IL-1β and IL-17 in cutaneous lupus erythematous skin biopsies: could immunohistochemicals indicate a tendency towards systemic involvement?

Abstract Background: Only a fraction of patients with cutaneous lupus erythematosus (CLE) will eventually progress toward systemic disease (SLE). Objective: To find inflammatory biomarkers which could predict the progression of cutaneous lupus erythematosus (CLE) into systemic lupus erythematosus (SLE) using immunohistochemical (IHC) assays. Methods: Immunohistochemical markers for cytotoxic, inflammatory, and anti-inflammatory responses and morphometric methods were applied to routine paraffin sections of skin biopsies, taken from lesions of 59 patients with discoid lupus, subacute lupus, and lupus tumidus. For the diagnosis of SLE, patients were classified by both the American College of Rheumatology (ACR-82) and the Systemic Lupus International Collaborating Clinics (SLICC-12) systems. Results: Skin samples from CLE/SLE +patients presented higher expression of IL-1β (ARC-82: p = 0.024; SLICC-12: p = 0.0143) and a significantly higher number of cells marked with granzyme B and perforin (ARC: p = 0.0097; SLICC-12: p = 0.0148). Biopsies from CLE/SLE- individuals had higher expression of IL-17 (ARC-82: p = 0.0003; SLICC-12: p = 0.0351) and presented a positive correlation between the density of granzyme A+and FoxP3+ cells (ARC-82: p = 0.0257; SLICC-12: p = 0.0285) and CD8+ cells (ARC-82: p = 0.0075; SLICC-12: p = 0.0102), as well as between granulysin-positive and CD8+ cells (ARC-82: p = 0.0024; SLICC-12: p = 0.0116). Study limitations: Patients were evaluated at a specific point in their evolution and according to the presence or not of systemic disease. The authors cannot predict how many more, from each group, would have evolved towards SLE in the following years. Conclusions: In this cohort, immunohistochemical findings suggested that patients with a tendency to systemic disease will show strong reactivity for IL-1β, while those with purely cutaneous involvement will tend to express IL-17 more intensely.

Detection of Bartonella henselae DNA in the blood of patients with livedoid vasculopathy

Abstract Background: Livedoid vasculopathy (LV) manifests as ulcers and atrophic white scars on the lower extremities. The main known etiopathogenesis is hypercoagulability with thrombus formation, followed by inflammation. Thrombophilia, collagen and myeloproliferative diseases may induce LV, but the idiopathic (primary) form predominates. Bartonella spp. may cause intra-endothelial infection and skin manifestations caused by these bacteria may be diverse, including leukocytoclastic vasculitis and ulcers. Objective: The aim of this study was to investigate the presence of bacteremia by Bartonella spp. in patients with difficult-to-control chronic ulcers diagnosed as primary LV. Methods: Questionnaires and molecular tests (conventional PCR, nested PCR and real-time PCR) were applied and liquid and solid cultures were performed in the blood samples and blood clot of 16 LV patients and 32 healthy volunteers. Results: Bartonella henselae DNA was detected in 25% of LV patients and in 12.5% of control subjects but failed to reach statistically significant differences (p = 0.413). Study limitations: Due to the rarity of primary LV, the number of patients studied was small and there was greater exposure of the control group to risk factors for Bartonella spp. infection. Conclusion: Although there was no statistically significant difference between the groups, the DNA of B. henselae was detected in one of every four patients, which reinforces the need to investigate Bartonella spp. in patients with primary LV.

Congenital solitary reticulohistiocytosis (Hashimoto - Pritzker)

Abstract Congenital and self-healing Hashimoto-Pritzker reticulohistiocytosis is the benign variant of the Langerhans cell histiocytosis (LCH) group. It is characterized by multiple skin lesions (congenital or appearing during the first days after birth), without systemic manifestations and spontaneous resolution in days to months. The authors report the case of a boy with a single congenital leg skin lesion, a rare disease variant. Through histopathology, a dense skin infiltration of S100 protein-, CD1a-, CD207-immunomarked cells was found. KI67 index was high (62%). A complete spontaneous resolution occurred 07 days after the biopsy (25 days after birth). Monolesional disease, distal limb lesion, absence of lesions in the mucous membrane or seborrheic area, and less than 25 percent of LCs with Birbeck granules were said to be possible clues for a favorable prognosis in LCs histiocytosis. But, as a precautionary measure, the child will be followed up until at least 2 years of age.

