Multi-failure psoriasis patients: characterization of the patients and response to biological therapy in a multicenter Italian cohort.

INTRODUCTION: Patients with psoriasis who have failed multiple biologic drugs have been defined as "multi-failure," although there are no clear data on the characteristics, comorbidities, and best treatment strategies for this population. Nowadays, given the next generation and the number of biologics available, patients are considered multi-failure when ≥4 biologics fail to achieve a good response. METHODS: Demographic characteristics and efficacy of anti-interleukin drugs in multi-failure patients were compared to a cohort of general psoriatic patients treated with IL-23 or IL-17 inhibitors. RESULTS: In total 97 multi-failure patients (≥4 lines of biologics) were compared with 1,057 patients in the general cohort. The current drugs in the multi-failure group were risankizumab (34), ixekizumab (23), guselkumab (21), brodalumab (7), tildrakizumab (5), ustekinumab (4), secukinumab (2), and certolizumab pegol (1). A significant difference was found in the multi-failure cohort for age of psoriasis onset (mean 29.7 vs. 35.1, P < 0.001), concurrent psoriatic arthritis (45.4 vs. 26.9%, P < 0.001), diabetes mellitus (30.9 vs. 10.9%, P < 0.001), and cardiovascular comorbidity (54.6 vs. 39.8%, P = 0.005). In multi-failure patients, current biological therapy showed a good initial response (PASI 90 and 100 of 41.24 and 27.84%, respectively, at 16 weeks); the response tended to decline after 40 weeks. Anti-IL-17 agents showed clinical superiority over IL-23 agents in terms of achieving PASI90 at 28 weeks (P < 0.001) and 40 weeks (P = 0.007), after which they reached a plateau. In contrast, IL-23 agents showed a slower but progressive improvement that was maintained for up to 52 weeks. A similar trend was also seen for PASI100 (28 weeks P = 0.032; 40 weeks P = 0.121). CONCLUSIONS: The multi-failure patient is characterized by many comorbidities and longstanding inflammatory disease that frequently precedes the introduction of systemic biologic therapy. Further studies are needed to identify more specific criteria that could be applied as a guideline by clinicians.

Circadian Oscillations of Minimal Erythema Dose (MED) are Also Influenced by Diet in Patients with Psoriasis: A Chronomedical Study.

INTRODUCTION: Minimal erythema dose (MED) remains a parameter of paramount importance to orient narrow-band (NB)-UVB phototherapy in psoriatic (PsO) patients. Recently, circadian rhythm and diet were recognized as potential MED modulators, but their mutual interaction remains understudied. Thus, we aimed to evaluate the potential diet modulation of MED circadian oscillations. METHODS: In the first phase, a cohort study was performed comparing potential MED oscillations (morning, afternoon, and evening) among omnivorous psoriatic patients before and after a phototherapy cycle and omnivorous healthy controls. The two groups were age-, gender-, skin-type-, MED-, and diet-matched. Then, in the second phase, another cohort study was carried out comparing MED oscillations 24 h after the last phototherapeutic session only in psoriatic patients cleared with NB-UVB and undergoing different diets (vegan, vegetarian, paleo , ketogenic, intermittent circadian fasting, and omnivore). Patients with different diets were age-, gender-, and skin-type matched. RESULTS: In the first phase, we enrolled only omnivores, specifically 54 PsO patients and 54 healthy individuals. Their MED before and after NB-UVB therapy changed significantly among the three different time-points (morning, afternoon, and evening) (p < 0.001). The time effect was statistically significant in both groups before and after phototherapy. In the second phase, we enrolled 144 PsO patients (vegan, vegetarian, paleo, ketogenic, intermittent circadian fasting, and omnivore). MED circadian oscillations preserved a significant difference also after clearance and were influenced by diet type and time of day (p < 0.001). In particular, vegans displayed the lowest MED values, whilst Ramadan fasting showed the highest values in morning, afternoon, and evening. CONCLUSIONS: Diet, like other ongoing therapies, should be reported in the medical records of patients with psoriasis undergoing NB-UVB and patients with lower MEDs should be preferentially treated in the morning when the MED is higher.

Medicinal cannabis products for the treatment of acute pain.

