The measurement performance of the EQ-5D-5L versus EQ-5D-3L in patients with hidradenitis suppurativa.

PURPOSE: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects up to 1% of the population in Europe. The EQ-5D is the most commonly used generic instrument for measuring health-related quality of life among HS patients. This study aims to compare the measurement properties of the two adult versions of EQ-5D (EQ-5D-3L and EQ-5D-5L) in patients with HS. METHODS: We recruited 200 consecutive patients with HS (mean age 37 years, 38% severe or very severe HS) to participate in a multicentre cross-sectional survey. Patients completed the EQ-5D-3L, EQ-5D-5L, Dermatology Life Quality Index (DLQI) and Skindex-16 questionnaires. RESULTS: More than twice as many different health state profiles occurred in the EQ-5D-5L compared to the EQ-5D-3L (101 vs. 43). A significant reduction in ceiling effect was found for the mobility, self-care and usual activities dimensions. A good agreement was established between the EQ-5D-3L and EQ-5D-5L with an intraclass correlation coefficient of 0.872 (95% CI 0.830-0.903; p < 0.001) that was confirmed by a Bland-Altman plot. EQ-5D-5L improved both the absolute and relative informativity in all dimensions except for anxiety/depression. EQ-5D-3L and EQ-5D-5L demonstrated similar convergent validity with DLQI and Skindex-16. EQ-5D-5L was able to better discriminate between known groups of patients based on the number of comorbidities and disease severity (HS-Physician's Global Assessment). CONCLUSION: In patients with HS, the EQ-5D-5L outperformed the EQ-5D-3L in feasibility, ceiling effects, informativity and known-groups validity for many important clinical characteristics. We recommend using the EQ-5D-5L in HS patients across various settings, including clinical care, research and economic evaluations.

Visualization of Keratin with Diffuse Reflectance and Autofluorescence Imaging and Nonlinear Optical Microscopy in a Rare Keratinopathic Ichthyosis.

Keratins are one of the main fluorophores of the skin. Keratinization disorders can lead to alterations in the optical properties of the skin. We set out to investigate a rare form of keratinopathic ichthyosis caused by KRT1 mutation with two different optical imaging methods. We used a newly developed light emitting diode (LED) based device to analyze autofluorescence signal at 405 nm excitation and diffuse reflectance at 526 nm in vivo. Mean autofluorescence intensity of the hyperkeratotic palmar skin was markedly higher in comparison to the healthy control (162.35 vs. 51.14). To further assess the skin status, we examined samples from affected skin areas ex vivo by nonlinear optical microscopy. Two-photon excited fluorescence and second-harmonic generation can visualize epidermal keratin and dermal collagen, respectively. We were able to visualize the structure of the epidermis and other skin changes caused by abnormal keratin formation. Taken together, we were able to show that such imaging modalities are useful for the diagnosis and follow-up of keratinopathic diseases.

Psoriasis and Gut Microbiome-Current State of Art.

Psoriasis is a chronic, immune-mediated inflammatory disease that affects around 125 million people worldwide. Several studies concerning the gut microbiota composition and its role in disease pathogenesis recently demonstrated significant alterations among psoriatic patients. Certain parameters such as Firmicutes/Bacteroidetes ratio or Psoriasis Microbiome Index were developed in order to distinguish between psoriatic and healthy individuals. The "leaky gut syndrome" and bacterial translocation is considered by some authors as a triggering factor for the onset of the disease, as it promotes chronic systemic inflammation. The alterations were also found to resemble those in inflammatory bowel diseases, obesity and certain cardiovascular diseases. Microbiota dysbiosis, depletion in SCFAs production, increased amount of produced TMAO, dysregulation of the pathways affecting the balance between lymphocytes populations seem to be the most significant findings concerning gut physiology in psoriatic patients. The gut microbiota may serve as a potential response-to-treatment biomarker in certain cases of biological treatment. Oral probiotics administration as well as fecal microbial transplantation were most reported in bringing health benefits to psoriatic patients. However, the issue of psoriatic bacterial gut composition, its role and healing potential needs further investigation. Here we reviewed the literature on the current state of the relationship between psoriasis and gut microbiome.

Altered Glycosylation of Human Alpha-1-Acid Glycoprotein as a Biomarker for Malignant Melanoma.