Dermatological manifestations relating to nutritional deficiencies after bariatric surgery: case report and integrative literature review

ABSTRACT BACKGROUND: The number of bariatric surgeries performed worldwide is growing. Among the main short, medium or long-term complications after surgery are nutritional deficiencies. Many of these, such as those of Zn, Cu and vitamins A, B1, B3, B6 and B12, are manifested by dermatological lesions before potentially fatal systemic disorders occur. OBJECTIVE: To identify the main dermatological manifestations associated with nutritional deficiencies after bariatric surgery, and the associated variables. DESIGN AND SETTING: Integrative literature review carried out at a public university in Brazil. METHODS: This was a case report and a review of health research portals and databases of national and international biomedical journals, without publication date limitation. The descriptors used for searches followed the ideal methodology for each database/search portal: "bariatric surgery", "skin", "skin disease", "skin manifestation", "deficiency disease" and "malnutrition". RESULTS: A total of 59 articles were selected, among which 23 were review articles or articles that addressed specific dermatological manifestations. The other 36 articles described 41 cases, which were organized into a table with the clinical variables. CONCLUSIONS: Although nutritional deficiencies are expected as complications after bariatric surgery, few articles relating them to their dermatological manifestations were found. It is important to recognize skin changes caused by nutritional deficiencies in patients treated via bariatric surgery, as these may occur before systemic complications appear and are easier to diagnose when the patient does not have any systemic symptoms yet. However, there is generally a delay between the appearance of skin lesions and making the diagnosis of nutritional deficiency.

Chronic type 2 reaction possibly triggered by an asymptomatic Bartonella henselae infection in a leprosy patient

ABSTRACT As leprosy and leprosy reactions are the most prevalent infectious cause of physical disability, it is important to commit efforts to better understand these chronic reactions. Infections, even when asymptomatic, can trigger leprosy reactions and Bartonella spp. in turn, can cause chronic infections. We presented a case of a 51-year-old man who was admitted presenting with chronic type 2 leprosy reactions. He had a lepromatous form of leprosy that was histologically diagnosed six months after the onset of signs and symptoms compatible with a chronic type 2 reaction. He reported a history of a previous hepatitis B diagnosis. During a 24-month multidrug therapy (MDT), chronic reactions were partially controlled with prednisone and thalidomide. Thirty-three months following the leprosy treatment, he still experienced chronic reactions, and whole bacilli as well as globi were found on a new skin biopsy. Since coinfections can trigger type 2 reactions and the patient had close contact with animals and ticks, we investigated the presence of a Bartonella sp. infection. Bartonella henselae DNA was detected in a skin fragment obtained before the beginning of the leprosy retreatment. However, even after six months of a second leprosy MDT, he continued to experience type 2 chronic reactions. He was admitted to the hospital to undergo an intravenous antibiotic therapy for 14 days and then complete the treatment per os for ten more weeks. Leprosy reactions improved following the treatment for B. henselae. After completing the MDT treatment, he has been accompanied for sixty months with no signs of leprosy or leprosy reactions. The asymptomatic infection by B. henselaein this patient was considered the putative trigger of chronic leprosy reactions and leprosy relapse.

Acantholytic pityriasis rubra pilaris associated with topical use of imiquimod 5%: case report and literature review

Abstract Topical use of immune response modifiers, such as imiquimod, has increased in dermatology. Although its topical use is well tolerated, it may be associated with exacerbations of generalized cutaneous inflammatory diseases, possibly through the systemic circulation of pro-inflammatory cytokines. This report describes a case of development of pityriasis rubra pilaris, a rare erythematous-papulosquamous dermatosis, in a woman aged 60 years during treatment with imiquimod 5% cream for actinic keratosis. It evolved with erythrodermic conditions and palmoplantar keratoderma, presenting progressive clinical resolution after the introduction of methotrexate. The authors emphasize the importance of recognizing possible systemic reactions associated with the topical use of imiquimod.

