Congenital Deficiency of Conventional Dendritic Cells Promotes the Development of Atopic Dermatitis-Like Inflammation.

Atopic dermatitis (AD) is a common pruritic inflammatory skin disease characterized by impaired epidermal barrier function and dysregulation of Thelper-2 (TH2)-biased immune responses. While the lineage of conventional dendritic cells (cDCs) are implicated to play decisive roles in T-cell immune responses, their requirement for the development of AD remains elusive. Here, we describe the impact of the constitutive loss of cDCs on the progression of AD-like inflammation by using binary transgenic (Tg) mice that constitutively lacked CD11chi cDCs. Unexpectedly, the congenital deficiency of cDCs not only exacerbates the pathogenesis of AD-like inflammation but also elicits immune abnormalities with the increased composition and function of granulocytes and group 2 innate lymphoid cells (ILC2) as well as B cells possibly mediated through the breakdown of the Fms-related tyrosine kinase 3 ligand (Flt3L)-mediated homeostatic feedback loop. Furthermore, the constitutive loss of cDCs accelerates skin colonization of Staphylococcus aureus (S. aureus), that associated with disease flare. Thus, cDCs maintains immune homeostasis to prevent the occurrence of immune abnormalities to maintain the functional skin barrier for mitigating AD flare.

Uncommon Association Between Diabetic Ketoacidosis, Thyrotoxicosis, Cutaneous Abscess and Acute Pericarditis in an Immunocompetent Patient: A Single Case Report and Literature Review.

INTRODUCTION: The typical factors precipitating diabetic ketoacidosis (DKA) include infections (30%), cessation of antidiabetic medication (20%), and a new diagnosis of diabetes (25%). The etiology remains unknown in 25% of cases. Less frequent causes cited in the literature include severe thyrotoxicosis and, infrequently, pericarditis. Few publications have described the role of human T lymphotropic virus type 1 (HTLV-1) in endocrine and metabolic disorders. Based on a clinical case associated with several endocrine and metabolic disorders, we suggest a potential role for HTLV-1, an endemic virus in the Amazonian area, and review the literature concerning the role of this virus in thyroiditis, pericarditis and diabetes mellitus. CASE REPORT: A fifty-year-old Surinamese woman without any medical history was admitted for diabetic ketoacidosis. No specific anti-pancreatic autoimmunity was observed, and the C-peptide level was low, indicating atypical type-1 diabetes mellitus. DKA was associated with thyrotoxicosis in the context of thyroiditis and complicated by nonbacterial pericarditis and a Staphylococcus aureus subcutaneous abscess. The patient was infected with HTLV-1. CONCLUSION: To our knowledge, this uncommon association is described for the first time. Few studies have analyzed the implications of HTLV-1 infection in thyroiditis and diabetes mellitus. We did not find any reports describing the association of pericarditis with HTLV-1 infection. Additional studies are necessary to understand the role of HTLV-1 in endocrine and cardiac disorders.

Correlación de colonización de Staphylococcus aureus en mucosa nasal e infecciones faciales de origen no odontogénico / Corelation between Staphylococcus aureus colonization in nasal mucosa and facial infections from non-odontogenic origin

En la actualidad, las tasas que se conocen de colonización de piel y mucosa por el staphylococcus aureus están incrementando día a día. Se ha encontrado una fuerte correlación de la invasión de estos en otras partes del cuerpo (zona axilar, mucosa nasal, entre otras) con la aparición de celulitis y/o abscesos faciales. Se demostró que la flora nasal es muy diversa, encontrándose patógenos como streptococcus viridans, staphylococcus aureus, staphylococcus coagulasa negativa y Corynebacterium sp, pero sin posibilidad de definir con exactitud cuál es la constancia de los mismos pudiendo presentarse variaciones de esta. A su vez, esto se ve agravado por la falta de adherencia al tratamiento por parte de los pacientes y de otras condiciones como, el mismo contagio o predisposición del medio (sudoración, altas temperaturas, mala higiene, etc.), que facilitan la capacidad de dicho microorganismo de tornarse más resistente, incrementar su población y aumentar así la patogenicidad a través de la codificación de una exotoxina llamada Pantón Valentín (SAMR). Se demostrará entonces, la metodología que se llevó a cabo a través de un análisis descriptivo transversal de los casos tratados en el Hospital Mariano y Luciano de La Vega, con el fin de correlacionar causalidad y efecto (AU)