For thousands of years, medicinal cannabis has been used for pain treatment, but its use for pain management is still controversial. Meta-analysis of the literature has shown contrasting results on the addition of cannabinoids to opioids compared with placebo/other active agents to reduce pain. Clinical studies are mainly focused on medicinal cannabis use in chronic pain management, for which the analgesic effect has been proven in many studies. This review focuses on the potential use of medical cannabis for acute pain management in preclinical studies, studies on healthy subjects and the few pioneering studies in the clinical setting.

Frequency of phototherapy for treating psoriasis: a systematic review.

INTRODUCTION: Narrow band ultraviolet B (NB-UVB) and psoralen-ultraviolet A (PUVA) remain inexpensive and effective anti-psoriatic therapies adopted worldwide with different frequency protocols. We aimed to systematically assess the evidence on the effects of different frequency protocols of phototherapy in treating psoriasis. EVIDENCE ACQUISITION: We used the following terms, namely "photochemotherapy," "phototherapy," "psoriasis," "UVB," "UVA" and "ultraviolet therapy," to search the Cochrane Controlled Register of Trials, MEDLINE and Embase databases on August 1, 2019. We organized results using a PRISMA diagram and analyzed bias risks with RoB-2 tool. EVIDENCE SYNTHESIS: We included five randomized controlled trials (RCTs) on oral PUVA and three RCTs on NB-UVB. The five studies on PUVA included a total of 1452 patients with plaque psoriasis and did not find any significant difference in efficacy comparing two- vs. three- vs. four times weekly protocols. The three studies on NB-UVB included a total of 248 patients with plaque psoriasis. No differences in efficacy were reported in comparing different frequencies in delivering NB-UVB, namely twice vs. thrice weekly, twice vs. four times weekly, and thrice- vs. five times weekly protocols. Although protocols with higher treatments frequency per week achieved clearance faster than lower frequency ones, but they did not differ in terms of efficacy. CONCLUSIONS: PUVA and NB-UVB remain effective anti-psoriatic treatments; however further studies are needed to elucidate which protocol may be more effective in different skin phototypes.

Diet-Related Phototoxic Reactions in Psoriatic Patients Undergoing Phototherapy: Results from a Multicenter Prospective Study.

Vegans and vegetarians often consume foods containing photosensitizers capable of triggering phytophotodermatitis. The potential effect of vegan and vegetarian diets on the response of psoriatic patients undergoing phototherapy is not well characterized. We assessed clinical outcomes of vegan, vegetarian and omnivore adult psoriatic patients undergoing band ultraviolet B phototherapy (NB-UVB). In this multicenter prospective observational study, we enrolled 119 adult, psoriatic patients, of whom 40 were omnivores, 41 were vegetarians and 38 were vegans, with phototherapy indication. After determining the minimum erythemal dose (MED), we performed NB-UVB sessions for 8 weeks. The first irradiation dosage was 70.00% of the MED, then increased by 20.00% (no erythema) or by 10.00% (presence of erythema) until a maximum single dose of 3 J/cm2 was reached and constantly maintained. All the enrolled patients completed the 8 weeks of therapy. Severe erythema was present in 16 (42.11%) vegans, 7 (17.07%) vegetarians and 4 (10.00%) omnivores (p < 0.01). MED was lowest among vegans (21.18 ± 4.85 J/m2), followed by vegetarians (28.90 ± 6.66 J/m2) and omnivores (33.63 ± 4.53 J/m2, p < 0.01). Patients with severe erythema were more likely to have a high furocumarin intake (OR 5.67, 95% CI 3.74-8.61, p < 0.01). Vegans consumed the highest amount of furocumarin-rich foods. A model examining erythema, adjusted for gender, age, skin type, MED, phototherapy type, number of phototherapies and furocumarin intake, confirmed that vegans had a lower number of treatments. Vegans had more frequent severe erythema from NB-UVB, even after adjustment of the phototherapy protocol for their lower MED. Assessing diet information and adapting the protocol for vegan patients may be prudent.

NB-UVB plus oral Polypodium leucotomos extract display higher efficacy than NB-UVB alone in patients with vitiligo.

