COVID 19-associated chilblain-like acral lesions among children and adolescents: an Italian retrospective, multicenter study.

BACKGROUND: Since the COVID-19 pandemic started, great interest has been given to this disease, especially to its possible clinical presentations. Besides classical respiratory symptoms, dermatological manifestations occur quite often among infected and non-infected patients, particularly in children. A prominent IFN-I response, that is generally higher in children compared to adults, may not only cause chilblain lesions, but it could also prevent infection and viral replication, thus justifying the negative swab results, as well as the absence of relevant systemic symptoms in positive cases. Indeed, reports have emerged describing chilblain-like acral lesions in children and adolescents with either proven or suspected infection. METHODS: Patients aged from 1 to 18 years old were enrolled in this study from 23 Italian dermatological units and were observed for an overall period of 6 months. Clinical pictures were collected along with data on the location and duration of skin lesions, their association with concomitant local and systemic symptoms, presence of nail and/or mucosal involvement, as well as histological, laboratory and imaging findings. RESULTS: One hundred thirty-seven patients were included, of whom 56.9% were females. Mean age was 11.97±3.66 years. The most commonly affected sites were the feet (77 patients, 56.2%). Lesions (48.5%) featured cyanosis, chilblains, blisters, ecchymosis, bullae, erythema, edema, and papules. Concomitant skin manifestations included maculo-papular rashes (30%), unspecified rashes (25%), vesicular rashes (20%), erythema multiforme (10%), urticaria (10%) and erythema with desquamation (5%). Forty-one patients (29.9%) reported pruritus as the main symptom associated with chilblains, and 56 out of 137 patients also reported systemic symptoms such as respiratory symptoms (33.9%), fever (28%), intestinal (27%), headache (5.5%), asthenia (3.5%), and joint pain (2%). Associated comorbid conditions were observed in 9 patients presenting with skin lesions. Nasopharyngeal swabs turned out positive in 11 patients (8%), whereas the remainder were either negative (101, 73%) or unspecified (25, 18%). CONCLUSIONS: COVID-19 has been credited as the etiology of the recent increase in acro-ischemic lesions. The present study provides a description of pediatric cutaneous manifestations deemed to be potentially associated with COVID-19, revealing a possible association between acral cyanosis and nasopharyngeal swab positivity in children and teenagers. The identification and characterization of newly recognized patterns of skin involvement may aid physicians in diagnosing cases of asymptomatic or pauci-symptomatic COVID patients.

Photodynamic Therapy Used to Treat an HIV Patient with an Efflorescence of Viral Warts after HAART Therapy.

Healing from viral warts lesions can be hard to achieve in immunocompromised subjects like HIV-positive patients. The therapeutic target in immunocompetent subjects can be reached using different methods, including topical ointments, cryotherapy, laser therapy, imiquimod, and photodynamic therapy (PDT). We present a case of a male HIV-positive patient who came to the Dermatology department with multifocal wart lesions on his face, auricular, and retro-auricular areas after treatment with highly active antiretroviral therapy (HAART). In our case, surprisingly, only one session of PDT proved to induce complete regression of lesions which, despite their thickness, had a much more robust response to treatment than we could have possibly expected. After a brief review of the literature, it is possible to state that PDT revealed itself to be a valid option in immunocompromised patients who have a major risk of relapse.

Treatment of Severe Atopic Dermatitis with Dupilumab in Three Patients with Renal Diseases.

BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease that can affect patients' quality of life. Dupilumab is the first biologic agent approved for the treatment of patients with inadequately controlled moderate-to-severe AD and its mechanism of action is based on the inhibition of the interleukin (IL)-4 and IL-13 signaling. There are only a few data on the safety of dupilumab in AD patients with comorbidities, including kidney disorders. MATERIALS AND METHODS: Descriptive retrospective series of three patients with chronic kidney diseases (Alport syndrome, IgA nephropathy, and hypertensive nephrosclerosis, respectively) receiving dupilumab for their concomitant severe AD. RESULTS: Treatment with a standard dosage of dupilumab caused a relevant improvement of AD in all patients without any adverse events or worsening of renal function. In a patient with severe renal failure, the drug was effective and well tolerated without the need for any dose adjustments, also after the initiation of peritoneal dialytic treatment. CONCLUSION: Our case series suggests the use of dupilumab as an effective and safe treatment for AD patients suffering from renal diseases, although additional studies are required to confirm such preliminary findings.

A Case of Purpura Annularis Telangiectodes of Majocchi after Anti-SARS-CoV-2 Pfizer-BioNTech Vaccine: Is There an Association?

