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1.
Psoriasis (Auckl) ; 14: 79-86, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38946911

RESUMO

Purpose: Multiple biological therapies have been developed for the treatment of inflammatory diseases, including moderate to severe plaque psoriasis. Choosing the optimal treatment for psoriasis can depend on several factors and is strongly influenced by a drug's efficacy and safety profile. Continuous treatment with biological therapies is recommended to achieve effective disease management in patients with psoriasis. However, in real-world, patients often discontinue biologic therapy within the first year of treatment. Therefore, in this study, we aimed to investigate the effectiveness and drug survival of two anti-interleukin 17 agents (ixekizumab and secukinumab) in a group of adult patients with moderate to severe psoriasis from Bucharest, Romania. Patients and Methods: We designed an observational, non-interventional, retrospective study of 255 adult patients with moderate to severe psoriasis receiving ixekizumab and secukinumab. We performed descriptive statistics and inferential methods, such as z-test, median test and Kaplan Meier curve comparison, to characterize the groups with two biological treatments. Results: Patients treated with ixekizumab had a longer drug survival compared to those treated with secukinumab with lower risks of non-persistence, discontinuation and switching therapy. Patients age-groups and psoriasis durations found to be significant factors in drug survival. Conclusion: This study contributes to the understanding of the drug survival profile and the factors that may influence it in ixekizumab and secukinumab treatment in a real-world setting.

2.
Life (Basel) ; 14(1)2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38255729

RESUMO

Psoriasis is a chronic immune-mediated disease, linked to local and systemic inflammation and predisposing patients to a higher risk of associated comorbidities. Cytokine levels are not widely available for disease progression monitoring due to high costs. Validated low-cost and reliable markers are needed for assessing disease progression and outcome. This study aims to assess the reliability of blood-count-derived inflammatory markers as disease predictors and to identify prognostic factors for disease severity. Patients fulfilling the inclusion criteria were enrolled in this study. Patients were divided into three study groups according to disease severity measured by the Body Surface Area (BSA) score: mild, moderate, and severe psoriasis. White blood cell count (WBC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), derived neutrophil-to-lymphocyte ratio (d-NLR), systemic immune index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) positively were correlated with disease severity (p < 0.005). d-NLR, NLR, and SII are independent prognostic factors for mild and moderate psoriasis (p < 0.05). d-NLR is the only independent prognostic factor for all three study groups. Moderate psoriasis is defined by d-NLR values between 1.49 and 2.19. NLR, PLR, d-NLR, MLR, SII, SIRI, and AISI are useful indicators of systemic inflammation and disease severity in psoriasis.

3.
Int J Mol Sci ; 24(23)2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38069218

RESUMO

Psoriasis is an immune-mediated, chronic disorder that significantly alters patients' quality of life and predisposes them to a higher risk of comorbidities, including liver fibrosis. Various non-invasive tests (NITs) have been validated to assess liver fibrosis severity, while blood-count-derived inflammatory markers have been proven to be reliable in reflecting inflammatory status in psoriatic disease. The fibrosis-4 (FIB-4) index became part of the newest guideline for monitoring psoriasis patients undergoing systemic treatment. Patients with psoriasis vulgaris and fulfilling inclusion criteria were enrolled in this study, aiming to assess for the first time in the literature whether such inflammatory markers are useful in predicting liver fibrosis. Based on internationally validated FIB-4 index values, patients were divided into two study groups: a low risk of significant fibrosis (LR-SF) and a high risk of significant fibrosis (HR-SF). Patients from HR-SF were significantly older and had higher values of the monocyte-to-lymphocyte ratio (MLR) (p < 0.001), which further significantly correlated with fibrosis severity (p < 0.001). Platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), platelet-to-white blood cell ratio (PWR), and aggregate index of systemic inflammations (AISI) significantly correlated negatively with liver fibrosis (p < 0.001). PWR proved to be the most reliable inflammatory predictor of fibrosis severity (AUC = 0.657). MLR, PWR, and AISI were independent inflammatory markers in multivariate analysis (p < 0.001), while the AST to platelet ratio index (APRI) and AST to ALT ratio (AAR) can be used as additional NITs for significant liver fibrosis (p < 0.001). In limited-resources settings, blood-count-derived inflammatory markers such as MLR, PWR, and AISI, respectively, and hepatic indexes APRI and AAR prove to be of particular help in predicting significant liver fibrosis.