A high-resolution HILIC-MS/MS method was developed to analyze anthranilic acid derivatives of N-glycans released from human serum alpha-1-acid glycoprotein (AGP). The method was applied to samples obtained from 18 patients suffering from high-risk malignant melanoma as well as 19 healthy individuals. It enabled the identification of 102 glycan isomers separating isomers that differ only in sialic acid linkage (α-2,3, α-2,6) or in fucose positions (core, antenna). Comparative assessment of the samples revealed that upregulation of certain fucosylated glycans and downregulation of their nonfucosylated counterparts occurred in cancer patients. An increased ratio of isomers with more α-2,6-linked sialic acids was also observed. Linear discriminant analysis (LDA) combining 10 variables with the highest discriminatory power was employed to categorize the samples based on their glycosylation pattern. The performance of the method was tested by cross-validation, resulting in an overall classification success rate of 96.7%. The approach presented here is significantly superior to serological marker S100B protein in terms of sensitivity and negative predictive power in the population studied. Therefore, it may effectively support the diagnosis of malignant melanoma as a biomarker.

Dermatologic aspects of bed bug epidemic: an atlas of differential diagnosis.

Bed bug infestation rate has gone through an unforeseen increase in the past decades worldwide. Their resurgence is a consequence of numerous factors, including growing population density, increased international travel and the spread of insecticide resistance. Bed bug infestation is often revealed by skin symptoms appearing after their bite in sensitive patients. Medical professionals encountering patients with bed bug bites have responsibility for recognizing the condition and for instructing patients about the necessary measures for eradication. Setting the correct diagnosis, however, is not unequivocal as several skin diseases with autoimmune, immune-mediated aetiology or other arthropod stings and bites may present with similar symptoms. In this review we provide a differential diagnostic guide and an atlas of clinical pictures assigned to the diagnoses. We highlight those dermatological findings where the possibility of bed bug bite arises and identify key elements that help in the differentiation so as to avoid unnecessary diagnostic tests and force early start of extermination.

Emergency dermatology: Three-month experience from an Italian academic outpatient clinic during lockdown for COVID-19 pandemic.

Dermatology is a field of medicine where urgent cases occur commonly. However, access to specialized emergency dermatology services is very limited. Following the declaration of the COVID-19 pandemic, the cessation of all elective dermatology visits was widely urged. Accordingly, in Italy, a country severely affected by the pandemic, various measures were applied and the care at university clinics was limited to urgent cases. Here we retrospectively analyzed data of patients who presented at an Italian academic outpatient clinic reserved only for emergency cases. In total, 252 patients (109 males and 143 females) with a mean age of 55.25 ± 20.99 years were cared for at our clinic during a three-month period. We classified 10 patients (4%) as real emergency cases. Pityriasis rosea was diagnosed in three patients. Many patients sought care for skin cancer screening. In 131 patients (52%) dermoscopic skin examinations were performed. In 39 patients (15%), actinic keratosis or nonmelanoma skin cancer was detected, while melanoma was diagnosed in three patients, two of which were proven later as in situ melanoma. About 111 patients (44%) visited our clinic for other, nonurgent skin diseases. Our results imply that many patients felt that their skin problems required immediate attention, even if this could not be justified. Melanoma care may be considered an emergency care for its highly malignant potential and the possibility of rapid spreading. Adequately taken photos with a dermoscope may be readily read without the presence of specialist in the emergency room to prevent unnecessary delay in diagnosing oncologic skin diseases.

Nonlinear optical microscopy is a novel tool for the analysis of cutaneous alterations in pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE, OMIM 264800) is a rare autosomal recessive disorder with ectopic mineralization and fragmentation of elastin fibers. It is caused by mutations of the ABCC6 gene that leads to decreased serum levels of inorganic pyrophosphate (PPi) anti-mineralization factor. The occurrence of severe complications among PXE patients highlights the importance of early diagnosis so that prompt multidisciplinary care can be provided to patients. We aimed to examine dermal connective tissue with nonlinear optical (NLO) techniques, as collagen emits second-harmonic generation (SHG) signal, while elastin can be excited by two-photon excitation fluorescence (TPF). We performed molecular genetic analysis, ophthalmological and cardiovascular assessment, plasma PPi measurement, conventional histopathological examination, and ex vivo SHG and TPF imaging in five patients with PXE and five age- and gender-matched healthy controls. Pathological mutations including one new variant were found in the ABCC6 gene in all PXE patients and their plasma PPi level was significantly lower compared with controls. Degradation and mineralization of elastin fibers and extensive calcium deposition in the mid-dermis was visualized and quantified together with the alterations of the collagen structure in PXE. Our data suggests that NLO provides high-resolution imaging of the specific histopathological features of PXE-affected skin. In vivo NLO may be a promising tool in the assessment of PXE, promoting early diagnosis and follow-up.

