Future treatment options for atopic dermatitis – Small molecules and beyond

Atopic dermatitis (AD) is a common eczematous skin disease with a chronic and relapsing course. Current therapeutic options for moderate to severe AD in children and adults are unsatisfactory. Along with the success of basic research to define pathogenesis-related targets, novel small molecule inhibitors and biologics for the treatment of AD have been developed.These compounds focus on the specific reduction of pruritus, interfere with the pro-allergic Th2-deviation of the immune system or inhibit inflammatory pathways in the skin. Based on studies registered at ClinicalTrials.gov we present novel treatment strategies of AD, their molecular mechanisms of action, and discuss the current status of the clinical results. As many of the new compounds target pathogenesis-related traits of the disease, we face a new era in the treatment and understanding of AD.     

Telogen Effluvium – a review of the science and current obstacles

Telogen effluvium (TE) is a common cause of diffuse non-scarring hair loss that is usually precipitated by physiological stress such as childbirth or sudden weight loss. Despite its high rate of remission, this phenomenon of sudden excessive hair loss can be very worrisome and upsetting for affected individuals and may significantly impact their quality of life. Due to the multifactorial causes and precipitants of TE, it is often challenging to diagnose and manage. Further, the mechanisms through which physiological stress influences the human hair cycle is unknown, and there are no targeted treatments for the management of TE. This review will describe the approach in making a diagnosis of TE, summarize the latest developments made in understanding the mechanisms of TE, outline the treatments tried, and recommend ways for advancing the study of this dermatological condition.     

Assessing absorbent products’ effectiveness for the prevention and management of incontinence-associated dermatitis caused by urinary,faecal or double adult incontinence: A systematic review

ObjectiveAdults who suffer from incontinence are at substantial risk of developing incontinence-associated dermatitis (IAD). In healthcare settings, several interventions have been implemented to prevent or manage IAD, and several absorbent products have been developed for incontinent patients; however, there is no systematic review that has reported on which absorbent products are effective for the prevention or management of incontinence-associated dermatitis. We conducted a systematic review to investigate the effectiveness of absorbent products in the prevention and management of IAD.MethodsMEDLINE (1946–August 31, 2020), CINAHL (1982–August 31, 2020), and Cochrane Library (August 31, 2020) were searched for relevant articles. Results: Eight studies met the eligibility criteria and were included in this review, including two randomized controlled trials that were designed to evaluate the efficacy of absorbent products on the prevention or management of incontinence-associated dermatitis. Quality of evidence was assessed as low or very low. The findings revealed that some outcomes related to IAD prevention or improvement of IAD can be positively affected by the introduction of a new absorbent product or a difference in the frequency of pad changing, which can control the overhydration of the skin.ConclusionsThe studies included in this review indicated that the problem of control of overhydration of the skin associated with urine and/or faeces can be controlled by absorbent products and these products may be effective for the prevention or management of incontinence-associated dermatitis. Future research with high-quality studies is required.     

Actinic keratosis – review for clinical practice

Actinic keratosis (AK) is a lesion that arises as a result of excessive exposure to solar radiation and appearing predominantly on Fitzpatrick phototype I and II skin. Given that some AKs evolve into squamous cell carcinoma, these lesions are considered premalignant in nature, occurring mostly in elderly men and immunosuppressed individuals chronically exposed to ultraviolet (UV) radiation. There are several mechanisms for the formation of AKs; among them are oxidative stress, immunosuppression, inflammation, altered proliferation and dysregulation of cell growth, impaired apoptosis, mutagenesis, and human papillomavirus (HPV). Through the understanding of these mechanisms, several treatments have emerged. Among the options for AK treatment, the most commonly used include 5-fluorouracil (5-FU), cryotherapy, diclofenac, photodynamic therapy (PDT), imiquimod (IQ), retinoids, and ingenol mebutate (IM). There have been recent advances in the treatment options that have seen the emergent use of newer agents such as resiquimod, betulinic acid, piroxicam, and dobesilate. The combination between therapies has presented relevant results with intention to reduce duration of therapy and side effects. All AK cases must be treated because of their propensity to transform into malignancy and further complicate treatment. In addition to medical or surgical care, education about sun exposure prevention remains the best and most cost-effective method for AK prevention. The objective of this article is to conduct a literature review of the clinical presentation of AK including advances in treatment options available.     

