HPV-57 Verruca Vulgaris Mimicking Epidermodysplasia Verruciformis.

ABSTRACT: Human papilloma virus (HPV) is the causative agent for a variety of cutaneous lesions including verruca vulgaris (VV) and epidermodysplasia verruciformis (EDV). There are more than 200 known genotypes of HPV, and specific HPV types are associated with different clinical manifestations and malignant potentials. Herein, we describe a case of a 43-year-old immunocompetent woman who presented with morphologically distinct lesions that were most consistent with EDV on clinical examination. However, further histopathological and viral analysis confirmed the lesions as HPV-57-positive VV. The risk of malignant transformation, and therefore treatment and surveillance, is dramatically different in VV versus EDV. Therefore, this case highlights the importance of a proper histopathological diagnosis with HPV viral testing when clinical presentations may vary or mimic other diseases.

Updated understanding of Staphylococcus aureus in atopic dermatitis: From virulence factors to commensals and clonal complexes.

Atopic dermatitis (AD) is a common inflammatory dermatosis that has multiple contributing factors including genetic, immunologic and environmental. Staphylococcus aureus (SA) has long been associated with exacerbation of AD. SA produces many virulence factors that interact with the human skin and immune system. These superantigens and toxins have been shown to contribute to adhesion, inflammation and skin barrier destruction. Recent advances in genome sequencing techniques have led to a broadened understanding of the multiple ways SA interacts with the cutaneous environment in AD hosts. For example, temporal shifts in the microbiome, specifically in clonal complexes of SA, have been identified during AD flares and remission. Herein, we review mechanisms of interaction between the cutaneous microbiome and SA and highlight known differences in SA clonal complexes that contribute to AD pathogenesis. Detailed knowledge of the genetic strains of SA and cutaneous dysbiosis is becoming increasingly relevant in paving the way for microbiome-modulating and precision therapies for AD.

Radiotherapy for Hidradenitis Suppurativa: A Systematic Review.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory dermatosis characterized by painful nodules, abscesses, sinus tracts, and scarring mainly in the intertriginous areas. Patients with HS often experience inadequate responses to traditional treatment consisting of lifestyle modification, topical and systemic antibiotics, hormonal modulators, biologics, and procedural modalities. Low-dose radiotherapy has been used in benign cutaneous conditions, including HS; however, there is a paucity of literature summarizing its evidence. Herein, we systematically review the current literature on the efficacy of radiotherapy for patients with HS. SUMMARY: This systematic review of the published literature reports the patient demographics, treatment regimens, efficacy, and adverse effects of radiotherapy in the treatment of HS. The historic timeline of these publications highlights the changes in management recommendations, introduction of more standardized outcome measures, and enhancements in treatment options. Radiotherapy appears to be an option for patients with treatment-resistant HS or who are poor surgical candidates. However, there remains a paucity of consensus on proper candidate selection, dosing, efficacy, and safety of the short- and long-term effects of radiotherapy.

Low Dose Naltrexone in Dermatology

Low-dose naltrexone (LDN) has been successfully studied as an immunomodulatory and anti-inflammatory therapy in a wide range of conditions including Crohn's disease, fibromyalgia, major depressive disorder, cancer, chronic regional pain syndrome, Charcot-Marie-Tooth, and multiple sclerosis.1-5 Recently, off label LDN has been shown to improve dermatologic conditions such as systemic sclerosis, Hailey-Hailey Disease, lichen planopilaris, and guttate psoriasis.6-9 In this article, we examine the existing evidence for use of LDN in skin disease and discuss its potential application in the treatment of atopic dermatitis (AD). J Drugs Dermatol. 2019;18(3):235-238.

A complicated path to the CRMO diagnosis - case of a 9 year old girl whose story comes full circle.

BACKGROUND: Chronic recurrent multifocal osteomyelitis (CRMO) is a rare idiopathic autoinflammatory bone disease that mostly affects children and adolescents. It is a diagnosis of exclusions since no clinical signs and symptoms are pathognomonic. Radiological tests are often essential, but bone biopsy may be needed in unclear cases. CASE PRESENTATION: A 9-year-old Caucasian girl with a history of bone pain. The data from the history and results of laboratory tests suggested osteomyelitis, but no adequate response to the treatment was observed. A number of imaging tests did not confirm the diagnosis, therefore a bone biopsy was necessary. CONCLUSIONS: Differential diagnosis of CRMO is challenging and it is based on exclusions. Since it might be misdiagnosed or mistreated, bone biopsy should be considered in patients reporting bone pain who are unresponsive to treatment.