Efficiency of long-term high-dose intravenous ascorbic acid therapy in locally advanced basal cell carcinoma - a pilot study.

INTRODUCTION: The anti-cancer properties of high-dose intravenous ascorbic acid have been demonstrated in various malignancies. In our recent study, we tested topically applied ascorbic acid to treat basal cell carcinoma (BCC), and achieved a good clinical response. AIM: Based on these results, we decided to examine the efficacy and tolerability of high-dose intravenous ascorbic acid (IVA) for locally advanced BCC. MATERIAL AND METHODS: In this pilot study, patients diagnosed with locally advanced BCC who were not amenable to radiation, surgical or local therapy (no other treatment option was available at the time) received intravenous ascorbic acid (1-1.8 g/kg), in an outpatient setting, 1-3 times per week for a mean duration of 42 ±23.6 weeks. This therapy was generally well tolerated. RESULTS: Among 4 patients who had a total of 165 (mean: 41 ±51, range: 1-114) skin lesions, 3 patients achieved stable disease and one had progressive disease. There was substantial variability in individual tumor response to therapy. With the aid of two-photon microscopy and second harmonic generation imaging techniques, alterations in collagen structure were observed between tumor nests during IVA therapy. CONCLUSIONS: Our results suggest that IVA is well tolerated in a small group of patients with extensive BCCs. However, in the era of smoothened (Smo) receptor inhibitors, it may only be considered as an adjuvant therapy in treatment-resistant cases.

Nonmelanoma skin cancer associated with Hydroxyurea treatment: Overview of the literature and our own experience.

Nonmelanoma skin cancer is the most common malignant tumor in the fair skin population, with each year several millions of diagnosed cases. Their most common risk factors are fair skin, a history of excessive ultraviolet light exposure, chronic inflammatory skin conditions, exposure to radiation, and contact with arsenic. Certain drugs can also be associated with a higher risk of nonmelanoma skin cancer. These include hydroxyurea, which acts as a metabolic inhibitor of ribonucleotide reductase and a potent nonalkylating myelosuppressive agent. It is used for the treatment of various myeloproliferative disorders, including chronic myeloid leukemia, polycythemia vera, and essential thrombocytopenia. Several publications describe an increased occurrence of skin manifestations following hydroxyurea treatment. A growing body of evidence indicates a possible role of hydroxyurea in skin cancer progression. In this review article, we summarize some relevant observations about the association of hydroxyurea and skin cancer, and we describe our own clinical experiences to provide up to date recommendations about the care of patients on hydroxyurea therapy.

Intralesional therapy for the treatment of keratoacanthoma.

Keratoacanthoma (KA) is a common epidermal tumor that originates from the hair follicle of the skin. It is generally considered as a benign neoplasm, but in rare cases, it can also transform into squamous cell carcinoma. Although surgical excision with a safety margin is considered to be the gold standard treatment for most subtypes of KA, several other treatment options are also available. Intralesional therapy is one of these options, which could be cosmetically and functionally a better alternative to surgical removal, while it provides similar outcomes. It is more effective than topical treatments, yet fewer side effects may be seen than in systemic treatments. Based on the literature, the most commonly used intralesional agent is methotrexate, followed by 5-fluorouracil and interferon alpha. Regardless of the advantages, which make intralesional therapy a desirable treatment alternative, guidelines for the intralesional treatment of KA are not yet established. A histopathological confirmation before the start of treatment is still recommended to prevent any possible misdiagnosis of KA for SCC. In our present study, we set out to review the current state of the art of the intralesional treatment of KA.

Diagnosis of Skin Cancer: From the Researcher Bench to the Patient's Bedside.

