Oral Methotrexate Treatment of Delayed-Onset Inflammatory Reactions to Dermal Fillers.

Background: In aesthetic practice, delayed-onset (late) inflammatory reactions (DIRs) to dermal fillers are encountered. The treatment of DIRs can be challenging, with a response to established therapies, including oral antibiotics, intralesional and oral steroids, and hyaluronidase injection, occasionally reported as unsatisfactory. Objectives: Evaluate the efficacy of low-dose oral methotrexate (MTX) therapy in treating recalcitrant DIRs. Methods: We retrospectively reviewed cases of recalcitrant DIRs treated with oral MTX. Data collected included individuals' gender and age, medical history, filler type, facial area(s) injected, previous treatments attempted to dissolve the DIR, MTX treatment dosage and duration, and outcome. Adverse events were monitored throughout the treatment. Results: Thirteen females with a mean age of 52.6 years (range, 31-67 years) who developed recalcitrant DIRs to dermal filler injection are included. Eight reactions were triggered by the injection of hyaluronic acid (HA) fillers, 4 by liquid injectable silicone (LIS), and 1 by polymethylmethacrylate (PMMA). The average starting dosage of MTX was 12.1 mg/week (range, 7.5-12.5 mg/week). Patients were treated for 2 to 3 months in most cases. The average follow-up post-MTX therapy was 11.8 months (range, 2-36 months). A complete response to MTX treatment was observed in 10 patients (6 HA and 4 LIS cases), partial response in 1 (HA case), and an unsatisfactory response in 2 (HA and PMMA cases). Treatment was well tolerated. Conclusions: A short course of low-dose oral MTX is a possible treatment for DIRs that have not responded to established therapies. The promising results of this report require validation by powered studies.

From Child to Old Man: A Slowly Evolving Case of Chromoblastomycosis Caused by Cladosporium cladosporioides.

Chromoblastomycosis is a chronic granulomatous mycosis of the skin and subcutaneous tissue caused by traumatic inoculation with dematiaceous fungi. This disease primarily affects agricultural workers, who are mostly men. We present a case of chromoblastomycosis in a 63-year-old male farmer patient with dermatosis over 50 years of evolution, with warty, erythematous, and scaly plaques that predominate on the left hemithorax. Direct examination with potassium hydroxide (KOH) revealed numerous fumagoid cells. Amplification and sequencing of the internal transcribed spacer (ITS) and translation elongation factor 1-alpha (TEF-1a) gene revealed that chromoblastomycosis was caused by Cladosporium cladosporioides. The chromoblastomycosis was treated with itraconazole and fluconazole without any improvement, and amphotericin B was administered with partial improvement.

A 5-year single-center study about onychomycosis with a focus on Aspergillus spp. in Albania.

BACKGROUND: Onychomycosis is a common nail infection caused by dermatophytes, nondermatophytes molds (NDM), and yeasts. The prevalence of Aspergillus spp. is increasing worldwide. This study aims to describe the epidemiological and microbiological features of onychomycosis, especially for Aspergillus spp. METHODS: This is a 5-year retrospective study of clinically suspected onychomycosis in one microbiological clinic in Albania. The mycological examination, which included direct microscopic examination of nail scrapings with 20% KOH and culture, was performed on 411 patients. After incubation, we studied the macroscopic characteristics of the colonies, size, shape, and color, and their microscopic examination. We evaluated positive cases for Aspergillus, all cases where Aspergillus was grown in the culture, the microscopy was positive, and the culture was negative for dermatophyte. RESULTS: Onychomycosis resulted positive in 267 patients (52.9% females vs. 47.1% males). A total of 62.2% resulted infected by dermatophytes, 29.6% by yeasts, and 8.2% by NDM. Onychomycosis resulted more frequent in the age group 15-64 years old (63%). Aspergillus spp. were found in 19 patients from 22 patients with NDM onychomycosis. Males (11 patients) and the age group 15-64 years old (14 patients) were more vulnerable to Aspergillus spp. A. niger, A. flavus, and A. terreus isolated from the nail cultures in our study. The culture resulted more superior to KOH examinations. CONCLUSIONS: Our study indicates that NDM, including Aspergillus spp., are still rare findings from fungal examinations. However, dermatologist's clinical suspicion and microbiologist's skills are mandatory in diagnosing and properly managing patients with Aspergillus spp.

Cyclin-Dependent Kinase 4/6 Inhibitors and Dermatologic Adverse Events: Results from the EADV Task Force "Dermatology for Cancer Patients" International Study.