Assuntos
Psoríase , Qualidade de Vida , Humanos , Contagem de Plaquetas , Cirrose Hepática/patologia , Fígado/patologia , Inflamação/patologia , Psoríase/complicações , Psoríase/patologia , Biomarcadores , Aspartato Aminotransferases , Estudos Retrospectivos
4.
Medicina (Kaunas) ; 59(9)2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37763651

RESUMO

Background: Due to its many benefits, indocyanine green (ICG) has gained progressive popularity in operating rooms (ORs) globally. This literature review examines its qualitative and quantitative usage in surgical treatment. Method: Relevant terms were searched in five international databases (1. Pubmed, 2. Sciencedirect, 3. Scopus, 4. Oxfordjournals, 5. Reaxys) for a comprehensive literature review. The main benefits of using ICG in colorectal surgery are: intraoperative fluorescence angiography; fluorescence-guided lymph node involvement detection and the sentinel technique; the fluorescent emphasis of a minute liver tumour, counting just 200 tumour cells; facilitation of fistula diagnosis; and tumour tattooing. This methodology can also be used with quantitative characteristics such as maximum intensity, relative maximum intensity, and in-flow parameters such as time-to-peak, slope, and t1/2max. This article concludes that fluorescence surgery with ICG and near-infrared (NIR) light is a relatively new technology that improves anatomical and functional information, allowing more comprehensive and safer tumour removal and the preservation of important structures.


Assuntos
Cirurgia Colorretal , Procedimentos Cirúrgicos do Sistema Digestório , Humanos , Verde de Indocianina , Linfonodos/patologia , Corantes , Biópsia de Linfonodo Sentinela/métodos
5.
Front Immunol ; 14: 1180221, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37600771

RESUMO

Scleroderma-like cutaneous lesions have been found in many pathological conditions and they have the clinical appearance of sclerotic or scleroatrophic lesions. Affected skin biopsies described histopathological changes similar to those of scleroderma located strictly on the skin or those of systemic sclerosis. These skin lesions can be found in inflammatory diseases with autoimmune substrate (generalized morphea, chronic graft versus host disease, eosinophilic fasciitis), tissue storage diseases (scleredema, scleromyxedema, nephrogenyc systemic fibrosis, systemic amyloidosis), metabolic diseases (porphyrya cutanea tarda, phenylketonuria, hypothyroidism, scleredema diabeticorum), progeroid syndromes. Given the multiple etiologies of sclerodermal lesions, a correct differential diagnosis is necessary to establish the appropriate treatment.


Assuntos
Diagnóstico Diferencial , Escleroderma Sistêmico , Escleroderma Sistêmico/classificação , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/patologia , Humanos
6.
Diagnostics (Basel) ; 13(5)2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36900113

RESUMO

High-frequency ultrasonography (HF-USG) is a relatively new imaging method that allows the evaluation in a non-invasive manner of the skin layers and skin appendages. It is a diagnostic tool with increasing usefulness in numerous dermatological pathologies. High reproducibility, non-invasiveness and short diagnostic time make this method an increasingly used tool in dermatological practice. The subepidermal low-echogenic band is a relatively newly described parameter that seems to be a marker not only of intrinsic and extrinsic skin aging, but also of inflammatory processes taking place at the skin level. This systematic review aims to evaluate the role that SLEB has in the diagnosis and monitoring of the treatment of some inflammatory and non-inflammatory dermatological conditions, as well as its utility as a disease marker.