The overall incidence and prevalence of skin cancer have shown a significant increase worldwide in the last several decades [...].

Do budget constraints limit access to health care? Evidence from PCI treatments in Hungary.

Under Hungary's single payer health care system, hospitals face an annual budget cap on most of their diagnoses-related group based reimbursements. In July 2012, percutaneous coronary intervention (PCI) treatments of acute myocardial infarction were exempted from that hospital level budget cap. We use countrywide individual-level patient data from 2009 to 2015 to map the effect of such a quasi-experimental change in monetary incentives on health provider decisions and health outcomes. We find that direct admissions into PCI-capable hospitals increase, especially in central Hungary, where there are several hospitals which can compete for patients. The proportion of PCI treatments at PCI-capable hospitals, however, does not increase, and neither does the number of patient transfers from non-PCI hospitals to PCI-capable ones. We conclude that only patient pathways, plausibly influenced by hospital management, were affected by the shift in incentives, while physicians' treatment decisions were not. While average length of stay decreased, we do not find any effect on 30-day readmissions or in-hospital mortality.

[Dermoscopy of genodermatoses]. / Dermatoskopie von Genodermatosen.

Genodermatoses are a group of inherited skin diseases whose diagnosis is challenging due to their rarity as well as their clinical and genetic diversity. The majority of genodermatoses are autosomal or X­linked inherited, but mosaic forms are also observed. Genodermatoses comprise various phenotypes ranging from limited cutaneous disease to severe cutaneous and extracutaneous involvement and may also be early warning signs of a multisystemic disorder. Despite recent advances in genetic technology and skin imaging modalities, dermoscopy can be useful for screening, diagnosis, and treatment follow-up. In ectopic mineralization and lysosomal storage disorders (pseudoxanthoma elasticum and Fabry disease, respectively), cutaneous manifestations may indicate involvement of other organs. In keratinization diseases (e.g., ichthyoses) and acantholytic skin fragility disorders (e.g., Darier and Hailey-Hailey disease), dermoscopy may help to assess treatment response by visualizing background erythema, hyperkeratosis, and interkeratinocyte space prominence. Dermoscopy is a noninvasive, easily accessible, useful, in vivo assessment tool that is well established in dermatology to recognize characteristic features of genodermatoses.

Correlation of systemic involvement and presence of pathological skin calcification assessed by ex vivo nonlinear microscopy in Pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE (OMIM 264800)) is an autosomal recessive connective tissue disorder mainly caused by mutations in the ABCC6 gene. PXE results in ectopic calcification primarily in the skin, eye and blood vessels that can lead to blindness, peripheral arterial disease and stroke. Previous studies found correlation between macroscopic skin involvement and severe ophthalmological and cardiovascular complications. This study aimed to investigate correlation between skin calcification and systemic involvement in PXE. Ex vivo nonlinear microscopy (NLM) imaging was performed on formalin fixed, deparaffinized, unstained skin sections to assess the extent of skin calcification. The area affected by calcification (CA) in the dermis and density of calcification (CD) was calculated. From CA and CD, calcification score (CS) was determined. The number of affected typical and nontypical skin sites were counted. Phenodex + scores were determined. The relationship between the ophthalmological, cerebro- and cardiovascular and other systemic complications and CA, CD and CS, respectively, and skin involvement were analyzed. Regression models were built for adjustment to age and sex. We found significant correlation of CA with the number of affected typical skin sites (r = 0.48), the Phenodex + score (r = 0.435), extent of vessel involvement (V-score) (r = 0.434) and disease duration (r = 0.48). CD correlated significantly with V-score (r = 0.539). CA was significantly higher in patients with more severe eye (p = 0.04) and vascular (p = 0.005) complications. We found significantly higher CD in patients with higher V-score (p = 0.018), and with internal carotid artery hypoplasia (p = 0.045). Significant correlation was found between higher CA and the presence of macula atrophy (ß = - 0.44, p = 0.032) and acneiform skin changes (ß = 0.40, p = 0.047). Based on our results, the assessment of skin calcification pattern with nonlinear microscopy in PXE may be useful for clinicians to identify PXE patients who develop severe systemic complications.

A Cross-Sectional Study of the Dermatological Manifestations of Patients with Fabry Disease and the Assessment of Angiokeratomas with Multimodal Imaging.