At present, the rates known for skin and mucosa colonization by Sthapylococcus aureus are increasing day by day. A strong correlation has been found of the invasion of these in other parts of the body (axillary area, nasal mucosa, among others, being the latter the most representative), with the appearance of cellulite and/or facial abscesses. It was shown that the nasal flora is very diverse, finding pathogens such as Streptococcus Viridans, Staphylococcus aureus (S aureus), coagulase negative Staphylococcus and Corynebacterium sp, but that has not been defined exactly the constancy of the same, can be presented variations of this. In turn, this is aggravated by the lack of adherence to treatment by patients and other conditions such as the same contagion or predisposition of the medium (sweating, high temperatures, poor hygiene, etc.), which facilitate the capacity of said Microorganism to become more resistant, increase its population and thus increase the pathogenicity through the codification of a exotoxin called Valentín Panty. To prove the methodology that was carried out through a transversal descriptive analysis of the cases treated at the Mariano Hospital and Luciano de La Vega in order to fulfil the objective of correlating causality and Effect (AU)

Histoire naturelle de la dermatite atopique: Natural History of Atopic Dermatitis.

Atopic dermatitis (AD) is a common frequent chronic inflammatory skin disease which begins frequently in infancy. The clinical expression of AD is a recurrent eczema on a dry skin. AD is a multifactorial disease characterized by two linked abnormalities: a skin barrier defect and a cellular inflammation, with type-2 main components. However, the pathophysiology of AD is not as simple as this description looks like. In this review, we will present a synthesis of current knowledge on natural history of AD and the involved factors, in order to clarify AD care. The evolution of AD is associated with many atopic comorbidities, following the "atopic march" scheme: IgE-mediated food allergy, allergic asthma and rhinitis occurring classically after AD. In fact, this is rarely the case, but the atopic march seems to be associated with AD severity. AD has also many neuropsychological complications which are essential to be detected. Other factors could influence the natural history of AD: genetic mutations on different genes (proteins of skin barrier, innate and adaptive immunity pathways), skin dysbiosis with colonization by Staphylococcus aureus, sensitization against environmental proteins. AD treatment is based on the restauration of the skin barrier using emollients and on anti-inflammatory drugs (notably topical corticosteroids) during the inflammatory flares. It is not recommended to treat the skin colonization by S. aureus, excepted in case of skin infection. The probiotics have no efficiency as curative treatment of AD, but could have an interest for the primary prevention, especially in at-risk populations. © 2019 Elsevier Masson SAS. All rights reserved.

Peroxisome Proliferator-Activated Receptor γ Is Essential for the Resolution of Staphylococcus aureus Skin Infections.

Skin/soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) represent serious healthcare burdens worldwide. The host initially controls these infections with a pro-inflammatory infiltrate. However, once established, MRSA viability remains constant. To clear established MRSA SSTIs, the host must transition into the post-inflammatory resolution phase marked by infiltration of alternatively activated macrophages. Here we show that the host nuclear receptor, peroxisome proliferation activator receptor γ (PPARγ), is essential for this transition and MRSA clearance. Chemical PPARγ inhibition or genetic ablation of PPARγ in myeloid cells results in an extended inflammatory phase and exacerbated MRSA SSTIs. Conversely, treating mice with PPARγ agonists hastens the onset of the resolution phase and improves MRSA clearance in a myeloid-dependent fashion. The resolving fibrotic abscess lacks abundant glucose and oxygen but is replete with antimicrobial peptides, which together contribute to MRSA clearance. Thus, PPARγ agonists may serve as viable treatment options for complicated MRSA SSTIs.

Extensive Cutaneous Botryomycosis With Subsequent Development of Nocardia-Positive Wound Cultures.

Botryomycosis is a rare, chronic granulomatous infection caused by a response to bacteria, most commonly Staphylococcus aureus. Cutaneous manifestations, such as subcutaneous nodules, nonhealing ulcers, or sinus tracks, typically occur following inoculation of bacteria after trauma. Drainage from the skin lesions may contain yellow grains resembling those seen in actinomycosis and nocardiosis. A 20-year-old Hispanic male presented over the course of several years with a chronic nonhealing left posterior scalp wound. A car hit the patient when he was 2 years old and injured the scalp in the location of the skin lesion. Multiple wound cultures grew methicillin-resistant Staphylococcus aureus (MRSA), and biopsies were consistent with botryomycosis. He was treated with multiple surgical debridements, skin grafts, and various courses of oral and intravenous antibiotics with slight improvement. One reason for poor response to therapy was noncompliance with long-term home antibiotics. The most recent tissue culture grew MRSA in addition to Nocardia mexicana, and he experienced improvement on linezolid and minocycline. Although it is important to exclude nocardiosis and actinomycosis when diagnosing botryomycosis, our patient was diagnosed with botryomycosis after multiple biopsies and positive MRSA cultures 2 years prior to 1 positive N mexicana culture. Our case is a unique presentation of botryomycosis in an individual who subsequently developed Nocardia-positive wound cultures.