Polypodium leucotomos displayed a synergic effect with NB-UVB in psoriasis, but its application on vitiligo remains understudied. The aim of this study was to investigate whether oral supplementation with leaves extract of Polypodium leucotomos (PL) improves narrow band (NB) UVB phototherapy-induced repigmentation. Forty-four patients with generalized vitiligo were enrolled in this randomized, prospective, placebo controlled study. Twenty-three patients were randomly selected to receive combined treatment with NB-UVB phototherapy and 480 mg oral PL twice daily while 21 patients received NB-UVB phototherapy combined with placebo. All subjects were treated with NB-UVB twice weekly for 6 months. Our results demonstrated that oral PL combined with NB-UVB improved repigmentation as well as increased the response rate compared with patients treated with NB-UVB alone (47.8% vs 22%). Our study suggests that oral supplementation of PL and NB-UVB phototherapy enhance the extent of repigmentation.

Nanodermatology-based solutions for psoriasis: State-of-the art and future prospects.

Nanodermatology is an emerging, multidisciplinary science, arising from the convergence of nanotechnology, pharmacology, physics/biophysics, chemistry/biochemistry, chemical engineering, material science, and clinical medicine. Nanodermatology deals with (a) skin biology, anatomy, and physiology at the nanoscale ("skin nanobiology"), (b) diagnosis performed by means of novel diagnostic devices, assisted by nanobiotechnologies ("nanodiagnosis"), and (c) treatment through innovative therapeutic agents, including phototherapy ("photonanotherapy"/"photonanodermatology") and systemic/topical drug administration ("nanotherapy") at the nanoscale, and drug delivery-such as transdermal or dermal drug delivery (TDDD/DDD)-enhanced and improved by nanostructures and nanodrugs ("nanodrug delivery"). Nanodermatology, as a super-specialized branch of dermatology, is a quite recent specialty: the "Nanodermatology Society" founded by the eminent dermatologist Dr. Adnan Nasir, was established in 2010, with the aim of bringing together different stakeholders, including dermatologists, nanotechnology scientists, policy-makers and regulators, as well as students and medical residents. Psoriasis has a prevalence of 2-3% worldwide and imposes a severe clinical and societal burden. Nanodermatology-based solutions appear promising for the proper treatment and management of psoriasis, assisting and enhancing different steps of the process of health-care delivery: from the diagnosis to the therapeutics, paving the way for a personalized approach, based on the specific dysregulated biomarkers.

Italian guidelines for therapy of atopic dermatitis-Adapted from consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis).

Atopic dermatitis (AD) therapeutic approach calls for a long-term treatment. Treatment options for AD have recently undergone a revolutionary change by the introduction of the first biologic drug. Availability in daily practice of the last version of international AD guidelines, taking peculiarities of the country into account, can contribute to good clinical practice in Italy. To adapt European Dermatology Forum (EDF) guidelines for AD to the Italian medical-legal context, the EDF guidelines were assessed independently by two independent Italian renowned experts in the field and further integrated with articles published and systematically reviewed before May 2019. The first draft was collegially corrected and updated by the members of the SIDEMAST, ADOI, and SIDAPA. Recommendation levels (A; B; C; D) were graded based on the evidence levels (1-4). The adapted guidelines presented here focus on topical and systemic therapies in AD patients, both children and adults. As opposed to previous Italian guidelines, they include indications about biologics. New relevant evidence available from very recent literature and peculiarities of the Italian medical and legal context have been integrated in the revision process. If compared to general guidelines for AD not adapted to a specific national and cultural context, a revision for specific Italian needs is now available: It comprises the option of implementing the new biologic treatments and is likely to provide an important contribution to the improvement of clinical practice in Italy. Cooperation between patients, dermatologists, allergologists, and pediatricians remains mandatory in AD management. The authors of the present revision recommend an update of the Italian guidelines to be performed at least every second year.

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) demonstrates distinct autoimmune and autoinflammatory disease associations according to the adjuvant subtype: Insights from an analysis of 500 cases.

