Clinical course and disease burden of patients with generalized pustular psoriasis in Portugal: a multicenter retrospective cohort study.

OBJECTIVES: Generalized pustular psoriasis (GPP) is a rare, life-threatening skin inflammatory disorder. This study aimed to describe the disease course, treatment strategies, and healthcare utilization among patients with GPP in Portugal. METHODS: This multicentric, observational, retrospective study included consecutive adult patients with GPP undergoing a dermatology evaluation in different reporting institutions by experienced dermatologists between 2002 and 2023. RESULTS: A total of 59 patients were assessed. Most of the cohort had a previous history of plaque psoriasis (71%) and 83% presented at least one comorbidity. At the initial encounter, 64% of the cohort needed hospitalization. Systemic involvement was common, including fever (37%), and elevated white blood cell count and erythrocyte sedimentation rate/C-reactive protein (49%). Nearly, 73% of patients initiated systemic drugs, and 70% had to discontinue the first treatment. During the study, 98% of patients experienced at least one flare. At the last visit, 3.4% of patients had died, and 71.2% exhibited signs of active disease despite undergoing treatment. CONCLUSIONS: Our study demonstrates that GPP is a chronic, debilitating condition associated with systemic involvement, frequent flares, and hospitalizations, despite receiving multiple systemic treatments. Improved disease awareness and new treatments are needed to improve patient care and decrease the burden of the disease.

Combination of Naltrexone and Isotretinoin for the Treatment of Darier Disease.

Darier disease (DD) is an autosomal-dominant genodermatosis in which mutations in the ATP2A2 gene result in impaired intercellular adhesion and epidermal blistering. Treatment options usually rely on systemic retinoids, but a refractory disease is still a therapeutical challenge. Given the similarity of DD pathogenesis with Hailey-Hailey disease, concomitant treatment with low-dose-naltrexone (LDN) has been proposed. We present the case of a 34-year-old woman with a 20-year history of severe, biopsy-proven DD, previously treated with several unsuccessful topical and systemic treatments, including oral isotretinoin, cyclosporine, doxycycline, methotrexate, acitretin, and subcutaneous adalimumab. At presentation, she had widespread keratotic, crusted, brown papules on her trunk and proximal extremities. Treatment with oral LDN (4.5 mg/day in manipulated tablets) was then initiated while maintaining the current isotretinoin therapy. After three months, there was a nearly complete clearance of the lesions, and no adverse effects were reported.

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.

Dermatologists' attitude towards psoriasis treatment during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic introduced new challenges in several dimensions in healthcare services. Herein, we describe the real-life strategies and therapeutic options adopted by dermatologists regarding their patients with psoriasis being treated with or with an indication for systemic therapy during the first COVID-19 lockdown period in Portugal. METHODS: The study involves a web-based survey on the clinical management of systemic therapy for psoriasis during the COVID-19 pandemic administered to Portuguese dermatologists. The survey consisted of 55 questions (4 open-ended questions; 51 closed-ended questions), grouped into 6 sections. RESULTS: A total of 60 dermatologists voluntarily participated in this survey. Nearly 63% of the participants opted for suspending biologics during the COVID-19 lockdown period and 23.3% increased the time between drug administrations. Eighty percent of the participants agreed that biologics did not change the probability of acquiring COVID-19 and 58.4% believed that these drugs decreased or did not change the severity of the disease. Approximately one-third of the participants opted not to prescribe a biological agent in patients despite clinical indication over the duration of the pandemic. Nearly 25% of the participants opted for suspending traditional immunosuppressant administration. Virtual appointments were an option for 93.3% of the participants. CONCLUSION: The COVID-19 pandemic has significantly affected the management of patients with psoriasis being treated with or with an indication for systemic therapy. Some of the decisions made during the first lockdown period were contrary to what we know today. These decisions might have had a significant impact on patients' quality of life and on future therapeutic success. An adequate interpretation and analysis of the available data will be extremely important to an insightful adaptation of the clinical practice in future confinement or restrictive scenarios.

Portuguese recommendations for the treatment of psoriasis with biologic therapy.

Psoriasis is a highly prevalent chronic, inflammatory multisystem disease with a considerable impact on patients' quality of life and the healthcare system. This report presents the recommendations developed by the Portuguese Psoriasis Group of the Portuguese Society of Dermatology and Venereology that address several clinical questions arising during the management and care of psoriasis with biologic therapy, based on the available evidence. The recommendations were generated following thorough evaluation of existing guidelines on the treatment of psoriasis, publications concerning new biologic treatments that have not yet been considered in existing guidelines, as well as expert-based recommendations. Considerations regarding the severity of psoriasis, indications for initiating biologic therapy, parameters to be considered in treatment choice (in particular, treatment goals), as well as recommendations for using and monitoring therapy and screening programmes are also included.