The clinical course of Behçet's disease in pregnancy: a retrospective analysis and review of the literature

Although Behçet's disease is mainly diagnosed during the reproductive periods of life, we know little about the influence of pregnancy on the clinical course of Behçet's disease. Therefore, we analyzed the relationship between Behçet's disease and pregnancy retrospectively, in order to detect any possible interaction between the two multisystemic processes, particularly in regard to the influence of pregnancy on the clinical course of Behçet's disease. We studied 44 pregnancies in 28 women with Behçet's disease. The diagnoses were made according to the criteria of the International Study Group for Behçet's disease. The patients were observed during pregnancy and puerperium periods at monthly intervals. The existence and incidence of symptoms were recorded during these periods. There was remission of Behçet's disease during 23 (52.3%) pregnancies, although the disease had been in a stage of exacerbation before pregnancy. The disease became exacerbated during 12 (27.3%) pregnancies, although it had been in a stage of remission before pregnancy. There were no changes in the clinical course of Behçet's disease in 9 (20.4%) pregnancies. The most frequent manifestations of the clinical exacerbation were increases in the intensity and severity of outbreaks of oral ulcers during pregnancy. Outbreaks of genital ulcers, eye inflammations, and arthritis were other signs of exacerbation. Other than spontaneous abortion in three patients, we did not observe maternal or fetal complications. Although Behçet's disease tends toward remission during pregnancy, the influence of pregnancy on its clinical course is quite variable between patients and even during different pregnancies in the same patient. On the basis of our and previous results, we speculate that pregnancy in general does not seem to markedly affect the natural course of Behçet's disease.     

Annular lichenoid dermatitis of youth: a separate entity or on the spectrum of mycosis fungoides? Case report and review of the literature

Annular lichenoid dermatitis (ALDY) is a rare dermatosis that is most often seen in children and young adults and is characterized by annular patches with raised borders, most frequently on the trunk and the groin. A distinct lichenoid tissue reaction involving the base of the rete, resulting in squared‐off rete ridges, helps to differentiate this from other lichenoid dermatoses and mycosis fungoides (MF). Herein, we report an additional case of this condition in a 7‐year‐boy, whose biopsy exhibited the typical quadrangular rete alteration and also contained distinct aggregates of CD8+ lymphocytes, Langerhans cells and colloid bodies within the involved rete. A literature review with emphasis on the clinical and histopathological differential diagnosis reveals additional clinical features of ALDY to potentially help differentiate this entity from annular presentations of mycosis fungoides.     

Temperature and humidity affect the incidence of hand,foot, and mouth disease: a systematic review of the literature – a report from the International Society of Dermatology Climate Change Committee

Hand, foot, and mouth disease (HFMD) is an enterovirus-mediated condition that predominantly affects children under 5 years of age. The tendency for outbreaks to peak in warmer summer months suggests a relationship between HFMD and weather patterns. We reviewed the English-language literature for articles describing a relationship between meteorological variables and HFMD. Seventy-two studies meeting criteria were identified. A positive, statistically significant relationship was identified between HFMD cases and both temperature (61 of 67 studies, or 91.0%, reported a positive relationship) [CI 81.8–95.8%, P = 0.0001] and relative humidity (41 of 54 studies, or 75.9%) [CI 63.1–85.4%, P = 0.0001]. No significant relationship was identified between HFMD and precipitation, wind speed, and/or sunshine. Most countries reported a single peak of disease each year (most commonly early Summer), but subtropical and tropical climate zones were significantly more likely to experience a bimodal distribution of cases throughout the year (two peaks a year; most commonly late spring/early summer, with a smaller peak in autumn). The rising global incidence of HFMD, particularly in Pacific Asia, may be related to climate change. Weather forecasting might be used effectively in the future to indicate the risk of HFMD outbreaks and the need for targeted public health interventions.     

Are infantile seborrheic and atopic dermatitis clinical variants of the same disease?

BACKGROUND: The relationship between infantile seborrheic dermatitis (ISD) and infantile atopic dermatitis (IAD) is controversial. METHODS: Ninety-six children aged 2-12 months diagnosed with atopic dermatitis and a comparable control group of healthy children were evaluated. Demographic data, personal history of ISD and personal or family history of atopy was considered in both groups. RESULTS: A personal history of ISD was found in 49% of IAD cases and in 17% of controls (P < 0.05). CONCLUSIONS: Our result and those of the literature do not demonstrate a relationship between ISD and IAD. However, a number of cases of AD have an ISD-like clinical picture. It is probable that ISD is a syndrome and not a disease.     

