Sex differences in adverse events from systemic treatments for psoriasis: A decade of insights from the Swiss Psoriasis Registry (SDNTT).

BACKGROUND: Psoriasis is a disease that often requires prolonged systemic treatment. It is important to determine the safety of available therapies. There is currently little insight into sex-specific differences in the safety of systemic psoriasis therapies. OBJECTIVES: To examine the real-world, long-term safety of systemic psoriasis therapies with sex stratification in drug-related adverse events (ADRs). METHODS: Ten-year data from adults with moderate-to-severe psoriasis requiring systemic treatment (conventional systemic therapies [CST], biologics) were obtained from the Swiss psoriasis registry (SDNTT). ADRs were categorized according to the international terminology Medical Dictionary for Regulatory Activities (MedDRA). Safety was assessed by calculating event rates per 100 patient-years (PY). We used descriptive statistics for patient and disease characteristics, and binomial and t-tests to compare treatment groups and sex. RESULTS: In total, 791 patients (290 females) were included with a mean age of 46 years. 358 (45%) received CSTs and 433 (55%) biologics; both groups had similar baseline characteristics except for more joint involvement in patients using biologics (26.86% vs. 14.8%, p < 0.0001). CSTs were associated with a 2.2-fold higher ADR rate (40.43/100 PY vs. 18.22/100 PY, p < 0.0001) and an 8.0-fold higher drug-related discontinuation rate than biologics (0.16/PY vs. 0.02/PY, p < 0.0001). Trends showed non-significant higher serious adverse event rates per 100 PY for biologics (8.19, CI 6.87-9.68) compared to CSTs (7.08, CI 5.39-9.13) (p = 0.3922). Sex stratification revealed a significantly higher overall ADR rate for all treatments in females (1.8-fold for CSTs [57.30/100 PY vs. 31.69/100 PY] and 2.0-fold for biologics [27.36/100 PY vs. 13.9/100 PY], p < 0.0001), and drug-related discontinuation rates for most CSTs in females. CONCLUSION: Females were associated with a significantly higher rate of ADRs and drug-related discontinuation rates. Sex stratification should be taken into consideration when designing studies in the patient-tailored management of psoriasis.

Variables associated with joint involvement and development of a prediction rule for arthritis in patients with psoriasis. An analysis of the Italian PsoReal database.

BACKGROUND: Limited data exist to predict the development of psoriatic arthritis (PsA) in patients with psoriasis (PsO). OBJECTIVE: To analyze factors associated with incident PsA in patients with PsO, and to develop a predictive algorithm for progression to arthritis using a full set of variables and a restricted one applicable to administrative data. METHODS: Cohort study within the PsoReal registry in Italy. Multivariable generalized linear models were used to assess factors associated with PsA and to derive a predictive model. RESULTS: Among 8895 patients, 226 PsA cases were identified (incidence 1.9 per 100 patient-years). Independent predictors in the full model were as follows: female sex, age 40 to 59 years, body mass index ≥ 25, chronic-plaque PsO features, presence of palmoplantar pustulosis, hospitalization for PsO in the last 5 years, and previous use of systemic PsO therapy (area under the receiver operating characteristic curve = 0.74). Female sex, age 40 to 59 years, hospitalization for PsO, and previous use of systemic PsO therapy were independent predictors in the restricted model (area under the receiver operating characteristic curve = 0.72). LIMITATIONS: Lack of other potential predictors for PsA. CONCLUSION: Our models could be used by clinicians and health authorities when planning intervention and population surveillance. Future studies should confirm our models using larger datasets and additional variables.

Adverse events in patients treated with Jak-inhibitors for alopecia areata: A systematic review.