A fresh look at angiogenesis in juvenile idiopathic arthritis.

Angiogenesis is the complex process of creating new capillaries from preexisting blood vessels due to hypoxemia, injury or inflammation of the tissues. Numerous cytokines and cell mediators have been identified to induce and stimulate angiogenesis, but vascular endothelial growth factor (VEGF) is a key regulator. The role of proangiogenic factors in the pathogenesis of chronic arthritis is currently a subject of intensive investigations in adult patients with rheumatoid arthritis (RA) and, to a limited extent, in children with juvenile idiopathic arthritis (JIA). Recent studies has shown a significant correlation between proangiogenic marker concentrations and the severity of inflammation in either RA or JIA patients. The serum neovascularization markers correlate with the power Doppler ultrasound image of the inflamed joint and hypertrophic synovium, which may be connected with the disease activity. The aim of this paper is to describe the state of the art on the important role of angiogenesis in adult and childhood rheumatoid arthritis.

Macrophages - silent enemies in juvenile idiopathic arthritis.

The inflammatory response by secretion of cytokines and other mediators is postulated as one of the most significant factors in the pathophysiology of juvenile idiopathic arthritis (JIA). The effect of macrophage action depends on the type of their activation. Classically activated macrophages (M1) are responsible for release of molecules crucial for joint inflammation. Alternatively activated macrophages (M2) may recognize self antigens by scavenger receptors and induce the immunological reaction leading to autoimmune diseases such as JIA. Molecules essential for JIA pathophysiology include: TNF-α, the production of which precedes synovial inflammation in rheumatoid arthritis; IL-1 as a key mediator of synovial damage; chemotactic factors for macrophages IL-8 and MCP-1; IL6, the level of which correlates with the radiological joint damage; MIF, promoting the secretion of TNF-α and IL-6; CCL20 and HIF, significant for the hypoxic synovial environment in JIA; GM-CSF, stimulating the production of macrophages; and IL-18, crucial for NK cell functions. Recognition of the role of macrophages creates the potential for a new therapeutic approach.

Novel insights into the peritoneal inflammation of rainbow trout (Oncorhynchus mykiss).

The peritoneal cavity has been extensively used as a laboratory model of inflammation in many species, including the teleost fish. Although, the peritoneal cavity of rainbow trout (Oncorhynchus mykiss) was previously shown to contain a resident population of leukocytes, closer information about their exact composition and their functional response to pathogens is still missing. In the presented work, flow cytometric analysis using monoclonal antibodies was performed to characterize this cell population and evaluate its traffic during the first 72 h after antigenic stimulation and infection with Aeromonas salmonicida. Obtained results indicate that the unstimulated peritoneal cavity represents rather a lymphoid niche, dominated by the IgM(+) B cells. Expectedly, the composition changed rapidly after stimulation, which resulted in two complete changes of dominant cell type within first 72 h post injection. While the first stage of inflammation was dominated by myeloid cells, lymphocytes predominated at the later time points, with IgM(+) B cells representing more than two thirds of all cells. Later, the infection experiment elucidated the peritoneal infection and identified the key differences to the antigenic stimulation. Additionally, the data indicate that the resolution of the inflammation depends more on the bacterial clearance by myeloid cells than on regulation by lymphocytes. Taken together, obtained results represent the first complete description of the immune reaction protecting the peritoneal cavity of the fish and shed some light on the conservation of these processes during the evolution.

Bibliometric Analysis of Hidradenitis Suppurativa Publication Trends from Asia and Australasia.

