Dietary habits of psoriatic patients treated with dimethyl fumarate and drug-related side effects: results from an observational study.

BACKGROUND: Despite its favorable long-term safety profile, side effects during dimethyl fumarate (DMF) treatment for psoriasis are not uncommon and may lead to treatment suspension. The association between side effects, especially gastrointestinal, and dietary habits has not yet been specifically addressed. METHODS: This observational, cross-sectional study aimed to assess the dietary habits of patients with moderate-to-severe plaque psoriasis in treatment with DMF who attended three Italian psoriasis clinics. Demographic and clinical data, including any side effects, were collected from the patients' medical records. A self-administered questionnaire recorded and scored: 1) if meals are eaten regularly or not; 2) daily intake at meals of fatty foods, milk and dairy products, alcohol, fruit and vegetables; and 3) in the case of side effects, the time between eating and their onset. RESULTS: We included 53 patients in treatment with DMF at a daily dose of 232.4±194.1 mg for 38±29.8 weeks. Thirty-eight (71.7%) reported side effects, namely flushing (60.5%), diarrhea (44.7%), gastralgia (29%) and nausea (15.8%). Overweight seemed associated with the occurrence of side effects. In 47.4% of subjects, side effects appeared within 2 hours of having a meal. Daily fat intake appeared to protect against side effects, albeit without statistical significance; skipping meals was correlated with their onset in subjects complaining of diarrhea. CONCLUSIONS: Finding some correlation between dietary habits and occurrence of side effects during DMF treatment requires further investigation with the aim of developing possible strategies to improve its tolerability and retention rate.

A New Hybrid Therapeutic Approach to Solitary Keratoacanthoma: Complete Recovery in Six Patients.

Introduction: Solitary keratoacanthoma (SKA) is generally considered as a well-differentiated form of squamous cell carcinoma, but it usually runs a benign course and a not aggressive behavior. Diagnostic criteria, prognosis, and treatment of SKA are not fully defined yet. Surgical treatment with fusiform excision represents the gold standard; nonoperative intralesional therapy of KA is uncommon but may provide a valid option in some categories of patients. Case Series Presentation: We report our experience regarding the treatment of SKA with a hybrid treatment consisting of a minimally invasive technique such as curettage followed by intralesional corticosteroid administration in the same session. Six patients affected with KA were treated ending in a complete resolution, with good esthetic outcome, no relapse after 1 year, and satisfaction of the patients. Discussion and Conclusion: The combined treatment allows us on the one hand to avoid radical surgery in selected patients and particular anatomic areas and on the other the side effects that the use of intralesional chemotherapy/immunosuppressive drugs can entail.

Secukinumab Loss of Efficacy Is Perfectly Counteracted by the Introduction of Combination Therapy (Rescue Therapy): Data from a Multicenter Real-Life Study in a Cohort of Italian Psoriatic Patients That Avoided Secukinumab Switching.

Since psoriasis (PsO) is a chronic inflammatory disease, patients may experience a drug failure also with very effective drugs (i.e., secukinumab) and, consequently, dermatologists have two therapeutic options: switching or perform a combination therapy (rescue therapy) to save the drug that had decreased its efficacy. At the moment no studies focused on combination/rescue therapy of secukinumab, so we performed a 52-weeks multicenter retrospective observational study that involved 40 subjects with plaque psoriasis that experienced a secondary failure and were treated with combination therapy (ciclosporin (n = 11), MTX (n = 15), NB-UVB (n = 7) and apremilast (n = 7)). After 16 weeks of rescue/combination therapy, PASI and a DLQI varied respectively from 8 [7.0-9.0] and 13 [12.0-15.0], to 3 [2.8-4.0] and 3 [2.0-3.3]), suggesting a significant improvement of daily functionality and quality of life. Results were maintained at 52 weeks. No side effects were experienced during the study. Secukinumab remains a safety and effective drug for PsO patients also in the IL-23 and JAK inhibitors era. The rescue therapy is a valid therapeutic option in case of secukinumab secondary failure.

Use of Apremilast® in the psoriasis treatment: a real-life multicenter Italian experience.

BACKGROUND: Apremilast® (Amgen, Thousand Oaks, CA, USA) is the first small molecule approved for the treatment of moderate-to-severe psoriasis in adult patients; however, real-life data are still limited. We investigated the effectiveness and safety of this drug in a multicenter real-world setting. METHODS: We retrospectively reviewed data from all psoriatic patients who received at least one dose of Apremilast® (Amgen) and collected demographic data and medical history at baseline and periodically for 36 months. RESULTS: A total of 111 patients entered in the study. The mean drug survival duration was 21.8±10.6 months; however, it was significantly shorter when comorbidities were ≥3 and if biologic drugs were previously administered. ΔPASI90 was achieved in 29% of patients and ΔPASI50 in 68% at T4; the rate of ΔPASI improvement increased progressively at T12, T24, T36 in patients who continued to receive Apremilast® (Amgen). At the end of the study 50 patients discontinued the treatment because of adverse events (19.8%), primary failure (19%) or secondary failure (6.3%). CONCLUSIONS: Apremilast® (Amgen) proved to be an effective, safe, and manageable drug, showing effectiveness also in difficult-to-treat patients with psoriasis, with a favorable tolerability profile and a potentially valid weight loss effect. We believe that treating patients with few comorbidities who are naive to biological therapy may result in higher response rates and longer mean drug survival.

