Oral isotretinoin in the treatment of juvenile acne and psychiatric adverse effects - a systematic review.

PURPOSE: Acne vulgaris is a very prevalent dermatological condition, especially among adolescents and young adults up to 25 years old, classifying it as juvenile acne. One of the most effective treatments for severe acne is isotretinoin, a derivative of retinoic acid. Despite its high efficacy, this drug has been linked to several side effects including psychiatric adverse alterations, such as anxiety, depression and even suicide. With this systematic review we aim to determine if it is possible to establish a causal relation between oral isotretinoin in the treatment of juvenile acne and the appearance of psychiatric adverse effects. MATERIALS AND METHODS: We searched two distinct databases, PubMed and Web of Science, and considered the work published between January 2000 and November 2021. RESULTS: Out of the 599 identified articles, we included 19 studies in this systematic review. Globally, the results we found do not support an association between the use of isotretinoin for acne treatment and mental side effects and the safety of this drug appears to be assured. However, the individual characteristics of each adolescent and their environment should be considered; the personal and family history of mental disorders are pointed out as red flags we should look out for when treating these patients. CONCLUSION: Despite this being a highly debated topic, especially among the dermatology community, more studies with larger populations and randomised controlled trials are necessary to increase the strength of the evidence presented.

Systematic review - alopecia areata and tofacitinib in paediatric patients.

INTRODUCTION: Alopecia Areata is a nonscarring hair loss disorder and is the most common hair loss cause in children. It is a chronic autoimmune disorder with a severe psychological impact in patients' lives. JAK inhibitors, in particular Tofacitinib, have been having promising results on Alopecia Areata Treatment. In this study we aimed to do a Systematic Review on the role of Tofacitinib (either orally or topically), considering efficacy and safety, in treating children with Alopecia Areata. MATERIALS AND METHODS: PubMed, Cochrane and Web of Science databases were searched (up to 1st of September of 2021) looking for Tofacitinib (all text/all fields) and MeSH/Keyword term Alopecia Areata. RESULTS AND CONCLUSIONS: We included 14 studies and 64 cases in the Systematic Review. From these, 12 were considering systemic administration (47 patients) and two were considering topical administration (17 patients). Responsiveness was as high as 81.3%. The responsiveness was similar among different genders (78.6% in males and 80.0% in females) and either whether administration was topic (70.6% responsiveness) or systemic (85.1% responsiveness). Adverse effects were rare and, when present, were mild. Studies shows promising results in what considers the efficacy and safety of Tofacitinib in the treatment of Alopecia Areata. As the available evidence to date is of low quality, further randomised studies are required to confirm these findings.

Cutaneous Richter Syndrome mimicking a lower limb cellulitis infection - a case report and review of the literature.

Richter syndrome (RS) is characterized by the development of a high-grade lymphoma in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Herein, we present the case of an 85-year-old woman with a 3-year history of stable asymptomatic CLL that developed a cutaneous RS. The patient presented with painless inflammation in the left leg and foot that was initially diagnosed as a cellulitis infection. She was treated accordingly with ceftriaxone and clindamycin. However, after completing the antibiotic regimen, not only did the inflammation persist, but also superimposed painless nodules gradually appeared on the left leg and foot over the course of four months. The histopathological examination of the nodules revealed a large B-cell cutaneous lymphoma. The patient underwent chemotherapy with CVP, followed by R-CHOP, resulting in a reduction of size of the nodules and remission of the inflammation. The patient died five months after the diagnosis owing to a bacterial pneumonia. We identified in previous reports a total of fifteen cases of cutaneous RS. Most cases presented with rapidly growing tumors or multiple erythematous nodules, similar to our case. This case of a cutaneous RS mimicking a cellulitis infection underlines the importance of a low threshold for performing biopsies of suspicious skin lesions in patients with CLL/SLL.

Tildrakizumab for the treatment of moderate-to-severe psoriasis: a 52-week, real-world Portuguese multicentric study.

