Atopic dermatitis in the elderly: a review of clinical and pathophysiological hallmarks.

BACKGROUND: Atopic dermatitis (AD) is a multifactorial and complex disease, characterized by an impaired skin barrier function and abnormal immune response. Many elderly patients present with pruritus and xerosis to dermatology, allergy and primary care clinics, and there is a lack of information available to clinicians regarding the proper diagnosis and management of these patients. Although the elderly are described as having a distinct presentation of AD and important comorbidities, most investigations and clinical care guidelines pertaining to AD do not include patients aged 60 years and older as a separate group from younger adults. OBJECTIVES: To summarize current information on pathophysiology, diagnosis and management of AD in the elderly population and identify areas of insufficient information to be explored in future investigations. METHODS: We carried out a systematic review of published literature, which assessed changes in the skin barrier and immune function with ageing and current information available for physicians to use in the diagnosis and treatment of AD in elderly patients. RESULTS: Many age-related changes overlap with key hallmarks observed in AD, most notably a decline in skin barrier function, dysregulation of the innate immune system, and skewing of adaptive immunity to a type-2 T helper cell response, in addition to increased Staphylococcus aureus infection. CONCLUSIONS: While general physiological alterations with ageing overlap with key features of AD, a research gap exists regarding specific ageing-related changes in AD disease development. More knowledge about AD in the elderly is needed to establish firm diagnostic and treatment methodologies. What's already known about this topic? Atopic dermatitis (AD) is a common inflammatory skin disease that causes significant burden worldwide. Recently, elderly patients have been considered a subgroup of patients with distinct AD manifestation. Limited studies have characterized the clinical presentation and role of IgE-mediated allergy in elderly patients with AD. What does this study add? This review offers a summary of age-related skin and immune alterations that correspond to pathogenic changes noted in patients with AD. The role of itch, environmental factors and skin microbiota in AD disease presentation in ageing patients is explored.

The role of bacterial skin infections in atopic dermatitis: expert statement and review from the International Eczema Council Skin Infection Group.

Patients with atopic dermatitis (AD) have an increased risk of bacterial skin infections, which cause significant morbidity and, if untreated, may become systemic. Staphylococcus aureus colonizes the skin of most patients with AD and is the most common organism to cause infections. Overt bacterial infection is easily recognized by the appearance of weeping lesions, honey-coloured crusts and pustules. However, the wide variability in clinical presentation of bacterial infection in AD and the inherent features of AD - cutaneous erythema and warmth, oozing associated with oedema, and regional lymphadenopathy - overlap with those of infection, making clinical diagnosis challenging. Furthermore, some features may be masked because of anatomical site- and skin-type-specific features, and the high frequency of S. aureus colonization in AD makes positive skin swab culture of suspected infection unreliable as a diagnostic tool. The host mechanisms and microbial virulence factors that underlie S. aureus colonization and infection in AD are incompletely understood. The aim of this article is to present the latest evidence from animal and human studies, including recent microbiome research, to define the clinical features of bacterial infections in AD, and to summarize our current understanding of the host and bacterial factors that influence microbial colonization and virulence.

Doxycycline as an anti-inflammatory agent: updates in dermatology.

Doxycycline, a tetracycline antibiotic, is widely used in the field of dermatology for its antibiotic properties, anti-inflammatory properties and good safety profile. Over the past decades, numerous studies have clarified some of the anti-inflammatory mechanisms of doxycycline. In this review article, we aimed to provide an update on recent data on the anti-inflammatory properties of doxycycline and its potential role in cutaneous inflammatory diseases. Better understanding of these mechanisms might offer the practicing clinicians a better use of this therapeutic tool. In addition, research in this field could help clarify pathogenic aspects of inflammatory dermatologic diseases responsive to this medication. Further research is needed to fully elucidate the potential of doxycycline as an anti-inflammatory agent, and the development of new topical vehicles could open ways to new therapeutic possibilities for dermatologists.

ΔNp63 regulates IL-33 and IL-31 signaling in atopic dermatitis.

Atopic dermatitis (AD) is the most common inflammatory skin disease with no well-delineated cause or effective cure. Here we show that the p53 family member p63, specifically the ΔNp63, isoform has a key role in driving keratinocyte activation in AD. We find that overexpression of ΔNp63 in transgenic mouse epidermis results in a severe skin phenotype that shares many of the key clinical, histological and molecular features associated with human AD. This includes pruritus, epidermal hyperplasia, aberrant keratinocyte differentiation, enhanced expression of selected cytokines and chemokines and the infiltration of large numbers of inflammatory cells including type 2 T-helper cells - features that are highly representative of AD dermatopathology. We further demonstrate several of these mediators to be direct transcriptional targets of ΔNp63 in keratinocytes. Of particular significance are two p63 target genes, IL-31 and IL-33, both of which are key players in the signaling pathways implicated in AD. Importantly, we find these observations to be in good agreement with elevated levels of ΔNp63 in skin lesions of human patients with AD. Our studies reveal an important role for ΔNp63 in the pathogenesis of AD and offer new insights into its etiology and possible therapeutic targets.

Epidermal tight junctions in health and disease.