Study of factors affecting the incidence of skin cancer in patients after liver transplant

Abstract: Background: Many factors are currently being identified as potential inductors of skin cancer in patients after a liver transplant, among them, immunosuppressive regimen. Objective: To study the factors that influence the incidence of skin cancer in patients after liver transplant. Methods: We have carried out a retrospective and observational study with 170 transplanted patients who had undergone transplantation from 1997 to 2010. We have adjusted the multiple logistic regression model (saturated model) to the ensemble of collected data using skin cancer as dependent variable, indicated in anatomopathological analysis between 1997 and 2014. Results: Incidence of skin cancer was 9.4%. Predictors were incidence of diabetes in the third year after the transplantation (p=0.047), not using tacrolimus in the first year after the transplantation (p=0.025) and actinic keratosis (p=0.003). Study Limitations: An important limitation is that the interpretation of the results was based on information collected of patients undergoing transplantation at a single center. Future research, multicentric and involving larger and more diverse populations, are needed. Conclusions: Factors found might contribute to Brazilian surveillance programs associated with decreased incidence of skin cancer.

Correção cirúrgica de rinofima grave / Surgical repair of severe rhinophyma

A rosácea pode manifestar-se com a formação de fima, que se caracteriza por hipertrofia de glândulas sebáceas e proliferação de tecido conectivo e vasos sanguíneos. Considerada complicação grave, a fima é mais comum em homens, e mais frequente no nariz, quando é denominada rinofima. Rosácea e rinofima podem trazer prejuízos funcionais e estéticos com piora da qualidade de vida dos pacientes. Nos estádios iniciais realizam-se terapêuticas farmacológicas, às quais, porém, a forma fimatosa responde pobremente. Relatamos um caso de correção cirúrgica de rinofima gigante pela técnica de shaving e eletrocoagulação, com excelente resultado cosmético e funcional.

Rosacea can develop into phyma, which is characterized by hypertrophy of sebaceous glands and proliferation of connective tissue and blood vessels. Regarded as a serious complication, phymas are more common in men, being more frequent in the nose ­ when it is called rhinophyma. Rosacea and rhinophyma can cause functional and aesthetic impairment, leading to a worsening in the patients' quality of life. Pharmacological and physical therapies are performed in initial stages, however phymatous variants of the condition respond poorly to the first. The authors of the present article report a case of surgical correction of a giant rhinophyma using the shaving and electrocoagulation techniques, with excellent aesthetic and functional outcomes.

The importance of superficial basal cell carcinoma in a retrospective study of 139 patients who underwent Mohs micrographic surgery in a Brazilian university hospital

OBJECTIVE: Mohs micrographic surgery is a specialized surgical procedure used to treat skin cancer. The purpose of this study was to better understand the profile of the patients who underwent the procedure and to determine how histology might be related to complications and the number of stages required for complete removal. METHODS: The records of patients who underwent Mohs micrographic surgery from October 2008 to November 2013 at the Dermatology Division of the Hospital of the Campinas University were assessed. The variables included were gender, age, anatomical location, histology, number of stages required and complications. RESULTS: Contingency tables were used to compare the number of stages with the histological diagnosis. The analysis showed that patients with superficial basal cell carcinoma were 9.03 times more likely to require more than one stage. A comparison between complications and histological diagnosis showed that patients with superficial basal cell carcinoma were 6.5 times more likely to experience complications. CONCLUSION: Although superficial basal cell carcinoma is typically thought to represent a less-aggressive variant of these tumors, its propensity for demonstrating “skip areas” and clinically indistinct borders make it a challenge to treat. Its particular nature may result in the higher number of surgery stages required, which may, as a consequence, result in more complications, including recurrence. Recurrence likely occurs due to the inadequate excision of the tumors despite their clear margins. Further research on this subtype of basal cell carcinoma is needed to optimize treatments and decrease morbidity.