7.
Life (Basel) ; 12(12)2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36556415

RESUMO

Psoriasis is not optimally controlled in spite of newly developed treatments, possibly due to the difficulty of objectively quantifying the disease's severity, considering the limitations of the clinical scores used in clinical practice. A major challenge addresses difficult-to-treat areas, especially in the absence of significant body surface involvement. It is controversial whether the severity evaluation of patients with several affected areas (having at least one difficult-to-treat area) should be done differently from current methods. Scores used for special areas (PSSI, NAPSI and ESIF) allow an accurate assessment of disease severity in difficult-to-treat areas, but the issue of whether to integrate these scores into PASI, BSA or DLQI remains. The review's purpose resides in providing an overview of the main current issues in determining psoriasis severity in patients with psoriasis in difficult-to-treat areas and suggesting possible solutions for the optimal integration of the area assessment in current scores: severity can be either established according to the highest calculated score (PASI or PSSI or NAPSI or ESIF) or by adding a correction factor in the calculation of PASI for special areas.

8.
Clin Cosmet Investig Dermatol ; 15: 2087-2095, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36199384

RESUMO

Although basal cell carcinoma is a well-known tumor with confirmed clinical and histopathology traits, prognosis factors and treatment options, new facets of this tumor emerge as innovative approach methods develop. Reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) allow a basal cell carcinoma's in vivo analysis of its depth of invasion, tumor margins prior to surgical approach and the tumor's response to a non-invasive treatment, evaluating simultaneously the tumor's vasculature. By RCM and OCT analysis, basal cell carcinoma has registered a groundbreaking discovery regarding a small (but with predictive factor potential) trait - the cleft, developing in between the tumor islands/nodules/chords and the surrounding tumor stroma; it was considered to date as a consequence of the tissue's histopathology processing. RCM and OCT revealed that the "clefting artifact", as it is frequently found in the medical literature, is not actually an artifact of laboratory processing, but a tumor trait found in vivo, with apparent mucin deposits. This review aims at merging the methods of evaluating basal cell carcinoma, both non-invasive (dermoscopy, RCM, OCT) and invasive ones (histopathology - with newly proposed classification), with special emphasis on the cleft issue - its assessment with the aforementioned techniques, with potential implications in the patient's prognosis.

9.
Int J Gen Med ; 15: 7169-7172, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118185

RESUMO

There are a wide variety of disfiguring dermatological conditions whose pathologic substrate is represented by the unwanted deposition of collagen from dermal fibroblasts. Pirfenidone has demonstrated efficiency in the treatment of disordered collagen production when applied topically. Due to a similar mechanism of action, we also hypothesize that a similar medication, nintedanib, might have similar applications. We also propose that a liposomal technology may assist in the penetration of nintedanib and enhance its clinical effects.

10.
Diagnostics (Basel) ; 12(9)2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36140455

RESUMO

According to European consensus-based interdisciplinary guidelines for melanoma, cutaneous melanoma (CM) is the most deadly form of dermatological malignancy, accounting for 90% of the deaths of skin cancer patients. In addition to cutaneous melanoma, mucosal melanoma occurs in four major anatomical sites, including the upper respiratory tract, the conjunctiva, the anorectal region, and the urogenital area. As this cancer type metastasizes, a classification used in the current medical literature is the distinction between secondary lesions and primary malignant melanoma of the abdominal cavity. Given that malignant melanoma is the most common cancer that spreads to the gastrointestinal tract, different imaging modalities compete to diagnose the phenomenon correctly and to measure its extension. Treatment is primarily surgery-based, supported by immunotherapy, and prolongs survival, even when performed at stage IV illness. In the end, special forms of malignant melanoma are discussed, such as melanoma of the genito-urinary tract and amelanotic/achromic melanoma. The importance of this present literature review relies on yielding and grouping consistent and relevant, updated information on the many aspects and challenges that a clinician might encounter during the diagnosis and treatment of a patient with intra-abdominal melanoma.