Effect of prophylactic cefalexin treatment on the development of bacterial infection in acute radiation-induced dermatitis in dogs: a blinded randomized controlled prospective clinical trial.

BACKGROUND: Acute radiation-induced dermatitis (ARID) is a common sequela of radiation therapy and carries the risk of secondary bacterial skin infection. No standard of care exists for managing canine ARID and evidence-based guidelines are lacking; however, prophylactic use of antibiotics is common. HYPOTHESIS/OBJECTIVES: To evaluate the impact of prophylactic cefalexin on the prevalence and severity of bacterial infection in canine ARID. ANIMALS: Seventeen dogs treated with definitive-intent radiotherapy. METHODS: All dogs were treated with definitive-intent radiation therapy (48-57.5 gray) targeted to the skin surface. Dogs were randomized to receive either prophylactic cefalexin (22 mg/kg twice daily) beginning halfway through the prescribed radiotherapy course (cohort A) or to serve as controls (cohort B). Aerobic skin cultures and surface cytological evaluation were performed at first onset of moist desquamation and one week following completion of radiation therapy. Skin toxicity grading and owner quality of life (QoL) questionnaires were performed weekly. The rate of infection, multidrug resistance status, toxicity severity and QoL between cohorts were compared. RESULTS: Staphylococcus schleiferi and S. pseudintermedius were the most frequent bacterial agents isolated in both cohorts. There was no significant difference in prevalence of bacterial infection or overall QoL between cohorts at either time point; however, multidrug-resistant infections were significantly increased in cohort A versus cohort B. Clinician- and client-perceived severity of toxicity was significantly greater and median duration of moist desquamation was significantly longer in cohort A than cohort B. CONCLUSIONS AND CLINICAL IMPORTANCE: Prophylactic use of cefalexin for management of canine ARID is not recommended.

Inflammatory dermatoses, infections, and drug eruptions are the most common skin conditions in hospitalized cancer patients.

BACKGROUND: Dermatologic conditions cause morbidity and mortality among hospitalized cancer patients. An improved understanding is critical for implementing clinical and research programs in inpatient oncodermatology. OBJECTIVE: To characterize inpatient dermatology consultations at a large comprehensive cancer center. METHODS: Retrospective database query of new admissions and medical record review of initial inpatient dermatology consultations comparing inpatients consulted and not consulted during January-December 2015. RESULTS: In total, 412 of 11,533 inpatients received 471 dermatology consultations (54% male, median age 59.5 years). Patients with hematologic cancers were 6 times more likely to receive dermatologic consultations compared with nonhematologic cancers (odds ratio 6.56, 95% confidence interval 5.35-8.05, P < .0001). Patients consulted by a dermatologist had a significantly longer length of stay than inpatients not consulted by dermatology (median 11 vs 5 days, P < .0001). Among the 645 dermatologic conditions diagnosed, the most common categories were inflammatory diseases, infections, and drug reactions; the most frequent conditions were contact dermatitis, herpes zoster, and chemotherapy-induced drug eruptions. LIMITATIONS: The study's retrospective nature and single-institution setting are potential limitations. CONCLUSION: Hematologic malignancies are a significant risk factor for dermatology inpatient consultations. A significantly longer length of stay was associated with dermatology consultations, suggesting high comorbidities in these patients. Increased dermatologic care of these inpatients might improve quality of life, dermatologic health, and ability to receive anticancer agents.

Differential Diagnosis of Diaper Dermatitis.

Mild diaper dermatitis often occurs in children before toilet training is complete, particularly from 9 to 12 months of age, and the most common presentation is an irritant contact dermatitis. Diaper dermatitis may account for up to 25% of dermatology visits to health care providers during the first year of life. Fortunately, since the introduction of hypoallergenic, superabsorbent modern disposable diapers, the incidence and severity of irritant and allergic contact dermatitis has decreased dramatically. Diaper dermatitis broadly refers to skin disorders that occur in the diaper area, such as skin eruptions triggered by diapers, rashes exacerbated by the diaper, and other events that occur in the diaper area. A number of skin conditions that can occur anywhere on the skin may present with distinctive findings in the diaper area. The following discussion will review the most common triggers of diaper dermatitis and contact irritant dermatitis, while focusing on the skin conditions that may be associated or overlap clinically with contact dermatitis.

Congenital erythropoietic porphyria (Gunther disease) - long-term follow up of a case and review.

