL-6. In the post-COVID-19 group, subjects with long COVID-19 had higher levels of IL-17 and IL-2 (p<0.05), and subjects without sequelae had higher levels of IL-10, IL-6 and IL- 4 (p<0.05). Our results suggest that advanced age, comorbidities and elevated serum IL-6 levels are associated with severe COVID-19 and are good markers to differentiate severe from mild cases. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 and IL-10 appear to constitute a cytokine profile of long COVID-19, and these markers are potential targets for COVID-19 treatment and prevention strategies.

Muscle dysfunction in the long coronavirus disease 2019 syndrome: Pathogenesis and clinical approach.

In long coronavirus disease 2019 (long COVID-19), involvement of the musculoskeletal system is characterised by the persistence or appearance of symptoms such as fatigue, muscle weakness, myalgia, and decline in physical and functional performance, even at 4 weeks after the onset of acute symptoms of COVID-19. Muscle injury biomarkers are altered during the acute phase of the disease. The cellular damage and hyperinflammatory state induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may contribute to the persistence of symptoms, hypoxaemia, mitochondrial damage, and dysregulation of the renin-angiotensin system. In addition, the occurrence of cerebrovascular diseases, involvement of the peripheral nervous system, and harmful effects of hospitalisation, such as the use of drugs, immobility, and weakness acquired in the intensive care unit, all aggravate muscle damage. Here, we review the multifactorial mechanisms of muscle tissue injury, aggravating conditions, and associated sequelae in long COVID-19.

Different cell death mechanisms are involved in leprosy pathogenesis.

Leprosy is a chronic granulomatous disease that remains a serious public health problem in developing countries. According to the Madrid classification, leprosy presents in four clinical forms: two immunologically unstable forms (indeterminate and borderline) and two stable polar forms (tuberculoid and lepromatous). In leprosy, the relationship of cell death to clinical disease outcome remains unclear. Therefore, we investigated the extent of autophagy and different cell death mechanisms-such as apoptosis, necroptosis, and pyroptosis-in cutaneous lesions of patients with leprosy, as well as the role of these mechanisms in clinical disease progression. This cross-sectional analytical study included 30 patients with a confirmed diagnosis of leprosy, with 10 patients in each of the following groups: lepromatous (LL), tuberculoid (TT), and indeterminate (II) leprosy groups. For histopathological analysis, skin samples were subjected to haematoxylin-eosin staining and immunostaining for apoptotic and necroptotic markers. The results indicated that FasL expression was much higher in the LL form than in the TT and II forms. Similar results (higher expression in the LL form than in the TT and II forms) were observed for caspase 8, RIP1, and RIP3 expressions. MLKL, BAX, and caspase 3 expression levels were highest in the LL form, especially in globular foamy macrophages. Beclin-1 expression was highest in the TT form but was low in LL and II forms. Caspase 1 expression was highest in the LL form, followed by that in the TT and II forms. In conclusion, our study elucidates the role of different cell death mechanisms in the pathophysiology of various forms of leprosy and suggests measures that may be used to control the host response to infection and disease progression.

Lessons from dermatology about inflammatory responses in Covid-19.

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.

Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology.

BACKGROUND: Atopic dermatitis is a highly prevalent inflammatory and pruritic dermatosis with a multifactorial etiology, which includes skin barrier defects, immune dysfunction, and microbiome alterations. Atopic dermatitis is mediated by genetic, environmental, and psychological factors and requires therapeutic management that covers all the aspects of its complex pathogenesis. OBJECTIVES: The aim of this article is to present the experience, opinions, and recommendations of Brazilian dermatology experts regarding the therapeutic management of atopic dermatitis. METHODS: Eighteen experts from 10 university hospitals with experience in atopic dermatitis were appointed by the Brazilian Society of Dermatology to organize a consensus on the therapeutic management of atopic dermatitis. The 18 experts answered an online questionnaire with 14 questions related to the treatment of atopic dermatitis. Afterwards, they analyzed the recent international guidelines on atopic dermatitis of the American Academy of Dermatology, published in 2014, and of the European Academy of Dermatology and Venereology, published in 2018. Consensus was defined as approval by at least 70% of the panel. RESULTS/CONCLUSION: The experts stated that the therapeutic management of atopic dermatitis is based on skin hydration, topical anti-inflammatory agents, avoidance of triggering factors, and educational programs. Systemic therapy, based on immunosuppressive agents, is only indicated for severe refractory disease and after failure of topical therapy. Early detection and treatment of secondary bacterial and viral infections is mandatory, and hospitalization may be needed to control atopic dermatitis flares. Novel target-oriented drugs such as immunobiologicals are invaluable therapeutic agents for atopic dermatitis.

Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology

Abstract: BACKGROUND: Atopic dermatitis is a highly prevalent inflammatory and pruritic dermatosis with a multifactorial etiology, which includes skin barrier defects, immune dysfunction, and microbiome alterations. Atopic dermatitis is mediated by genetic, environmental, and psychological factors and requires therapeutic management that covers all the aspects of its complex pathogenesis. OBJECTIVES: The aim of this article is to present the experience, opinions, and recommendations of Brazilian dermatology experts regarding the therapeutic management of atopic dermatitis. METHODS: Eighteen experts from 10 university hospitals with experience in atopic dermatitis were appointed by the Brazilian Society of Dermatology to organize a consensus on the therapeutic management of atopic dermatitis. The 18 experts answered an online questionnaire with 14 questions related to the treatment of atopic dermatitis. Afterwards, they analyzed the recent international guidelines on atopic dermatitis of the American Academy of Dermatology, published in 2014, and of the European Academy of Dermatology and Venereology, published in 2018. Consensus was defined as approval by at least 70% of the panel. RESULTS/CONCLUSION: The experts stated that the therapeutic management of atopic dermatitis is based on skin hydration, topical anti-inflammatory agents, avoidance of triggering factors, and educational programs. Systemic therapy, based on immunosuppressive agents, is only indicated for severe refractory disease and after failure of topical therapy. Early detection and treatment of secondary bacterial and viral infections is mandatory, and hospitalization may be needed to control atopic dermatitis flares. Novel target-oriented drugs such as immunobiologicals are invaluable therapeutic agents for atopic dermatitis.

Blastic plasmacytoid dendritic cell neoplasm: an early presentation.

A blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a cutaneous lymphoma derived from a plasmacytoid dendritic precursor cell that exhibits aggressive clinical behavior. Herein, we report a 46-year-old woman with a complaint of a painless nodule on the back, associated with pruritus. The nodule grew and new growths appeared over six months of evolution. The histopathological examination of one of the left upper limb lesions showed a dense lymphoid cell infiltrate with atypia in the superficial and deep dermis. Immunohistochemistry showed positivity for CD45, S-100 protein, CD123, and TCL 1. About two months after the initial evaluation, the patient was admitted to the Emergency Hospital of Marituba-PA with dyspnea. She progressed to cardiorespiratory arrest and death within 12 hours of admission. There is still no consensus for the treatment of BPDCN. Intensive therapy for acute leukemia can be useful, but allogeneic bone marrow transplantation has a greater chance of long-term survival.

The inflammasome in leprosy skin lesions: an immunohistochemical evaluation.

OBJECTIVE: Leprosy is a chronic infectious disease presenting with a spectrum of clinical manifestations that correspond to the type of immune response that develops in the host. Factors that may be involved in this process include inflammasomes, cytosolic proteins responsible for the activation of caspase 1, IL-1ß and IL-18 secretion, and induction of a type of death called pyroptosis. PATIENTS AND METHODS: We evaluated the expression of inflammasome markers (nucleotide-binding oligomerization domain-like receptor containing pyrin domain 1 [NLRP1], nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 [NLRP3], caspase 1, IL-1ß, and IL-18) by immunohistochemistry in 43 samples of skin lesions of leprosy patients from the groups indeterminate (I) leprosy (13 patients), tuberculoid (TT) leprosy (15 patients), and lepromatous leprosy (LL; 15 patients). RESULTS: The evaluated markers were most upregulated in LL lesions, followed by lesions of TT leprosy and I leprosy. Differences were statistically significant between the I leprosy and LL leprosy forms and between the I leprosy and TT leprosy forms. Positive and significant correlations were found between IL-18 and caspase 1 in LL (r=0.7516, P=0.0012) and TT leprosy (r=0.7366, P=0.0017). In I leprosy, correlations were detected between caspase 1 and IL-1ß (r=0.6412, P=0.0182), NLRP1 and IL-18 (r=0.5585, P=0.473), NLRP3 and IL-18 (r=0.6873, P=0.0094), and NLRP1 and NLRP3 (r=0.8040, P=0.0009). CONCLUSION: The expression of inflammasome markers in LL lesions indicates the ineffectiveness of this protein complex in controlling the infection. Caspase 1 may be involved in the pyroptotic cell death in the lepromatous form of the disease. Inflammasomes may act together in the initial phase of I leprosy; this phenomenon may influence the clinical outcome of the disease.

Langerin (CD207)-positive cells in leprosy: Possible implications for pathogenesis of the disease with special emphasis on dermal immunoreactivity.

Leprosy is a disease caused by Mycobacterium leprae, which is characterized by two distinct poles, the tuberculoid pole and the lepromatous pole, depending on the immune response to the bacillus. Langerin-positive cells are dendritic cells that appear to play an essential role in the development of the disease. These cells are specialized in the processing and presentation of antigens, exerting an important function in the activation of the immune system. To evaluate the expression of langerin-positive cells (CD207+) in skin lesion fragments of patients with a diagnosis of M. leprae infection and to associate the expression of these cells with the polar forms of the disease. Langerin-positive cells were detected in larger numbers in lesions of patients with the tuberculoid form compared to those with the lepromatous form. The presence of a larger number of these cells in patients with the tuberculoid form suggests an important participation of langerin-positive cells, capturing antigens and favoring an effective immune response to infection with M. leprae.

