RESUMO
Biological therapies are safer and more effective against psoriasis than conventional treatments. Even so, 30-50% of psoriatic patients show an inadequate response, which is associated with individual genetic heterogeneity. Pharmacogenetic studies have identified several single nucleotide polymorphisms (SNPs) as possible predictive and prognostic biomarkers for psoriasis treatment response. The objective of this study was to determine the link between several SNPs and the clinical response to biological therapies in patients with moderate-severe psoriasis. A set of 21 SNPs related to psoriasis and/or other immunological diseases were selected and analysed from salivary samples of patients (n = 88). Treatment effectiveness and patient improvement was assessed clinically through Relative Psoriasis Area and Severity Index (PASI), also called 'PASI response', as well as absolute PASI. Associations between SNPs and PASI factors were assessed at 3 and 12 months for every treatment category of IL-17, IL-23, IL-12&23 and TNF-α inhibitors. Multivariate correlation analysis and Fisher's exact test were used to analyse the relationship between SNPs and therapy outcomes. Several SNPs located in the TLR2, TLR5, TIRAP, HLA-C, IL12B, SLC12A8, TNFAIP3 and PGLYRP4 genes demonstrated association with increased short and long-term therapy-effectiveness rates. Most patients achieved values of PASI response ≥75 or absolute PASI<1, regardless of the biological treatment administered. In conclusion, we demonstrate a relationship between different SNPs and both short- and especially long-term effectiveness of biological treatment in terms of PASI. These polymorphisms may be used as predictive markers of treatment response in patients with moderate-to-severe psoriasis, providing personalized treatment.
Assuntos
Psoríase , Fator de Necrose Tumoral alfa , Humanos , Fator de Necrose Tumoral alfa/genética , Interleucina-12/genética , Polimorfismo de Nucleotídeo Único , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Resultado do Tratamento , Psoríase/tratamento farmacológico , Psoríase/genética , Imunidade , Índice de Gravidade de DoençaRESUMO
BACKGROUND AND OBJECTIVES: The increasing use of biologics in the treatment of inflammatory diseases has led to more cases of leishmaniasis in patients subjected to iatrogenic immunosuppression. The main objective was to describe the characteristics of the patients with cutaneous (CL) or mucocutaneous (MCL) leishmaniasis who were receiving a biological therapy at the time of diagnosis. PATIENTS AND METHODS: A multicenter retrospective study was design based on a cohort of patients diagnosed with CL or MCL. All patients who were being treated with biologicals were included. For each case, two matched non-exposed patients were included for comparison. RESULTS: 38 patients were diagnosed with CL or MCL while being treated with tumor necrosis factor alpha (TNF-α) inhibitors. Leishmaniasis presented more frequently as a plaque (58.3%) with a larger median lesion size (2.5 cm), ulceration (92.1%), and required a greater median number of intralesional meglumine antimoniate infiltrations (3 doses) (P < 0.05) than in non-exposed patients. We found no systemic involvement in patients being treated with anti-TNF-α. We did not find differences regarding the treatment characteristics whether biologic therapy was modified or not. CONCLUSIONS: Although management should be individualized, maintenance of biologic therapy does not seem to interfere with treatment of CL or MCL.
Assuntos
Antiprotozoários , Leishmaniose Cutânea , Leishmaniose Mucocutânea , Humanos , Leishmaniose Mucocutânea/diagnóstico , Leishmaniose Mucocutânea/tratamento farmacológico , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/patologia , Estudos Retrospectivos , Inibidores do Fator de Necrose Tumoral , Antimoniato de Meglumina/uso terapêutico , Fatores Imunológicos/uso terapêutico , Antiprotozoários/uso terapêuticoRESUMO
Sonidegib is a Hedgehog signalling pathway inhibitor approved for use in patients with advanced basal cell carcinoma (BCC) not eligible for surgery or radiotherapy. This report describes clinical experience with sonidegib in two patients with locally advanced BCC (one with a tumour adjacent to the right eye and the other with a tumour associated with the left ear) and in one patient with Gorlin syndrome. Two of the patients had recurrent and intractable tumours. Treatment with sonidegib 200 mg/day led to remission in both patients with locally advanced BCC within 7 months and to a reduction in the size and number of lesions after 4 months in the patient with Gorlin syndrome. Adverse effects reported in these patients were cramps, alopecia, ageusia and weight loss, all of which were mild and consistent with the known toxicity profile for sonidegib. Sonidegib has an important role to play in the effective treatment of challenging cases of advanced BCC. In parallel, a need remains to improve management protocols for patients with advanced BCC, particularly through earlier intervention and a multidisciplinary team approach.