11.
Diagnostics (Basel) ; 12(7)2022 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-35885460

RESUMO

Male breast cancers are uncommon, as men account for less than 1 percent of all breast carcinomas. Among the predisposing risk factors for male breast cancer, the following appear to be significant: (a) breast/chest radiation exposure, (b) estrogen use, diseases associated with hyper-estrogenism, such as cirrhosis or Klinefelter syndrome, and (c) family health history. Furthermore, there are clear familial tendencies, with a higher incidence among men who have a large number of female relatives with breast cancer and (d) major inheritance susceptibility. Moreover, in families with BRCA mutations, there is an increased risk of male breast cancer, although the risk appears to be greater with inherited BRCA2 mutations than with inherited BRCA1 mutations. Due to diagnostic delays, male breast cancer is more likely to present at an advanced stage. A core biopsy or a fine needle aspiration must be performed to confirm suspicious findings. Infiltrating ductal cancer is the most prevalent form of male breast cancer, while invasive lobular carcinoma is extremely uncommon. Male breast cancer is almost always positive for hormone receptors. A worse prognosis is associated with a more advanced stage at diagnosis for men with breast cancer. Randomized controlled trials which recruit both female and male patients should be developed in order to gain more consistent data on the optimal clinical approach.

12.
Exp Ther Med ; 23(4): 258, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35251324

RESUMO

The ongoing COVID-19 pandemic, declared by the World Health Organisation in March 2020, with the emergence of new, possibly more contagious and more virulent strains, remains a research subject, with the complex systemic involvement better described and understood, but also with a variety of skin and mucosal lesions described in the literature. Mucocutaneous lesions associated with SARS-CoV-2 infection are still under investigation, due to their polymorphic clinical aspect and incompletely understood pathogenic mechanism. The cutaneous inflammatory, exanthematous and purpuric rashes, erythemato-purpuric enanthems, oral ulcers, lichenoid oral lesions, conjunctivitis, conjunctival pseudomembranes, or corneal lesions have been described in patients with COVID-19. Several classifications have been proposed based on the clinical pattern, histological findings, and possible pathogenic mechanisms. The pathogenic mechanism, the diagnostic criteria, the prognostic importance of these lesions are still being debated. The diverse clinical aspects of dermatological manifestations render the diagnosis difficult. However, several clinical patterns strongly associated with COVID-19, such as chilblains, papulovesicular exanthems, and febrile rash require increased awareness and changes to the investigation protocols for these conditions, to include testing for SARS-CoV-2. In the present review, the mucocutaneous findings associated with the novel coronavirus infection, reported thus far in the literature, was provided.

13.
Exp Ther Med ; 23(4): 259, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35251325

RESUMO

Since the introduction of modern phototherapy in 1903 by Nobel Prize-winner Niels Ryberg Finsen, the usage of this therapy in the medical field has grown, techniques have been refined and developed, and it has gained widespread acceptance. Psoriasis vulgaris, parapsoriasis, lichen planus, atopic dermatitis, neonatal jaundice, urticaria, morphea, vitiligo, granuloma annulare and cutaneous T cell lymphoma are only a few dermatological indications that come along with satisfactory results. Most often, it is a 2nd or 3rd line therapy being an alternative in more severe or refractory diseases. Despite the side effects that may occur after phototherapy, which are often minor, the benefits can be significant. Unfortunately, the absolute contraindications limit the use of this type of treatment and implicitly the management of these patients. The current review aimed to combine the recommendations of phototherapy in dermatology, the types of phototherapy that can be suitable for certain dermatological diseases and to emphasize its importance in certain conditions that are associated with significant remission rates.