Recently, the impressive efficacy of JAK-inhibitors (JAK-I) in alopecia areata (AA) has been described in several studies; however, to date, there is limited information on the safety of JAK-I in AA patients. For this reason, on 18 August 2022, a systematic review was performed to collect the premarketing and postmarketing data on the safety of JAK-I in patients treated for AA, evaluating for each molecule the reported adverse events (AEs) in indexed literature and their frequency. The keywords 'alopecia areata' AND 'Jak-inhibitors OR Janus-kinase Inhibitors' were searched on PubMed, Embase and Cochrane databases. Of 407 studies retrieved, 28 papers met the requirements and were used in our review, including five RCTs and 23 case series; overall, 1719 patients were included, and the safety of 6 JAK-I was assessed (baricitinib, brepocitinib, deuruxolitinib, ritlecitinib, ruxolitinib and tofacitinib). Systemic JAK-I were well-tolerated, most of the AEs were mild, and the withdrawal rate for AEs was very low and inferior to placebo in controlled studies (1.6% vs. 2.2%). Laboratory abnormalities represented 40.1% of AEs associated with oral JAK-I, which mostly included the rise in cholesterol, transaminase, triglycerides, creatine phosphokinase (CPK) and sporadic cases of neutro/lymphocytopenia. The remaining AEs involved the respiratory tract (20.8%), the skin (17.2%), the urogenital (3.8%), or the gastroenterological (3.4%) tract. Increased rates of infections involved not only the upper (19.0%) and lower (0.3%) respiratory tract, but also the urogenital system (3.6%) and the skin (4.6%). Isolated cases of grade 3 to 4 AEs have been reported, including myocardial infarction, hypertensive urgencies, cellulitis, rhabdomyolysis, neutropenia and high elevation of creatinine kinase. No fatal outcomes were reported. AEs reported with topical formulation included scalp irritation and folliculitis. The main limit of this review is the lack of data related to postmarketing surveillance, which should be maintained on a long-term basis.

Skin hyperpigmentation after sclerotherapy with polidocanol: A systematic review.

Skin hyperpigmentation after sclerotherapy with polidocanol-containing sclerosants is a common local side effect. Sclerotherapists should be familiar with factors that trigger hyperpigmentation after sclerotherapy with polidocanol-containing sclerosants. A systematic literature review of works reporting hyperpigmentation after sclerotherapy for telangiectasias, reticular veins, side branches and truncal varices with polidocanol-containing sclerosants was performed. Reported incidence rates, follow-up periods and potentially triggering factors were assessed and analysed. The search yielded 1687 results; of these, 27 reports met the inclusion criteria. The incidence of hyperpigmentation seemed to increase with higher concentrations of polidocanol and was more evident after sclerotherapy for epifascial veins than for intrafascial truncal veins when the polidocanol concentration was more than 0.25%. Regarding sclerotherapy for telangiectasias and reticular veins, the incidence of hyperpigmentation ranged between 2% and 25% for polidocanol 0.25% (liquid and foam), between 12.5% and 67.9% for polidocanol 0.5% (liquid and foam) and between 13% and 73% for polidocanol 1% (liquid and foam). Regarding truncal veins, the incidence ranged from 7% to 45.8% for polidocanol 1% (liquid and foam), from 16% to 17% for polidocanol 2% (foam) and from 7.4% to 32.5% for polidocanol 3% (liquid and foam). Regarding the treatment of side branches, the incidence of hyperpigmentation ranged from 5.6% to 53% for both foam and liquid sclerotherapy. Regarding the duration of hyperpigmentation, there are few data describing reticular veins and telangiectasias. Hyperpigmentation persisting for more than 6 months has been reported to have an incidence of up to 7.5%. Hyperpigmentation persisting for more than 1 year after foam polidocanol 1%-3% treatment for truncal veins has an incidence ranging from 8.1% to 17.5%. Other factors such as higher volumes and compression therapy after treatment seem to have a minor influence. Data regarding hyperpigmentation after polidocanol-related sclerotherapy are poor and should be improved by higher-quality research.

Dimethyl Fumarate Used as an Effective Treatment for Granuloma Annulare Disseminatum: An Immunohistochemical Case Study.

