Exogenous factors in the pathogenesis of atopic dermatitis: Irritants and cutaneous infections.

Atopic dermatitis (AD) is a chronic relapsing inflammatory cutaneous disease that is often associated with other atopic symptoms, such as food allergy, allergic rhinitis and asthma, leading to significant morbidity and healthcare costs. The pathogenesis of AD is complicated and multifactorial. Although the aetiology of AD remains incompletely understood, recent studies have provided further insight into AD pathophysiology, demonstrating that the interaction among genetic predisposition, immune dysfunction and environmental provocation factors contributes to its development. However, the increasing prevalence of AD suggests that environmental factors such as irritation and cutaneous infection play a crucial role in triggering and/or aggravating the disease. Of note, AD skin is susceptible to bacterial, fungal and viral infections, and microorganisms may colonize the skin and aggravate AD symptoms. Overall, understanding the mechanisms by which these risk factors affect the cutaneous immunity of patients with AD is of great importance for developing a precision medicine approach for treatment. This review summarizes recent developments in exogenous factors involved in the pathogenesis of AD, with special emphasis on irritants and microbial infections.

Hospital-acquired Skin and Skin-structure Infection in COVID-19 Infected Patient with Prolonged Hospitalization.

Acute bacterial skin and skin-structure infections (ABSSSI) is defined in 2013 by the US Food and Drug Administration as a bacterial cellulitis/erysipelas, major skin abscesses, and wound infections. The Infectious Diseases Society of America (IDSA) in 2014 classifies skin and soft-tissue infection (SSTI) as either non-purulent (which includes cellulitis, erysipelas, and necrotizing infection) or purulent (including furuncle, carbuncle, and abscess). Among hospitalized patients with SSTI, healthcare-associated infections account for 73.5% of all cases. Notably, skin and skin-structure infections caused by Pseudomonas aeruginosa, a common hospital pathogen, was reported to cause higher total cost and longer hospital length of stay compared to non-P. aeruginosa cases, despite causing only approximately 5.7% of all healthcare-associated SSTIs. Infection with P. aeruginosa should always be considered in non-healing skin infections in patients with prolonged hospitalization and antibiotic exposure. Tissue culture, preferably taken by surgical debridement, should be promptly performed; and when hospital-infection is suspected, appropriate antibiotics should be started along with removal of all devitalized tissue and to promote skin and soft tissue healing. Expedited discharge should be considered when possible, with adequate antibiotic treatment and follow up for definitive wound treatment.

Identification of risk factors for failure in patients with skin and soft tissue infections.

PURPOSE: The purpose was to determine significant predictors of treatment failure of skin and soft tissue infections (SSTI) in the inpatient and outpatient setting. METHODS: A retrospective chart review of patients treated between January 1, 2005 to July 1, 2016 with ICD-9 or ICD-10 code of cellulitis or abscess. The primary outcome was failure defined as an additional prescription or subsequent hospital admission within 30 days of treatment. Risk factors for failure were identified through multivariate logistic regression. RESULTS: A total of 541 patients were included. Seventeen percent failed treatment. In the outpatient group, 24% failed treatment compared to 9% for inpatients. Overweight/obesity (body mass index (BMI) > 25 kg/m2) was identified in 80%, with 15% having a BMI >40 kg/m2. BMI, heart failure, and outpatient treatment were determined to be significant predictors of failure. The unit odds ratio for failure with BMI was 1.04 (95% [Cl] = 1.01 to 1.1, p = 0.0042). Heart failure increased odds by 2.48 (95% [Cl] = 1.3 to 4.7, p = 0.0056). Outpatients were more likely to fail with an odds ratio of 3.36. CONCLUSION: Patients with an elevated BMI and heart failure were found to have increased odds of failure with treatment for SSTIs. However, inpatients had considerably less risk of failure than outpatients. These risk factors are important to note when making the decision whether to admit a patient who presents with SSTI in the emergency department. Thoughtful strategies are needed with this at-risk population to prevent subsequent admission.

BRAF inhibitor-associated cutaneous squamous cell carcinoma: new mechanistic insight, emerging evidence for viral involvement and perspectives on clinical management.