INTRODUCTION: Hidradenitis suppurativa (HS), once an orphan disease, has gained increased interest world-wide. The most highly cited works in HS are from North America and Europe despite known phenotypic and epidemiological differences globally. Herein, we perform a bibliometric analysis to characterize HS publication trends in Asia and Australasia (AA) over the last decade. METHODS: PubMed database was searched to identify HS-related articles and were analyzed for senior authorship, country of origin, article topic, and study design. RESULTS: The search criteria yielded 163 articles from AA. Rapid increase in publications started in 2015 with 75% (123/163) of total articles published in the last half of the decade. Case reports/series were consistently the most published study type yearly and overall (49%, 80/163). Efforts were made to increase high level of evidence publications with both randomized controlled trials from Japan and Turkey including all Asian patients. China, Japan, and India were the leading publishing countries with Australia, Israel, and Turkey increasingly contributing in the last half of the decade. CONCLUSIONS: Advancements in HS research are encouraging with increases in publication numbers and diversity; however, more geographical diversity is needed in order to garner a better understanding of the disease and treatment options.

Gender differences in sexual health impairment in hidradenitis suppurativa: A systematic review.

Hidradenitis suppurativa (HS) is a chronic inflammatory dermatosis characterized by painful nodules, sinus tracts, and scarring, with a predilection for intertriginous areas. HS is particularly prevalent in women of childbearing age and can have varying psychological and physical consequences. The chronic and debilitating nature of this disease can lead to significant impairments in patients' sexual health and overall quality of life. This systematic review examines gender differences in the impact of HS on sexual health. In addition, we review gaps in the management of sexual health for patients with HS and outline recommendations to adequately address sexual concerns and optimize care.

Concentration of survivin in children with oligo- and polyarticular juvenile idiopathic arthritis (JIA): diagnostic and prognostic value-a single-center study.

AIM: The goal of the study was to assess the diagnostic and prognostic utility of survivin in patients with juvenile idiopathic arthritis (JIA). METHODS: Seventy children with JIA-59 newly diagnosed and 11 biologically treated (46 girls and 17 boys) aged 1.5-18 years and 29 healthy children as a control group, appropriately matched in terms of sex and age, were included in the study. The disease activity was established on the basis of the JADAS-27 criteria. The concentration of survivin was assessed by an ELISA test in serum and also 18 matched synovial fluid samples collected from patients with JIA. RESULTS: Children with JIA were divided according to the subtype of the JIA. In 65.7% of patients, oligoarthritis was diagnosed. The largest group comprised children of low disease activity (62.9%) according to JADAS-27. The serum concentration of survivin was significantly higher in children with JIA compared to the controls (p < 0.001). The concentration of survivin was higher among patients positive for anti-cyclic citrullinated peptide autoantibodies (ACPA) (p = 0.001). In all synovial fluid samples, the concentration of survivin was higher than in matched serum (p = 0.003). Serum survivin concentration was not significantly associated with radiological damage status or active synovitis assessed by joint ultrasonography. Survivin level was not significantly associated with disease duration time or treatment with TNF-α inhibitors in DMARD's non-responders. CONCLUSIONS: Survivin should be considered as a biomarker of joint inflammation helpful in the diagnosis of oligo- and polyarticular JIA and probably not dependent on treatment with TNF-α inhibitors.

Staphylococcus aureus in Atopic Dermatitis: Past, Present, and Future.

: The role of Staphylococcus aureus (SA) in the pathogenesis and management in atopic dermatitis is rapidly evolving. The modern understanding of SA in atopic dermatitis now includes an expanded array of virulence factors, the interplay of clonal and temporal shifts in SA populations, and host factors such as filaggrin and natural moisturizing factor. New, emerging therapies that focus on long-term, targeted elimination of SA colonization are currently under investigation (Br J Dermatol 2017;17(1)63-71). Herein, we discuss and review the latest staphylococcal and microbiome-modifying therapies including topical antibiotics, topical natural oil fatty acids, anti-SA vaccines, microbial transplantation, vitamin D supplementation, dupilumab and proposed future investigative directions.

Diet and Chronic Urticaria: Dietary Modification as a Treatment Strategy.

