In vivo confocal microscopy of dermoscopic suspicious lesions in patients with xeroderma pigmentosum: A cross-sectional study.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare genetic disease characterized by extreme photosensitivity, resulting in a higher incidence of cutaneous tumors. Reflectance confocal microscopy (RCM) is a noninvasive imaging method for diagnosing cutaneous lesions. OBJECTIVE: To explore the application of RCM in the follow-up of patients with XP. METHODS: Patients with XP underwent RCM for suspicious lesions from January 2010 through April 2019. Lesions with malignant RCM features were excised, and the results were compared with their histopathologic features. Benign lesions on RCM were monitored every 3 months. We recorded the confocal features that were related to malignancy and specifically to melanoma. RESULTS: A total of 61 suspicious lesions from 13 patients with XP were included. Thirty-three lesions (54%) were malignant (14 melanomas, 15 basal cell carcinomas, and 4 squamous cell carcinomas). Nonvisible papillae (OR, 11.8; 95% CI, 2.6-53.1; P = .001) and atypical cells at the dermoepidermal junction (OR, 11.7; 95% CI, 2.7-50.3; P = .001) were independent predictors of malignancy. LIMITATIONS: There were limited numbers of patients and lesions. Most cases were retrospectively included, and some did not have a histologic analysis. CONCLUSIONS: RCM is a valuable tool in the follow-up of patients with XP, reducing the need for excisions by 35%.

Ulcers in leprosy patients, an unrecognized clinical manifestation: a report of 8 cases.

BACKGROUND: Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae. It is a polymorphic disease with a wide range of cutaneous and neural manifestations. Ulcer is not a common feature in leprosy patients, except during reactional states, Lucio's phenomenon (LP), or secondary to neuropathies. CASES PRESENTATION: We report eight patients with multibacillary leprosy who presented specific skin ulcers as part of their main leprosy manifestation. Ulcers were mostly present on lower limbs (eight patients), followed by the upper limbs (three patients), and the abdomen (one patient). Mean time from onset of skin ulcers to diagnosis of leprosy was 17.4 months: all patients were either misdiagnosed or had delayed diagnosis, with seven of them presenting grade 2 disability by the time of the diagnosis. Reactional states, LP or neuropathy as potential causes of ulcers were ruled out. Biopsy of the ulcer was available in seven patients: histopathology showed mild to moderate lympho-histiocytic infiltrate with vacuolized histiocytes and intact isolated and grouped acid-fast bacilli. Eosinophils, vasculitis, vasculopathy or signs of chronic venous insufficiency were not observed. Skin lesions improved rapidly after multidrug therapy, without any concomitant specific treatment for ulcers. CONCLUSIONS: This series of cases highlights the importance of recognizing ulcers as a specific cutaneous manifestation of leprosy, allowing diagnosis and treatment of the disease, and therefore avoiding development of disabilities and persistence of the transmission chain of M. leprae.

A case report of erythroderma in a patient with borderline leprosy on reversal reaction: a result of the exacerbated reaction?

BACKGROUND: Erythroderma is characterized by erythema and scaling affecting more than 90% of the body surface area. Inflammatory, neoplastic and, more rarely, infectious diseases may culminate with erythroderma. Diagnosis of the underlying disorder is therefore crucial to institute the appropriate therapy. Leprosy is a chronic infectious disease that is endemic in Brazil. Here we present an unusual case of leprosy and reversal reaction causing erythroderma, and we discuss the underlying immunological mechanisms which could contribute to the generalized skin inflammation. CASE PRESENTATION: We report a case of a patient with reversal reaction (RR) in borderline borderline leprosy presenting with erythroderma and neural disabilities. Histopathology of the skin showed regular acanthosis and spongiosis in the epidermis and, in the dermis, compact epithelioid granulomas as well as grouped and isolated bacilli. This duality probably reflects the transition from an anergic/multibacillary state to a state of more effective immunity and bacillary control, typical of RR. Leprosy was successfully treated with WHO's multidrug therapy, plus prednisone for controlling the RR; the erythroderma resolved in parallel with this treatment. Immunologic studies showed in situ predominance of IFNγ + over IL-4+ lymphocytes and of IL-17+ over Foxp3+ lymphocytes, suggesting an exacerbated Th-1/Th-17 immunoreactivity and poor Th-2 and regulatory T-cell responses. Circulating Tregs were also diminished. We hypothesize that the flare-up of anti-mycobacteria immunoreactivity that underlies RR may have triggered the intense inflammatory skin lesions that culminated with erythroderma. CONCLUSIONS: This case report highlights the importance of thorough clinical examination of erythrodermic patients in search for its etiology and suggests that an intense and probably uncontrolled leprosy RR can culminate in the development of erythroderma.