Cutaneous infection by different Alternaria species in a liver transplant recipient.

Fungal invasive infections are rare in general population but are an emergent cause of infection in the immunocompromized population, especially in the solid organ transplant recipients. Herein the authors report a clinical case of a liver transplanted patient suffering a cutaneous co-existent infection with A. alternata as well as A. infectoria. To our knowledge this is the first case of cutaneous concomitant infection due to those two species reported not only in Portugal but also worldwide. The patient was treated with surgical excision of the lesions and oral itraconazol without relapse.

[Skin disease in liver and kidney transplant recipients referred to the department of dermatology and venereology]. / Patologia dermatológica em doentes transplantados hepáticos e renais referenciados à consulta de dermatologia e venereologia.

INTRODUCTION: Several skin disorders, immunosuppression-induced, have been described in transplant recipients. The aim of our study is to characterize the clinical spectrum of skin disorders and to compare the findings in liver and kidney transplant recipients. MATERIAL AND METHODS: A retrospective descriptive study was conducted. Data were collected from the medical records of all liver and kidney transplant recipients from 2000 - 2010 who had been referred to our Dermato-Venereology Department. RESULTS: Three hundred nineteen transplant recipients (23.5%) have been seen, resulting in 410 diagnoses (230 in the subpopulation of liver transplant recipients and 180 in the subpopulation of kidney transplant recipients) grouped into 4 categories: 1) cutaneous infections; 2) skin cancer or premalignant skin lesions; 3) cutaneous side-effects; 4) non-iatrogenic skin disorders. Cutaneous infections were the most common presentations (42.2%), on average 32.7 months after transplantation. The latter group included 20.5% of fungal, 12.7% viral and 8.5% bacterial infections. Skin cancer and premalignant skin lesions made up 11.7% of all diagnoses, over a mean of 44.8 months post transplant and occurring primarily in kidney transplant recipients (20.6% vs 4.8% in liver transplantation patients; P < 0.001). The kidney transplant population had a squamous cell carcinoma (SCC) to basal cell carcinoma (BCC) ratio of 1.3:1 with SCC predominance, and the liver transplant population had a BCC:SCC ratio of 3.5:1. We also identified 10.5% of cutaneous side-effects and 35.6% of non-iatrogenic skin disorders. DISCUSSION: Although neoplastic pathology is more frequently mentioned in the literature, cutaneous infections were the most common diagnoses in our study. The significant differences between the two subpopulations studied may be related to higher immunosuppression after kidney transplantation. CONCLUSION: The high number of skin disorders reported in these patients makes it essential for Dermato-Venereology to be included within the multidisciplinary post-transplant care provided.

Introdução: Foram descritas várias doenças cutâneas em doentes transplantados, em relação com a terapêutica imunossupressora instituída. Pretendemos caracterizar o espectro clínico das patologias dermatológicas e comparar os diagnósticos entre os doentes transplantados hepáticos e os doentes transplantados renais.Material e Métodos: Estudo descritivo e retrospectivo através da consulta de processos clínicos de todos os doentes submetidos a transplante hepático ou renal entre 2000 - 2010 referenciados à Consulta de Dermatologia e Venereologia.Resultados: Observámos 319 doentes transplantados (23,5%) e apurámos 410 diagnósticos (230 na sub-população com transplante hepático e 180 na sub-população com transplante renal), divididos em quatro grupos: 1) infecções cutâneas; 2) cancro cutâneo ou lesões precursoras; 3) manifestações cutâneas relacionadas com efeitos secundários de fármacos; 4) outras patologias dermatológicas não iatrogénicas. As infecções cutâneas foram as mais observadas (42,2%), em média 32,7 meses após o transplante. Este grupo incluiu 20,5% de infecções fúngicas, 12,7% virais e 8,5% bacterianas. Identificámos patologia tumoral e lesões precursoras em 11,7% dos casos, em média 44,8 meses após o transplante e assumindo maior importância na sub-população com transplante renal (20,6%vs 4,8% nos transplantados hepáticos; P < 0,001). Os transplantados renais apresentaram predomínio de carcinomas espinocelulares (CEC) sobre os casos de carcinomas basocelulares (CBC), numa razão CEC:CBC de 1,3:1 mas nos transplantados hepáticos verificou- se uma razão CBC: carcinomas de 3,5:1. Ocorreram efeitos secundários de fármacos em 10,5% dos casos e outras patologiasdermatológicas não iatrogénicas em 35,6%.Discussão: Apesar da patologia tumoral ser a mais referida na literatura, as infecções cutâneas foram as mais observadas na nossa amostra. As diferenças significativas entre as duas sub-populações estudadas podem estar relacionadas com o maior grau de imunossupressão a que os doentes transplantados renais estão sujeitos.Conclusão: Dada a elevada frequência de patologia cutânea nestes doentes é essencial incluir o acesso a consultas de Dermatologia e Venereologia nos cuidados multi-disciplinares pós-transplante.

