Gleison Vieira Duarte

Psoriasis: classical and emerging comorbidities

Psoriasis is a chronic inflammatory systemic disease. Evidence shows an association of psoriasis with arthritis, depression, inflammatory bowel disease and cardiovascular diseases. Recently, several other comorbid conditions have been proposed as related to the chronic inflammatory status of psoriasis. The understanding of these conditions and their treatments will certainly lead to better management of the disease. The present article aims to synthesize the knowledge in the literature about the classical and emerging comorbidities related to psoriasis.

Psoriasis and obesity: literature review and recommendations for management

Recent studies have found a relationship between obesity and chronic inflammation, confirmed by the association of high levels of tumor necrosis factor (TNF-_), interleukin six (IL-6,) and reactive C-protein with an increase in body mass index (BMI). In obese individuals, this inflammatory condition could contribute to the development or aggravation of psoriasis. Analogous phenomena have already been described in other inflammatory chronic diseases, such as rheumatoid arthritis and Crohns disease. Epidemiological studies have identified a high prevalence of cardiovascular comorbidities, secondary to the metabolic alterations associated with psoriasis and obesity. A few aspects of this association remain unclear, such as the impact of obesity in the clinical forms of dermatoses, in the response to treatment, and its relationship with comorbidities.

Association between obesity measured by different parameters and severity of psoriasis

Background  Obesity has been associated with the severity of psoriasis, but this relationship is not completely understood.

Correlation between psoriasis' severity and waist-to-height ratio

In the absence of ideal biomarkers, the research for clinical markers correlated to the severity of psoriasis and/or its comorbidities becomes crucial. Recently, studies have shown positive correlation between body mass index and prevalence and severity of psoriasis. Abdominal circumference showed stronger correlation with disease severity than body mass index. We evaluated the waist-to-height ratio in a sample of 297 adult patients with psoriasis and observed that it has a significant correlation with body mass index and PASI, and together with body mass index allows the identification of central obesity, reducing its subdiagnosis.

Osteopontin, CCL5 and CXCL9 are independently associated with psoriasis, regardless of the presence of obesity

Psoriasis is an autoimmune disease associated with the production of pro-inflammatory cytokines. The identification of these molecules in the pathogenesis of psoriasis facilitated the use of monoclonal antibodies to block their actions as a treatment for severe psoriasis. An increased inflammatory response has been documented in patients with obesity, a condition that is associated with the occurrence and severity of psoriasis. Osteopontin (OPN), TNF and CXCL9 levels are enhanced in patients with psoriasis, although OPN has been documented in the adipose tissue of obese patients without psoriasis. The prevalence of obesity is much higher in psoriasis patients compared with the general population. Thus, we aimed to evaluate the relationship between cytokine levels and psoriasis in the context of obesity. We compared OPN and CXCL9 plasma levels among 117 psoriasis patients and 27 healthy body mass index-matched subjects using ELISA. We also analyzed the TNF, CCL2 and CCL5 levels in a smaller subgroup of patients and matched controls. Median OPN, CCL5 and CXCL9 levels were significantly higher in psoriasis patients compared with the controls, independent of obesity. There was no difference between the median CCL2 levels in the psoriasis patients and the controls (P<0.05), although the CCL2 levels were elevated in obese patients compared with non-obese psoriasis patients (P<0.001). Facial involvement and the psoriasis area severity index (PASI) score were not associated (P<0.05) with OPN levels or elevated levels of chemokines. There was no significant correlation between the OPN and CXCL9 levels or the OPN and TNF levels in psoriasis patients. This work confirms that OPN, CCL5 and CXCL9 plasma levels are higher in psoriasis patients and provides evidence that their higher levels are not a consequence of obesity. Furthermore, the results demonstrate that OPN production is independent of TNF-α and CXCL9.

Epidemiology and treatment of psoriasis: a Brazilian perspective

Psoriasis is a chronic immune-mediated systemic disease that is influenced by genetic and environmental factors, is associated with comorbidities, and has a negative impact on the quality of life of affected individuals. The prevalence of psoriasis varies among different ethnic groups, but this topic has not been studied in Brazil to date. In this review, we evaluate the epidemiology and treatment of psoriasis from a Brazilian perspective. We focused on studies that involved Brazilian subjects. The prevalence of psoriasis in Brazil is estimated to be 2.5%, but no population study has been performed previously. Environmental factors, such as tropical climate, in association with genetic factors, such as miscegenation, may exert a beneficial impact on the course and frequency of psoriasis in Brazil. A number of studies have advanced our understanding of the cardiovascular, ophthalmic, and oral comorbidities that are associated with psoriasis. Concerns about biological therapy, such as endemic leprosy, human T-cell lymphotropic virus (HTLV), and tuberculosis infections, are discussed. The nonavailability of treatment options for psoriasis in the public health system contradicts the Brazilian Society of Dermatology guidelines, stimulating the judicialization of access to medicines in psoriasis care.