Carcinoma de células escamosas cutâneo-invasivo - relato de caso / Invasive cutaneous squamous cell carcinoma - Case report

O carcinoma de células escamosas cutâneo é resultante da proliferação maligna dos queratinócitos. Costuma surgir da evolução de lesões precursoras, mas pode crescer espontaneamente na pele normal ou cronicamente inflamada. O carcinoma de células escamosas invasivo corresponde à segunda forma mais comum de câncer da pele não melanoma e representa 20% de todas as neoplasias cutâneas. Este trabalho relata um caso clínico de carcinoma de células escamosas cutâneo, rapidamente progressivo e com metástases regionais, que mesmo com a ressecção completa e esvaziamento ganglionar, apresentou pouca resposta terapêutica e evoluiu a óbito.

Cutaneous squamous cell carcinoma (SCC) results from malignant proliferation of keratinocytes. It usually arises from the development of precursor lesions, however it may grow spontaneously on normal or chronically inflamed skin. Invasive SCC is the second most common type of non-melanoma skin cancer and accounts for 20% of all cutaneous neoplasms. The present paper reports a clinical case of cutaneous SCC, rapidly progressive and with regional metastases, which, even after complete resection of the tumor and regional lymph nodes, showed little therapeutic response and evolved to death.

Ocular manifestations of psoriasis.

PURPOSE: We aimed to report the ocular manifestations observed in patients with psoriasis. METHODS: Patients were included and referred to our ophthalmology clinic from dermatology clinics of Universidade do Estado do Pará between October 2013 and August 2014. Clinical interviews were conducted to identify relevant epidemiological data, clinical features, and treatment details, and data were recorded using the same protocol. Subsequent dermatological examinations were performed and disease severity was rated using the Psoriasis Area and Severity Index and the Dermatological Life Quality Index. Complete eye examination was conducted, including visual acuity, biomicroscopy, tonometry, fundoscopy, Schirmer I test, tear breakup time, rose bengal staining, ocular surface disease index, and glaucoma tests. RESULTS: In total, we included 43 patients with psoriasis and 86 controls. Patients with psoriasis had statistically higher incidences of dry eye (16.28%), likely dry eye (32.56%), and blepharitis (16.28%). Furthermore, the rose bengal and ocular surface disease tests were more abnormal in patients with psoriasis (p<0.05). CONCLUSIONS: Patients with psoriasis should undergo regular eye exams, regardless of risk factors, to monitor for the progression of symptomatic or asymptomatic ocular manifestations.

Ocular manifestations of psoriasis / Manifestações oculares observadas em pacientes com psoríase

ABSTRACT Purpose: We aimed to report the ocular manifestations observed in patients with psoriasis. Methods: Patients were included and referred to our ophthalmology clinic from dermatology clinics of Universidade do Estado do Pará between October 2013 and August 2014. Clinical interviews were conducted to identify relevant epidemiological data, clinical features, and treatment details, and data were recorded using the same protocol. Subsequent dermatological examinations were performed and disease severity was rated using the Psoriasis Area and Severity Index and the Dermatological Life Quality Index. Complete eye examination was conducted, including visual acuity, biomicroscopy, tonometry, fundoscopy, Schirmer I test, tear breakup time, rose bengal staining, ocular surface disease index, and glaucoma tests. Results: In total, we included 43 patients with psoriasis and 86 controls. Patients with psoriasis had statistically higher incidences of dry eye (16.28%), likely dry eye (32.56%), and blepharitis (16.28%). Furthermore, the rose bengal and ocular surface disease tests were more abnormal in patients with psoriasis (p<0.05). Conclusions: Patients with psoriasis should undergo regular eye exams, regardless of risk factors, to monitor for the progression of symptomatic or asymptomatic ocular manifestations.

RESUMO Objetivos: Relatar as manifestações oculares observadas em pacientes com psoríase atendidos no Ambulatório de Dermatologia da X e encaminhados ao Y, no período de outubro de 2013 a agosto de 2014. Métodos: A amostra foi constituída por um grupo composto por 43 pacientes com psoríase e um grupo controle com 86 pacientes sem psoríase. Foi realizada uma entrevista clínica com dados epidemiológicos, aspectos clínicos da doença e terapia empregada, sendo todas as informações registradas em protocolo próprio. Posteriormente, realizou-se o exame dermatológico, no qual foi avaliado o índice de gravidade da Psoríase por área (PASI) e índice dermatológico de qualidade de vida (DLQI), e o exame oftalmológico completo, incluindo: Acuidade Visual, Biomicroscopia, Tonometria, Fundoscopia, Teste de Schirmer I, Tempo de Ruptura do Filme Lacrimal (TBUT), rosa bengala, índice de doença da superfície ocular (OSDI) e exames para glaucoma. Resultados: Observou-se que nos pacientes com psoríase houve frequência estatisticamente maior de envolvimento ocular, como olho seco (16,28%), provável olho seco (32,56%) e blefarite (16,28%). Além disso, os valores do rosa bengala e do OSDI apresentaram-se mais alterados nos pacientes com psoríase (p<0,05). Conclusão: Dessa forma, sugere-se que esses pacientes realizem exames oftalmológicos periódicos, já que as manifestações oculares podem progredir sem sintomatologia e ocorrer independentemente de fatores de risco.