Phototherapy for pityriasis lichenoides: our experience.

Pityriasis lichenoides is a benign disease that includes a continuous spectrum with two polar ends: pityriasis lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica (PLC). Although its benign and self-limited character, treatment is required, both for itch relief and for cosmetic issues. The present study is a retrospective analysis of 13 patients (11 PLC and 2 PLEVA) treated in our institution with psoralen plus ultraviolet A (PUVA) or ultraviolet A combined with ultraviolet B (UVA/UVB) during the period 1998-2011. In the PUVA group, complete response was achieved in five patients and partial response in two. Total cumulative UVA dose was 84.4 J/cm(2). One patient quit therapy without therapeutic response. In the UVA/UVB group, complete response was achieved in two patients and partial response in an equal number of patients. One patient did not reach a significant improvement. Total cumulative doses were: 26.1 J/cm(2) for UVA and 3.62 J/cm(2) for UVB. There were no acute side effects in either therapeutic group. In the present study, PUVA phototherapy was preferred for patients with more widespread or long-evolving disease, while UVA/UVB was selected for patients who presented more recent disease or contraindications for PUVA therapy. Regardless of the absence of clinical guidelines, both therapeutic options proved to be successful, ascertaining phototherapy as an effective and safe option for pityriasis lichenoides patients.

Psoriasis phototherapy experience from a Lisbon unit: a still valid therapeutic approach in the 21st century.

INTRODUCTION: During the last half of the 20th century, the use of UVB therapy and photochemotherapy (PUVA), were one of the mainstays of treatment for psoriasis. However, accompanying to the advent of the most recent era of psoriasis, with targeted biologic therapy has been a decline in the frequency of phototherapy. This does not diminish its known clinical effects. OBJECTIVE: To perform a retrospective analysis of demographic, clinical and therapeutic variables of psoriatic patients treated with phototherapy in the last 10 years, when biological therapies become available. Also, review some of the published phototherapy and biological therapy data in psoriasis. METHODS: Psoriatic patients were treated between 1st January 2000 and 31st December 2010 in a Lisbon Phototherapeutic unit. Psoriatic arthritis patients were excluded. Regimes used included PUVA (systemic or topical), Re PUVA, UVAB (broad band) or combined options. RESULTS: During this period, 211 patients were treated with phototherapy; 40% (85/211) UVAB, 31% (64/211) topical PUVA, 23% (49/211) systemic PUVA and 6% (13/211) Re PUVA. Mean follow-up period was 18 months (Min 1; Max 120). The average age was 45 years old (mean 44.80; Min 10; Max 80; SD 16.31), 54% (114/211) of patients were female and 46% (97/211) were male. Of all 211 psoriasis patients, 54% (144/211) had plaque psoriasis diagnosis, 31% (66/211) palmoplantar psoriasis and 15% (41/211) guttate psoriasis. Regardless the phototherapy modality used, substantial BSA improvements were achieved in all psoriasis groups. DISCUSSION: Current advancements in therapeutics enjoyed today include the advent of the biologics and other immunomodulating systemic agents. However, attending to the responses achieved, and considering other variables like well-known side effects and cost, photo(chemo)therapy will remain an essential method of treatment for psoriasis vulgaris in the 21st century.

[Guidelines for high-quality use of biologic therapies in adults with plaque psoriasis]. / Normas de Boa Prática Para o Tratamento da Psoríase em Placas em Idade Não Pediátrica com Biológicos.