Mutations in the BRAF proto-oncogene occur in the majority of cutaneous melanomas. The commonly detected valine (V) to glutamate (E) mutation (V600E) is known to drive melanomagenesis and has thus been the target of two highly selective chemotherapeutic agents: vemurafenib and dabrafenib. While BRAF inhibitor therapy has revolutionized the treatment of metastatic melanoma, unanticipated cutaneous toxicities, including the development of cutaneous squamous cell carcinomas (cSCCs), are frequently reported and hinder therapeutic durability. However, the mechanisms by which BRAF inhibitors induce cutaneous neoplasms are poorly understood, thus posing a challenge for specific therapies. In this review, we summarize the clinical and molecular profiles of BRAF inhibitor-associated cSCCs, with a focus on factors that may contribute to disease pathogenesis. In particular, we discuss the emerging evidence pointing towards viral involvement in BRAF inhibitor-induced cutaneous neoplasms and offer new perspectives on future therapeutic interventions. Continued clinical and mechanistic studies along this line will not only allow for better understanding of the pathogenic progression of BRAF inhibitor-induced cSCCs, but will also lead to development of new therapeutic and preventative options for patients receiving targeted cancer therapy.

[A case of cutaneous protothecosis]. / Nablyudenie prototekoza kozhi.

The paper describes a case of a rare opportunistic infection, such as skin lesion caused by achlorophyllic unicellular algae of the genus Prototheca. It provides a detailed pathologic description of the foci of cutaneous protothecosis, such as pandermal inflammatory infiltrate, granulomas, pseudoepitheliomatous hyperplasia, and intraepidermal abscesses. Criteria for pathogen detection in histological sections are given.

Classification of diabetic foot ulcers.

It is known that the relative importance of factors involved in the development of diabetic foot problems can vary in both their presence and severity between patients and lesions. This may be one of the reasons why outcomes seem to vary centre to centre and why some treatments may seem more effective in some people than others. There is a need therefore to classify and describe lesions of the foot in patients with diabetes in a manner that is agreed across all communities but is simple to use in clinical practice. No single system is currently in widespread use, although a number have been published. Not all are well validated outside the system from which they were derived, and it has not always been made clear the clinical purposes to which such classifications should be put to use, whether that be for research, clinical description in routine clinical care or audit. Here the currently published classification systems, their validation in clinical practice, whether they were designed for research, audit or clinical care, and the strengths and weaknesses of each are explored.

Epstein-Barr virus: dermatologic associations and implications: part I. Mucocutaneous manifestations of Epstein-Barr virus and nonmalignant disorders.

Epstein-Barr virus (EBV) is a ubiquitous virus that has been implicated in a wide range of human diseases, many of which have mucocutaneous manifestations. As a member of the herpesviridae family, EBV causes lifelong infection by establishing latency in B lymphocytes. An intact immune response is critical in preventing progression of EBV disease, and the clinical manifestations of infection are dependent on the intricate relationship between virus and host immune system. This review provides a comprehensive overview of the epidemiology, pathophysiology, and diagnostic testing in EBV infection. In part I of this continuing medical education article, the mucocutaneous manifestations of EBV infection are reviewed with an emphasis on pathophysiology and management.

Umbilical and periumbilical dermatoses.

The umbilicus may be the site of congenital and acquired malformations and may harbor clinical clues to the diagnosis of potentially fatal inherited disorders, primary skin conditions, and a variety of infectious diseases. Both benign and malignant tumors may involve the umbilicus, and some are unique to this site. Finally, cutaneous signs localized to this anatomic location may be found in diverse systemic diseases.

[Dermatologic manifestations associated with HIV/AIDS]. / Manifestaciones dermatológicas asociadas a la infección por VIH/SIDA.

The ongoing human immunodeficiency virus (HIV) infection epidemic coupled with more efficacious and available treatments has led to a larger number of patients living with HIV or AIDS. As a result, skin manifestations related to HIV/AIDS or its therapy have become increasingly more common and are reported to occur in as many as 95% of patients. Herein, we review the most common HIV/AIDS related cutaneous pathologies and classify them into inflammatory, HAART-associated, neoplastic, and infectious manifestations. Cutaneous manifestations should be promptly recognized and treated by physicians and health care personnel in order to provide optimal care.

Allogeneic blood and bone marrow cells for the treatment of severe epidermolysis bullosa: repair of the extracellular matrix.