Generalized lenticular atrophoderma of Pasini and Pierini.

We present a 16-year-old boy with multiple, well-circumscribed, atrophic, light-brown patches on his neck, chest, and back. The authors believe that it represents an unusual presentation of atrophoderma of Pasini and Pierini and suggest the designation "generalized lenticular APP."

Analysis of the dermoscopic features of excised melanomas and their relation with tumor thickness in a tertiary hospital in Brazil.

BACKGROUND: Dermoscopy is a non-invasive, cost-effective tool useful in the assessment of pigmented lesions. The aim of this study was to analyze the dermoscopic features in excised melanomas in a tertiary hospital in Brazil and the influence of Breslow thickness on the dermoscopic features observed. METHODS: An observational, cross-sectional study in which dermoscopic images of 43 melanomas were evaluated. The patients were divided into three groups: in situ, thin invasive melanoma (Breslow thickness <1 mm), and thick invasive melanoma (Breslow thickness ≥1 mm). RESULTS: We studied 33 patients with 43 melanomas. Twenty-one (48.8%) were melanoma in situ, 16 (37.2%) were thin melanomas, and 6 (14%) were thick melanomas. The most frequent dermoscopic criteria observed in all cases were atypical pigment network, multiple colors (3 or more), asymmetrical blotches, and peripheral asymmetric dots and globules. There was a statistically significant difference in the three groups regarding the frequency of atypical vessels, white scar areas, blue-white veil, shiny white structures, and radial streaming. The group of invasive melanomas presented with a higher frequency and statistical significance (P < 0.05) of atypical vessels, white scar areas, blue-white veil, and shiny white structures when compared to in situ melanomas. The presence of radial streaming and blue-white veil was more frequent in thick invasive melanomas than in thin invasive melanomas. The presence of a higher number of structures was seen in invasive melanomas, with a median of 5 and 7.5 structures for thin and thick invasive tumors, respectively. CONCLUSIONS: In line with prior data, we identified an association between invasive melanomas and structures linked to fibrosis and tumor vascularity. Specifically, we noted the presence of atypical vessels, scar-like white areas, a blue-white veil, and shiny white structures. Also, a higher number of dermoscopic structures was seen in invasive melanomas. In thicker melanomas, we observed additional findings, including a higher frequency of radial streaming and a blue-white veil.

Drug reaction with eosinophilia and systemic symptoms (DRESS): a complex interaction of drugs, viruses and the immune system.

The DRESS syndrome (drug reaction with eosinophilia and systemic symptoms), also known as DIHS (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, producing damage in several systems, especially kidney, heart, lungs, and pancreas. The pathogenesis is related to specific drugs (especially the aromatic anticonvulsants), altered immune response, sequential reactivation of herpes virus, and association with some HLA alleles. Glucocorticoids are the basis for the treatment of the syndrome, which may be given with intravenous immunoglobulin and, in selected cases, ganciclovir. This article reviews current concepts regarding the interaction of drugs, viruses and immune responses during this complex adverse-drug reaction.

How Coronavirus Disease 2019 Changed Dermatology Practice in 1 Year Around the World: Perspectives from 11 Countries.

Coronavirus disease 2019 (COVID-19) brought the world to its knees. As each nation grappled with launching an effective response while simultaneously minimizing repercussions on health care systems, economies, and societies, the medical and scientific landscape shifted forever. In particular, COVID-19 has challenged and transformed the field of dermatology and the way we practice. In this article, dermatologists from 11 countries share insights gained from local experience. These global perspectives will help provide a better framework for delivering quality dermatologic care and understanding how the field has evolved during this medical crisis.

Stevens-Johnson syndrome and toxic epidermal necrolysis - retrospective review of cases in a high complexity hospital in Brazil.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare conditions characterized by epidermal necrosis, mostly caused by drugs. Despite the rarity of these conditions, morbidity and mortality are high (even in previously healthy patients), and they may be associated with permanent sequelae. METHODS: A retrospective study conducted at a quaternary hospital in Brazil in a period of 10 years. RESULTS: The sample was composed by 41 patients with SJS, SJS/TEN, and TEN confirmed by skin biopsy. Antibiotics and anticonvulsants were the most frequently implied drug classes, and phenytoin was the most important individual culprit drug. In this study, 12.2% of the patients had sequelae, being ophthalmological lesions the most common and one case of a newly described hearing loss. The mortality rate was 16.7% in patients with TEN. CONCLUSIONS: This study describes the largest Latin American case series of SJS and TEN with the diagnosis proven by skin biopsy and adds important data regarding the profile of the disease in Brazil. It also describes a novel sequelae of hearing loss.