The advent of vaccines has drastically reduced the incidence, morbidity, and mortality related to COVID-19, and with the increase in the number of vaccinated subjects, there have been reports of some adverse events, including skin reactions. In this paper, we report a clinical case of Purpura Annularis Telangiectodes of Majocchi following a third-dose administration of the Pfizer-BioNTech COVID-19 vaccine. Almost 30 days after the third dose, the patient presented erythematous annular patches on the lower limbs with purpuric peripheral areas and a central clearing with no other symptoms. A dermoscopic examination showed capillaritis, reddish-brown dot-clods on a coppery-red background caused by leaky capillaries. To date, the causes of Majocchi's disease are not well-defined; in the literature, three vaccination-related cases have been reported: one after a flu vaccination and two after an anti-SARS-CoV-2 one. Dermatologists should be trained to promptly recognize these clinical manifestations after vaccination, which will likely become a common finding in daily clinical practice, especially given the large diffusion of SARS-CoV-2 vaccinations.

Allergic contact dermatitis from vitamins: A systematic review.

Background and Aims: Vitamins are bioactive compounds naturally found in many different types of food and required by the human body for many biological functions and enzymatic activities. Due to their antioxidant properties, certain vitamin derivatives have been synthesized for inclusion in many cosmetics, thus leading to an increasing incidence of allergic contact dermatitis (ACD) cases. Therefore, the present review may be helpful to provide an insight into the sensitizing role of at least certain vitamins and may also offer possible patch test alternatives for definitive diagnosis. Methods: This study was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Literature search regarding ACD cases to vitamins was performed using the Medline, PubMed, Scopus, EMBASE, and Google Scholar databases from January 1940 up to June 2021. Results: A total of 4494 articles matched the keywords used for the researched. Records removed before screening included 15 duplicate articles and 3429 not eligible articles (e.g., not written in English, studies on animals, not relevant to the topic). A total of 1050 articles underwent the screening phase and 258 were therefore excluded as they were not primary studies. Subsequentially, 792 articles were considered eligible for the review and 688 of them were finally excluded as they did not report the outcome of interest. Therefore, 104 articles were definitely included in the present review. Conclusion: ACD to vitamins is still probably an underestimated issue in cosmetology, as many vitamins are considered "natural" and therefore "safe" ingredients. On the contrary, according to current literature, almost all vitamins contained in topical products are able to induce allergic reactions, with the exception of vitamin B2 and vitamin B9. Patch tests are not standardized, thus leading to difficulties in diagnosis.

Self-inflicted pathological cutaneous disorders. Part II.

Self-inflicted skin disorders are artefact diseases inflicted by the use of multiple different means, for various different purposes. They account for about 2% of dermatology patient visits, and include disorders with a denied or hidden pathological behavior (factitious disorders) and disorders with a non-denied and non-hidden pathological behavior (compulsive disorders). In turn, factitious skin disorders are subdivided into 2 groups: factitious disorders without an external incentive (considered in a preceding work) and factitious disorders with external incentives. In the second eventuality, the simulator is motivated by illicit intent, wishing to evade civil duties or a prison sentence, for instance, or to exploit situations of an occupational nature, and is fully aware of his action and his intention. Apart of the two groups of pathomimic artefacts and malingering, some self-inflicted dermatoses are due to behavioral disorders involving compulsive habits (tics, psychological excoriations). The great majority of subjects suffering from the latter disturbances are quick to confess their urge to self-inflict lesions. The management, including both psychiatric and dermatological assessment, concludes this second part of the work regarding the self-inflicted cutaneous diseases.

Self-inflicted pathological cutaneous disorders. Part I.

Self-inflicted skin disorders are artefact diseases inflicted by the use of multiple different means, for various different purposes. They account for about 2% of dermatology patient visits and include disorders with a denied or hidden pathological behavior (factitious disorders) and disorders with a non-denied and non-hidden pathological behavior (compulsive disorders). In turn, factitious skin disorders are subdivided into two groups: factitious disorders without an external incentive and factitious disorders with external incentives. In addition to the general diagnostic criteria, the present work examines the clinical forms of diseases of the first group (including dermatitis artefacta, Munchausen Syndrome, Munchausen Syndrome by proxy, and Morgellons Syndrome). In this case, the subject suffers from psychological problems and generally aims to attract the attention of the people around him, and in particular of his general practitioner, or else is reacting to difficult or unfavorable environmental conditions by means of an involuntary somatization at the level of the skin. The second part of the work on self-inflicted skin disorders will comprise the factitious disorders with external incentives and the compulsive disorders.

Occupational risk of cutaneous larva migrans: A case report and a systematic literature review.