Does psoriasis influence female sexual dysfunction? A multicentric Italian case-control study.

BACKGROUND: Psoriasis has a significant impact on quality of life and affects the sexual sphere in 25-70% of patients. The aim of this study is to determine the prevalence of sexual dysfunction in female patients with psoriasis and to assess the possible correlation of sexual dysfunction with disease severity, genital involvement, age and some comorbidities. METHODS: In this prospective case-control study, all female patients with psoriasis followed at three Psoriasis Outpatient Services were divided into two groups depending on psoriasis severity assessed by the Psoriasis Area Severity Index. Both psoriatic patients and female controls without psoriasis were given the Female Sexual Function Index (FSFI) questionnaire. RESULTS: One hundred forty female patients with psoriasis were evaluated, 70 with mild disease and 70 with moderate-severe disease, and compared with 70 female controls without psoriasis. According to FSFI Score, prevalence of sexual dysfunctions was significantly higher in moderate-severe psoriatic patients compared to controls. Psoriatic women under the age of 46 presented lower FSFI scores than women over 46. No correlation between genital localization of psoriasis and worsening of sexual health was found. Diabetes mellitus and hypertension were significantly associated with sexual dysfunction, whereas the smoking habit did not significantly affect the sexual sphere of these patients. CONCLUSIONS: Sexual dysfunction should be routinely investigated in female patients with psoriasis in the case of moderate-severe disease due to its negative impact on quality of life, especially in younger women and in presence of diabetes mellitus and hypertension.

Seven years-experience of adalimumab therapy for Hidradenitis Suppurativa in a real-life dermatologic setting.

INTRODUCTION: Hidradenitis Suppurativa (HS) often causes severe impairment of the quality of life of patients affected, as it is characterized by recurrent relapses of inflammation and predisposes to retractive scars, with severe alteration of anatomy of the affected regions. Adalimumab is currently the only approved long-term biological therapy for this disease. MATERIAL AND METHOD: We retrospectively review the data of HS patients treated with Adalimumab at the 'Hidradenitis Suppurativa Clinic', University of Ferrara, Italy since the drug was first available to October 2020. The aim is to describe our real-life experience in a clinical outpatient service. We assessed the main demographic features, therapy duration, reasons of suspension and efficacy (evaluated by HiSCR - Hidradenitis Score) in relation to surgical procedures, hospitalization, number of areas involved by the disease and BMI > 30. We also assessed the aspects related to the use of adalimumab's biosimilar. RESULTS: Data on 76 patients, with a mean age of 38.26 ± 14.74 years and mean BMI 28.10 ± 5.92 were collected. Most of the treated patients had Hurley stage III (58/76); mean Sartorius score was 115.5 ± 55.86, mean IHS4 was 76.1 ± 44.3. A statistically significant correlation between hospitalization and cessation of adalimumab, the loss of the achievement of the HiSCR, and surgery was found. No need to do surgery was a protective factor against the failure of adalimumab treatment, meaning that the most severe cases are more likely to fail the biological therapy. CONCLUSION: New scenarios are opening up in clinical practice: the arrival of biosimilars allow greater sustainability of expenditure, while the anti-IL17 allow the patient who has failed therapy with adalimumab a valid and safe therapeutic option to be undertaken. A comprehensive care including hospitalization, a specific antibiotic therapy and surgical treatment is often mandatory to achieve a satisfactory control of the disease.

Cutaneous squamous cell carcinoma in patients with chronic lymphocytic leukemia: a systematic review of the literature.