14.
Diagnostics (Basel) ; 12(3)2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35328289

RESUMO

Basal cell carcinoma (BCC) is the most common form of cutaneous neoplasia in humans, and dermoscopy may provide valuable information for histopathological classification of BCC, which allows for the choice of non-invasive topical or surgical therapy. Similarly, dermoscopy may allow for the identification of incipient forms of BCC that cannot be detected in clinical examination. The importance of early diagnosis using the dermoscopy of superficial BCC forms is proven by the fact that despite their indolent clinical appearance, they can be included in high-risk BCC forms due to the rate of postoperative recurrence. Nodular pigmentary forms of BCCs present ovoid gray-blue nests or multiple gray-blue dots/globules associated with arborized vessels, sometimes undetectable on clinical examination. The management of BCC depends on this, as pigmentary forms have been shown to have a poor response to photodynamic therapy. High frequency ultrasound examination (HFUS) aids in the diagnosis of BCC with hypoechoic tumour masses, as well as in estimating tumour size (thickness and diameter), presurgical margin delineation, and surgical planning. The examination is also useful for determining the invasion of adjacent structures and for studying local recurrences. The use of dermoscopy in combination with HFUS allows for optimisation of the management of the oncological patient.

15.
Exp Ther Med ; 23(3): 201, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35126704

RESUMO

Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders, involving hyperproliferative keratinocytes and infiltration of T cells, dendritic cells, macrophages, and neutrophils. Multiple factors appear to play important roles in the pathogenesis of psoriasis. These environmental (e.g., infectious agents and trauma), genetic, and immunologic factors are reviewed in this article. Although the pathogenesis of psoriasis remains to be established, data suggesting immune cell dysregulation in the skin are available. The involvement of the immune system, particularly T cells, in the etiopathogenesis of psoriasis is discussed in this review, indicating a potential justification for innovative treatment intervention. Besides describing pathogenic T cells, the aim of the review was to assess the function of newly identified antimicrobial peptides (AMPs), interleukin (IL)-23, IL-17, and tissue resident memory cells (TRMs), and their role in psoriasis. Furthermore, new insights were presented regarding TRMs, a recently identified subset of memory T cells, and the role they play in the local memory of disease, making them a potential new therapeutic target in psoriasis. Finally, current developments in T-cell research and cytokine-targeted therapy for psoriasis treatment are reviewed.

16.
Exp Ther Med ; 23(2): 151, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35069832

RESUMO

Acne is a chronic inflammatory condition affecting the pilosebaceous unit that was traditionally viewed as a disease of the adolescence. However, over the past several years, an increasing number of adult women have been reported to suffer from this condition. The prevalence of adult female acne ranges between 12 and 54%. Two clinical types can be distinguished in this population, a 'retentional' and an 'inflammatory' type, which usually tend to overlap. In terms of evolution, three main subtypes can be identified: Persistent acne, which is the most frequent subtype, late-onset acne and recurrent acne. This type of acne is mainly mild-to-moderate in severity and may be refractory to conventional treatment. The etiopathogenesis is complex and has yet to be fully elucidated. It appears to involve an interaction among genetic predisposition, hormonal factors, and chronic activation of the innate immune system overlapping with external factors, such as daily stress, Western-type diet, use of tobacco and cosmetics. The treatment may be challenging and a holistic approach is required, with special attention to the individual needs and particularities of adult women. Both topical and systemic treatments are available, with hormonal therapies being of special value in this population. The aim of the present article was to provide up-to-date, evidence-based information on the clinical presentation, etiopathogenesis and treatment of adult female acne.

17.
Exp Ther Med ; 23(2): 152, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35069833

RESUMO

Long considered a skin-limited condition, psoriasis is currently defined as a chronic, immune-mediated inflammatory disease, presenting, besides the skin changes, important systemic manifestations, the most common being: psoriatic arthritis, cardiovascular disease, metabolic syndrome, diabetes, inflammatory bowel disease and nonalcoholic steatohepatitis. It is a disease with a strong psycho-emotional and social impact, both through skin changes such as pruritic, scaly erythematous plaques, and through the association of comorbidities that influence morbidity and mortality. It has been shown that psoriasis is an independent cardiovascular risk factor, with patients developing ischemic heart disease/acute coronary syndrome, hypertension, peripheral arterial disease, or stroke. The chronic inflammatory status of psoriasis and the production of specific cytokines may be the etiopathogenic link to atherosclerosis and cardiovascular disease. Biological therapy may affect atherosclerosis, leading to the arrest of the evolution or even regressing the changes in the atheromatous plaque. The aim of this review was to re-evaluate the current knowledge regarding the cardiovascular comorbidities associated with psoriasis for optimal management of the patients.