Background: Real-world evidence plays a pivotal role in validating the efficacy of biologic drugs beyond the controlled environment of randomized trials. This study aimed to evaluate the effectiveness of tildrakizumab in treating moderate-to-severe psoriasis within a real-world setting over a 52-week period in Portugal. Methods: This multicentric, prospective, observational study included adult patients with moderate-to-severe psoriasis. All participants received tildrakizumab 100 mg at weeks 0 and 4, followed by a maintenance dose every 12 weeks, and were monitored for 52 weeks. Primary endpoints were determined based on Psoriasis Area and Severity Index (PASI) assessments at baseline, 16 (±2) weeks, 28 (±2) weeks and 52 (±2) weeks. Results: A total of 54 patients were enrolled in the study (56% men, mean age of 50.3 ± 14.4 years). Half of the sample (n=27) had no prior experience with biologic treatments. About 74% of patients (n=40) presented at least one comorbidity during the study, with psoriatic arthritis being the most prevalent (29.6%). By week 52, there was a significant decrease in the mean PASI from 17.8±10.3 at baseline to 1.3±1.9 (p<0.001), indicating an overall improvement of 93%. By week 52, more than 85% of patients attained PASI ≤5, more than 80% reached PASI ≤3, and nearly 60% achieved PASI ≤1. Infections were observed in 9.3% of patients, and one patient required hospitalization (1.9%). The cumulative proportion of patients continuing treatment at 52 weeks was 88.9%. Conclusions: This study demonstrates that tildrakizumab is an effective and safe agent for the treatment of moderate-to-severe psoriasis in a diverse, real-world setting.

Influence of Clinical and Psychosocial Factors on the Adherence to Topical Treatment in Psoriasis.

(1) Background: Psoriasis is a common chronic inflammatory skin disease with different manifestations, affecting the quality of life at social, emotional, and professional dimensions and requiring long-term treatment. This study aimed to investigate the effect of psychosocial and clinical factors on adherence to topical treatment in psoriasis. (2) Methods: Self-reported measures and weighing the medicines were used to assess adherence. Psychopathological symptoms were measured using the Brief Symptoms Inventory (BSI). Social and clinical factors were assessed by a sociodemographic and clinical questionnaire. Adherence to treatment with topical medication was assessed using a sample of 102 psoriasis patients. (3) Results: The explanatory models of adherence to topical treatment in psoriasis translated into positive associations between adherence and the education level (higher education) (p = 0.03; φ = 0.23), the single-family household (p = 0.01; φ = 0.44), active employment status (p = 0.05; φ = -0.19), familiar history of psoriasis (p = 0.04; φ = -0.21), and the presence of obsessive-compulsive symptoms (p = 0.01; d = 0.29). (4) Conclusions: In patients who present the characteristics identified that influence non-adherence, instructions should be reinforced to increase adherence. The experimental mortality (39.6%) reduced the sample size, representing a limitation of the study.

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.

Catechol-O-methyltransferase activity in psoriasis patients treated with psoralen plus ultraviolet A therapy.

BACKGROUND: Catechol-O-methyltransferase (COMT) activity is increased in patients with mild/moderate psoriasis. Narrowband ultraviolet B (nbUVB) phototherapy decreases COMT activity. However, the effect of psoralen plus ultraviolet A (PUVA) on this enzyme activity is unknown, and it remains to be clarified if the nbUVB-induced effect in COMT activity is related to clinical response. The aim of this study is to evaluate COMT activity in moderate/severe psoriasis and assess whether PUVA therapy modifies this activity. METHODS: An observational study was conducted on 18 patients with moderate/severe psoriasis and 13 matched controls. Patients were treated with PUVA twice weekly during 6 weeks, and they were evaluated for Psoriasis Area and Severity Index (PASI) and COMT activity before photochemotherapy, at the end of it and 4 weeks after stopping. RESULTS: Before PUVA therapy, S(soluble)-COMT activity was significantly (P < 0.05) higher in psoriasis patients than in controls. After photochemotherapy, no significant differences were found in S-COMT activity at all end points. Photochemotherapy significantly decreased PASI but COMT activity values remained higher than those of control population. CONCLUSION: Psoriasis patients with moderate/severe disease present higher S-COMT activity than controls. Although a good clinical response was observed, PUVA therapy does not change S-COMT activity. This differential COMT effect of PUVA and nbUVB suggests a wavelength-specific regulation.

Efficacy of topical vitamin C in melasma and photoaging: A systematic review.