Cutaneous larva migrans (CLM) is a parasitic zoonosis of warm tropical and subtropical areas, although autochthonous cases have been increasingly reported in Western European countries. Data on the prevalence of CLM as an occupational disease in workers exposed to potentially contaminated soil or in close contact with dogs and cats are scant. Herein, we report an autochthonous case of CLM in a dog breeder from southern Italy (Apulia region), along with a systematic literature review describing the risk of CLM infection, mainly according to job categories. The patient was referred to the dermatology unit presenting a serpiginous lesion on his hand, raising the suspected CLM diagnosis. In non-endemic areas, CLM might represent a challenge for physicians in terms of diagnosis, treatment, and prevention, particularly in workplaces. The multidisciplinary approach in the diagnosis of CLM with the involvement of different scientific competences (i.e., dermatologists, veterinarians, and occupational physicians) may contribute to further assess the distribution of human CLM and associated risk factors, toward reducing the risk for the infection.

Squamous Cell Carcinoma in Patients with Inherited Epidermolysis Bullosa: Review of Current Literature.

Epidermolysis bullosa (EB) is a group of rare congenital diseases caused by mutations in structural proteins of the dermal/epidermal junction that are characterized by extreme epithelial fragility, which determines the formation of bullae and erosions either spontaneously or after local mechanical traumas. In EB patients, skin fragility leads to many possible complications and comorbidities. One of the most feared complications is the development of cutaneous squamous cell carcinomas (SCCs) that particularly in the dystrophic recessive EB subtype can be extremely aggressive and often metastatic. SCCs in EB patients generally arise more often in the extremities, where chronic blisters and scars are generally located. SCCs represent a big therapeutic challenge in the EB population. No standard of care exists for the treatment of SCC in these patients, and therapy is based on small case studies. Moreover, the pathogenesis of cSCC in EB patients is still unclear. Many theories have been indeed postulated in order to explain why cSCC behaves so much more aggressively in EB patients compared to the general population. cSCC in EB seems to be the result of many complex interactions among cancer cells, skin microenvironment, susceptibility to DNA mutations and host immune response. In this review, we analyze the different pathogenetic mechanisms of cSCC in EB patients, as well as new therapies for this condition.

Aquaporins Are One of the Critical Factors in the Disruption of the Skin Barrier in Inflammatory Skin Diseases.

The skin is the largest organ of the human body, serving as an effective mechanical barrier between the internal milieu and the external environment. The skin is widely considered the first-line defence of the body, with an essential function in rejecting pathogens and preventing mechanical, chemical, and physical damages. Keratinocytes are the predominant cells of the outer skin layer, the epidermis, which acts as a mechanical and water-permeability barrier. The epidermis is a permanently renewed tissue where undifferentiated keratinocytes located at the basal layer proliferate and migrate to the overlying layers. During this migration process, keratinocytes undertake a differentiation program known as keratinization process. Dysregulation of this differentiation process can result in a series of skin disorders. In this context, aquaporins (AQPs), a family of membrane channel proteins allowing the movement of water and small neutral solutes, are emerging as important players in skin physiology and skin diseases. Here, we review the role of AQPs in skin keratinization, hydration, keratinocytes proliferation, water retention, barrier repair, wound healing, and immune response activation. We also discuss the dysregulated involvement of AQPs in some common inflammatory dermatological diseases characterised by skin barrier disruption.

Quality of life in patients with allergic and immunologic skin diseases: in the eye of the beholder.

Allergic and immunologic skin diseases negatively impact the quality of life (QoL) of affected patients with detrimental consequences. Nonetheless, in everyday clinical practice the evaluation of QoL is often overlooked. Considering the increasing prevalence of atopic dermatitis, allergic contact dermatitis, hereditary angioedema, cutaneous mastocytosis, and urticaria, it is essential to determine the effects of allergic and immunologic skin diseases on QoL. A joint meeting (GET TOGETHER 2021) of the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC) and the Italian Society of Allergological, Occupational and Environmental Dermatology (SIDAPA) aimed to summarize the features of the main QoL tools used in these diseases and to describe the extent of QoL impairment as well as the impact of treatments on QoL, particularly biologic therapies. The assessment of QoL in patients with allergic and immunologic skin diseases relies on generic, organ-specific and disease-specific questionnaires. While generic and organ-specific questionnaires allow comparison between different diseases, disease-specific questionnaires are designed and validated for specific cohorts: the QoL Index for Atopic Dermatitis (QoLIAD) and the Childhood Atopic Dermatitis Impact Scale (CADIS) in atopic dermatitis, the ACD-11 in allergic contact dermatitis, the Angioedema QoL Questionnaire (AE-QoL) and the Hereditary Angioedema QoL questionnaire (HAE-QoL) in hereditary angioedema, the Mastocytosis QoL Questionnaires (MCQoL e MQLQ) in cutaneous mastocytosis, and the Chronic Urticaria QoL questionnaire (CU-Q2oL) in urticaria. Among the many factors that variably contribute to QoL impairment, pruritus can represent the leading cause of patient discomfort. Biologic therapies significantly ameliorate QoL in atopic dermatitis, hereditary angioedema, mastocytosis and chronic urticaria. In general, adequate management strategies are essential for improving QoL in patients with allergic and immunologic skin diseases.