The continuous improvement of life expectancy of patients with chronic lymphocytic leukemia (CLL) has resulted in increased risk of second primary malignancy that potentially may affect survival and quality of life of CLL patients. We performed a systematic review to assess the risk and the clinical-pathological features and prognosis of cutaneous squamous cell carcinoma (cSCC) in patients with CLL. We searched PubMed, Embase, and Cochrane Central Register of Control Trials databases for articles published from database inception to December 31, 2019. English-language studies reporting original data on patients with a specific diagnosis of CLL and cSCC were included. Data were extracted using a standardized extraction form, and any discordance was resolved by consensus. Descriptive data were generated by pooling patients from eligible studies. Of the 4588 non-duplicate records identified, 55 articles met our inclusion criteria. These studies reported that CLL patients have a 3.2% prevalence of cSCC, with an 11.5% cSCC-related lethality and an overall risk of metastasis of 5.7% (7.3% for regional lymph node involvement and 3.8% for distant metastasis). The quality of evidence was limited by the high heterogeneity in the design, populations, and objectives of the included studies. This systematic review suggests that cSCC in CLL patients tends to behave less aggressively compared with the solid organ transplant recipients but has a higher morbidity and mortality than in the general population. Future prospective studies are needed to increase the quality of evidence and to determine the best treatment modalities and screening intervals for these patients.

Switching infliximab in psoriatic patients during COVID-19 pandemics: A real-life retrospective study comparing intra-versus interclass switching strategies.

During this pandemic, dermatological infusion centers were partially unavailable, suspended or even reconverted to guest COVID-19 patients, consequently infliximab (IFX) infusions became challenging for their both logistic arrangement and also for patients' COVID-19 phobia. This 48 weeks follow-up retrospective observational study included 37 PsO patients that underwent IFX SB2 during pandemic in two primary dermatological referral centers. In 23 (62.1%) we had to switch from IFX to other biologics, not motivated by adverse reactions, contraindication or even loss of response but only to pandemic related conditions. Nine patients underwent interclass switching and 15 underwent intraclass switching; interestingly 2 patients that underwent adalimumab SB-5 switched back to IFX. Interclass switching was privileged in elder patients and smokers. All patients at week 48 achieved PASI 100. Intra- and interclass switchings are both safe and effective strategies in psoriatic patients with COVID-19 phobia and/or difficulties to undergo infliximab infusions.

Dimethyl fumarate treatment for psoriasis in a real-life setting: A multicentric retrospective study.

Dimethyl fumarate (DMF) is a fumaric acid esters derivate approved for plaque psoriasis as first-line systemic therapy. It has been available in Italy since 2017 and an increasing number of patients are treated with this drug. To evaluate DMF effectiveness, side effects and drug survival in a dermatological real-life setting. We performed a retrospective multi-center study in five dermatologic clinics in Emilia-Romagna, Northern Italy, which included all consecutive patients affected by moderate-severe psoriasis treated with DMF. We assessed effectiveness (in terms of PASI50 and PASI75 in an intention to treat observation) and safety (occurrence of side effects) of DMF and their association with demographic and disease characteristics, mean daily dose taken and treatment discontinuation. We included 103 patients, 78 (75.72%) had at least one comorbidity including 19 (18.44%) with a history of cancer; the mean treatment duration was 23.61 ± 17.99 weeks (min 4, max 130) and the mean daily dose was 262.13 ± 190.94 mg. Twenty-four patients (23.30%) reached PASI75 at week 12, while a further 18 patients (17.47%) reached it at week 26. Side effects occurred in 63 patients (61.16%), the most frequent were diarrhea, epigastric discomfort, nausea, and flushing. Sixteen patients (15.53%) showed an alteration of laboratory tests. In some cases side effects were transitory, while in 53 patients (51.45%) they led to cessation of therapy. The median daily dose showed a direct association with PASI50 achievement and an indirect association with treatment discontinuation. Our study shows the peculiarities of DMF in a real-world setting: effectiveness is often reached after 12 weeks of treatment and side effects could limit the continuation of the therapy but, at the same time, DMF has no major contraindications and, due to the wide range of dosage, it can allow both to manage side effects and to personalize the prescription for each patient.

Integrated metabolomic analysis and cytokine profiling define clusters of immuno-metabolic correlation in new-onset psoriasis.

The association between the metabolic profile and inflammatory cytokines in psoriasis is poorly understood. We analyzed the metabolic and cytokine/chemokine profiles in serum and skin from patients with new-onset psoriasis and healthy subjects (n = 7/group) by HR-MAS NMR and Bio-Plex immunoassay. Immuno-metabolic correlation matrix was analyzed in skin and serum to identify a potential immune-metabolic signature. Metabolomics analysis showed a significant increase in ascorbate and a decrease in scyllo-inositol, and a trend towards an increase in eight other metabolites in psoriatic skin. In serum, there was a significant increase of dimethylglycine and isoleucine. In parallel, psoriatic skin exhibited an increase of early inflammatory cytokines (IL-6, IL-8, TNF-α, IL-1ß) and correlation analysis highlighted some major clusters of immune-metabolic correlations. A cluster comprising scyllo-inositol and lysine showed correlations with T-cell cytokines; a cluster comprising serine and taurine showed a negative correlation with early inflammatory cytokines (IL-6, G-CSF, CCL3). A strong positive correlation was enlightened between glutathione and inflammatory cytokines/angiogenesis promoters of psoriasis. The integration of metabolic and immune data indicated a molecular signature constituted by IL-6, IL1-ra, DMG, CCL4, Ile, Gly and IL-8, which could discriminate patients and healthy subjects and could represent a candidate tool in the diagnosis of new-onset psoriasis.