Expansion and suppressive capacity of regulatory T cells isolated from patients across the leprosy spectrum: a pilot study.

Knowledge of the role of Tregs in the immunopathogenesis of the different clinical outcomes within the leprosy spectrum remains limited due to the lack of studies directly assessing their suppression capacity. We thus tested a protocol to expand Tregs from the peripheral blood of patients across the leprosy spectrum and analyzed their suppressive capacity in autologous TCD4+ responses. Results of these pilot assays show that Tregs can be expanded and exert suppressive capacity, but also that their rate of expansion and suppressive capacity are influenced by the patient's clinical classification, suggesting that they possibly retain some in vivo characteristics.

Prevalence of dermatoses in patients referred for evaluation in an outpatient clinic of specialties.

BACKGROUND: Brazilian Unified Health System presents a long waiting period for a dermatology appointment, varying from 34 to 239 days. OBJECTIVES: Analyze the prevalence of cutaneous diseases evaluated by dermatologists in a specialized center, in patients referred from the primary care, and to present possible interventions for the primary units. METHODS: Retrospective analyses of the International Codes of Diseases (ICD-10) described in every dermatology appointment in a specialty center in Sao Paulo from January 2014 to August 2015. RESULTS: A total of 7.350 consultations were included. Superficial mycosis corresponded to 1,058 (14.4%) of the main complaints and dermatophytosis was the most frequently used ICD, corresponding to 481 individual consultations (6.5%), followed by onychomycosis, responsible for 464 consultations (6.3%), acne in 347 (4,7%). and contact dermatitis in 311 consultations (4,2%). STUDY LIMITATIONS: The study was based on retrospective analysis of ICD described and no previous orientation for a solid use of the codes was performed to the dermatology team; consultations in which the ICD was not informed or a non-especific ICD was used were excluded; different dermatologists were responsible for the consultations. CONCLUSION: Superficial mycosis corresponded to 14.4% of the chief complaints in the studied period and was the most frequent cause of reference from primary care doctors to dermatologists. Prevalence data obtained in the present study could assist the capacitation policies in the primary care system, focusing the dermatology teaching in the most prevalent dermatological disorders.

Dermatoscopy: an auxiliary resource for the diagnosis of poroid neoplasms.

Poroid neoplasms are benign epithelial proliferations with eccrine sweat gland differentiation. They are a challenging diagnosis because of the clinical heterogeneity, being able to mimic several malignant neoplasms. They are classified into classic poroma, hidroacanthoma simplex, dermal duct tumor and poroid hidradenoma. Association of histological subtypes occurs in more than 25% of cases. We report a case of a combined poroid neoplasia of classical poroma and poroid hidradenoma, reviewing its dermatoscopic features.

Histoid leprosy: clinical and histopathological analysis of patients in follow-up in University Clinical Hospital of endemic country.

BACKGROUND: Histoid leprosy (HL) is a rare form of lepromatous leprosy, characterized by hyperchromic indurated nodules above normal skin. Its main histopathological aspect is spindle cells. Because it may simulate other aspects, such as dermatofibroma and neurofibroma, histoid leprosy poses itself as a diagnostic challenge. METHODS: This is a retrospective study with all patients having been selected from the leprosy clinic of the Hospital das Clínicas da Universidade de São Paulo from 2006 to 2016. RESULTS: There were 12 patients in this study, eight in the histoid group and four in the lepromatous leprosy group. The prevalence of HL was 1.12% in all leprosy subjects. All individuals from HL group were "de novo" cases, and the histopathological analysis of skin lesions presented spindle cells generating a storiform pattern. Immunohistochemistry for CD68, vimentin, and anti-BCG were positive in all 12 cases. Factor XIIIa was visualized only in the papillary dermis, and S100 protein was negative in all biopsies. Smooth-muscle actin was present in 62.5% of the HL samples. CONCLUSION: The prevalence of HL was similar to previous reports. However, all histoid patients were "de novo" cases, differing from published studies. Fusocellular macrophage transformation could be explained by the differences in cytoskeleton proteins expressed in histoid lesions in comparison to other leprosy variants, with emphasis on vimentin and smooth muscle actin.