Formalin-Fixed and Paraffin-Embedded Samples for Next Generation Sequencing: Problems and Solutions.

Over the years, increasing information has been asked of the pathologist: we have moved from a purely morphological diagnosis to biomolecular and genetic studies, which have made it possible to implement the use of molecular targeted therapies, such as anti-epidermal growth factor receptor (EGFR) molecules in EGFR-mutated lung cancer, for example. Today, next generation sequencing (NGS) has changed the approach to neoplasms, to the extent that, in a short time, it has gained a place of absolute importance and diagnostic, prognostic and therapeutic utility. In this scenario, formaldehyde-fixed and paraffin-embedded (FFPE) biological tissue samples are a source of clinical and molecular information. However, problems can arise in the genetic material (DNA and RNA) for use in NGS due to fixation, and work is being devoted to possible strategies to reduce its effects. In this paper, we discuss the applications of FFPE tissue samples in the execution of NGS, we focus on the problems arising with the use of this type of material for nucleic acid extraction and, finally, we consider the most useful strategies to prevent and reduce single nucleotide polymorphisms (SNV) and other fixation artifacts.

Cutaneous Metastases from Primary Liver Cancers: The Need for Knowledge and Differential Diagnosis.

Primary skin tumors are certainly more frequent than metastatic tumors, but the latter can sometimes be the first sign of otherwise unrecognized neoplastic pathology and always correspond to an advanced stage of the disease. Among the various neoplasms that can metastasize in cutaneous districts, skin metastases from primary malignant neoplasms from the liver and biliary tract are infrequent, and when they do occur they can pose differential diagnosis problems to the pathologist. Here we present two cases of metastatic skin lesions, respectively originating from the liver and the intrahepatic biliary tract, and we conduct a brief review of the current literature.

Topical beta-blockers in dermatologic therapy.

An increasing use of beta-blockers in dermatology has been described over the last 10 years, despite the fact that their use in diseases other than infantile hemangiomas is off-label. This review discusses the emerging role of topical beta-blockers in the treatment of infantile hemangioma, but also pyogenic granuloma, Kaposi sarcoma, wounds and nail paronychia. Data in literature demonstrate that topical beta-blockers are a safe and valid therapeutic option in numerous cutaneous diseases. Side effects are mainly restricted to the application site. Further studies and randomized trials may contribute to reinforce the role of topical beta-blockers in the dermatological armamentarium.

Topical antibiotics in the dermatological clinical practice: Indications, efficacy, and adverse effects.

Topical antibiotic therapy is a central component of patient management for several skin conditions, including acne, hidradenitis suppurativa, rosacea, impetigo or other superinfected dermatitis, and prevention of wound infections. Moreover, particular situations, such as skin diseases of bacterial origin in pregnancy and infants often warrant topical therapy. However, the occurrence of local delayed hypersensitivity reactions and the rising rate of antibiotic resistance are becoming great challenges faced by many dermatologists today. This narrative review provides an overview of the main topical antibiotics used in dermatology, focusing on their clinical role in the most common dermatological indications. For this purpose, a review of MEDLINE and PubMed for pertinent, scientific, and clinical publications until March 2020 was performed. Only articles published in the English language were included.

"Less is better"-always true?

OBJECTIVE: The aim of the study is to try to explain what an overtreatment is and which ones are the possible risks related to an excess of simplification in the medical practice, through the description of an emblematic clinical case. METHODS: In the present article, we report the case of a female patient aged 57 who complained about lower back pain and crural neuralgia and had a lumbar and sacral magnetic resonance imaging performed in the Department of Neuroradiology in Bari showing suspicious repetitive bone lesions; therefore, the patient underwent several medical procedures and laboratory exams which ended with a surgical removal of a left L3-L4 foraminal disc herniation and a bone biopsy. RESULTS: When it was finally possible to exclude any other diseases including thyroid neoplasms, a "reassuring" osteoporosis diagnosis has been made since the lesions were likely to be degenerative and the patient underwent menopause 7 years ago. However, the multiplicity of the lesions of the vertebrae and of the pelvic bones as well as their signal could not be ignored, so that a close magnetic resonance imaging follow-up has been recommended. CONCLUSIONS: The present case is therefore a good example of overtreatment which may lead to delicate questions, investigating any possible mistakes in the diagnosis procedure as well as the role that defensive medicine is playing nowadays on medical procedures and the economic impact that all this can have on our healthcare system. In the end, we may ask ourselves: is "less" better or is "more" always "more?"