18.
Exp Ther Med ; 23(2): 179, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35069860

RESUMO

Psoriasis is a chronic inflammatory and immune-mediated condition, which is no longer considered as being limited to the skin, but may affect the entire body. Epidemiological studies have shown that certain disorders, including obesity, diabetes, liver abnormalities, elevated lipid levels in the blood and metabolic syndrome, may occur more frequently in patients with psoriasis compared with the general population. As psoriasis is a chronic disease, the frequently associated comorbidities must be identified early to ensure timely treatment and, possibly, their prevention. Comorbidities often manifest clinically 1-2 years after the onset of psoriasis and are commonly seen in patients with severe forms of the disease. The association between psoriasis and its comorbidities is not coincidental, but rather based on common pathophysiological mechanisms and risk factors that underlie the increased frequency of comorbidities in patients with psoriasis. The aim of the present review was to emphasize the important role of dermatologists in the early recognition of comorbidities in patients with psoriasis, with a focus on metabolic comorbidities, precisely because the dermatologists are usually the first medical contact due to the predominance of skin lesions. Therefore, these specialists have the responsibility to inform patients on the association between psoriasis and possible multiple comorbidities, devise prevention and treatment plans, or even redirect patients to other specialists.

19.
Diagnostics (Basel) ; 11(12)2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34943598

RESUMO

Tuberculosis (TB) is a public health issue that affects mostly, but not exclusively, developing countries. Abdominal TB is difficult to detect at first, with the incidence ranging from 10% to 30% of individuals with lung TB. Symptoms are non-specific, examinations can be misleading, and biomarkers commonly linked with other diseases can also make appropriate diagnosis difficult. As a background for this literature review, the method used was to look into the main characteristics and features of abdominal tuberculosis that could help with differentiation on the PubMed, Science Direct, and Academic Oxford Journals databases. The results were grouped into three categories: A. general features (the five forms of abdominal tuberculosis: wet and dry peritonitis, lymphadenopathy, lesions at the level of the cavitary organs, lesions at the level of the solid organs), B. different intra-abdominal organs and patterns of involvement (oesophageal, gastro-duodenal, jejunal, ileal, colorectal, hepatosplenic, and pancreatic TB with calcified lymphadenopathy, also with description of extraperitoneal forms), and C. special challenges of the differential diagnosis in abdominal TB (such as diagnostic overlap, the disease in transplant candidates and transplant recipients, and zoonotic TB). The study concluded that, particularly in endemic countries, any disease manifesting with peritonitis, lymphadenopathy, or lesions at the level of the intestines or solid organs should have workups and protocols applied that can confirm/dismiss the suspicion of abdominal tuberculosis.

20.
Exp Ther Med ; 22(6): 1429, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34707710

RESUMO

Psoriasis is a common long-lasting, inflammatory disease that mainly affects the skin. The incidence of this condition has increased significantly over time and at this point, it affects approximately 1% of children. Psoriasis can appear at any age, including childhood and adolescence, with a higher frequency in girls, an earlier onset being associated with severe psoriasis. The pathology is the result of the interaction between genetics and trigger factors such as infections, stress, diet, obesity, and chemical irritants. Paradoxically, tumor necrosis factor (TNF)-α inhibitors (infliximab, adalimumab) may induce psoriasis in children. Psoriasis is a long-term condition with periods of exacerbation; thus, the quality of life can be affected and patients should receive psychosocial support. Although most children have mild disease and topical treatment is efficient, some cases are challenging to treat. The aim of this review was to provide an overview of the current knowledge concerning the epidemiology, etiology, pathogenesis, clinical features, comorbidities, and treatment of psoriasis in children and also to emphasize the need for a multidisciplinary approach to this complex pathology.

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