Elias Oussedik

Interleukin-17 inhibition: role in psoriasis and inflammatory bowel disease

Abstract Introduction: Interleukin 17 (IL-17) antagonism provides a highly effective approach for treating psoriasis. Exacerbations of inflammatory bowel disease have been reported in anti-IL-17 psoriasis trials. Aim: To characterize the relationship between IL-17 inhibition and inflammatory bowel disease. Methods: A review of English-language articles was performed. Search terms included IL-17, psoriasis, inflammatory bowel disease, secukinumab, ixekizumab and brodalumab. Results: IL-17 A inhibition, IL-17RA inhibition and IL-17 knockout led to induction or exacerbation of colitis in mouse models. The placebo groups fared better than the treatment group in controlled trials of anti-IL-17 antibody and anti-IL-17 receptor for Crohn’s disease (CD). A brodalumab study (N = 1576) revealed one reported CD case. An ixekizumab study (N = 3736) evaluating moderate-to-severe psoriasis, four patients reported CD and seven reported UC while ixekizumab every 2 weeks led to a moderate exacerbation of UC in one patient and new-onset CD in one patient. A secukinumab study (N = 3430) revealed exposure adjusted incidence rates of 0.11 and 0.15 per 100 patient-years for CD and UC, respectively. Discussion: Anti-IL-17 medications are associated with IBD exacerbation. Caution should be used in prescribing these medications in patients with diagnosed IBD or personal history suggestive of IBD.

Interleukin-31 Pathway and its Role in Atopic Dermatitis: A Systematic Review

Abstract Background: Atopic dermatitis, a chronic inflammatory disease, has a lifetime prevalence of 10–20%. Atopic dermatitis reduces quality of life, primarily due to pruritus. Interleukin-31 and its target receptor are newly discovered entities that are involved in pruritus. Purpose: To summarize the current understanding of interleukin-31 and its role in atopic dermatitis, potential therapeutic interventions and future prospects. Methods: A systematic review was designed to identify articles related to interleukin-31 and its role in pruritus. Predefined queries containing interleukin-31 and related key terms were searched with no past date restriction, through 31 August 2016, using MEDLINE, Cochrane Controlled Trials Register, ClinicalTrials.gov and the International Clinical Trials Registry Platform Search Portal database. Results: Of 151 identified articles, 61 met eligibility criteria. Interleukin-31 receptors are expressed constitutively on the surface of keratinocytes, eosinophils and small diameter neurons. Overexpression of interleukin-31, independent of mast cells and lymphocytes, induces clinical and histological features consistent with atopic dermatitis. In addition, overexpression of interleukin-31 causes reversible alopecia. Human monoclonal interleukin-31 antagonist, CIM331, decreased pruritus in phase-I and phase-II clinical trials. Conclusions: Interleukin-31 plays an important role in atopic dermatitis and alopecia. Inhibiting this pathway may provide an alternative to antihistamines for the pruritus of atopic dermatitis.

An Anchoring-Based Intervention to Increase Patient Willingness to Use Injectable Medication in Psoriasis

This study examines the association of anchoring with patient willingness to use a monthly injectible medication for psoriasis.

Recent Advances in Small Molecule and Biological Therapeutic Approaches in the Treatment of Psoriasis

New treatments continue to be developed for psoriasis. In this review, we aim to summarize the results of the major published studies on biologic and small molecule drugs for the treatment of psoriasis. We emphasize the safety, efficacy, and tolerability of these treatment options. A review of the MEDLINE database was conducted for each class of medication. Randomized controlled trials were identified for each medication; data on efficacy, safety, and tolerability were reviewed. Biologic and small molecule treatment options are more effective than placebo, although there were few head‐to‐head trials to assess relative efficacy between biologics and small molecule treatments. These drugs offer favorable safety profiles with only rare serious adverse events reported. Biologic and small molecule drugs offer diverse therapeutic regimens, particularly in patients with recalcitrant disease.