This investigation demonstrates the use of dimethyl fumarate (DMF) for the treatment of disseminated granuloma annulare (GAD), a rare and chronic inflammatory skin disease. In this case, progressive GAD was treated with DMF, resulting in significant improvement of skin lesions within 5 weeks and complete healing within 7 months. Clinical response was associated with a reduction in inflammatory cells, including both T cell subsets (CD4+ > CD8+), CD183+/CXCR3+ cells, Langerhans cells (CD1a+), myeloid DCs, M1- and M2-like macrophages and the activation marker HLA-DR in immunohistochemical analysis. These findings support the use of DMF as a promising treatment option for this rare skin condition.

Effect of topical application of platelet-rich plasma on chronic venous leg ulcerations.

Wound products that reliably support healing of chronic leg ulcers remain a huge unmet need in clinical practice. Due to the lack of standardized comparable protocols and different systems for platelet-rich plasma (PRP) preparation, there is limited data on healing rates in chronic venous ulcers. In our case series with a total of seven chronic leg ulcers in four patients, we investigated the healing rates based on standardized digital photographs of chronic venous ulcers after application of topical PRP using a digital imaging software. In 5 out of 7 ulcers, the PRP-treated wound half showed faster healing as compared the control half of the wound. In this case series, PRP-treated sides of chronic venous leg ulcers showed a tendency for accelerated healing as compared to nontreated collateral wound side. Our data support the evaluation of topical PRP treatment in the management of chronic venous leg ulcers.

Long-Term Effectiveness and Drug Survival of Apremilast in Treating Psoriasis: A Real-World Experience.

BACKGROUND: Apremilast is an oral phosphodiesterase 4 (PDE4) inhibitor used for the treatment of moderate to severe psoriasis. Long-term data on the effectiveness and drug survival of patients treated with apremilast are limited. OBJECTIVE: The aim of this study was to analyze the characteristics, effectiveness, and drug survival of patients treated with apremilast in a real-world setting. METHODS: We conducted a retrospective cohort study of patients with psoriasis who received at least 1 dose of apremilast between 2015 and 2018. We documented sex; age; type, duration, and severity (using Psoriasis Area Severity Index [PASI] and Dermatology Life Quality Index [DLQI]) of psoriasis; comorbidities; previous treatment modalities; adverse events; and reasons for therapy discontinuation. For drug survival, estimates and efficacy analysis with Kaplan-Meier statistics were used. RESULTS: The drug survival rate of the 93 reviewed patients was 69.5% at 6 months, 34.7% at 12 months, and 25.8% at 24 months after initiating therapy. The median survival duration was 8.0 months. Therapy was discontinued in 66.6 and 27.8% due to loss of efficacy and adverse events, respectively. At 24 months, 35.9% had achieved PASI75 response and 23.7% had achieved PASI90 response. Most observed adverse events were gastrointestinal issues, weight loss, and headache. CONCLUSIONS: Apremilast is an effective and well-tolerated therapy for patients with moderate to severe psoriasis, especially for patients with difficult-to-treat locations and/or contraindications to other biologics. Furthermore, apremilast was used for patients with a history of nonresponse to biologics and was favored for patients with relatively low PASI (<10) and a high DLQI.

Reliability Assessment and Validation of the Skin Hyperpigmentation Index Compared to the Physician Global Assessment Score.

BACKGROUND: The skin hyperpigmentation index (SHI), a new objective method for measuring skin hyperpigmentation, needs validation. OBJECTIVE: To gain evidence of the reliability and validity of the SHI. METHODS: Fifteen raters were divided into 3 groups (5 dermatologists, 5 nondermatologist physicians, and 5 nonphysician clinicians). Each rated 5 pigmented mole lesions with mild-to-severe hyperpigmentation to determine intra- and interrater reliability. All raters photographed the lesions and rated them using the subjective Physician Global Assessment (PGA) score. The same photographs were then assessed based on automatic computer measurement software using the online SHI tool (https://shi.skinimageanalysis.com). RESULTS: The SHI reliability was excellent for all intra- and interrater assessments, while most PGA assessments showed good intra- and interrater agreement. Between-group reliability was excellent for SHI, while moderate-to-good for PGA evaluations. Concordance between the SHI and PGA assessments was strong across all groups of assessors. CONCLUSION: There is evidence that the SHI is a reliable instrument for measuring skin hyperpigmentation, and can be used by nonexperienced clinicians.

