Clio Dessinioti

Cutaneous side effects of anti–tumor necrosis factor biologic therapy: A clinical review

BACKGROUND Anti-tumor necrosis factor (anti-TNF) biologic agents have been associated with a number of adverse events. OBJECTIVE To review the cutaneous reactions that have been reported in patients receiving anti-TNF therapy. METHODS We performed a systematic MEDLINE search of relevant publications, including case reports and case series. RESULTS Reported cutaneous events included infusion and injection site reactions, psoriasiform eruptions, lupus-like disorders, vasculitis, granulomatous reactions, cutaneous infections, and cutaneous neoplasms. Infusion reactions and injection site reactions were definitely associated with anti-TNF administration, whereas all other events had a varying strength of association and severity, not necessarily requiring drug discontinuation. LIMITATIONS Most information was derived from spontaneous case reports, where ascertainment biases and frequency of reporting may impair detection methodology and causal relationships. CONCLUSIONS As anti-TNF biologic agents are progressively being used in clinical practice, cutaneous adverse events will be encountered more frequently. Until more data are accumulated with respect to their pathogenesis and potential association with anti-TNF therapy, dermatologists should become more familiar with the clinical presentation and management of such events.

The role of Propionibacterium acnes in acne pathogenesis: facts and controversies

We have come a long way since 1896, when it was first suggested that Propionibacterium acnes, found in acne lesions, was the cause of acne. Although several lines of evidence suggest the direct role of P acnes in acne, the mechanism by which P acnes contributes to the pathogenesis of acne is debated. The importance of P acnes in the induction and maintenance of the inflammatory phase of acne has been established. Emerging data that inflammatory events occur in the very earliest stages of acne development have reopened the debate about the potential involvement of this microorganism in comedogenesis and acne initiation.

A review of genetic disorders of hypopigmentation: lessons learned from the biology of melanocytes

Abstract:  Inherited diseases of pigmentation were among the first traits studied in humans because of their easy recognition. The discovery of genes that regulate melanocytic development and function and the identification of disease‐causative mutations have greatly improved our understanding of the molecular basis of pigmentary genodermatoses and their underlying pathogenetic mechanisms. Pigmentation mutants can account for hypo‐/amelanosis, with or without altered melanocyte number, resulting in different phenotypes, such as Waardenburg syndrome, piebaldism, Hermansky‐Pudlak syndrome, Chediak‐Higashi syndrome, oculocutaneous albinism and Griscelli syndrome. In this review, we summarize the basic concepts of melanocyte biology and discuss how molecular defects in melanocyte development and function can result in the development of hypopigmentary hereditary skin diseases.

Melanocortin 1 Receptor Variants: Functional Role and Pigmentary Associations

The significance of human cutaneous pigmentation lies in its protective role against sun‐induced DNA damage and photocarcinogenesis. Fair skin and red hair are characterized by a low eumelanin to pheomelanin ratio, and have been associated with increased risk of skin cancer. Cutaneous pigmentation is a complex genetic trait, with more than 120 genes involved in its regulation, among which the melanocortin 1 receptor gene (MC1R) plays a key role. Although a large number of single nucleotide polymorphisms (SNPs) have been identified in pigmentation genes, very few SNPs have been examined in relation to human pigmentary phenotypes and skin cancer risk. Recent GWAS have identified new candidate determinants of pigmentation traits, but MC1R remains the best characterized genetic determinant of human skin and hair pigmentation as well as the more firmly validated low‐penetrance skin cancer susceptibility gene. In this review, we will address how the melanocortin system regulates pigmentation, the effect of MC1R variants on the physiologic function of the MC1 receptor, and how specific MC1R variants are associated with distinct human pigmentation phenotypes.

Acne-associated syndromes: models for better understanding of acne pathogenesis.

Acne, one of the most common skin disorders, is also a cardinal component of many systemic diseases or syndromes. Their association illustrates the nature of these diseases and is indicative of the pathogenesis of acne. Congenital adrenal hyperplasia (CAH) and seborrhoea‐acne‐hirsutism‐androgenetic alopecia (SAHA) syndrome highlight the role of androgen steroids, while polycystic ovary (PCO) and hyperandrogenism‐insulin resistance‐acanthosis nigricans (HAIR‐AN) syndromes indicate insulin resistance in acne. Apert syndrome with increased fibroblast growth factor receptor 2 (FGFR2) signalling results in follicular hyperkeratinization and sebaceous gland hypertrophy in acne. Synovitis‐acne‐pustulosis‐hyperostosis‐osteitis (SAPHO) and pyogenic arthritis‐pyoderma gangrenosum‐acne (PAPA) syndromes highlight the attributes of inflammation to acne formation. Advances in the understanding of the manifestation and molecular mechanisms of these syndromes will help to clarify acne pathogenesis and develop novel therapeutic modalities.