Psoriasis is an inflammatory dermatosis, affecting approximately 2% of the population, with predominantly skin and joint involvement but also associated with considerable comorbidities. Approximately 20% to 30% of patients have moderate to severe disease uncontrollable with topical therapy. Traditional systemic therapy ­ oral PUVA, retinoids, cyclosporin and methotrexate ­ may induce organ specific toxicity and a significant number of patients are unresponsive, intolerant or have specific contraindications to its use. With the increased understanding of the pathogenesis of psoriasis, multiple biologic agents have been introduced. In the last years there has been an increased utilization of these agents and several studies were designed to evaluate their efficacy and safety. Currently, four biologics have been already approved by EMEA (European Medicines Agency) for the treatment of plaque psoriasis, 3 anti-TNFα (adalimumab, etanercept and infliximab) and one anti-IL12/23p40 (ustecinumab). In the present article we update the prior published guidelines (Trabalhos da SPDV 2010;68(1):47-68 and 2011;69(4):531-553) due to the recent progress in the knowledge and therapeutic options in these area. These recommendations should be used with caution and treatment should be tailored to meet individual patient's needs and each specific clinical situation.

Phaeohyphomycosis caused by Alternaria infectoria presenting as multiple vegetating lesions in a renal transplant patient

Las especies del género Alternaria son mohos ubicuos que se caracterizan por presentar colonias de color gris; parecen ser cada vez más frecuentes como agente causal de las feohifomicosis subcutáneas, en especial entre pacientes inmunocomprometidos. Un paciente de 53 años de edad, que se había sometido a un trasplante renal, consultó por presentar tumores verrugosos en el tercio distal de las extremidades. La histopatología y cultivo positivos, además de la secuenciación de la región de transcripción interna ITS del rDNA, permitieron la identificación del aislamiento fúngico como Alternaria infectoria. Se instauró tratamiento con itraconazol oral durante 10 meses y, a los 15 meses de seguimiento, se demostró la ausencia de signos de infección. Las manifestaciones clínicas de la alternariosis cutánea son muy variables y tan sólo se han descrito unos pocos casos en los que se presenta en forma de tumoraciones verrugosas. Aunque el tratamiento de elección sigue siendo motivo de controversia, el paciente presentado en este estudio fue tratado satisfactoriamente con itraconazol(AU)

The genus Alternaria is one of the most common black moulds and appears to be increasing as a causative agent of subcutaneous phaeohyphomycosis, particularly among immunosuppressed patients. A 53-year-old patient who had received a kidney transplant presented with multiple verrucous lesions on the distal extremities. Positive histopathology and cultures, in addition to rDNA ITS region sequencing, identified the fungal isolate as Alternaria infectoria. Oral itraconazole was administered for 10 months. A follow-up at 15 months demonstrated no signs of infection. Clinical manifestations of cutaneous alternariosis vary significantly and only a few cases have been described in the literature. Although optimal treatment options remain controversial, this case of phaeohyphomycosis was successfully treated with itraconazole monotherapy(AU)

Intertriginous pattern of toxic erythema of chemotherapy.

Chemotherapeutic agents may induce both local and systemic cutaneous toxicity, and evaluation of these reactions in oncologic patients constitutes a real challenge. The authors describe a 78-year-old Caucasian woman, with a past medical history relevant for right radical mastectomy with axillary dissection because of stage 2 breast invasive ductal carcinoma (T2N3M0), referred to our department because of an intertriginous eruption in her groin. Two weeks before the eruption, a chemotherapy regime with cyclophosphamide, methotrexate, and 5-fluorouracil was performed. Examination revealed erythematous and dusky violaceous papules coalescing into edematous patches in the inguinal intertriginous area, including the internal surface of her thighs, groin, genital area, and intergluteal cleft. Skin cultures for bacteria and fungus were negative. Clinical and histological data were consistent with an intertriginous pattern of toxic erythema of chemotherapy (TEC). Oral prednisolone therapy (0.5 mg/kg) was started, tapered over a 1-week period, and along with general measures that included topical zinc oxide suspension, cutaneous lesions cleared completely within the first days. Although patient reassurance, she refused any kind of new chemotherapy infusions. Due to their high metabolic rate, the skin, mucous membranes, and annexes are one of the most important target organs of the toxicity associated with systemic chemotherapy. Several patterns of cutaneous eruptions to chemotherapy have been reported in the literature. Trying to resolve this issue, recently recommended was a new clinically descriptive term, TEC, in order to emphasize the overlapping features of these entities. Early recognition of this entity is critical, not just from a prognostic standpoint, but also to avoid unnecessary, potentially harmful therapeutic interventions.