Efficacy Assessment of the High-Frequency High-Intensity Focused Ultrasound as a New Treatment for Actinic Keratosis.

BACKGROUND: Actinic keratosis (AK) is the most common precancerous cutaneous lesion, with risk of progression to cutaneous squamous cell carcinoma. In the current study, we evaluated the efficacy of 20-MHz high-intensity focused ultrasound (HIFU), as a new treatment modality for AK. MATERIALS AND METHODS: Patients with AK lesions (grades I-III) treated with HIFU were included in the study. The clinical assessment was performed 3 months after therapy. RESULTS: Twenty-one patients (14 men, 7 women) with 108 AK lesions (grades I-III) were included in the current study. Ages ranged from 62 to 85 years (mean 72.6 years). Clinically complete resolution of the actinic damage in the treated area was detected in 72.2% of lesions. Furthermore, 28 lesions (26%) showed a reduction of the AK grade, or partial response, after the therapy. Most of the patients experienced annoying but short pain during the procedure. However, late adverse effects of the therapy, such as hypopigmentation, hyperpigmentation and erythema were reported only in a small portion of the lesions. CONCLUSIONS: 20-MHz HIFU could be an effective and safe alternative treatment for AK.

Successful Treatment of Iatrogenic Cutaneous Siderosis with Pigment Lasers: A Retrospective Study in 15 Consecutive Patients.

Intravenous ferric carboxymaltose is increasingly used to treat iron deficiency. However, a common side-effect is paravenous extravasation of iron preparations, resulting in cutaneous siderosis. Quality-switched (QS) lasers and, recently, picosecond (PS) lasers have been used to treat these hyperpigmentations with variable success. The optimal treatment protocol remains unclear. The aims of this study were to assess the response of cutaneous siderosis to treatment with pigment lasers and to determine the optimal wavelength, number of treatment sessions and pulse duration. Fifteen patients with cutaneous siderosis on the arms were included. The effectiveness of laser treatment was evaluated using a 5-point standard Physician Global Assessment (PGA) grading system. Differences in continuous variables between distinct groups of patients were assessed with a Mann-Whitney U test. In all 15 patients clearance of at least 50% was obtained. In 12 patients, at least 75% of pigment was removed. In conclusion, pigment lasers are an effective and safe method to treat cutaneous siderosis.

Acute Generalized Exanthematous Pustulosis: Pathogenesis, Genetic Background, Clinical Variants and Therapy.

Acute generalized exanthematous pustulosis (AGEP) is a severe, usually drug-related reaction, characterized by an acute onset of mainly small non-follicular pustules on an erythematous base and spontaneous resolution usually within two weeks. Systemic involvement occurs in about 20% of cases. The course is mostly benign, and only in rare cases complications lead to life-threatening situations. Recent studies highlight the importance of genetic variations in interleukin-36 receptor antagonist gene (IL-36RN) in the pathogenesis of this disease. The physiopathology of AGEP remains unclear, but an involvement of innate and acquired immune cells together with resident cells (keratinocytes), which recruit and activate neutrophils via production of cytokines/chemokines such as IL-17, IL-36, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNFα) and chemokine (C-X-C motif) ligand 8 (CXCL8)/IL-8, has been postulated. Treatment is based on the removal of the causative drug, supportive care, infection prevention and use of potent topical or systemic steroids.

Safety of Antiandrogens for the Treatment of Female Androgenetic Alopecia with Respect to Gynecologic Malignancies.