Contrary to the prevailing professional opinion of the past few decades, recent experimental and clinical data support the fact that protein replacement therapy by allogeneic blood and marrow transplantation is not limited to freely diffusible molecules such as enzymes, but also large structural proteins such as collagens. A prime example is the cross-correction of type VII collagen deficiency in generalised severe recessive dystrophic epidermolysis bullosa, in which blood and marrow transplantation can attenuate the mucocutaneous manifestations of the disease and improve patients' quality of life. Although allogeneic blood and marrow transplantation can improve the integrity of the skin and mucous membranes, today's accomplishments are only the first steps on the long pathway to cure. Future strategies will be built on the lessons learned from these first transplant studies.

Obesity and the risk and outcome of infection.

The interactions between obesity and infectious diseases have recently received increasing recognition as emerging data have indicated an association between obesity and poor outcome in pandemic H1N1 influenza infection. Obesity is an established risk factor for surgical-site infections, nosocomial infections, periodontitis and skin infections. Several studies indicate that acute pancreatitis is more severe in the obese. Data are controversial and limited as regards the association between obesity and the risk and outcome of community-acquired infections such as pneumonia, bacteremia and sepsis and obesity and the course of HIV infection. As the cause-effect relationship between obesity and infection remains obscure in many infectious diseases, further studies are warranted. The consequences of obesity may have substantial effects on the global burden of infectious diseases.

Efficacy of extracorporeal shockwave therapy in the treatment of postherpetic neuralgia: A pilot study.

Established conventional treatments for postherpetic neuralgia (PHN) and postherpetic itch (PHI) are difficult and often disappointing. In this study, the authors investigated the effect and mechanisms of extracorporeal shockwave therapy (ESWT) on pain and itch associated with PHN and PHI.Thirteen patients, 50 to 80 years of age, with symptoms associated with PHN or PHI (duration of persistent pain >3 months) and complaints of pain or itch rated >4 on a numerical rating scale (NRS), were included. ESWT was administered using a shockwave device (Piezo Shockwave, Richard Wolf GmbH, Knittlingen, Germany) to skin areas affected by pain or itch. An energy flux density of 0.09 to 0.16 mJ/mm at a frequency of 5 Hz and 2000 impulses was administered at 3-day intervals for 6 sessions. The NRS, 5D-Itch Scale, and Patients Global Impression of Change (PGIC) scale were used to evaluate the efficacy of ESWT.NRS scores of pain and itch and 5D-Itch Scale scores decreased significantly compared with before treatment and at the end of the treatment sessions (P < .0001, P = .001, P = .0002, respectively). There was a statistically significant difference between PGIC scores, which were checked every 2 sessions (P < .0001).ESWT is a noninvasive modality that significantly reduced PHN-associated pain and itch.

Prevalence and severity of abscesses and cellulitis, and their associations with other health outcomes, in a community-based study of people who inject drugs in London, UK.

BACKGROUND: Skin and soft tissue infections (SSTI) are a common but preventable cause of morbidity and mortality among people who inject drugs (PWID). They can be severe, and hospitalisations of PWID with SSTI are rising. The most common SSTI presentations are abscesses and cellulitis. METHODS: We used data from Care & Prevent, a cross-sectional community survey of PWID in London. We reported the lifetime prevalence of SSTI, severity of infections, key risk factors, and associated sequelae. Pictorial questions were used to assess SSTI severity. RESULTS: We recruited 455 PWID. SSTI lifetime prevalence was high: 64% reported an abscess and/or cellulitis. Over one-third (37%) reported a severe infection, 137 (47%) reported hospitalisation. SSTIrisk factors were: aged 35+ years, injecting once or more times a day, subcutaneous or intra-muscular injections, and making four or more attempts to achieve an injection. Those who reported having other health conditions were at higher odds of having an abscess or cellulitis, with risk tending to increase with number of reported conditions. Half (46%) employed self-care for their worst SSTI, and 43% waited for ten or more days before seeking medical care or not seeking medical care at all. CONCLUSIONS: Abscess and cellulitis are very common among PWID in London. We corroborate findings indicating SSTIs are associated with risks, e.g. venous access problems, as well as other co-morbid conditions: septicaemia, endocarditis, DVT, and kidney disease. These co-morbidities may impact SSTIs severity and outcomes. Delayed healthcare seeking potentially exacerbates infection severity, which in turn increases poorer health outcomes and complications.