Patients with chronic urticaria (CU) often ask about dietary modification. Research has indicated that specific dietary changes may be helpful in a subset of patients. Immunological food reactions are rare, but potential triggers of CU include those seen in certain settings, as in patients with a history of tick bites, a history of raw or marinated fish ingestion, or those with celiac disease. Nonimmunological food intolerances may also contribute, although mechanism of action is not well understood. Trials of pseudoallergen-free diets and low-histamine diets have resulted in partial remission in a subset of patients, while oral provocation testing has confirmed that some patients experience worsening of symptoms after ingestion of food additives, tomatoes, herbs, seafood, alcohol, and other foods. An increased prevalence of vitamin D deficiency has also been noted in patients with CU compared with healthy controls. While oral antihistamines remain the mainstay of therapy in CU, education on potential dietary factors may be offered to a selection of the group of patients. For those at risk or reporting symptoms suggestive of celiac disease, vitamin D deficiency, delayed reactions to mammalian meat, or exposure to raw fish, further workup is recommended. While education on dietary modification may be offered to other patients, this approach may benefit only a subset, and no test is available to identify these patients. A minimum of 3 weeks may be needed to determine response, and only specific diets that have been systematically studied should be considered. Any elimination diet should be used with caution because of the potential for nutritional deficiencies.

Fabric Selection in Atopic Dermatitis: An Evidence-Based Review.

BACKGROUND: Clothing fabrics interact closely with the skin to shape our cutaneous microenvironment. Cotton and silk have been traditionally recommended for patients with atopic dermatitis because of reported patient comfort. New synthetic fabrics combine anti-microbial, anti-inflammatory, moisture-wicking, and soothing properties that may augment conventional management strategies in atopic patients. OBJECTIVE: We review existing and emerging evidence for fabric selection in patients with atopic dermatitis including cotton, wool, lyocell, silk, anionic, cellulosic/cellulose based, zinc oxide coated, citric acid coated, chitosan coated, silver coated, borage seed oil coated, ethylene vinyl, and polyurethane and offer practical suggestions for clothing and bedding choices. METHODS: A systematic search was conducted on PubMed and EMBASE electronic databases for articles from 1 January, 1994 to 1 January, 2020. Studies were included based on the following inclusion criteria: clinical trial, published in English, and fabric as the main agent being evaluated. Case reports, case series, conference abstracts, reviews, animal studies, and duplicates were excluded. Studies were then manually screened by title, abstract, and full-text articles and selected to specifically describe the effects of fabrics in patients with atopic dermatitis. Both adult and pediatric patient studies were included. RESULTS: There appears to be an advantage to modern fabric manufacturing and processing techniques that have created smaller diameter, smoother fibers such as super- and ultrafine merino wool and anti-microbial finishes. Traditional cotton and silk fabrics have mixed evidence in improving atopic dermatitis symptoms and severity but have shown to be generally safe. Large-diameter wool has been shown to induce itching and irritation; ultra- or superfine merino wool is non-pruritic and may be recommended as an alternative. Emerging fabrics with potential efficacy in reducing atopic dermatitis severity and Staphylococcus aureus burden include silver-coated, chitosan-coated, and cellulose-based fabrics. Zinc oxide-coated, acid-coated, polyurethane-coated, borage seed oil-coated, anionic, lyocell, and ethylene vinyl fabrics have sparse evidence and require further study before conclusions can be made. CONCLUSIONS: Appropriate fabric selection can reduce the symptom severity and exacerbations of atopic dermatitis.

Cutaneous metastases: A great imitator.

Neoplastic cells originating from a primary cancer can uncommonly spread to the skin, where they suggest a poor prognosis for the patient. In women, melanoma, breast, ovarian, oral cavity, and lung are the most common primary sources; in men, melanoma, lung, colon, and squamous cell carcinoma of the head and neck predominate. The classic presentation of cutaneous metastases is a firm, painless, flesh-colored to an erythematous dermal nodule (or nodules); however, several other presentations, including inflammatory, cicatricial, and bullous lesions, have been reported. Cutaneous metastases may also mimic benign conditions such as lipomas, hemangiomas, or cellulitis. A high degree of clinical suspicion is necessary, and the diagnosis is confirmed by biopsy, which may also be used to establish the primary malignancy if unknown, as the histopathologic appearance of the metastatic tissue may mimic the primary tumor. Treatments include excision of the metastases, chemotherapy, immunotherapy, radiation, and/or palliative care.

A Practical Approach to Recalcitrant Face and Neck Dermatitis in Atopic Dermatitis.