BACKGROUND: The introduction of cyclin-dependent kinase inhibitors (CDK4/6i) was a great advance in therapeutics for patients with estrogen receptor+/human epidermal growth factor receptor (HER2) locally advanced and metastatic breast cancer. Despite the increasing use of these agents, their adverse drug-related events have not yet been fully characterized. We describe the spectrum of cutaneous adverse reactions occurring in advanced breast cancer patients treated with cyclin-dependent kinase inhibitors, analyzing types, severity, time to onset, and possible treatment outcomes. METHODS: We performed a multicentric retrospective study including patients with advanced breast cancer who developed cutaneous lesions during treatment with CDK4/6i in the period from June 2020 to June 2021. Patients > 18 years were recruited at eleven onco-dermatology units located in Albania (1), Argentina (1), France (1), Greece (3), Italy (3), and Spain (2). We evaluated patients' epidemiological and clinical characteristics, types of cutaneous adverse events, their time to onset, and treatment outcomes. The severity of the skin reactions was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 score. RESULTS: Seventy-nine patients (median age: 62.3 years; range 39-83 years) were included in the study, and, collectively, we recorded a total of 165 cutaneous adverse events during follow-up visits. The most frequent cutaneous reactions were pruritus (49/79 patients), alopecia (25/79), and eczematous lesions (24/79). Cutaneous toxicities were usually mild in severity (>65%) and occurred after a median of 6.5 months. Only four patients (5%) required treatment discontinuation due to the severity of the skin lesions. The majority of the skin reactions were managed with topical treatments. CONCLUSIONS: To the best of our knowledge, we present the largest case series of cutaneous adverse events developing in advanced breast cancer patients treated with CDK4/6i. We showed that cutaneous toxicities are usually mild in severity, and manageable with standard supportive care; however, in selected cases, they can lead to treatment discontinuation with possible implications for patients' clinical outcomes.

Pathogenesis and Clinical Relevance of Candida Biofilms in Vulvovaginal Candidiasis.

The ability of Candida spp. to form biofilms is crucial for its pathogenicity, and thus, it should be considered an important virulence factor in vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC). Its ability to generate biofilms is multifactorial and is generally believed to depend on the site of infection, species and strain involved, and the microenvironment in which the infection develops. Therefore, both cell surface proteins, such as Hwp1, Als1, and Als2, and the cell wall-related protein, Sun41, play a critical role in the adhesion and virulence of the biofilm. Immunological and pharmacological approaches have identified the NLRP3 inflammasome as a crucial molecular factor contributing to host immunopathology. In this context, we have earlier shown that Candida albicans associated with hyphae-secreted aspartyl proteinases (specifically SAP4-6) contribute to the immunopathology of the disease. Transcriptome profiling has revealed that non-coding transcripts regulate protein synthesis post-transcriptionally, which is important for the growth of Candida spp. Other studies have employed RNA sequencing to identify differences in the 1,245 Candida genes involved in surface and invasive cellular metabolism regulation. In vitro systems allow the simultaneous processing of a large number of samples, making them an ideal screening technique for estimating various physicochemical parameters, testing the activity of antimicrobial agents, and analyzing genes involved in biofilm formation and regulation (in situ) in specific strains. Murine VVC models are used to study C. albicans infection, especially in trials of novel treatments and to understand the cause(s) for resistance to conventional therapeutics. This review on the clinical relevance of Candida biofilms in VVC focuses on important advances in its genomics, transcriptomics, and proteomics. Moreover, recent experiments on the influence of biofilm formation on VVC or RVVC pathogenesis in laboratory animals have been discussed. A clear elucidation of one of the pathogenesis mechanisms employed by Candida biofilms in vulvovaginal candidiasis and its applications in clinical practice represents the most significant contribution of this manuscript.

Are military personnel at a more risk for skin cancers?

NMSC is the most common cancer in countries with a largely fair skin phenotype population and moderate sun exposure. Assessing risk factors in the military personnel. Comparing the risk factors in this occupational group to the general population. 200 active-duty military members and 1000 individuals (the control group) were randomly selected from the general population. We used transversal data collection through a questionnaire, filled in by all participants in the study based on self-report on general data, skin type, habits, lifestyle and inheritance risk for cutaneous cancer. Analyzing the connection between risk factors reported and incidence for NMSC and melanoma, the following factors resulted significant: The control group the age variable >50 yo and BMI ≥25 were significant. The study group (military personnel), among the variables statistically examined through Pearson's test resulted significant: age > 50 years old, fair skin phenotype, sunburn during childhood, familial history of cutaneous cancer, dark spots (>20) on the arm, and coffee consumption as a protective factor. Military personnel has more significant risk factors for developing cutaneous cancer compared to other population groups therefore, prevention and early detection strategies are needed.

Case report: SARS-CoV-2-induced urticaria or just a concomitance?

The association between urticaria and different virus infections has been reported in many studies. Different virus infections have been reported to be comorbidities of spontaneous urticaria. In this paper, we report the case of a male patient with acute urticaria 7 days after he left the hospital where he was treated for coronavirus disease 2019 (COVID-19). This infection may act as a causative or a facilitating factor for the initiation of acute urticaria and additional cofactors such as stress may contribute for the urticaria phenotype to be expressed. Additional facts for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) virus in future will clarify if urticarial rash is one of the COVID's multiple faces.