Tetracyclines and photosensitive skin reactions: A narrative review.

Tetracyclines are a group of broad-spectrum antibiotics largely employed in infectious, dermatological and surgical fields. Some adverse events may occur during treatment, including photosensitivity reactions, which are divided in phototoxic or photoallergic. We performed a systematic search on Pubmed, Cochrane and Embase from database inception to August 9, 2020 aim to summarize all available papers on photosensitive reactions related to tetracyclines in all clinical settings where they are used on human being. On the basis of our inclusion criteria, we selected only randomized controlled trials, open comparative trials and prospective cohort studies performed on both volunteers and patients, moreover we included a pharmacovigilance register. Thirty-eight articles met inclusion criteria, describing photo-sensitive effects due to doxycycline, minocycline, tetracycline, lymecycline, sarecycline, demethylchlortetracycline, chlortetracycline and metacycline, across six diagnoses (acne, Lyme disease, Gulf Veteran Illness, adbominal aortic aneurysms, traveler's diarrhea and pterygium) and several volunteers who were deliberately exposed to natural or artificial light sources. Not all drugs belonging to tetracyclines class are available to date, moreover the studies included lacked a homogeneous design and most of them involved a scarce number of patients, including reactions induced in volunteers during photo-testing. Available data on incidence, severity and clinical relevance of tetracyclines-related photo-sensitive reactions are scarce, heterogeneous and weak. What we can extrapolate is that some tetracyclines are more often related to phototoxic skin reactions than others and some of those seem to have a very low risk of phototoxicity.

Comparative study of imiquimod 3.75% vs. photodynamic therapy for actinic keratosis of the scalp.

BACKGROUND/PURPOSE: To assess efficacy, tolerability, adverse effects, recurrence, and aesthetic results of imiquimod 3.75% vs. photodynamic therapy with 5-aminolaevulinic acid (MAL-PDT) for actinic keratosis (AK). METHODS: A small randomized, intraindividual right-left pilot study for AK treatment of multiple scalp lesions was performed. Patients were treated with imiquimod and subsequently MAL-PDT (on opposite sides of the scalp) 14 days apart. Study end points were evaluated with clinical and dermoscopic examinations at 1, 3, 6, and 12 months. RESULTS: Nine male bald patients were enrolled. Imiquimod achieved a slightly higher overall clearance rate than MAP-PDT (68.1% vs 56.5%). According to AK degree of severity, clearance rates were greater for degree I and III with imiquimod (68.8%, 64.5% and 75% with imiquimod vs. 48%, 69.8%, and 66.7% for MAL-PDT, respectively). At 12 months, a slightly higher total recurrence rate was noted for imiquimod compared with MAL-PDT (9.9% vs. 8.6%); new lesions were 2 degree I for imiquimod and 4 degree I for MAL-PDT. For both treatments, pain was moderate/strong (even if MAL-PDT seems to be less tolerable) adverse effects are common and transient; aesthetic results excellent. CONCLUSION: Both imiquimod and MAL-PDT were effective in the reduction in the number of AK. In the long-term, both present a good effectiveness maintained over time with excellent aesthetic results. A combination or sequential therapy could optimize the management of the cancerization field.

Helicobacter pylori infection in psoriatic patients during biological therapy.

BACKGROUND: Psoriasis is a relapsing inflammatory disease exacerbated by many triggers. Helicobacter pylori (H. pylori) is a Gram-negative bacterium causing the liberation of many cytokines and having a role in systemic inflammation. We assessed over a period of 12 months the presence of H. pylori in psoriatic patients undergoing biologic therapy and how PASI improved after its eradication. METHODS: We performed an interventional, prospective, cohort, exploratory and mono-centric study in patients affected by moderate-severe psoriasis during biological therapy to assess the correlation between psoriasis (moderate to severe forms), and H. pylori infection. We also checked if the bacterial eradication could improve the severity of psoriasis throughout the variation of PASI over a 12-month period. RESULTS: The prevalence of H. pylori was 35%. The average of PASI improved in H. pylori positive patients after the eradication (confidence interval: 33-44; P=0.023). H. pylori positive patients were more likely to have psoriatic arthropathy (P=0.049). Gastrointestinal symptoms (such as epigastric pain, postprandial heaviness, pyrosis) were found in only 31.3% of H. pylori positive patients. CONCLUSIONS: Since the H. pylori infection is often asymptomatic, it can be useful to perform the 13C-Urea breath test, and to eradicate it before to start the psoriasis therapy in order to decrease the level of inflammation.