Efficacy and safety of PAC-14028 cream – a novel,topical, nonsteroidal,selective TRPV1 antagonist in patients with mild-to-moderate atopic dermatitis: a phase IIb randomized trial

This research, from Korea, showed that a non-steroid containing cream, called PAC-14028, can be as effective in treating eczema symptoms as current creams on the market but with fewer side-effects. Eczema is one of the most common skin diseases. Available topical (applied to the skin) treatments can be very effective in treating eczema symptoms. However, they can also cause negative side-effects such as itching and burning, which can result in patients discontinuing their treatment. The research was conducted with 194 adults with mild to moderate eczema. Participants were split into four groups and treated with either a control cream or the new treatment, PAC-14028 cream, at one of three different concentrations (0.1%, 0.3% or 1.0%). Participants applied the cream twice daily for eight weeks. The results were primarily measured using the Investigator's Global Assessment (IGA). This is a visual scale for assessing the severity of eczema in a patient based upon typical symptoms. After eight weeks, 57.5 percent of patients in the group who received the highest concentration PAC-14028 cream, had an IGA score indicating that their symptoms of eczema were completely eradicated or reduced to an almost-clear level. IGA success rates at week eight were 15 percent for the control cream, compared to 43 percent for PAC-14028 cream at 0.1%, 38 percent for 0.3% and 57 percent 1.0%. The efficacy of PAC-14028 cream was similar to a commonly used non-steroidal cream called pimecrolimus but with a far lower incidence of unwanted side-effects.     

Atopic dermatitis – Perspectives and unmet medical needs

Atopic dermatitis (AD) is a chronic inflammatory skin disease for which many new insights have been gained in recent years through a better understanding of pathophysiology, concomitant diseases and therapeutics in particular. In this review, new and practice-relevant results from current research are presented. Many studies have been performed on the diagnosis of AD and on different subtypes, yet no diagnostic biomarker or clinical predictor of treatment response has been established. For topical treatment, some agents such as Janus kinase (JAK) inhibitors are in advanced stages of clinical trials or already approved in some countries, which will be available in Europe for the treatment of certain eczema subtypes in the foreseeable future. Current systemic therapies in Europe include two antibodies for inhibition of the interleukin (IL)-4/13 signaling cascades and three oral JAK inhibitors with somewhat different efficacy and safety profiles. Among the antibody therapies for AD already advanced in development, promising new targets include blockade of IL-31, of neurokinin-1 receptor on sensory neurons, and inhibition of the OX40/OX40L axis for cutaneous dendritic cell and T lymphocyte interaction. Primary prevention and modulation of sequential disease progression as well as effects on concomitant diseases by early therapeutic intervention will be important questions in future research on AD.     

Placebo response in phase 2 and 3 trials of systemic and biological therapies for atopic dermatitis—a systematic review and meta-analysis

A growing number of clinical trials of biological and systemic therapies have been conducted within adult atopic dermatitis (AD). No study has yet examined and meta-analysed the pooled placebo response in AD. We performed a systematic review and meta-analysis to examine the placebo response in clinical trials evaluating the effect of systemic and biological therapies in adult AD and compared it to results from clinical trials in psoriasis. Two screeners independently searched the databases ClinicalTrials.gov, Embase, Pubmed and Web of Science. A total of 2058 articles were identified, of which 78 were full-text reviewed. Overall, 25 trials were included in the qualitative analysis, of which 24 were further included in the quantitative analysis. At 12-week follow-up, EASI50, EASI75 and EASI90 placebo responses were 39.9% [95% confidence interval (CI), 36.7–43.2], 20.9% (95% CI, 18.2–23.8) and 9.0% (95% CI, 6.7–11.6), respectively. At week 12, the pooled proportion of placebo-treated AD patients that obtained EASI50, EASI75 and EASI90 was significantly higher than the pooled proportion of placebo-treated psoriasis patients obtaining PASI50, PASI75 and PASI90 (P < 0.05). Our findings emphasize the fluctuating nature of AD and show that correct and consistent use of topical treatments strongly reduces disease severity.