Eritema nodoso hansênico com apresentação vesiculosa simulando infecção herpética: um relato de caso / Erythema nodosum leprosum with vesicular presentation simulating herpetic infection: a case report

Contexto: As reações hansênicas são episódios inflamatórios agudos imunomediados que podem ocorrer em indivíduos com hanseníase. Lesões atípicas de eritema nodoso hansênico (ENH) são raras e podem se apresentar como pústulas, bolhas, necrose, úlceras e, eventualmente, podem simular outras doenças como a síndrome de Sweet e eritema multiforme. Descrição do caso: Paciente do sexo masculino, 24 anos de idade, com diagnóstico prévio de hanseníase virchowiana e realização de tratamento adequado, com término da poliquimioterapia quatro anos antes de comparecer ao nosso serviço quando foi avaliado, apresentando pequenas vesículas translúcidas agrupadas sobre uma base eritematosa e áreas com crostas necróticas, simulando lesões herpéticas, na porção superior das costas, parte inferior do pescoço e haste do pênis. O exame histopatológico da biópsia cutânea foi sugestivo de reação tipo 2 e o tratamento com talidomida foi satisfatório. Discussão: As reações na hanseníase representam episódios de hipersensibilidade aguda a antígenos de Mycobacterium leprae e podem se desenvolver antes, durante ou após o término do tratamento. Acredita-se que o ENH, ou reações do tipo 2, ocorram devido à deposição de imunocomplexos em múltiplos órgãos em pacientes que apresentam a forma multibacilar. Conclusões: As reações hansênicas são desafios no manejo da hanseníase, especialmente pelo fato de a maioria das sequelas permanentes ser secundária a esses episódios inflamatórios agudos. O conhecimento das possíveis apresentações atípicas das reações hansênicas é fundamental para o diagnóstico precoce e o tratamento adequado, a fim de prevenir morbidade grave relacionada à hanseníase.

Angiosarcoma in HIV-negative patients is not associated with HHV-8.

BACKGROUND:: Angiosarcoma is an aggressive, malignant neoplasm of vascular or lymphatic origin. Herpes virus 8 (HHV-8) is a member of the herpes family with a tropism for endothelial cells and it has been proven to induce vascular neoplasms, such as Kaposi's sarcoma. The role of HHV-8 in the pathogenesis of angiosarcoma has not been well defined. OBJECTIVE:: To investigate the relationship between the presence of HHV-8 and angiosarcoma. METHODS:: In this study, the team investigated the relationship between the presence of HHV-8, as determined by polymerase chain reaction, and angiosarcoma, using samples from patients with epidemic Kaposi's sarcoma as controls. RESULTS:: While all control cases with epidemic Kaposi's sarcoma were positive for HHV-8, none of the angiosarcoma cases was. CONCLUSION:: These findings support most previous studies that found no association between HHV-8 and angiosarcoma.

Development of Type 2, But Not Type 1, Leprosy Reactions is Associated with a Severe Reduction of Circulating and In situ Regulatory T-Cells.

Leprosy is frequently complicated by the appearance of reactions that are difficult to treat and are the main cause of sequelae. We speculated that disturbances in regulatory T-cells (Tregs) could play a role in leprosy reactions. We determined the frequency of circulating Tregs in patients with type 1 reaction (T1R) and type 2 reaction (T2R). The in situ frequency of Tregs and interleukin (IL)-17, IL-6, and transforming growth factor beta (TGF)-ß-expressing cells was also determined. T2R patients showed markedly lower number of circulating and in situ Tregs than T1R patients and controls. This decrease was paralleled by increased in situ IL-17 expression but decreased TGF-ß expression. Biopsies from T1R and T2R patients before the reaction episodes showed similar number of forkhead box protein P3+ (FoxP3+) and IL-17+ cells. However, in biopsies taken during the reaction, T2R patients showed a decrease in Tregs and increase in IL-17+ cells, whereas T1R patients showed the opposite: Tregs increased but IL-17+ cells decreased. We also found decreased expansion of Tregs upon in vitro stimulation with Mycobacterium leprae and a trend for lower expression of FoxP3 and the immunosuppressive molecule cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in T2R Tregs. Our results provide some evidence to the hypothesis that, in T2R, downmodulation of Tregs may favor the development of T-helper-17 responses that characterize this reaction.