BACKGROUND: Vitamin C is a micronutrient present in high concentrations in normal skin and a highly prescribed cosmeceutical, well known for protecting against ultraviolet-induced pigmentation and regulating collagen production. However, there is a lack of studies evaluating the efficacy of topical vitamin C in photoaging and melasma, with this systematic review being the first to assess the existing evidence. AIM: This systematic review aims to assess whether topical vitamin C could be effective in reversing photoaging signs and treating melasma. METHODS: Prospective, randomized controlled trials assessing protocols with topically applied vitamin C in patients with melasma or photodamage were searched in Medline, CENTRAL, and Scopus databases until the 12th of May 2022. Risk of bias was conducted in accordance with Cochrane Collaboration's tool for assessing the risk of bias in randomized trials, using RevMan 5.0. RESULTS: Seven publications were included, with 139 volunteers in total. Studies that evaluated the topography of skin indicated that the treated skin appeared smoother and less wrinkled, which was supported by biopsies data. On objective assessments of pigmentation, there was a significant lightening of the skin treated. Hydration improved equally in the vitamin C and placebo-treated sites. CONCLUSIONS: This study revealed that vitamin C is effective in treating uneven, wrinkled skin and has depigmenting properties, but long-term use may be needed to achieve noticeable changes. Q-switched Nd:YAG laser-associated protocols appear beneficial in enhancing vitamin C effects. Topical vitamin C may be a suitable alternative for melasma and photoaging, but more studies are needed to confirm these results and assess the ideal vitamin C concentration.

Metastatic hidradenocarcinoma: a report of two rare cases.

BACKGROUND: Hidradenocarcinoma is a rare malignant sweat gland tumour, characterized by a slow but aggressive course, with high rates of local recurrence and metastasis. Due to its rarity, histological criteria and therapeutic guidelines are poorly defined, posing a major challenge for clinicians and pathologists. OBJECTIVES: To present two new cases of metastatic hidradenocarcinoma as well as a review of the literature. MATERIALS & METHODS: We describe two case studies and a review of the literature based on a search using the MEDLINE (PubMed) electronic database. RESULTS: The first patient was a 61-year-old woman with a perimamillary hidradenocarcinoma that arose from the malignant transformation of a benign childhood lesion and developed regional lymph node metastases after wide excision and adjuvant radiotherapy. The second patient was a 63-year-old man who developed cutaneous and renal metastases several years after the complete excision of a lumbar hidradenocarcinoma. As far as we can ascertain, kidney metastasis from hidradenocarcinoma has not previously been described. CONCLUSION: Most authors recommend wide excision as the treatment of choice for hidradenocarcinoma, however, optimal adjuvant therapy remains to be determined. Our cases add to the limited knowledge available, but high-quality studies to find new effective treatments are needed.

Skin disorders in the neonatal intensive care unit of a central hospital.

Cutaneous abnormalities in the newborn are usually benign and transitory. However, they may sometimes be extremely distressing both for parents and the medical staff, presenting with significant morbidity and mortality. The aim of this study was to access the clinical features of different skin disorders in a series of newborns, at a level III neonatal intensive care unit (NICU) in the Northern Region of Portugal, and review some of the most impressive cases. Between January 1997 and December 2010, 27 patients were found to have an important cutaneous condition that required admission to the NICU. The most frequent presentations were vesicles and pustules (n=8; 29.6%), followed by erythroderma (n=7; 25.9%), atrophic (n=5; 18.5%) and vascular lesions (n=4; 14.8%). Four (14.8%) patients died in the neonatal period, and further 4 afterwards. Genetic studies, when available, revealed three chromosomal disorders and 6 gene mutations. Overall, skin disorders were not a leading cause of NICU admission (0.43%), but were associated with significant morbidity and mortality.

Ultraviolet B radiation differentially modifies catechol-O-methyltransferase activity in keratinocytes and melanoma cells.