Basal cell carcinoma: what's new under the sun.

Basal cell carcinoma (BCC) is the most common skin cancer in white populations with an increasing incidence worldwide, thereby imposing an important public health problem. Its etiology is still unclear, but existing data indicate that the risk for BCC development is of multifactorial origin and results from the interplay of both constitutional and environmental factors. Yet, UV radiation (UVR) is believed to be the predominant causative risk factor in the pathogenesis of BCC. For years, BCC and squamous cell carcinoma (SCC) have been grouped together as “nonmelanoma skin cancer.” However, it seems that there are considerable biologic differences between BCC and SCC, and thus each type of epithelial cancer should be addressed separately. The present review provides an overview of the intriguing etiologic link of BCC with UVR and attempts a comprehensive review of recent epidemiologic and molecular evidence that supports this association.

Hormonal therapy for acne: why not as first line therapy? facts and controversies

Standard systemic therapeutic agents used in acne include oral antimicrobials, isotretinoin, and hormonal agents. Appropriate patient selection is the key to decide when to use hormonal agents as first-line therapy as well as to achieve optimal results. Indications of hormonal therapy in acne in girls and women include proven ovarian or adrenal hyperandrogenism, recalcitrant acne, acne not responding to repeated courses of oral isotretinoin, acne tarda, polycystic ovary syndrome, or the presence of clinical signs of hyperandrogenism such as androgenic alopecia or the presence of the seborrhea, acne, hirsutism, alopecia syndrome. We describe the hormonal agents currently available for acne treatment, discuss their indications and contraindications, and address the question of whether they may be used as a first-line therapy in acne.

Seborrheic dermatitis: Etiology, risk factors, and treatments:: Facts and controversies

Seborrheic dermatitis (SD) is a common skin condition seen frequently in clinical practice. The use of varying terms such as sebopsoriasis, seborrheic dermatitis, seborrheic eczema, dandruff, and pityriasis capitis reflects the complex nature of this condition. Despite its frequency, much controversy remains regarding the pathogenesis of SD. This controversy extends to its classification in the spectrum of cutaneous diseases, having being classified as a form of dermatitis, a fungal disease, or an inflammatory disease, closely related with psoriasis. Some have postulated that SD is caused by Malassezia yeasts, based on the observation of their presence in affected skin and the therapeutic response to antifungal agents. Others have proposed that Malassezia is incidental to a primary inflammatory dermatosis that resulted in increased cell turnover, scaling, and inflammation in the epidermis, similar to psoriasis. The presence of host susceptibility factors, permitting the transition of M furfur to its pathogenic form, may be associated with immune response and inflammation. Metabolites produced by Malassezia species, including oleic acid, malssezin, and indole-3-carbaldehyde, have been implicated. SD also has been traditionally considered to be a form of dermatitis based on the presence of Malassezia in healthy skin, the absence the pathogenic mycelial form of Malassezia yeasts in SD, and its chronic course. As a result, proposed treatments vary, ranging from topical corticosteroids to topical antifungals and antimicrobial peptides.

Hidradenitis suppurrativa (acne inversa) as a systemic disease

Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic follicular occlusive skin disorder characterized by recurrent abscesses, draining sinuses, and scarring, with a multifactorial pathogenesis. The answer to the question whether HS may be considered a systemic disease relies on the presence of accompanying systemic manifestations, on the proof of association with other diseases or conditions, and on the occurrence of systemic implications. We address these questions based on a systemic review of the existing literature. There are several reports in the literature of the coexistence of HS with other diseases, including pyoderma gangrenosum, PASH syndrome, Adamantiades-Behcets disease, spondylarthropathy, Crohns disease, SAPHO, pachyonychia congenita, Dowling-Degos disease, and the keratitis-ichthyosis-deafness (KID) syndrome. Case series exist only for Crohns disease, while most other reports are anecdotal, thus, not providing high-quality scientific evidence. Based on well-designed studies, HS has been associated with the metabolic syndrome and with excess body weight or obesity. The link between HS and systemic associations may be attributed to common genetic or environmental factors or shared inflammatory pathways.

Clinical and Therapeutic Approach to Childhood Acne: An Update

Abstract:  There is a limited literature reporting on acne in childhood. Childhood acne can be classified in neonatal, infantile, mid‐childhood, and prepubertal acne, depending on the age of onset. In this review we will present an update on the clinical approach and therapeutic options when facing prepubertal acne in a child. The use of tetracyclines is contraindicated in children younger than 8 years, and oral isotretinoin is not recommended in children younger than 12 years of age according to the FDA and the European Commission. Nevertheless, there are case reports of 10 patients successfully treated with oral isotretinoin for recalcitrant infantile acne with scarring. Further studies are needed to investigate whether isotretinoin may improve the long‐term prognosis of infantile acne, which may be associated with more severe acne in adolescence.