The most common type of alopecia in women is female androgenetic alopecia (FAGA), characterized by progressive hair loss in a patterned distribution. Many oral therapies, including spironolactone (an aldosterone antagonist), androgen receptor blockers (e.g., flutamide/bicalutamide), 5-alpha-reductase inhibitors (e.g., finasteride/dutasteride), and oral contraceptives, target the mechanism of androgen conversion and binding to its respective receptor and therefore could be administered for the treatment of FAGA. Despite significant advances in the oral treatment of FAGA, its management in patients with a history of gynecological malignancies, the most common cancers in women worldwide, may still be a concern. In this review, we focus on the safety of antiandrogens for the treatment of FAGA patients. For this purpose, a targeted literature review was conducted on PubMed, utilizing the relevant search terms. To sum up, spironolactone seems to be safe for the systemic treatment of FAGA, even in high-risk populations. However, a general uncertainty remains regarding the safety of other medications in patients with a history of gynecologic malignancies, and further studies are needed to evaluate their long-term safety in patients with FAGA and risk factors to establish an optimal risk assessment and treatment selection protocol.

Successful Removal of 17 Tattoos Self-Administered Using Black Eyeliner Ink with Quality-Switched Neodymium-Doped Yttrium Aluminum Garnet 1,064-nm Laser: A Case Report.

Introduction: Tattooing has a rich historical presence in various human civilizations, with the earliest physical evidence dating back to around 3258 BC. While acceptance of tattoos is increasing in the Western world, negative associations remain. Short-pulsed lasers, such as Q-Switched (QS) or picosecond lasers, are the gold standard for tattoo removal. Case Presentation: This case report discusses the successful removal of 17 amateur tattoos, which were self-administered by a 19-year-old female patient using black eyeliner ink and sewing needles. The tattoos, distributed across her body, including the face and hands, were partially or completely removed over 10 sessions using the QS Neodymium-doped Yttrium Aluminum Garnet 1,064-nm laser. Conclusion: The factors that influence the efficacy of tattoo removal are highlighted, including tattoo type, location, and coexisting fibrosis. The psychological and social importance of effective tattoo removal is emphasized, particularly for young people seeking to disassociate from past experiences or affiliations.

Pool Toes: A Case Report.

Pool toes, a sport-related dermatosis, are caused by mechanical friction and water exposure, resulting in a special variant of irritant contact dermatitis. It is common in children, often misdiagnosed, and rarely reported. Here we report a case of a 7-year-old girl who developed this unusual type of frictional dermatitis; a pool toes diagnosis has been made. With topical corticosteroids, favorable results have been achieved. The recovery and healing process will be facilitated if one is aware of the underlying causes of such dermatitis and ceases the triggering factors.

Palmoplantar Pustulosis: A Systematic Review of Risk Factors and Therapies.

Palmoplantar pustulosis (PPP) is a chronic, relapsing, inflammatory disease that can occur alone or in association with arthritis. There is still controversy about whether it should be separated from psoriasis or classified as pustular psoriasis. Furthermore, drug-induced paradoxical PPP is a special variant of PPP that differs from classic PPP in several ways. Treatment of PPP is still challenging, and there are a number of treatment-resistant cases. This review summarizes the risk factors for the development of PPP and the currently available treatment modalities. Female sex, smokers or ex-smokers, obesity, thyroid dysfunction, and treatment with a tumor necrosis factor (TNF)-α inhibitor have been identified as risk factors for the disease's development, severity, and course. Topical treatments and phototherapy are effective for some patients and are used as a first-line or adjuvant treatment modality. Conventional treatments including retinoids and fumaric acid show good effects and can increase the efficacy of treatment with psoralen + ultraviolet light therapy (PUVA). Ciclosporin is fast acting, but relapse mostly occurs immediately after cessation. TNF-α inhibitors are efficient, and an even better response can be achieved with IL-17 and IL-23 blockers as well as apremilast. The effect of Janus kinase inhibitors seems to be promising according to case reports, but further investigations with larger cohorts are needed.