Angiogenic effects of cryosurgery with liquid nitrogen on the normal skin of rats, through morphometric study

BACKGROUND: Cryosurgery is an efficient therapeutic technique used to treat benign and malignant cutaneous diseases. The primary active mechanism of cryosurgery is related to vascular effects on treated tissue. After a cryosurgical procedure, exuberant granulation tissue is formed at the injection site, probably as a result of angiogenic stimulation of the cryogen and inflammatory response, particularly in endothelial cells. OBJECTIVE: To evaluate the angiogenic effects of freezing, as part of the phenomenon of healing rat skin subjected to previous injury. METHODS: Two incisions were made in each of the twenty rats, which were divided randomly into two groups of ten. After 3 days, cryosurgery with liquid nitrogen was performed in one of incisions. The rats' samples were then collected, cut and stained to conduct histopathological examination, to assess the local angiogenesis in differing moments and situations. RESULTS: It was possible to demonstrate that cryosurgery, in spite of promoting cell death and accentuated local inflammation soon after its application, induces quicker cell proliferation in the affected tissue and maintenance of this rate in a second phase, than in tissue healing without this procedure. CONCLUSIONS: These findings, together with the knowledge that there is a direct relationship between mononuclear cells and neovascularization (the development of a rich system of new vessels in injury caused by cold), suggest that cryosurgery possesses angiogenic stimulus, even though complete healing takes longer to occur. The significance level for statistical tests was 5% (p<0,05). .

Distribution of histological diagnoses of black and white skin in Campinas, diseases Brazil, from 1993 to 2009 / Distribuição dos diagnósticos histológicos das afecções da pele negra e branca, em Campinas, Brasil, entre 1993 e 2009

INTRODUCTION: Little is known about ethnic differences in the frequency of skin diseases, and even less in terms of Brazilian population, which is characterized by miscegenation. OBJECTIVE: To evaluate the distribution of skin disorders in black and Caucasian patients through pathological specimens. METHODS: 826 biopsies from black-skinned individuals and 1,652 from white-skinned patients were retrieved and studied from the files of the Pathology Department, UNICAMP Hospital within the period of 1993-2009. The clinical data were obtained from medical records and the results were tested by statistical methods. RESULTS: Non-melanoma cancer was the most frequent diagnosis in Caucasians (45%), differing from the frequency among black patients (8%), both arising in sun-exposed skin. Regarding topography and age, in white-skinned patients aged over 50 years, biopsies of "head and neck" prevailed. As to black patients, the disease predominated among female individuals aged from 15 to 50 years and in the genital area. In the comparative analysis of vulvar diseases, we observed differences in diagnoses of sexually transmitted diseases more common among black women. Excluding cancers and genital lesions, black patients had a higher percentage of infectious diseases. Among the non-infectious diseases, cutaneous lupus was the most frequent diagnosis in both groups. Lichen planus and drug reactions were more frequent in black patients. CONCLUSION: Apart from intrinsic differences among skin types, social factors may interfere in the distribution of diseases. Not only may these results be useful to public health programs, but they may also aid the approach to dermatological diseases in black skin patients.

INTRODUÇÃO: Pouco se conhece sobre as diferenças étnicas na frequência das doenças da pele e, menos ainda, na população brasileira, caracterizada pela miscigenação. OBJETIVO: Avaliar a distribuição das afecções da pele de indivíduos negros, comparativamente com a dos brancos, em material anatomopatológico. MÉTODOS: Foram estudadas 826 biópsias de indivíduos de pele negra e 1.652 dos de pele branca, obtidas do Departamento de Anatomia Patológica do Hospital das Clínicas da Universidade Estadual de Campinas (HC-UNICAMP), entre 1993 e 2009. Os achados clínicos foram obtidos dos prontuários e os resultados testados por métodos estatísticos. RESULTADOS: O câncer não melanoma foi o diagnóstico mais frequente nos brancos (45%), diferindo, significantemente, da frequência nos negros (8%), assestando-se, em ambos, na pele exposta ao sol. Quanto à topografia e à idade, nos brancos predominavam biópsias da "cabeça e pescoço", na faixa acima dos 50 anos. Nos negros, as doenças predominavam entre 15 e 50 anos, no sexo feminino, na topografia dos genitais. À análise comparativa das doenças vulvares, observou-se diferença nos diagnósticos de doenças sexualmente transmissíveis mais frequentes nas mulheres negras. Excluindo-se os cânceres e a topografia genital, os negros apresentaram porcentagem maior de doenças infecciosas. Entre as doenças não infecciosas, o lúpus cutâneo foi a mais frequente nos dois grupos; o líquen plano e a farmacodermia foram mais frequentes nos negros. CONCLUSÃO: Além das diferenças intrínsecas de tipos de pele, fatores sociais podem atuar na distribuição das doenças. Esses resultados podem ser úteis, tanto para os programas de saúde pública quanto para a abordagem das doenças dermatológicas nos pacientes de pele negra.

