Epidemiology of Psoriasis in Portugal: A Population-Based Study.

INTRODUCTION: Psoriasis is a common, chronic, and inflammatory skin disorder with a high personal, social and economic burden and important implications for healthcare systems. The aim of this study was to provide an epidemiological characterization of individuals with psoriasis in Portugal. MATERIAL AND METHODS: A large observational, cross-sectional, nationwide, population-based survey study developed by the Portuguese Psoriasis Group of the Portuguese Society of Dermatology and Venereology (GPP-SPDV). A structured questionnaire was designed and applied by experienced interviewers to a random, representative sample of Portuguese individuals with psoriasis and/or psoriatic arthritis. Patients were considered to have psoriasis if they replied positively to one of the following questions: "Does any physician have ever diagnosed you with psoriasis?" or "Do you have a skin disorder characterized by scaling, reddish skin lesions located in the elbows/knees/scalp?". RESULTS: A total of 6381 individuals were interviewed, of which 283 met the criteria for psoriasis, corresponding to a prevalence rate of 4.4% (95% CI 3.95 - 4.98). Out of the participants that met psoriasis criteria, 24% had suggestive signs/symptoms but did not have a clinical diagnosis established and were not being monitored by a physician. Although more than 70% of participants had active disease (scaling, erythema, or pruritus) and one third had joint symptoms, only 12% were on systemic treatment. Fifty percent of participants with psoriasis (n = 139) had relevant comorbidities (most frequently depression/anxiety and cardiometabolic diseases). Sixteen percent of participants with psoriasis (n = 46) reported that psoriasis interfered with their daily activities (median impact of 5 in a 0 - 10 scale) and 12% mentioned the disease had an impact in their sexual life (median impact of 5 in a 0 - 10 scale). CONCLUSION: The results of this study suggest that the prevalence rate of psoriasis is likely to be high in Portugal, and several gaps exist at different levels of healthcare delivery to these patients, from diagnosis to treatment. This study provides important data for the future planning of interventions targeting the improvement of psoriasis care in Portugal.

Pruritus, Allergy and Autoimmunity: Paving the Way for an Integrated Understanding of Psychodermatological Diseases?

Pruritus is a key symptom in allergology and dermatology, contributing to the global and huge impact on quality of life related to skin disorders, both those which are not related to a primary dermatosis (illness) and those which are linked with primary skin lesions (disease). This is particularly evident within psychophysiological dermatoses, a group of psychodermatological diseases where there is a primary dermatosis, where psychological stress plays a role, and where pruritus may represent a major and shared symptom. The etiopathogenesis of pruritus in those disorders sheds light on the link among psychopathological features, psychological stress and the subtle interface between allergic and autoimmune mechanisms, where mast cells play a pivotal role. Allergy has long been recognised as an altered reactivity to exogenous antigens (allergens), defined as an immediate hypersensitivity mediated by immunoglobulin E (IgE). In turn, the immunological understanding of atopy is related to an immediate hypersensitivity reaction to environmental antigens involving T-helper 2 (Th2) responses and the IgE production. Mast cells are major cells in the early phase of allergy, releasing the mediators involved in the symptoms associated with the allergic disease, including pruritus, when the allergen cross-links with IgE, whose mechanisms can be observed in acute urticaria and atopy. Some allergic reactions may persist and allergy may eventually lead to autoimmunity, with the development of a T-helper 1 (Th1) and then IgE-independent inflammation. For instance, in chronic spontaneous urticaria, the mast cell activation may include autoimmune mechanisms, where autoantibodies against the extracellular α subunit of the high-affinity IgE receptor (FcεRIα) and to IgE are observed, with the involvement of Th1 lymphocytes and the production of interferon-γ (INF-γ). The role of autoimmunity is also suggested in the etiopathogenesis of other psychophysiological dermatoses, namely psoriasis, atopic dermatitis and alopecia areata. In the latter, for example, mast cells were reported to be linked with the loss of immune privilege and they are the key cells involved in the experience of pruritus, whose intensity was reported to precede and be correlated with the onset of the hair loss. Furthermore, considering that the role of hair and skin is wide, from psychosocial aspects (communication and social interaction) to vital functions (such as, temperature control), it is straightforward that they are central in our interactions and synchronization with others and the world; thereby, we may admit that the psychophysiological dermatoses could represent a loss of such synchronization. Furthermore, they are often linked with psychopathology which strongly connects with the concept of desynchronization, namely, sleep disorders and depressive symptoms, the clinical expression of a dysfunction in the interplay among mast cells, pineal gland and melatonin, thus the circadian rhythm, as well as their connection with the hypothalamic corticotrophin-releasing hormone (CRH), well-known for its key role in stress response. Moreover, increasing evidence has supported the existence of cutaneous equivalents for these mechanisms, connecting with those central pathways. Thereby, taking all these concepts into consideration, this review intends to look into the updated evidence on the shared biological mechanisms between allergy and autoimmunity, underlining pruritus as a core element, then revisiting the key role of mast cells and discussing the connection with melatonin and immune-inflammatory pathways in the physiopathology of psychophysiological dermatoses, thus paving the way for the understanding of their psychosomatic correlates and a comprehensive psychodermatological approach.