Early Congenital Syphilis: Recognising Symptoms of an Increasingly Prevalent Disease:

Background: Congenital syphilis (CS) is an infectious disease resulting from transplacental transmission of Treponema pallidum spirochetes from an infected mother to fetus during pregnancy. While uncommon, CS has shown an increased incidence in Canada and the United States since 2001 and 2012, respectively. Case Report: We present the case of a 5-week-old female infant with blistering rash on the palms and soles. The infant displayed decreased movement of the left upper extremity, clinically consistent with Parrot pseudoparalysis. Cutaneous involvement was limited to few tan crusted papules on the palms and soles. Mother reported a “false-positive” result of rapid plasma reagin (RPR) testing at 31 weeks. Cerebrospinal fluid studies of the infant resulted with positive Venereal Disease Research Laboratory (VRDL) test and positive microhemagglutination assay (MHA-TP). Histopathology of a crusted papule revealed a lichenoid infiltrate composed of lymphocytes, histiocytes, and plasma cells. Immunohistochemical staining for T pallidum was negative. The patient completed treatment with a 10-day course of intravenous penicillin. Discussion: While CS is largely considered a historic entity, it has been increasing in incidence in the United States since 2012 and in Canada since the early 2000s. Diagnosis of CS can be difficult as infants may be asymptomatic or present with nonspecific signs. This case highlights the presentation of minimal cutaneous involvement as well as skeletal involvement after birth. RPR testing may result in false negatives or indeterminate results, further complicating diagnosis. Given these difficulties in screening and the increasing incidence of CS, clinicians may need to refamiliarise themselves with its clinical findings.

Accountability: a missing construct in models of adherence behavior and in clinical practice

Piano lessons, weekly laboratory meetings, and visits to health care providers have in common an accountability that encourages people to follow a specified course of action. The accountability inherent in the social interaction between a patient and a health care provider affects patients’ motivation to adhere to treatment. Nevertheless, accountability is a concept not found in adherence models, and is rarely employed in typical medical practice, where patients may be prescribed a treatment and not seen again until a return appointment 8–12 weeks later. The purpose of this paper is to describe the concept of accountability and to incorporate accountability into an existing adherence model framework. Based on the Self-Determination Theory, accountability can be considered in a spectrum from a paternalistic use of duress to comply with instructions (controlled accountability) to patients’ autonomous internal desire to please a respected health care provider (autonomous accountability), the latter expected to best enhance long-term adherence behavior. Existing adherence models were reviewed with a panel of experts, and an accountability construct was incorporated into a modified version of Bandura’s Social Cognitive Theory. Defining accountability and incorporating it into an adherence model will facilitate the development of measures of accountability as well as the testing and refinement of adherence interventions that make use of this critical determinant of human behavior.

Risk versus benefit or risk versus risk: Risk aversion in the medical decision making process

Psoriasis can be debilitating, as even objectively mild cases can have profound impact on a patient’s activities and social interactions. Highly efficacious treatment options are available (1). Despite their high degree of efficacy, however, patients may be hesitant to use treatments due to fear of adverse events, fears which are often exacerbated by risk aversion. Risk aversion is the tendency to avoid uncertain large risks by choosing another option with a more certain, but less beneficial, expected outcome. For example, a risk averse decision would be an investor electing a lower interest rate savings account instead of a high earning, high risk stock with a higher expected rate of return. Humans are naturally risk averse (2). In a study of patients’ risk attitude regarding their health, 74% were either moderately or decidedly risk averse (3). Risk aversion may lead to poor treatment decisions due to patients being unwilling to accept medication risks, despite the likelihood that the medication would be beneficial. When physicians present treatment information to patients, the benefits of treatment are often presented alongside their risks. The tendency toward risk aversion may lead patients to weigh risks more heavily than benefits and thus lead to poor treatment choices. To neutralize risk aversion, treatment benefits can be reframed in terms of the risk of not taking treatment. While the discussion of risk versus risk may not fully overcome patients’ fears, risk versus benefit makes it even more difficult (4). Consider a 60-year-old patient with severe psoriasis who has failed treatment with methotrexate. The next step would be the introduction of a biologic, for which the standard risk versus benefit discussion would revolve around data supporting the efficacy of biologics and their potential rare risks of infection, malignancy, etc (5). The benefits of treatment would be presented as the improvement of symptoms from the current state to an improved state. The decision would be framed around how willing the patient would be to accept the potential risks of the drug for potential disease improvement. This framing could very well discourage risk averse patients from the treatments that would help them. To neutralize the effects of risk aversion and to help patients make a more objective determination, the side effect risks can be compared to the risk of non-treatment. The risk of non-treatment includes continued suffering with skin disease or the development of comorbidities such as cardiac disease or arthritis (6). The patient is no longer presented with one risk and one benefit, but rather, there are now two possible risks being compared. This allows for neutralization of risk aversion and ultimately better positions the patient to make an informed decision regarding their treatment options (Figure 1).