Fabry disease (FD) is a multisystemic X-linked lysosomal storage disease that presents with angiokeratomas (AKs). Our objective was to investigate the clinical and morphologic features of AKs and to present two experimental techniques, multispectral imaging (MSI) and non-linear microscopy (NLM). A thorough dermatological examination was carried out in our 26 FD patients and dermoscopic images (n = 136) were evaluated for specific structures. MSI was used for the evaluation of AKs in seven patients. NLM was carried out to obtain histology samples of two AKs and two hemangiomas. Although AKs were the most common manifestation, the majority of patients presented an atypical distribution and appearance, which could cause a diagnostic challenge. Dermoscopy revealed lacunae (65%) and dotted vessels (56%) as the most common structures, with a whitish veil present in only 25%. Autofluorescence (405 nm) and diffuse reflectance (526 nm) images showed the underlying vasculature more prominently compared to dermoscopy. Using NLM, AKs and hemangiomas could be distinguished based on morphologic features. The clinical heterogeneity of FD can result in a diagnostic delay. Although AKs are often the first sign of FD, their presentation is diverse. A thorough dermatological examination and the evaluation of other cutaneous signs are essential for the early diagnosis of FD.

Scrofuloderma and granuloma annulare-like lesions: Challenges of diagnosing cutaneous tuberculosis in developed countries.

Tuberculosis remains a global health concern, as the increasing levels of urban poverty, higher number of immunodeficient patients and the development of drug resistance threaten the overall efforts made to induce a downward trend for the disease. Scrofuloderma, also known as tuberculosis cutis colliquativa is a subtype of cutaneous tuberculosis. Here we detail a case of a 70-year-old female patient presented with unilateral, left-sided, multiple palpable, painful, ulcerated and purulent cervical nodules, accompanied by persistent generalized erythematous popular granuloma annulare-like skin lesions on the upper extremities. Based on the result of the PCR assay, culture, imaging and histopathological findings, the diagnosis of scrofuloderma was established. To achieve prompt diagnosis and early treatment, it is crucial to include scrofuloderma in the differential diagnosis of ulcerated lesions in developed countries as well, and also be aware of the additional clinical symptoms, such as granuloma annulare-like lesions, possibly accompanying cutaneous tuberculosis.

Multispectral Imaging Analysis of Skin Lesions in Patients with Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is a rare disease, affecting around 1 in 3500 individuals in the general population. The rarity of the disease contributes to the scarcity of the available diagnostic and therapeutic approaches. Multispectral imaging is a non-invasive imaging method that shows promise in the diagnosis of various skin diseases. The device utilized for the present study consisted of four sets of narrow-band LEDs, including 526 nm, 663 nm, and 964 nm for diffuse reflectance imaging and 405 nm LEDs, filtered through a 515 nm long-pass filter, for autofluorescence imaging. RGB images were captured using a CMOS camera inside of the device. This paper presents the results of this multispectral skin imaging approach to distinguish the lesions in patients with NF1 from other more common benign skin lesions. The results show that the method provides a potential novel approach to distinguish NF1 lesions from other benign skin lesions.

Optical Coherence Tomography as a Valuable Tool for the Evaluation of Cutaneous Kaposi Sarcoma Treated with Imiquimod 5% Cream.

Kaposi sarcoma (KS) is a rare disease that was not frequently identified before the widespread occurrence of AIDS. Even today, it remains a challenge for physicians to diagnose, particularly in its early stages, often requiring referral to specialists and further investigations. Dermoscopy, a non-invasive imaging technique, reveals a distinctive rainbow pattern that strongly indicates KS. Moreover, advanced imaging tools like optical coherence tomography (OCT) can provide additional information though specific disease-related patterns have not been fully established yet. These emerging techniques show promise in facilitating early diagnosis of skin-related KS and monitoring the effectiveness of treatments. However, biopsy remains the definitive method for confirming the disease. In this study, we present two cases of cutaneous Kaposi sarcoma, documented using OCT, both before and after treatment with imiquimod 5% cream. The study highlights the potential of OCT in evaluating disease progression and treatment response, as well as the usefulness of dermoscopy in detecting early indicators of KS. By integrating these advanced imaging techniques, the diagnosis and management of cutaneous KS could be improved, leading to timely interventions and better patient outcomes.