Primary cutaneous alveolar rhabdomyosarcoma in an adolescent - A challenging diagnosis.

Primary cutaneous alveolar rhabdomyosarcoma is an extremely rare and highly aggressive soft tissue sarcoma that predominantly arises on the extremities and perineum of adolescents and young adults. Dermatologists should be aware of these tumors in order to promptly make the diagnosis and initiate treatment.

Elephantiasis nostras verrucosa in the setting of lymphoedema tarda and neurofibromatosis type 1.

Elephantiasis nostras verrucosa (ENV) comprises an uncommon skin disease characterised by dermal fibrosis with hyperkeratotic, verrucous and papillomatous lesions that usually occur after chronic lymphoedema. We describe the case of a 56-year-old-man with neurofibromatosis type 1, no known surgical history, no chronic medication and no travel history, presenting with worsening non-pitting oedema and impressive foul-smelling mossy plaques and cobblestone-like nodules in both legs and feet, especially on the right, compatible with the diagnosis of ENV.

Scrofuloderma: A Diagnosis to Bear in Mind in the Western World.

The incidence of tuberculosis has been increasing worldwide. Contrarily, a recent decrease in Portugal has been reported. Cutaneous tuberculosis comprises a low percentage of all cases. We report a 70-year-old female with a 2-month-history of painful, nodular, suppurative lesions in the groin area, bilaterally. Previous history was remarkable for Human Immunodeficiency Virus infection and stage-IIIB cervical cancer. A skin biopsy, stained with periodic acid-Schiff and Fite's stain, polymerase chain reaction on purulent discharge and mycobacterial culture of the skin were performed, leading to the diagnosis of scrofuloderma. Tuberculostatic therapy was initiated and complete response was observed. This case depicts an uncommon variant of tuberculosis, highlighting the need for awareness of the cutaneous variants of tuberculosis that, although rare, can still present in the clinic today.

A incidência de tuberculose tem vindo a aumentar globalmente. Em Portugal, porém, esta incidência diminuiu na última década. A tuberculose cutânea representa uma pequena percentagem de todos os casos. Apresenta-se o caso de uma mulher de 70 anos com nódulos supurativos da região inguinal bilateralmente, dolorosos, evoluindo há 2 meses. Como antecedentes relevantes, apresentava infeção por vírus da imunodeficiência humana e carcinoma do colo do útero, estadio IIIB. Foram realizadas biópsia cutânea (coloração pelo ácido periódico de Shiff e coloração de Fite), pesquisa de micobactérias por polymerase chain reaction e estudo microbiológico por cultura, tendo sido estabelecido o diagnóstico de escrofuloderma. Iniciou terapêutiva tuberculostática com resposta favorável. Este artigo realça a importância do reconhecimento das formas cutâneas de tuberculose e a necessidade de manter um elevado índice de suspeição, sobretudo em pacientes imunodeprimidos.