Patients with the rare genodermatosis congenitalerythropoietic porphyria (CEP, Gunther disease)develop erosions and scarring on sun-exposedsites caused by phototoxin mediated damage.Compromised skin barrier function places patientsat higher risk of infection and long term sequelaeinclude scarring. We report a long term follow up ofa 60 year old patient born with CEP and provide anextensive literature review of CEP including recentupdates on potential management options. Multiplepatient interviews and collection of biochemistry datawere conducted for the case discussion. All Australianpathology laboratories in each state performingporphyria testing were surveyed in mid 2015 to verifyexistence of other cases of CEP in Australia with onlyone case of true congenital porphyria identifiedand one adult onset case. Congenital erythropoieticporphyria is a rare condition with no cure currentlyavailable. It is important to diagnose patients earlyto prevent and minimize complications such asscarring and secondary infection, provide longterm skin checks, and advise patients about lifestylemodification.

Risks for Staphylococcus aureus colonization in patients with psoriasis: a systematic review and meta-analysis.

Evidence on whether patients with psoriasis have a higher risk for staphylococcal colonization than healthy controls remains controversial. To synthesize the current literature, we performed a systematic review on the prevalence and relative risk (RR) of Staphylococcus aureus colonization in patients with psoriasis. We modified the QUADAS-2 instrument to assess the reporting quality of individual studies and applied random-effects models in meta-analysis. Overall we identified 21 eligible studies, of which 15 enrolled one or more comparison groups. The pooled prevalence of staphylococcal colonization in patients with psoriasis was 35·3% [95% confidence interval (CI) 25·0-45·6] on lesional skin and 39·2% (95% CI 33·7-44·8) in the nares. Patients with psoriasis were 4·5 times more likely to be colonized by S. aureus than healthy controls were on the skin (RR 5·54, 95% CI 3·21-9·57) and 60% more in the nares (RR 1·60, 95% CI 1·11-2·32). Cutaneous and nasal colonization by meticillin-resistant S. aureus also appeared higher in patients with psoriasis (pooled prevalence 8·6%) than in healthy controls (2·6%), yet the difference was not statistically significant (P = 0·74). In contrast, despite of a similar risk for nasal staphylococcal colonization (RR 0·67, 95% CI 0·38-1·18), patients with psoriasis were less likely to carry S. aureus on lesional skin than atopic patients (RR 0·64, 95% CI 0·40-1·02). In summarizing the current literature, we found that patients with psoriasis were at an increased risk for staphylococcal colonization compared with healthy individuals. Prospective studies on how bacterial loads correlate with disease activity can guide the clinical management of bacterial colonization while preventing the emergence of drug-resistant strains.

Mycophenolate mofetil therapy for pediatric bullous pemphigoid.

Bullous pemphigoid (BP) is a common autoimmune blistering disease in the adult population, but extremely rare in the pediatric population. Childhood BP usually has a favorable prognosis and responds well to topical and oral steroids. However, for patients that do not respond to corticosteroids, therapeutic alternatives are scarce. We report a case of a toddler with recalcitrant BP who was successfully treated with mycophenolate mofetil (MMF).

[Autologous mesenchymal stem cells and cutaneus autograft as a treatment for chronic ulcer secondary to diabetes mellitus 2]. / Células troncales mesenquimales autólogas e injerto cutáneo autólogo para tratamiento de una úlcera crónica secundaria a diabetes mellitus tipo2.

BACKGROUND: Diabetes mellitus 2 has become a global problem. It is estimated that 15% to 25% of patients could develop a chronic ulcer in their life, and nearly 33% of direct care costs of the diabetes mellitus 2 is spent on treating these ulcers. Mesenchymal stem cells have emerged as a promising cell source for the treatment of these ulcers. CLINICAL CASE: The case is presented of a 67 year-old male with a history of diabetes mellitus, acute myocardial infarction, and food ulcer chronic involving right foot and part of his leg. He was treated with mesenchymal stem cell management, resulting in skin graft integration and full coverage of the lesion. CONCLUSION: The implementation of mesenchymal stem cell techniques for treatment of chronic ulcer is feasible. The impact on the population would lead to a significant improvement in their quality of life and reduce healthcare spending.

Antibiotic therapy in the management of atopic dermatitis.

Atopic dermatitis (AD), also known as atopic eczema, is a syndrome characterized by a chronic eczematous dermatitis, with associated pruritus, characteristic age-specific morphology and distribution of lesions and recurrent nature. Secondary infections in patients with AD are very common and difficult to treat. S. aureus colonizes almost all eczematous lesions in atopic patients and releases several super-antigens and exotoxins (i.e., toxic shock syndrome toxin-1, enterotoxins A-D, etc.), which sustain inflammatory reactions and promote tachyphylaxis. The topical antibiotics most commonly prescribed for mild/moderate secondary infections are gentamicin, fusidic acid and mupirocine. This article reviews existing therapeutic options and provides guidance for the management of secondary skin infection among patients with AD.