BACKGROUND: Catechol-O-methyltransferase (COMT) is a ubiquitous enzyme inactivating catecholic compounds. COMT is expressed also in human skin samples, and in melanoma cells it may be cytoprotective. A role of COMT in keratinocytes (HaCat) is unknown. OBJECTIVE: The objective of this study is: to investigate whether ultraviolet-B (UVB) radiation modifies COMT activity in melanocytes and HaCat and whether COMT inhibition plays a role in UVB-induced cell death. METHODS: Human cell lines of melanotic melanoma (SK-mel-1) and HaCat were used. COMT activity was evaluated under basal conditions and after UVB irradiation (311 nm) at a low (8 mJ/cm(2)) and a high dose (60 mJ/cm(2)). Tolcapone 1 µM was used to inhibit COMT. RESULTS: Both SK-mel-1 and Ha-Cat cells express COMT activity. In SK-mel-1, COMT activity is reduced nearly 50% both 24 h and 48 h after a high dose UVB. In Ha-Cat cells, COMT activity increased 24 h after a high dose UVB but decreased at 48 h. Tolcapone increases significantly the cytotoxic effect of high dose UVB irradiation only in HaCat. High concentrations of tolcapone reduced melanin levels in melanoma cells parallel to reduced cell numbers. CONCLUSIONS: Ultraviolet radiation differentially modifies COMT activity in melanoma cells and HaCat. Furthermore, tolcapone increased death of HaCat after irradiation but did not affect melanoma cells.

Aseptic Pustulosis of the Folds Successfully Treated with Methotrexate.

An otherwise healthy 47-year-old woman presented with confluent pustular lesions on the scalp for 5 months and asymptomatic pustular lesions on the trunk and extremities for 2 weeks. She did not have systemic clinical manifestations and was treated with oral antifungals and antibiotics (amoxicillin, and clavulanic acid and flucloxacillin), with no effect. The lesions were unrelated to her menstrual cycle, and she had no history of dermatosis, including acne, psoriasis, or folliculitis. (SKINmed. 2022;20:466-468).

Influence of psoriasis lesions' location and severity on psychosocial disability and psychopathology. Observational study and psychometric validation of the SAPASI Portuguese version.

OBJECTIVES: The psychosocial impact of psoriasis is well documented. However, the contributing role of clinical disease characteristics is not satisfactorily explored. This study aimed to validate the Self-administered Psoriasis Area and Severity Index (SAPASI) to a Portuguese population (SAPASI-PT) and to perform its cross-validation, assessing how the results will generalize to an independent data set, with the Psoriasis Area and Severity Index (PASI), in order to assess the influence of psoriasis' severity on psychosocial disability and psychopathology. METHODS: A cross-sectional study with 228 patients with psoriasis was carried out. Data was collected through a sociodemographic and clinical questionnaire, SAPASI-PT, the Psoriasis Disability Index (PDI) and the Brief Symptoms Inventory (BSI). The cultural and linguistic adaptation of SAPASI to a Portuguese version and the cross validation with PASI was carried out. Multiple associations between psychosocial disability, psychopathology and severity, discomfort and location of lesions were investigated through logistic regression models. RESULTS: A good adjustment model for SAPASI-PT is found. Also, associations between psychosocial disability, psychopathology and the psoriasis severity and discomfort are found. The existence of lesions is positively associated with the severity of the disease. Patients with lesions in hands or genitals are those reporting a greater discomfort. The presence of lesions in hands is positively associated with PDI, i.e., with leisure and with treatment, marginally. Additionally, patients scoring higher in the personal dimension are found to have a significantly greater percentage of lesions in the genitals. CONCLUSIONS: The psoriasis severity and location of lesions are important determinants of patients´ quality of life. Lesions on face, hands and genitals are associated with a higher impact on psychosocial wellbeing of patients. Psychological counselling should be considered within psoriasis treatment context in patients with the described disease manifestations.

Efficacy and safety of propranolol in the treatment of parotid hemangioma.

A 2-month-old female patient presented an extensive bilateral parotid hemangioma (PH) focally ulcerated. Additionally, hepatic ultrasonography revealed a hemangioendothelioma located at right lobe. She was treated with oral prednisolone (3 mg/kg/day) during 10 months with clinical improvement of PH, despite failure to thrive and arterial hypertension. However, regrowth of the lesion occurred after discontinuation of oral steroid. Propranolol hydrochloride (2 mg/kg/day divided into two doses) was then started and maintained for 16 months, with marked involution of the hemangioma and with no systemic side effects during treatment course. Curiously, also the liver hemangioendothelioma completely resolved after starting propranolol. PH is a threatening cervicofacial segmental hemangioma that frequently proliferates after the year of age and needs long-term treatment. On the other hand, hepatic hemangioendotheliomas may be associated with cutaneous hemangiomas in some patients and their natural history is similar to these, although patients may die of associated conditions. As for other infantile hemangiomas, propranolol proved to be an effective, safe, and well-tolerated treatment for PH. Its role in liver hemangiomas and hemangioendotheliomas should also be taken into account.