Functions of Varicella-zoster virus ORF23 capsid protein in viral replication and the pathogenesis of skin infection.

The assembly of herpesvirus capsids is a complex process involving interactions of multiple proteins in the cytoplasm and in the nucleus. Based on comparative genome analyses, varicella-zoster virus (VZV) open reading frame 23 (ORF23) encodes a conserved capsid protein, referred to as VP26 (UL35) in other alphaherpesviruses. Mutagenesis using a VZV bacterial artificial chromosome system showed that ORF23 was dispensable for replication in vitro. However, the absence of ORF23 disrupted capsid assembly in a melanoma cell line. Expression of ORF23 as a red fluorescent protein (RFP) fusion protein appeared to have a dominant negative effect on replication that was rescued by ORF23 expression from a nonnative site in the VZV genome. In contrast to its VP26 homolog, ORF23 has an intrinsic nuclear localization capacity that was mapped to an SRSRVV motif at residues 229 to 234 in the extreme C terminus of ORF23. In addition, coexpression with ORF23 resulted in nuclear import of the major capsid protein, ORF40. VZV ORF33.5 also translocated ORF40, which may provide a redundant mechanism in vitro but appears insufficient to overcome the dominant negative effect of the monomeric RFP-ORF23 (mRFP23) fusion protein. ORF23 was required for VZV infection of human skin xenografts, indicating that ORF33.5 does not compensate for lack of ORF23 in vivo. These observations suggest a model of VZV capsid assembly in which nuclear transport of the major capsid protein and associated proteins requires ORF23 during VZV replication in the human host. If so, ORF23 expression could be a target for a novel antiviral drug against VZV.

Primary hyperhidrosis increases the risk of cutaneous infection: a case-control study of 387 patients.

BACKGROUND: Although primary hyperhidrosis (PHH) has been frequently associated with diminished quality of life, the medical consequences of the condition are less well studied. OBJECTIVE: The objective was to study the clinical presentation of PHH and to determine its relationship to cutaneous infection. METHODS: A retrospective case-control study of patients encountered between 1993 and 2005 with the International Classification of Diseases, Ninth Revision diagnosis code for hyperhidrosis (HH) and meeting criteria for PHH was conducted. RESULTS: Of 387 patients with PHH included, 59% were female and 41% were male; mean age was 27.3 years (range 2-72). Sites of HH included soles (50.1%), palms (45.2%), and axillae (43.4%). Distributional patterns of HH were isolated axillary (27.6%), palmoplantar (24.3%), isolated plantar (15%), axillary/palmoplantar (5.7%), isolated palmar (5.7%), and craniofacial (5.2%). Axillary HH was more common in female patients (P = .004). The mean age of onset (18.6 +/- 12.3 years) indicated a mean duration of untreated symptoms of 8.9 years. Age at onset for palmoplantar HH (11.5 +/- 8 years) was significantly younger than for axillary HH (20.0 +/- 8.3 years; P < .0001), whereas onset of craniofacial HH (25.4 +/- 13.7 years) was older (P < .001). Exacerbating factors included stress/emotion/anxiety (56.7%) and heat/humidity (22%). The overall risk of any cutaneous infection was significantly (P < .0001) increased in HH compared with controls (odds ratio [OR] 3.2; 95% confidence interval [CI] 2.2-4.6). Site-specific risks of fungal infection (OR 5.0; 95% CI 2.6-9.8; P < .0001), bacterial infection (OR 2.6; 95% CI 1.2-5.7; P = .017), and viral infection (OR 1.9; 95% CI 1.2-3.0; P = .011) were all increased. Risks of pitted keratolysis (OR 15.4; 95% CI 2.0-117; P = .0003), dermatophytosis (OR 9.8; 95% CI 3.4-27.8; P < .0001), and verruca plantaris/vulgaris (OR 2.1; 95% CI 1.3-3.6; P = .0077) were particularly increased. Association with atopic/eczematous dermatitis (OR 2.9; 95% CI 1.5-55; P = .019) was observed. LIMITATIONS: Retrospective design and single-institution study are limitations. CONCLUSIONS: Patients with HH are at high risk of secondary infection. Management of HH may have a secondary benefit of decreasing this risk.

Outcome of necrotizing skin and soft tissue infections.