Analysis of the Prevalence of Mental Disorders in Psoriasis: The Relevance of Psychiatric Assessment in Dermatology.

BACKGROUND: The boundary between Dermatology and Psychiatry has increasing recognition. Psoriasis is a common psychophysiological skin disease with a major impact on patient's quality of life and a paradigmatic example of a pathology in that boundary. Studies are needed to exactly point out the prevalence of specific psychopathology and mental disorders associated with psoriasis. This work intends to analyse the prevalence of psychopathology and psychiatric comorbidities in patients with psoriasis. METHODS: A systematic review of the literature was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the "5S" model proposed by Haynes. From all the papers retrieved by this search, a total of 34 papers met the inclusion criteria and were then deeply analysed. RESULTS: The most prevalent mental disorders in these patients are sleep disorders (average prevalence: 62.0%), sexual dysfunction (45.6%), personality (35.0%), anxiety (30.4%), adjustment (29.0%), depressive (27.6%) and substance-related and addictive disorders (24.8%). Other mental disorders have been less described, namely somatic symptoms and related disorders, schizophrenia and other psychoses, bipolar disorder and eating disorders. CONCLUSIONS: This updated research shows that the prevalence of psychiatric conditions in psoriasis may range from 24% to 90%. The study of the mind-skin connection in psoriasis may improve the knowledge about psoriasis and its psychiatric comorbidities. The link between psoriasis and associated mental disorders is frequently forgotten or not considered in the clinical practice. Psychiatric disorders in patients with psoriasis may be underdiagnosed. These patients would really benefit from psychiatric assessment, with therapeutic relevance.

Psoriasis and Associated Psychiatric Disorders: A Systematic Review on Etiopathogenesis and Clinical Correlation.

INTRODUCTION AND OBJECTIVE: Psoriasis is a chronic skin disease with a high impact on self-esteem and patients' health-related quality of life. In the last decades some studies have pointed out mental disorders associated with psoriasis and the etiopathogenic mechanisms behind that co-existence. This work compiles psychopathology associated with psoriasis and further analyzes the etiopathogenesis of psoriasis and mental disorders. METHODS: A systematic review of the literature was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and using the "5S" levels of organization of evidence from healthcare research, as previously described. RESULTS: Psoriasis is linked with many mental disorders, both in the psychotic and neurotic sprectrum. Chronic stress diminishes hypothalamic-pituitary-adrenal axis and upregulates sympathetic-adrenal-medullary responses, stimulating pro-inflammatory cytokines. Then, it maintains and exacerbates psoriasis and some of its mental disorders. High levels of pro-inflammatory cytokines connect psoriasis, psychiatric conditions, and other comorbidities of psoriasis (such as atherosclerosis) within a vicious cycle. Furthermore, the etiopathogenesis of the link between each psychiatric comorbidity and psoriasis has its own subtleties, including the cooccurrence of other comorbidities, the parts of the body affected by psoriasis, treatments, and biological and psychosocial factors. CONCLUSION: The study of psychopathology can amplify our understanding about the etiopathogenesis of psoriasis and associated mental disorders. Patients would benefit from a psychodermatologic approach. The adequate treatment should take into account the mental disorders associated with psoriasis as well as the circumstances under which they occur.

Mycobacterium chelonae Is an Ubiquitous Atypical Mycobacterium.

The type of cutaneous infection varies mainly according to the patient's immune status, and the disseminated form is mostly found in the context of immunosuppression. We report the case of a 62-year-old male who was under long-term systemic corticosteroid therapy and presented with a 7-month history of multiple painless cutaneous lesions at various stages of development: papules, nodules, pustules and hemorrhagic crusts, as well as small erosions and ulcers distributed over the limbs and scalp. Cutaneous biopsy showed a suppurative granulomatous infiltrate with abscess formation. Fite stain revealed numerous extracellular bacilli, suggesting mycobacterial infection, particularly by atypical mycobacteria. Culture of a skin sample revealed Mycobacterium chelonae. The patient started multidrug therapy and showed clinical improvement despite of resistance to one of the antibiotics. This striking presentation underlines the role of immunosuppression with corticotherapy as a major risk factor for these infections. Multidrug therapy is advised and antibiogram is essential in directing treatment.