Therapeutic considerations and clinical characteristics of a sample of adolescent patients with acne vulgaris in Tirana, Albania: A cross-sectional study.

Acne vulgaris is a common adolescent disorder but the data related to acne vulgaris is insufficient in Albania. The aim of this study was to assess the epidemiologic features of acne vulgaris and to identify lifestyle and constitutional factors in formulating a proper management protocol. A cross-sectional study conducted on a representative sample of 2036 adolescents from 10 high schools located in Tirana. A self-administered questionnaire was administered to collect the data. The binary logistic regression was applied to assess the factors linked to the presence of acne vulgaris in adolescents. The mean age in the study population was 16.2 ± 0.9 years. The self-reported prevalence of acne was 50.3% (52.1% in females and 47.9% in males). Lifetime prevalence was 68.5%. The factors significantly associated with an increased likelihood over time were: frequent consumption of sweets, frequent endurance of stress, poor quality of sleep, positive family history of acne, oily and combination skin, menstrual disorders. Acne vulgaris is common among adolescents in our country. The identification of various modifiable factors related to acne generates opportunities to tailor and focus prevention efforts and better management and treatment planning in relevant high-risk groups.

A rare case of granulomatous Wegener with multiple pyoderma gangrenosum-like ulcers.

Wegener's granulomatosis, is a rare form of systemic vasculitis characterized by necrotic granulomas around the blood vessels. We report a case of a healthy 43-year-old man presented with multiple ulcerated lesions in head and all over the body, that has appeared spontaneously. It was characterized by a giant deep ulceration covered by thick purulent, in size from 3 to 4 cm, deep; sub febrile temperature, and minimal pain associated. Skin biopsies results pyoderma gangrenosum (PG)-like features: anti-neutrophil cytoplasmic antibody (cANCA) positive. Six months later, the patient developed dispea episodes. CT scan (CT) result with multiple focal opacities. He was diagnosed with wegener granulomatosis (WG) and was treated with corticosteroids and ciclophosphamide. Skin involvement in WG is not common and lesions in the skin vary from purpura, paniculitis to ulceration. In our case, skin elements are the first manifestations. Whether these elements are Wegener manifestation or we have coexistence of PG with WG, it remains a still uncertain question to answer. There is no histopathologic pathognomic elements for both. Skin involvement in WG with PG-like lesions have been rarely reported. In front of this type of widespread ulcerations, resistant to treatment we should be aware that one of the reasons may be a disease of autoimmune etiology such as WG.

Efficacy of biologic therapies in psoriasis vulgaris.

Psoriasis is a chronic, immune-mediated skin disease that also has systemic manifestations. Biologic preparates: Adalimumab, Etanercept, and Infliximab are licensed for psoriasis vulgaris treatment in Albania. To compare the efficacy of biologic therapies used for psoriasis based in our experience. A cohort prospective study during the years 2016-2018 at UHC "Mother Teresa" Tirana. In the study took place 78 patient diagnosed with psoriasis and treated with biologic therapies. Psoriasis Area Severity Index (PASI) 50 and PASI 75 index were the parameters of response outcomes. PASI 50 was achieved for 6.8, 7.02, and 7.2 weeks in patients with Etanercept, Adalimumab, and Infliximab respectively and PASI 75 for 12.8, 11.4, and 11.42 weeks. X2 = 0.076, p > .05, nonsignificant difference. PASI 50 was achieved in 27.2% of subject treated with Etanercept, 67.4% Adalimumab, and 55.5% with Infliximab for the weeks mentioned above. Meanwhile PASI 75 was achieved in 45.4% of subject treated with Etanercept, 61.7% Adalimumab, and 25% with Infliximab. X2 = 15.28, p < .05, significant difference. Biologics have revolutionized the treatment of psoriasis. To select the most appropriate agent for patient, should be considered multiple factors including adverse effects, tolerance, patient preference, cost, and mode of administration.

Oral lichen planus: therapy and phenotype.

BACKGROUND: Lichen planus (LP) is a mucocutaneous disease of chronic inflammatory nature. Although many therapeutic options are available, none are curative. The aim of this article was to describe a therapeutic algorithm that take into consideration the clinical futures of oral LP (OLP). METHODS: Patients affected by symptomatic OLP were enrolled into three groups to receive cyclosporine mouthwash, retinoic acid lotion 0.05%, and autologous platelet-rich plasma (PRP) gel in the treatment of reticular, plaque-like, and erosive-type respectively. The products were applied as follows: retinoic acid BID for 8 weeks, cyclosporine mouthwash OD for 8 weeks, PRP once a week for 8 weeks. Patients were assessed at 2, 4, 8, and 12 weeks. Improvement was evaluated as complete response, partial response and no response. RESULTS: A total of 20 Caucasian patients, 8 male and 12 female, mean age 56 years (range 40-74) concluded the study. Seven patients showed a complete response, 7 patients a partial response, and 6 patients no response. CONCLUSIONS: We propose a therapeutic algorithm that take into consideration the clinical features and symptoms of OLP. Long-term experience on larger series of cases are necessary to confirm our data.