BACKGROUND: Management of necrotizing skin and soft tissue infections (nSSTI) remains difficult, and the mortality rate has been high. We hypothesized that management of nSSTI by an emergency general surgery (EGS) service would improve outcomes. METHODS: Retrospective review of EGS patients with idiopathic nSSTI and comparison with historical controls. Demographic, co-morbidity, laboratory, and surgical data were collected. Non-parametric statistical analysis was used to evaluate differences between survivors and non-survivors. Logistic regression analysis was performed to identify risk factors for the primary outcome measure of death. RESULTS: Fifty-two patients met the inclusion criteria, with five deaths (9.6%). The median time to the operating room (OR) was 8.6 h. The Acute Physiology and Chronic Health Evaluation (APACHE) II score, serum lactic acid concentration, and intensive care unit length of stay were significantly different for non-survivors. The APACHE II score was an independent predictor of death when controlling for age and time to OR. CONCLUSIONS: An EGS service was associated with shorter time to OR, which may improve the outcome. Physiologic derangement, as estimated by the APACHE II score, is predictive of death from nSSTI.

What's eating you? Ixodes tick and related diseases, part 1: life cycle, local reactions, and lyme disease.

The Ixodes tick is an important arthropod vector in the transmission of human disease. This 3-part review highlights the biology of the Ixodes tick and manifestations of related diseases. Part 1 addresses the Ixodes tick biology and life cycle; local reactions; and Lyme disease, the most prevalent of associated diseases. Part 2 will address human granulocytic anaplasmosis, babesiosis, Powassan virus infection, Borrelia miyamotoi disease, tick-borne encephalitis, and tick paralysis. Part 3 will address coinfection with multiple pathogens as well as methods of tick-bite prevention and tick removal.

Correlation of Physical Exam Findings with Fever in Patients with Skin and Soft Tissue Infections.

INTRODUCTION: The objectives of this study were to determine the prevalence of fever in adult ED patients with skin and soft tissue infections (SSTI) and to determine which, if any, physical exam, radiograph and laboratory test findings were associated with fever. METHODS: We conducted a prospective, observational study at an urban county trauma center of adults who presented to the ED for evaluation of suspected SSTI. ED providers measured area of erythema and induration using a tape measure, and completed data sheets indicating comorbid conditions and the presence or absence of physical exam findings. Fever was defined as any recorded temperature ≥ 38°C during the first six hours of ED evaluation. RESULTS: Of the 734 patients enrolled, 96 (13.1%) had fever. Physical and laboratory exam findings associated with the presence of a fever in multivariable logistic regression were the area of erythema, particularly the largest quartile of area of erythema, 144 - 5,000 cm2, (odd ratio [OR] = 2.9; 95% confidence interval [CI] [1.6 - 5.2]) and leukocytosis (OR = 4.4, 95% CI [2.7 - 7.0]). Bullae, necrosis, streaks, adenopathy, and bone involvement on imaging were not associated with fever. CONCLUSION: Fever is uncommon in patients presenting to the ED for evaluation of suspected SSTI. Area of erythema and leukocytosis were associated with fever and should be considered in future decision rules for the evaluation and treatment of SSTI.

Common Skin Conditions in Children: Skin Infections.

Skin infections account for a significant subset of dermatologic conditions of childhood. Common cutaneous viral infections in children include warts, molluscum contagiosum, hand-foot-and-mouth disease, and herpes simplex. Although viral infections are self-limited and often only mildly symptomatic, they can cause anxiety, embarrassment, and health care use. Recognition of their common and atypical presentations is necessary to differentiate them from other skin conditions of similar morphology. Impetigo, cellulitis, and abscess comprise the majority of childhood bacterial skin infections and are treated with topical or systemic antibiotics that cover group A Streptococcus and Staphylococcus aureus. Common fungal dermatologic infections in children are oral and genital candidiasis, tinea capitis, and tinea corporis. Management consists of topical and systemic antifungals, including nystatin, triazoles, terbinafine, griseofulvin, and imidazoles. Scabies is the most common parasitic skin infection among children and is managed with topical permethrin. Although serious illness is not common among children returning from international travel, patients presenting with fever and rash, especially petechial or hemorrhagic lesions, require thorough evaluation. Of the numerous reportable conditions that present with childhood rash, tick-borne illnesses, measles, rubella, and varicella are the most common.