Multiple minute digitate hyperkeratosis--a peculiar entity.

Multiple minute digitate hyperkeratosis is a rare, non-follicular dermatosis, with fewer than 30 cases described worldwide. It can be either acquired or inherited in an autosomal dominant pattern. We describe the case of an 83-year old patient with life-long, multiple, digitate, milimetric lesions, and a positive family history for the same dermatosis.

Lower lip reconstruction with nasolabial flap--going back to basics.

Squamous cell carcinoma of the lower lip is frequent, and radical excision sometimes leads to complex defects. Many lip repair techniques are aggressive requiring general anesthesia and a prolonged post-operative period. The nasolabial flap, while a common flap for the repair of other facial defects, is an under-recognized option for the reconstruction of the lower lip. We describe the use of nasolabial flap for the repair of a large defect of the lower lip in a ninety year-old male, with good functional results and acceptable cosmetic outcome. We believe the nasolabial flap is a good alternative for intermediate-to-large lower lip defects in patients with impaired general condition.

Lower lip reconstruction with nasolabial flap - going back to basics

Squamous cell carcinoma of the lower lip is frequent, and radical excision sometimes leads to complex defects. Many lip repair techniques are aggressive requiring general anesthesia and a prolonged post-operative period. The nasolabial flap, while a common flap for the repair of other facial defects, is an under-recognized option for the reconstruction of the lower lip. We describe the use of nasolabial flap for the repair of a large defect of the lower lip in a ninety year-old male, with good functional results and acceptable cosmetic outcome. We believe the nasolabial flap is a good alternative for intermediate-to-large lower lip defects in patients with impaired general condition.

Multiple minute digitate hyperkeratosis - a peculiar entity

Multiple minute digitate hyperkeratosis is a rare, non-follicular dermatosis, with fewer than 30 cases described worldwide. It can be either acquired or inherited in an autosomal dominant pattern. We describe the case of an 83-year old patient with life-long, multiple, digitate, milimetric lesions, and a positive family history for the same dermatosis.

Systemic drugs inducing non-immediate cutaneous adverse reactions and contact sensitizers evoke similar responses in THP-1 cells.

Contact sensitizers induce phenotypic and functional changes in dendritic cells (DC) that enhance their antigen-presenting capacity and, ultimately, modulate the T cell response. To evaluate if there is a similar effect of drugs causing T-cell-mediated cutaneous adverse drug reactions (CADR), we studied the in vitro effect of drugs on THP-1 cells, a cell line widely used to evaluate the early molecular and cellular events triggered by contact sensitizers. The effect of allopurinol, oxypurinol, ampicillin, amoxicillin, carbamazepine and sodium valproate, at EC30 concentrations, was evaluated on p38 MAPK activation, by Western Blot, and on the expression of genes coding for DC maturation markers, pro-inflammatory cytokine/chemokines and hemeoxygenase 1 (HMOX1), by real-time RT-PCR. Results were compared with lipopolysaccharide (LPS), a DC maturation stimulus, and the strong contact sensitizer, 1-fluoro-2,4-dinitrobenzene (DNFB). All drugs studied significantly upregulated HMOX1 gene transcription and all, except the anticonvulsants, also upregulated IL8. Allopurinol and oxypurinol showed the most intense effect, in a magnitude similar to DNFB and superior to betalactams. Transcription of CD40, IL12B and CXCL10 genes by drugs was more irregular. Moreover, like DNFB, all drugs activated p38 MAPK, although significantly only for oxypurinol. Like contact sensitizers, drugs that cause non-immediate CADR activate THP-1 cells in vitro, using different signalling pathways and affecting gene transcription with an intensity that may reflect the frequency and severity of the CADR they cause. Direct activation of antigen-presenting DC by systemic drugs may be an important early step in the pathophysiology of non-immediate CADR.

Brodalumab: an evidence-based review of its potential in the treatment of moderate-to-severe psoriasis.