Pilot study of the feasibility of a double-blind, randomized, placebo-controlled localized area ultraviolet phototherapy trial methodology

Localized ultraviolet (UV) phototherapy is an effective treatment for many inflammatory dermatoses.1 Localized UV treatment modalities include excimer lasers, excimer nonlaser devices, and nonexcimer devices.2 In order to delineate the efficacy of the different options, wellcontrolled clinical trials are critical. However, trials comparing the efficacy of phototherapy devices are often not blinded, leading to participation and expectancy biases. The purpose of this study is to test a methodology suitable for robust doubleblind, randomized, placebocontrolled, localized area UV phototherapy intervention trials.

Future Therapeutics in Psoriasis

In recent years, investigations into psoriasis pathophysiology have expanded the development of immunomodulatory and biological molecules. These advancements have transformed treatment regimens for psoriasis by selectively targeting immune signaling molecules. The aim of this chapter is to review the clinical and research data surrounding these emerging treatments, ranging from those undergoing development to those already in clinical trials. Therapies are organized by method of administration (topicals, orals, and injectables) and then phase of clinical trial. Many of these promising medications are small-molecule inhibitors and biologics, while some draw from traditional mechanisms of actions like steroids and vitamin analogs. It is too soon to know how effective these future agents will be and where they will fit into treatment algorithms. It will remain critical for clinicians to be aware of the limitations, important monitoring, and drug safety when selecting these novel treatments. However, even as the psoriasis treatment armamentarium continues to expand, many psoriasis patients may continue to experience recalcitrant disease.

Patients’ preferences for different corticosteroid vehicles are highly variable

Abstract Introduction: Topical corticosteroids, available in an array of vehicles are used to control a variety of inflammatory skin diseases. Patients preferences for different vehicles may affect their willingness to use treatment. We assess corticosteroid vehicle preference and potential impact of topical characteristics on adherence and quality of life in patients with psoriasis. Methods: Subjects with psoriasis were recruited from Wake Forest University Dermatology Clinic. Subjects sampled desoximetasone 0.25% spray, betamethasone valerate 0.1% cream, triamcinolone acetonide 0.1% ointment, fluocinonide 0.05% gel, betamethasone valerate 0.1% lotion, clobetasol propionate 0.05% foam, and fluocinonide 0.05% solution in a predetermined randomized order. Subjects completed a Vehicle Preference Measure, Determinants of Adherence Measure, and a Determinants of Quality of Life Measure. Results: Patients preferences for the various products were highly variable. Regarding Determinants of Adherence, patients perception of absorption of the medication was ranked as ‘quite important/extremely important’ by 85% of total subjects. A majority of patients rated medication side effects as ‘quite important/extremely important’ when asked to consider topical characteristics effect on quality of life. Discussion: There was wide variation in patient preference for topical medication vehicles used for treating psoriasis. Several vehicle characteristics were considered important to adherence. Given the marked variation in vehicle preference, topical treatment should be individualized according to patients preferences.