Coma blisters after poisoning caused by central nervous system depressants: case report including histopathological findings / Bolhas do coma pós-intoxicação por depressores do sistema nervoso central: relato de caso incluindo achados histopatológicos

Blister formation and eccrine sweat gland necrosis is a cutaneous manifestation associated with states of impaired consciousness, most frequently reported after overdoses of central nervous system depressants, particularly phenobarbital. The case of a 45-year-old woman who developed "coma blisters" at six distinct anatomic sites after confirmed (laboratory) phenobarbital poisoning, associated with other central nervous system depressants (clonazepam, promethazine, oxcarbazepine and quetiapine), is presented. A biopsy from the left thumb blister taken on day 4 revealed focal necrosis of the epidermis and necrosis of sweat gland epithelial cells; direct immunofluorescence was strongly positive for IgG in superficial blood vessel walls but negative for IgM, IgA, C3 and C1q. The patient was discharged on day 21 with no sequelae.

Formação de bolhas e necrose de glândula sudoríparas écrinas é uma manifestação cutânea associada com estados de diminuição da consciência, mais frequentemente relatada após superdosagens de depressores do sistema nervoso central, particularmente fenobabital. Relatamos o caso de uma paciente de 45 anos que desenvolveu "bolhas do coma" após tentativa de suicídio por fenobarbital (confirmada laboratorialmente), associada a outros depressores do sistema nervoso central (clonazepam, prometazina, oxcarbazepina e quetiapina). Biópsia da bolha do 1o quirodáctilo esquerdo no 4o dia de internação revelou necrose focal da epiderme e necrose de células epiteliais de glândula sudorípara; a imunofluorescência direta foi fortemente positiva para IgG na parede superficial dos vasos sanguíneos, mas negativa para IgM, IgA, C3 e C1q. A paciente teve alta no 21o dia, sem seqüelas.

Cirurgia micrográfica de Mohs em tricoblastoma recidivado / Mohs Micrographic Surgery on recurrent trichoblastoma

O tricoblastoma é tumor anexial raro, benigno, de crescimento lento e bem-circunscrito. Apesar de ser considerado neoplasia benigna, existem casos de tricoblastomas com comportamento agressivo. Relata-se o caso de uma paciente do sexo feminino, de 66 anos, com lesão tumoral recidivante e de crescimento contínuo na asa nasal direita tratada com cirurgia micrográfica de Mohs.

Trichoblastoma is a slow-growing and well-circumscribed rare adnexal tumor. Although considered a benign neoplasm, there are cases of aggressive trichoblastomas. This paper reports a case of a 66-year-old female patient with a recurrent and continuously growing tumor in the right nasal wing that was treated with Mohs Micrographic Surgery.

Angioceratoma da vulva / Angiokeratoma of the vulva

Os angioceratomas são tumores benignos caracterizados por ectasia dos vasos sanguíneos da derme papilar associada à acantose e hiperceratose da epiderme. Ao exame dermatológico, os angioceratomas de Fordyce caracterizam-se por lesões papulo-ceratóticas de coloração eritemato-violácea. São mais comuns no escroto, sendo raramente relatada a localização vulvar. A histopatologia é particularmente importante para difer enciá-los de outros tumores benignos e malignos. O artigo relata o caso de uma mulher negra de meia idade com história de obstipação intestinal, varizes de membros inferiores e cesárea há 20 anos que apresentava múltiplos angioceratomas vulvares há três meses.