Advances in knowledge regarding the pathogenesis of psoriasis have allowed the development of a new class of agents known as biologic drugs. Data confirm that T helper (Th)17 and interleukin (IL)-17 signaling has a crucial role in the pathogenesis of the disease. High levels of IL-17 and Th17-related cytokines have been reported in psoriasis, leading to the suggestion of agents targeting IL-17 as a potential therapeutic strategy in psoriasis. Brodalumab is a human monoclonal antibody that targets IL-17 receptor A, blocking the effects of IL-17A, IL-17F, and IL-17E. Data from Phase I and Phase II clinical trials indicate that brodalumab has a favorable safety and tolerability profile, with strong clinical activity, suggesting that it is a potential tool for use in the treatment of moderate-to-severe psoriasis.

Bullous pemphigoid and comorbidities: a case-control study in Portuguese patients.

BACKGROUND: Although rare, bullous pemphigoid (BP) is the most common autoimmune blistering disease. Recent studies have shown that patients with bullous pemphigoid are more likely to have neurological and psychiatric diseases, particularly prior to the diagnosis of bullous pemphigoid. OBJECTIVE: The aims were: (i) to evaluate the demographic and clinical features of bullous pemphigoid from a database of patients at a Portuguese university hospital and (ii) to compare the prevalence of comorbid conditions before the diagnosis of bullous pemphigoid with a control group. METHODS: Seventy-seven patients with bullous pemphigoid were enrolled in the study. They were compared with 176 age- and gender-matched controls, which also had the same inpatient to outpatient ratio, but no history of bullous or cutaneous malignant disease. Univariate and multivariate analyses were used to calculate odds ratios for specific comorbid diseases. RESULTS: At least one neurologic diagnosis was present in 55.8% of BP patients compared with 20.5% controls (p<0.001). Comparing cases to controls, stroke was seen in 35.1 vs. 6.8%, OR 8.10 (3.80-17.25); dementia in 37.7 vs. 11.9%, OR 5.25 (2.71-10.16); and Parkinson's disease in 5.2 vs. 1.1%, OR 4.91 (0.88-27.44). Using multivariate analysis, all diseases except Parkinson's retained their association with BP. Patients under systemic treatment were eight times more likely to have complications than those treated with topical steroids (p< 0.017). CONCLUSIONS: The results of this study substantiate the association between BP and neurological diseases. In addition, they highlight the potential complications associated with the treatment of BP.

Bullous pemphigoid and comorbidities: a case-control study in Portuguese patients

BACKGROUND: aAlthough rare, bullous pemphigoid (BP) is the most common autoimmune blistering disease. Recent studies have shown that patients with bullous pemphigoid are more likely to have neurological and psychiatric diseases, particularly prior to the diagnosis of bullous pemphigoid. OBJECTIVE: The aims were: (i) to evaluate the demographic and clinical features of bullous pemphigoid from a database of patients at a Portuguese university hospital and (ii) to compare the prevalence of comorbid conditions before the diagnosis of bullous pemphigoid with a control group. METHODS: Seventy-seven patients with bullous pemphigoid were enrolled in the study. They were compared with 176 age- and gender-matched controls, which also had the same inpatient to outpatient ratio, but no history of bullous or cutaneous malignant disease. Univariate and multivariate analyses were used to calculate odds ratios for specific comorbid diseases. RESULTS: At least one neurologic diagnosis was present in 55.8% of BP patients compared with 20.5% controls (p<0.001). Comparing cases to controls, stroke was seen in 35.1 vs. 6.8%, OR 8.10 (3.80-17.25); dementia in 37.7 vs. 11.9%, OR 5.25 (2.71-10.16); and Parkinson's disease in 5.2 vs. 1.1%, OR 4.91 (0.88-27.44). Using multivariate analysis, all diseases except Parkinson's retained their association with BP. Patients under systemic treatment were eight times more likely to have complications than those treated with topical steroids (p< 0.017). CONCLUSIONS: The results of this study substantiate the association between BP and neurological diseases. In addition, they highlight the potential complications associated with the treatment of BP. .