Face and neck dermatitis in the atopic dermatitis patient is a diagnostically challenging entity with broad differential diagnoses. Recent case reports reporting face and neck dermatitis in patients on dupilumab therapy have added further complexity to diagnosis and management. Herein, we discuss a broad diagnostic algorithm and practical management strategy for recalcitrant face and neck dermatitis in the atopic patient with an emphasis on face and neck dermatitis associated with dupilumab therapy. Our aim is to raise awareness about the probable entity of drug-associated face and neck dermatitis and share a practical management strategy that may also be applied broadly to atopic dermatitis patients presenting with face and neck dermatitis.

Impact of EHR-based rounding tools on interactive communication: A prospective observational study.

OBJECTIVE: Structured rounding tools have shown to improve the overall efficiency and perceived satisfaction with the rounding process. However, little is known about how EHR-integrated rounding tools impact the content, structure and interactivity of communication during rounds. METHOD: We conducted a prospective pre-post evaluation with two rounding tools: a Microsoft Word-based fillable rounding tool (usual tool), and an EHR-integrated rounding report tool (RRT). 27 clinicians across two teams participated in rounds for 169 patients (nusual=84, nRRT=85). We audio-recorded and coded communication during rounds using conversational analysis methods. Using the coded communication interactions, we investigated differences between the two tools on: clinical content discussed, questions raised, and breakdowns in interactive communication. Additionally, we gathered clinician perspectives on the rounding tools through follow-up interviews. RESULTS: We found that the use of RRT was associated with significantly more discussion of patient identifiers (e.g., name), and action items (e.g., to-do list) and significantly less discussion of imaging (e.g., X-rays) than the usual tool. RRT was also associated with fewer questions (t = 3.1, p = 0.03), and correspondingly, fewer responses (t = 3.2, p = 0.02). Communication breakdowns related to incorrect responses was fewer during the use of RRT (t = 0.5, p = 0.01). There were no statistically significant differences in the time spent for rounding between the two tools. CONCLUSIONS: Our findings showed that RRT impacted rounding workflow: during pre-rounding, by saving time and effort in gathering information from multiple sources; during rounding, by streamlining content of the conversations using the structured RRT template; and during post-rounding, by supporting explicit discussion of patient tasks and action items for patient care planning and management.

Paraneoplastic Peripheral Nervous System Manifestations of Renal Cell Carcinoma: A Case Report and Review of the Literature.

Neurologic symptoms secondary to a paraneoplastic syndrome may be the presenting manifestation of a previously undiagnosed cancer, and alertness to these syndromes may provide an opportunity for early detection and treatment of a cancer. Paraneoplastic weakness is a rare manifestation of renal cell carcinoma and may present with variable electrophysiological features. We present a case of a patient with progressive weakness, sensory changes, and urinary retention, with electrophysiological features suggestive of a complex peripheral nervous system syndrome. Ultimately, a renal cell mass was detected and resected, resulting in significant clinical improvement. We review the literature, cataloging the known neurologic syndromes and antibodies associated with renal cell carcinoma. This case highlights that paraneoplastic neurological disorders associated with RCC can take on many features and provides a resource to practitioners for early detection of a neurologic paraneoplastic syndrome arising from renal cell carcinoma.

When a patient suspected with juvenile idiopathic arthritis turns out to be diagnosed with an infectious disease - a review of Lyme arthritis in children.

The Lyme arthritis is a common manifestation of infection with Borrelia burgdorferi spirochete. Despite its infectious background, the inflammation clinically and histopatologically resembles juvenile idiopathic arthritis. As it affects a considerable number of Lyme disease patients, it should be routinely considered in differential diagnosis. Development of arthritis is partially dependent on spirochetal factors, including the ribosomal spacer type and the sequence of outer surface protein C. Immunological background involves Th1-related response, but IL-17 provides an additional route of developing arthritis. Autoimmune mechanisms may lead to antibiotic-refractory arthritis. The current diagnostic standard is based on a 2-step testing: ELISA screening and immunoblot confirmation. Other suggested methods contain modified two-tier test with C6 ELISA instead of immunoblot. An initial 28-day course of oral antibiotics (doxycycline, cefuroxime axetil or amoxicillin) is a recommended treatment. Severe cases require further anti-inflammatory management. Precise investigation of new diagnostic and therapeutic approaches is advisable.