Assuntos
Melanoma/epidemiologia , Doenças da Unha/epidemiologia , Neoplasias Cutâneas/epidemiologia , Neoplasias das Glândulas Sudoríparas/epidemiologia , Glândulas Sudoríparas/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Pé , Mãos , Humanos , Masculino , Margens de Excisão , Melanoma/etiologia , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Doenças da Unha/patologia , Doenças da Unha/cirurgia , Unhas/patologia , Unhas/cirurgia , Pele/patologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Neoplasias das Glândulas Sudoríparas/etiologia , Neoplasias das Glândulas Sudoríparas/patologia , Neoplasias das Glândulas Sudoríparas/cirurgia , Glândulas Sudoríparas/cirurgiaAssuntos
Erupções Acneiformes/induzido quimicamente , Inibidores da Angiogênese/efeitos adversos , Proteínas Recombinantes de Fusão/efeitos adversos , Erupções Acneiformes/patologia , Adenocarcinoma/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Fatores de Crescimento do Endotélio VascularRESUMO
Programmed cell death receptor 1 inhibitors (anti-PD-1) constitute a form of immunotherapy for the treatment of several cancers. They are associated with cutaneous immune-related adverse events (irAE), occurring in up to 50% of patients. Lichenoid dermatitis is frequent and several presentations have been described. Although attempts have been made to study these reactions, they are yet to be fully characterized and the relationship with tumor response is unclear. We describe a case of digital ulcerative lichenoid dermatitis resembling ulcerative cutaneous lichen planus that occurred during pembrolizumab therapy for oral squamous cell carcinoma. The patient developed a painful ulcer on his index finger 18 months into therapy. Biopsy revealed epidermal ulceration with intense lichenoid dermatitis. Immunohistochemical study revealed intense CD8 positivity at the ulcer's edges and marked CD163 positivity at its base. Although idiopathic forms of this type of lichenoid dermatitis are particularly recalcitrant, our case was successfully managed with topical therapy and oncologic treatment did not require modification. One year after ending treatment the patient remains free of disease progression. It is unclear if this reaction is associated with his favorable oncologic response. This report adds an undescribed reaction to the increasing diversity of cutaneous irAE associated with anti-PD-1 therapy.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Erupções Liquenoides/induzido quimicamente , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Úlcera Cutânea/induzido quimicamente , Administração Cutânea , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Betametasona/administração & dosagem , Betametasona/análogos & derivados , Carcinoma de Células Escamosas/tratamento farmacológico , Combinação de Medicamentos , Gentamicinas/administração & dosagem , Humanos , Erupções Liquenoides/tratamento farmacológico , Erupções Liquenoides/patologia , Masculino , Neoplasias Bucais/tratamento farmacológico , Pele/patologia , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/patologiaRESUMO
Apocrine hidrocystoma is a rare, benign, cystic tumor of the apocrine sweat glands. They are most commonly located around the eyes and may also be found on the scalp and neck. However, despite the fact that the nipple and areola contain numerous apocrine sweet glands, apocrine hydrocystomas have not been described previously in this area to the best of our knowledge. We report the first case of this cyst in this unsual location.
Assuntos
Glândulas Apócrinas/patologia , Mamilos/patologia , Neoplasias das Glândulas Sudoríparas/patologia , Adulto , Feminino , Humanos , Mamilos/diagnóstico por imagem , Neoplasias das Glândulas Sudoríparas/diagnóstico por imagem , Ultrassonografia MamáriaRESUMO
Cowden syndrome (CS) is an infrequent genodermatosis caused by mutations in the phosphatase and tensin homolog (PTEN) gene in the majority of cases. As such, it belongs to the PTEN hamartoma tumor syndrome spectrum. This disease has a variable clinical expression characterized by the development of multiple hamartomatous tumors in different organs, usually during the second and third decades of life, and a high cumulative risk of several malignancies. We present a case of Cowden syndrome with late diagnosis presenting with a florid dermatological expression and multiple benign tumors, but no malignancies. A novel PTEN mutation was identified.