The skin, the largest organ of the body, is an essential barrier that under homeostatic conditions efficiently protects and/or minimizes damage from both environmental (e.g. microorganisms, physical trauma, ultraviolet radiation) and endogenous (e.g., cancers, inflammation) factors. This formidable barrier function resides mainly in the epidermis, a dynamic, highly-stratified epithelium. The epidermis has 2 major barrier structures: stratum corneum, the outmost layer and tight junctions, intercellular junctions that seal adjacent keratinocytes in the stratum granulosum, found below the stratum corneum. In recent years there have been significant advances in our understanding of tight junction function, composition and regulation. Herein we review what is known about tight junctions in healthy skin and keratinocyte culture systems and highlight the dynamic crosstalk observed between tight junctions and the cutaneous immune system. Finally we discuss the preliminary observations suggesting that tight junction function or protein expression may be relevant for the pathogenesis of a number of common cutaneous inflammatory and neoplastic conditions.

Lupus vulgaris developing at the site of misdiagnosed scrofuloderma.

Cutaneous tuberculosis is a rare form of extrapulmonary tuberculosis primarily occurring in developing countries. The recent increase in the incidence of tuberculosis, especially due to human immunodeficiency virus (HIV) infections, has led to a resurgence of extrapulmonary forms of this disease. We describe a case of lupus vulgaris in a 33-year-old woman who had a 5-year history of a slowly growing plaque on her neck. The lesion was located at the site of surgery repairing the scar resulting from the incision of a subcutaneous abscess during childhood. This lesion was misdiagnosed as bacterial abscess. Histopathologic examination of the plaque revealed non-caseating tuberculoid granulomas consisting of lymphocytes, epithelioid and giant cells. Staining for acid-fast bacilli and culture from biopsied tissue was negative. Polymerase chain reaction (PCR) for detection of Mycobacterium tuberculosis DNA, performed on a skin biopsy specimen, was positive. A diagnosis of lupus vulgaris developing at the site of a previous misdiagnosed scrofuloderma was made. Conventional antitubercular therapy with rifampicin, isoniazid and ethambutol was administered for 6 months, resulting in resolution of the lesion.

[Transitional cell carcinoma of the bladder in the first four decades of life]. / Il carcinoma a cellule di transizione della vescica nelle prime quattro decadi di vita.

BACKGROUND: The transitional cell carcinoma of the bladder is uncommon below the age of 40 years (1%). There is no univocity on the prognosis of such neoplasm. According to some authors such tumours are non invasive low-grade tumours with low recurrence and therefore an improved prognosis. But according to other authors bladder tumours do not have a different progression compared to tumours arising in older patients. METHODS: The authors present their experience on 28 patients, of whom 8 were under 30 years and 29 between 30 and 40 years of age. All patients had transitional carcinoma of the bladder with different grade and stage of tumour. All patients underwent an endoscopic or surgical treatment. RESULTS AND CONCLUSIONS: The follow-up of these patients show that tumours have a low grade of recurrence (5-10%) and an improved prognosis particularly in patients under 30 years.

Leiomyoma of the female urethra.

Benign smooth muscle tumors of the female urethra are rare. A case of urethral leiomyoma which had been present for 18 years before surgical removal is reported. The pathogenesis and the clinical aspects of this unusual clinical condition are discussed.

[Prognostic factors in operated breast carcinoma]. / Fattori prognostici del carcinoma mammario operato.

The traditional prognostic factors (tumour size, lymph node involvement, receptor status) have now been shown to have limits in terms of prognostic definition. These limits may be partially overcome when parameters exist to determine the extent of tumour biological aggression and the patient's degree of immune response. It is important to clarify these links because they may lead to more precise indications regarding the prognosis and choice of therapy, above all in cases of breast cancer operated with no lymph node involvement. Breast carcinoma is often surrounded by inflammatory cells showing host and tumour interaction. The aim of this study was to evaluate the prognostic value of lymphocyte infiltration in operated breast cancer. The degree of lymphocyte infiltration observed in 56 breast cancer patients was compared with other prognostic factors (tumour size, lymph node status, histological variants, necrotic areas and desmoplastic reaction). This preliminary study allowed the authors to examine the degree of peritumoral lymphocyte density as an important predictive index of overall survival in patients with breast cancer and N-.

Asynchronous bilateral non-Hodgkin's lymphoma of the testis: report of three cases.

Asynchronous involvement of both testes by non-Hodgkin's lymphoma was observed in 3 patients ranging in age from 38 to 82 years. According to the Working Formulation, all cases were classified as large cell immunoblastic lymphomas, and immunohistochemical studies demonstrated a T-cell phenotype in 1 patient and a B-cell phenotype in 2 patients. Relapse to the contralateral testis occurred after a mean interval of 6 months. The negative prognostic impact of these neoplasms is confirmed in the present series, since 2 patients died of disease 7 and 9 months after diagnosis and 1 patient had a laterocervical and Waldeyer's ring recurrence after 1 year.

[Clinical evaluation of the efficacy of the combined determination of serum markers CEA, CA 19.9, CA 72.4 as indexes of gastro-intestinal tract neoplasms]. / Valutazione clinica dell'efficacia dell'associazione dei markers sierici CEA, CA 19.9, CA 72.4 come indici di neoplasia del tratto gastro-intestinale.

The aim of our study was to evaluate the usefulness of the tumor markers CA 72.4, CEA and CA 19.9 in the monitoring of gastrointestinal carcinomas. Our experience demonstrated the usefulness of the determination of CA 72.4 in the follow up of patients with gastrointestinal neoplasms.