Angiokeratomas are benign tumors characterized by ectasia of blood vessels in the papillary dermis associated with acanthosis and hyperkeratosis of the epidermis. Dermatological examination of angiokeratomas of Fordyce is characterized by papular keratotic lesions of erythematous-violet color. They are more common in the scrotum, and vulvar involvement is rarely reported. Histopathology is particularly important to distinguish them from other benign and malignant tumors. The article reports the case of a middle-aged black woman with a history of chronic constipation, varicose veins of the lower limbs and cesarean section performed 20 years ago who had had multiple vulvar angiokeratomas for three months.

Angiogenesis in the progression of cutaneous squamous cell carcinoma: an immunohistochemical study of endothelial markers

OBJECTIVE: To demonstrate the role of angiogenesis in the progression of cutaneous squamous cell carcinoma. INTRODUCTION: Angiogenesis is a pivotal phenomenon in carcinogenesis. Its time course in cutaneous squamous cell carcinoma has not yet been fully established. METHODS: We studied the vascular bed in 29 solar keratoses, 30 superficially invasive squamous cell carcinomas and 30 invasive squamous cell carcinomas. The Chalkley method was used to quantify the microvascular area by comparing panendothelial (CD34) with neoangiogenesis (CD105) immunohistochemical markers. The vascular bed from non-neoplastic adjacent skin was evaluated in 8 solar keratoses, 10 superficially invasive squamous cell carcinomas and 10 invasive squamous cell carcinomas. RESULTS: The microvascular area in CD105-stained specimens significantly increased in parallel with cutaneous squamous cell carcinoma progression. However, no differences between groups were found in CD34 sections. Solar keratosis, superficially invasive squamous cell carcinoma and invasive squamous cell carcinoma samples showed significant increases in microvascular area for both CD34- and CD105-stained specimens compared with the respective adjacent skin. DISCUSSION: The angiogenic switch occurs early in the development of cutaneous squamous cell carcinoma, and the rate of neovascularization is parallel to tumor progression. In contrast to panendothelial markers, CD105 use allows a dynamic evaluation of tumor angiogenesis. CONCLUSION: This study demonstrated the dependence of skin carcinogenesis on angiogenesis.

Vasculonecrotic reactions in leprosy

Multibacillary, lepromatous or borderline leprosy patients may present two types of vasculonecrotic reactions: Lucio phenomenon and that associated with erythema nodosum leprosum. Despite they can be distinguished through clinical and histological characteristics; both are often used as synonyms. It is said that leprosy reaction should be properly classified for therapeutic reasons, since it is well known that in Lucio phenomenon there is not a good response to thalidomide. The authors reported two cases of vasculonecrotic phenomena in lepromatous leprosy sharing clinical and histopathological characteristics of both reaction subtypes. The findings may indicate the spectral nature of the reaction phenomena in leprosy and emphasize the importance of the clinic-pathological correlation for proper classification. Our findings may contribute to the understanding of leprosy reactions pathogenesis, broaden the knowledge about their outcome with standard treatment, and provide the scientific background to design better therapeutic strategies for these complications.

Diagnóstico da infecção por Bartonella spp.: a propósito de um caso de angiomatose bacilar / Diagnosis of Bartonella spp. infection: study of a bacillary angiomatosis case

Várias dermatoses são consideradas idiopáticas. Muitas vezes, afecções como eritema nodoso ou eritema multiforme, por exemplo, não podem ter sua etiologia definida. A infecção humana por Bartonella spp. pode determinar várias expressões clínicas sindrômicas. A partir de um caso de angiomatose bacilar com documentação clínica, histológica e ultra-estrutural, foi feita a revisão da literatura médica para avaliar os critérios diagnósticos disponíveis para a infecção por esses agentes. Conclui-se que a avaliação histológica é, na prática, um importante e útil método diagnóstico, especialmente quando a sorologia não estiver disponível.

Several dermatoses are considered idiopathic diseases. Many times lesions such as erythema nodosum or erythema multiformis, for example, cannot have their etiology defined. Human infection caused by Bartonella spp. may determine several clinical syndromic expressions. Starting with a clinically, histologically and ultrastructurally documented bacillary angiomatosis case, a review of medical literature was undertaken to evaluate the available diagnostic criteria regarding infection caused by these agents. Histological evaluations were concluded to be, practically speaking, an important and useful diagnostic method, especially when serology is not available.