BACKGROUND: We investigated the pattern of reported immune diseases in the international ASIA syndrome registry. METHODS: Data from 500 subjects exposed to adjuvants from the ASIA syndrome international registry were analysed. RESULTS: The patient mean age was 43 ±â€¯17 years and 89% were female. Within the reported immune diseases, 69% were well-defined immune diseases (autoimmune, autoinflammation, and mixed pattern diseases). Among the well-defined immune diseases following the exposure to adjuvants, polygenic autoimmune diseases were significantly higher than autoinflammatory disorders (92.7% vs 5.8%, respectively, p < 0.001). Polygenic autoimmune diseases such as connective tissue diseases were significantly linked to the exposure to HBV vaccine (OR 3.15 [95%CI 1.08-9.23], p = 0.036). Polygenic autoinflammatory diseases were significantly associated with the exposure to influenza vaccination (OR 10.98 [95%CI 3.81-31.67], p < 0.0001). CONCLUSIONS: Immune conditions following vaccination are rare, and among these, polygenic autoimmune diseases represent the vast majority of the well-defined immune diseases reported under the umbrella ASIA syndrome. However, vaccines benefit outweighs their autoimmune side effects.

The Impact of Ramadan Fasting on the Reduction of PASI Score, in Moderate-To-Severe Psoriatic Patients: A Real-Life Multicenter Study.

Fasting during the month of Ramadan consists of alternate abstinence and re-feeding periods (circadian or intermittent fasting). Nothing is currently known on the impact of this kind of fasting on psoriasis. A sample of 108 moderate-to-severe plaque psoriasis patients (aged 42.84 ± 13.61 years, 62 males, 46 females) volunteered to take part in the study. A significant decrease in the "Psoriasis Area and Severity Index" (PASI) score after the Ramadan fasting (mean difference = -0.89 ± 1.21, p < 0.0001) was found. At the multivariate regression, the use of cyclosporine (p = 0.0003), interleukin-17 or IL-17 blockers (p < 0.0001), and tumor necrosis factor or TNF blockers (p = 0.0107) was independently associated with a low PASI score, while the use of apremilast (p = 0.0009), and phototherapy (p = 0.0015) was associated with a high PASI score before the Ramadan fasting. Similarly, the consumption of cyclosporine (p < 0.0001), IL-17 blockers (p < 0.0001), mammalian target of rapamycin or mTOR inhibitors (p = 0.0081), and TNF blockers (p = 0.0017) predicted a low PASI score after the Ramadan fasting. By contrast, narrow band ultraviolet light B or NB-UVB (p = 0.0015) was associated with a high PASI score after Ramadan fasting. Disease duration (p = 0.0078), use of apremilast (p = 0.0005), and of mTOR inhibitors (p = 0.0034) were independent predictors of the reduction in the PASI score after the Ramadan fasting. These findings reflect the influence of dieting strategy, the biological clock, and circadian rhythm on the treatment of plaque psoriasis.

Fasting and Its Impact on Skin Anatomy, Physiology, and Physiopathology: A Comprehensive Review of the Literature.

Skin serves as the first protective line and barrier of the body. Like many other organs, skin can be affected by several disorders in response to external factors such as pathogens, ultraviolet light, and pollution, as well as endogenous alterations related to aging and/or oxidative stress disturbance. Researchers have reported new insights into how skin cells are altered in response to caloric restriction diets in mammals. One of the most well-known caloric restriction diets is the Ramadan intermittent fasting, which is a radical change in the diet plan of practitioners for the period of one lunar month. Ramadan fasting represents the fourth of the five pillars of the Islamic creed. Even though infirm individuals are waived to take part in this religious duty, patients with various health problems, including those with different skin disorders, might choose to share this event with peers and family members. No standardized protocols or guidelines exist, however, to advise their physicians on the proper management of their patients' condition during fasting. With an increasing Muslim population living in Western countries, this topic has started to draw substantial attention, not only of Middle-Eastern physicians, but also of clinicians in the West. For this purpose, we carried out a comprehensive overview on the topic. Our main findings are that: (1) there is a strong need for evidence-based suggestions and guidance. Literature on the impact of the Ramadan fasting, as well as of other kinds of fasting, on skin diseases is scarce and of poor quality, as well as the information available from the Internet; (2) patients willing to fast should be advised about the importance of taking proper treatments or consider alternative options including administration of trans-dermal/topical drugs, as they are permitted during daylight hours. Further, non-compliance has important, clinical and economic implications for an effective patient management.