Efficacy and safety of infliximab in psoriatic patients over the age of 65.

BACKGROUND: Clinical data on the long-term safety and efficacy of infliximab on psoriatic patients who are older than 65 years are limited. OBJECTIVES: The aim is to report the long-term efficacy, safety and tolerance of infliximab in geriatric patients. METHODS: This was a retrospective study conducted at the Department of Dermatology of the University of Rome Tor Vergata. Clinical data were reported at week 12, 52, 104, 208. RESULTS: 151 charts were evaluated. A total of 27 patients were included. Range of the age was between 65 and 85 years; mean age was 73 years ±5.4; female to male ratio was 1:2; mean age of onset of psoriasis was 43 years±17. The average of treatment duration was 39 months ±27 (range 1-100). Fourteen patients suffered from plaque type psoriasis and 13 from psoriatic arthritis. At the baseline the mean PASI score was 15.6 ± 10.2. At week 12, 52, 104, and 208 the mean PASI was 2, 2.3, 1.9 and 1.8 respectively. A reduction in the mean PASI was maintained in the long-term treatment in 12 patients (p < 0.001). CONCLUSION: Our data suggest that long-term treatment with infliximab is effective and safe in patients over 65 years old and that IV therapy is also associated with a high compliance.

Small molecules and antibodies for the treatment of psoriasis: a patent review (2010-2015).

INTRODUCTION: Psoriasis is a chronic condition whose therapeutic armamentarium is increasingly being discussed, particularly when compared to past decades. The use of biologic agents has profoundly changed the history of this disease, as well as the management of psoriatic patients. Due to the enormous interest in psoriasis, as demonstrated within the scientific community and pharmaceuticals, new therapeutic targets have been identified and novel patented therapeutics are being tested. AREAS COVERED: This review sought to give an overview of small molecules and antibodies patented in the last five years for the treatment of psoriasis. Therapeutic agents either in the early or advanced phase of development have been described, primarily based on a systematic search using the PubMed Medline database. EXPERT OPINION: Though the recent introduction of new antipsoriatic agents has facilitated the management of long-term psoriasis, there is still a strong desire for alternative therapeutic options. Indeed, there remain unmet needs regarding safety and efficacy of psoriasis treatment that should be addressed. In this context, recently patented drugs may prove valid, interesting, and promising within the therapeutic paradigm.

Serum Protein Profile Changes in Psoriatic Patients Undergoing Treatment With Infliximab.

UNLABELLED: The therapeutic paradigm in psoriasis includes antitumor necrosis alpha agents that have been proved effective and safe as long-term therapy. Recently, it has been described a correlation between the use of biologic agents and the occurrence of monoclonal gammopathies, which are haematological conditions characterized by clonal plasma cells proliferation producing a monoclonal immunoglobulin that accumulates in the blood. OBJECTIVE: The aim of this study is to detect electrophoretic abnormalities in psoriatic patients undergoing treatment with infliximab. RESEARCH DESIGN AND METHODS: A retrospective study evaluating all charts from the clinic database of all patients treated with infliximab. The evaluation of serum protein profile is routinely performed in the clinical setting during biologic therapies. We reported the occurrence MGUS in infliximab-treated patients. RESULTS: The study analysis included 141 charts. Overall, 23 patients showed a MGUS in their electrophoretic profile, though in 6 cases MGUS was detected at the baseline. Thereby, 17 cases (12.06% of the study population) developed MGUS during infliximab therapy. CONCLUSIONS: Serum protein electrophoresis test represents a useful tool to detect and monitor any potentially harmful condition that could occur during treatment with a biologic agent. Particularly, it could be crucial for the detection of MGUS, which does not affect clinical response, and it does not represent a criteria to withdraw the treatment.

Dermatomycosis frequency and localization sites.

INTRODUCTION: Since the prevalence of skin mycotic infections is changing and is area depended we aimed to analyze the frequency of the skin myocotic infections and the appearance sites. MATERIAL AND METHODS: There were involved 560 patients referred to the Dermatology Clinic of University Clinical Center of Kosova during a period of one year. RESULTS: The mean age of our study group was around thirties with a predominance of female and rural patients. Although most of cases presented with single site disease localization, we observed the increase in number of cases with more than one site localization with age. CONCLUSION: The increased prevalence skin mycotic infections, as well as more than one place of localization deserve a multidimensional approach.