Assuntos
Fibroma/genética , Síndrome do Hamartoma Múltiplo/genética , Neoplasias Bucais/genética , PTEN Fosfo-Hidrolase/genética , Neoplasias Cutâneas/genética , Feminino , Fibroma/diagnóstico , Fibroma/etiologia , Fibroma/patologia , Folículo Piloso , Síndrome do Hamartoma Múltiplo/complicações , Síndrome do Hamartoma Múltiplo/diagnóstico , Síndrome do Hamartoma Múltiplo/patologia , Humanos , Pessoa de Meia-Idade , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/etiologia , Neoplasias Bucais/patologia , Mutação , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologiaRESUMO
The differential diagnosis of Grover disease (GD) includes pemphigus foliaceus. However, the focal nature of the histologic findings and negative direct immunofluorescent point to the diagnosis of GD. It has been associated with a variety of systemic and cutaneous diseases, but its association with other primary acantholytic disorders has been rarely documented. In this article, we describe the first case of GD in association with pemphigus foliaceus.
Assuntos
Acantólise/complicações , Carcinoma Basocelular/complicações , Ictiose/complicações , Pênfigo/complicações , Neoplasias Cutâneas/complicações , Carcinoma Basocelular/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Cutâneas/cirurgiaAssuntos
Condiloma Acuminado/tratamento farmacológico , Diterpenos/administração & dosagem , Papillomaviridae/isolamento & purificação , Doenças do Pênis/tratamento farmacológico , Doenças do Pênis/patologia , Adolescente , Adulto , Condiloma Acuminado/diagnóstico , Condiloma Acuminado/patologia , Diterpenos/uso terapêutico , Géis , Humanos , Masculino , Resultado do TratamentoRESUMO
Palmoplantar psoriasis is a particularly challenging variant of psoriasis. Psoriasis at this location has a significant impact on health-related quality of life and is often recalcitrant. However, difficult cases may respond to biologic therapies. Paradoxical reactions during treatment with biological agents have been described, mostly during anti-tumor necrosis factor therapy. These typically present as a change in morphology or distribution of lesions. We present a patient with palmoplantar psoriasis treated with ixekizumab who achieved a favorable response that was coupled with a rare paradoxical reaction, reversed plantar involvement. The reason for this phenomenon and its clinical course are uncertain, but these new lesions are proving recalcitrant to complementary therapies. Provided the increasingly widespread use of biologic therapies, the incidence and diversity of paradoxical reactions are expected to increase.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Dermatoses do Pé/induzido quimicamente , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Antineoplásicos/efeitos adversos , Vasculite por IgA/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos , Sunitinibe/efeitos adversos , Adulto , Biópsia , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Dermoscopia , Feminino , Humanos , Vasculite por IgA/diagnóstico , Vasculite por IgA/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Pele/diagnóstico por imagem , Pele/patologiaRESUMO
We report the case of a 32-year-old man with measles in which skin biopsy helped to establish a definitive diagnosis. Follicular involvement is a common histopathologic feature of measles. Multinucleated epidermal and follicular cells are distinctive findings.
Assuntos
Células Gigantes/patologia , Folículo Piloso/patologia , Queratinócitos/patologia , Sarampo/patologia , Glândulas Sebáceas/patologia , Adulto , Biópsia , Humanos , Masculino , Sarampo/diagnósticoRESUMO
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most devastating malignancies in developed countries because of its very poor prognosis and high mortality rates. By the time PDAC is usually diagnosed only 20-25% of patients are candidates for surgery, and the rate of survival for this cancer is low even when a patient with PDAC does undergo surgery. Lymph node invasion is an extremely bad prognosis factor for this disease. METHODS: We analyzed the mRNA expression profile in 30 PDAC samples from patients with resectable local disease (stages I and II). Neoplastic cells were isolated by laser-microdissection in order to avoid sample 'contamination' by non-tumor cells. Due to important differences in the prognoses of PDAC patients with and without lymph node involvement (stage IIB and stages I-IIA, respectively), we also analyzed the association between the mRNA expression profiles from these groups of patients and their survival. RESULTS: We identified expression profiles associated with patient survival in the whole patient cohort and in each group (stage IIB samples or stage I-IIA samples). Our results indicate that survival-associated genes are different in the groups with and without affected lymph nodes. Survival curves indicate that these expression profiles can help physicians to improve the prognostic classification of patients based on these profiles.