Você conhece esta síndrome

Pachyonychia Congenita is a rare genodermatosis of keratinization, first described in 1906 by Jadassohn and Lewandowsky. Besides not being well known, phenotypic variability and oligosymptomatic subtypes make the diagnosis difficult. We report a family with three generations affected, until recently not diagnosed. The active search for familial cases in patients with suspicious manifestations and identification of peculiar characteristics of its subtypes, as multiplex steatocystoma, provide early clinical diagnosis. In addition, nurture the family counseling and informations about prognosis.

Thrombophilia: the dermatological clinical spectrum

The aim of this article is to review the hypercoagulable states (thrombophilia) most commonly encountered by dermatologists, as well as their cutaneous signs, including livedo racemosa, cutaneous necrosis, digital ischemia and ulcerations, reticulated purpura, leg ulcers, and other skin conditions. Recognizing these cutaneous signs is the first step to proper treatment. Our aim is to describe which tests are indicated, and when, in these clinical settings. Introduction The possible causes of vascular occlusion can be divided into three large groups: (i) abnormalities of the vascular wall, (ii) changes in blood flow, and (iii) hypercoagulation of the blood [1]. The term thrombophilia was introduced in 1965 by Egeberg [2] and is currently used to describe conditions resulting from hereditary (or primary) and/or acquired hyper-coagulation of the blood that increase the predisposition to thromboembolic events [3]. Various risk factors, whether genetic or acquired, make up the pathogenesis of thrombosis in both arteries and veins [3]. Some individuals develop recurring thromboses despite preventative measures or develop thromboses in unusual locations [46] and can exhibit a state of hidden hypercoagulability [4]. With regard to acquired thrombophilia, the following conditions are observed: cryoglobulinemia, thrombotic thrombocytopenic purpura, myeloproliferative syndromes, nephrotic syndrome, hypercoagulability associated with cancer, and antiphospholipid syndrome [1]. Table 1 shows the hereditary and acquired risk factors most related to venous thrombosis [3]. Risk factors for venous thromboembolism (VTE) (advanced age, prolonged immobilization, surgery, fractures, use of hormonal contraceptives, pregnancy, puerperium, neoplasms, and antiphospholipid syndrome [5]) differ from those for arterial thrombotic disease (arterial hypertension, smoking, dyslipidemia, and diabetes mellitus) [5]. In Western countries, the incidence of VTE per year is approximately 1 in every 1,000 individuals [7,8]. Screening for states of hypercoagulability in the general population is not practical from either a clinical or economic point of view [4]. The scope of this article is to review the states of hypercoagulability (thrombophilia) most likely to be encountered by the dermatologist, their clinical manifestations, which exams are indicated in these situations, and when such exams are indicated. Hereditary thrombophilia Since the 1950s, the description of states of “hypercoagulability” – a group of abnormalities associated with hyperactivity of the clotting system and/or the occurrence of thrombotic phenomena – changed the view of VTE [9]. Hereditary thrombophilia can be classified into three large groups according to the pathogenic mechanism [1]: (i) Reduction of anticoagulant capacity: There are two systems capable of blocking the clotting cascade and preventing the development of a massive and uncontrollable thrombosis: natural anticoagulants (antithrombin III, protein C, and protein S) and fibrinolysis (plasminogen-plasmin system). A congenital deficit in any one of these components constitutes a possible cause of primary thrombophilia. (ii) Increase in coagulant capacity: Within this group is included the following: a. Resistance to activated protein C. In approximately 90 to 95% of cases, resistance to activated protein C is due to a unique mutation in clotting factor V known as factor V Leiden. There are other causes of resistance to activated protein C that are not due to factor V Leiden such as antiphospholipid syndrome and other, rarer mutations. b. Mutation of the prothrombin G20210A gene. c. Elevated levels of clotting factors VIII, IX, and XI. d. Dysfibrinogenemia. (iii) Other conditions: This group primarily includes hyperhomocysteinemia. Levels of homocysteine can be elevated due to acquired causes (chronic renal insufficiency, hypothyroidism, and deficiencies in folic acid or vitamin B12) and to genetic factors. Among the causes of hyper-homocysteinemia, the most frequent is mutation of the methylenetetrahydrofolate reductase gene (MTHFR) (mutation C677T). Inherited deficiencies in antithrombin (AT), protein C (PC), and its co-factor protein S (PS) were the first identified causes of thrombophilia [10]. Over the last decade, two common genetic polymorphisms were Correspondence to: Paulo Ricardo Criado, Rua Carneiro Leão 33, Vila Scarpelli Santo André São Paulo – Brazil, CEP: 09050-430, E-mail: prcriado@uol.com.br

Severe infliximab-induced psoriasis treated with adalimumab switching

Background  Antitumor necrosis factor (anti‐TNF) agents are a well‐established treatment for various medical conditions, including psoriasis and psoriatic arthritis. However, anti‐TNF agents may themselves induce psoriasis in some patients.

Discussion about alopecia areata emergence as a class-dependent effect of anti-TNFα

The authors refer to the emergence of alopeciaareata (AA) in a single patient, classifying it as a ran-dom adverse effect and stating that this event has notyet been described in the literature. However, similarreactions have been previously reported in the litera-ture and seem to be class-dependent rather than aspecific effect of infliximab. These reactions havebeen associated with immune dysfunction due to theinhibitory effect of the following anti-TNFα agents:infliximab, adalimumab and etanercept.