Does the Vehicle Matter? Real-World Evidence on Adherence to Topical Treatment in Psoriasis.

The influence of the vehicle in topical treatment adherence remains to be elucidated. The aim of this study is to analyze the influence of the pharmaceutical dosage form on adherence to topical treatment in psoriasis patients, taking into consideration the mechanical features. The adherence was evaluated in a sample of 102 psoriasis patients, followed for approximately 45 days. Adherence was calculated with a new combined methodology using a log and medication weights. The effect of the group formulation was evaluated using logistic regression models. A complex effect of the vehicle on adherence was found, mediated by the affected area. The adherence was significantly higher for patients applying gels and creams than for those using ointments, whenever the body area affected was extensive. The opposite was found when the affected area was small. Mechanical properties can partially explain the findings since gels and creams may be easier to apply. Patient beliefs and preferences regarding vehicles and their sensory attributes might also explain the results. It is noteworthy that adherence was strikingly low, with more than 75% non-adherent patients. This real-world evidence provides an insight for pharmaceutical industries and guidance for treatment prescription by physicians aiming to address the public health emergency of treatment non-adherence.

A multidisciplinary approach in psoriatic disease: the different models of dermatology-rheumatology collaborations in Portugal.

Psoriatic disease (Psoriasis and Psoriatic Arthritis, PsD) is a condition that affects the skin, the musculoskeletal system, and beyond, impairing patients' quality of life. A multidisciplinary approach of combined dermatology-rheumatology clinics is recommended and valuable to respond to PsD diagnosis, management, and treatment challenges. In Portugal, five Hospitals have implemented a multidisciplinary clinic for PsD assessment. This report aims to describe how these multidisciplinary clinics were developed, their characteristics, and the main obstacles to their implementation. Although the different hospitals adopted distinct functional models, a consensus respecting the minimal core set assessment for PsD in Multidisciplinary Dermatology/Rheumatology Clinics should comprise all disease manifestations and, if possible, quality of life. The main objective of these clinics is to achieve remission/minimal disease activity. Limitations to these multidisciplinary approaches are discussed, namely financial, time management, and human resources obstacles that can be a handicap in their implementation, despite the benefits of PsD integrated care.

Mechanism of action and clinical benefits of colloidal oatmeal for dermatologic practice.

Colloidal oatmeal has a long history of beneficial use in dermatology. It is a natural product that has an excellent safety record and has demonstrated efficacy for the treatment of atopic dermatitis, psoriasis, drug-induced rash and other conditions. In recent years, in vitro and in vivo studies have begun to elucidate the multiple mechanisms of action of naturally derived colloidal oatmeal. Evidence now describes its molecular mechanisms of anti-inflammatory and antihistaminic activity. The avenanthramides, a recently described component of whole oat grain, are responsible for many of these effects. Studies have demonstrated that avenanthramides can inhibit the activity of nuclear factor kappaB and the release of proinflammatory cytokines and histamine, well known key mechanisms in the pathophysiology of inflammatory dermatoses. Topical formulations of natural colloidal oatmeal should be considered an important component of therapy for atopic dermatitis and other conditions and may allow for reduced use of corticosteroids and calcineurin inhibitors.

Incontinentia Pigmenti with vesicular stage in utero.

Incontinentia pigmenti (IP) is a genodermatosis with a characteristic evolution of skin lesions. Most patients present with vesicles at birth or within the first weeks of life. We report a case of a female infant with genetically confirmed sporadic IP who presented with verrucous and hyperpigmented lesions with no previous vesicular stage.

Mycobacterium marinum skin infection with tenosynovitis successfully treated with doxycycline.

Skin infection with Mycobacterium marinum can rarely spread to deeper structures, making it more difficult to treat. We report a case of a M. marinum skin infection and hand tenosynovitis that showed a good response to monotherapy with doxycycline in spite of severe hand movement impairment.