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.

Lasers for the treatment of psoriasis: a systematic review.

INTRODUCTION: Phototherapy has been one of the first and still frequently used treatment modality for psoriasis. In the last decades, different types of lasers have been used for the treatment of psoriasis and other inflammatory skin diseases with variable success. AREAS COVERED: Efficacy and safety of laser devices and intense pulsed light for the treatment of psoriasis. The literature search was conducted using the bibliographic databases MEDLINE, EMBASE, and Cochrane. Search terms included 'laser' AND 'psoriasis,' 'IPL' AND 'psoriasis,' 'intense pulsed light' AND 'psoriasis.' EXPERT OPINION: Due to its high efficacy and safety profile, 308-nm Excimer laser retains its specific place in the treatment of plaque psoriasis as a first- or second-line therapy in mild disease or as an adjuvant treatment in case of partial response to systemic treatments in moderate-to-severe disease. Vascular lasers remain a last line therapy that can be tried in patients with recalcitrant limited plaques or nail affection. They are easy to apply and have a very good safety profile and tolerability, but the efficacy is limited. Fractional ablative lasers for application of laser-assisted drug delivery appear interesting and a topic for further research. When using lasers for psoriasis, a good pre-treatment is mandatory.

Integrated care pathways and the hub-and-spoke model for the management of non-melanoma skin cancer: A proposal of the Italian Association of Hospital Dermatologists (ADOI).

The term non-melanoma skin cancer (NMSC) refers to skin cancer different from melanoma, and it is usually restricted to basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and their pre-cancerous lesions, e.g., actinic keratosis. These conditions represent the most frequent tumors in Caucasians and are characterized by an increasing incidence worldwide and a high socio-economic impact. The term Integrated Care Pathway (ICP) refers to "a complex intervention for the mutual decision making and organization of care processes for a well-defined group of patients during a well-defined period". The purpose of this paper is to present a proposal from the Italian Association of Hospital Dermatologists (ADOI) for an ICP organization of care of NMSC, considering the hub-and-spoke model in the different geographical areas. This proposal is based on the most recent literature and on documents from the Italian Association of Medical Oncology (AIOM), the European consensus-based interdisciplinary guidelines from the European Association of Dermato- Oncology (EADO), and the National Comprehensive Cancer Network (NCCN). We initially discuss the NMSC outpatient clinic, the role of the multidisciplinary working groups, and the hub-and-spoke model regarding this topic. Then, we define the ICP processes specific for BCC and SCC. The ICP for NMSC is an innovative strategy to guarantee the highest possible quality of health care while the hub-andspoke model is crucial for the organization of different health care structures. Considering the importance on this topic, it is essential to create a valid ICP together with an efficient organization within the different geographical areas.

Biological treatment for psoriasis and the risk of herpes zoster: results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR).

Purpose: To describe the risk of herpes zoster (HZ) in patients with psoriasis and its relation to non-biologic systemic therapies or biologic treatment. Materials and methods: Psoriasis Longitudinal Assessment and Registry (PSOLAR) is an international, prospective, registry that follows adult patients with psoriasis eligible to receive non-biologic systemic therapies or biologic therapies. Mutually exclusive therapy cohorts were defined. HZ incident rates were calculated for each therapy cohort and rates between cohorts were compared using hazard ratios (HR) adjusted for potential confounders, in new users and prevalent-exposure patients. Results: A total of 55 HZ events were identified in 10,469 patients in PSOLAR. The adjusted hazard ratio in the overall study population (new user and prevalent-exposed patients) was 2.22 (95% CI: 0.82-5.97; p = .116) for tumor necrosis factor-α (TNF) inhibitors, 2.73 (0.98-7.58; p = .054) for ustekinumab, and 1.04 (0.20-5.41; p = .966) for methotrexate versus reference (combined phototherapy, systemic steroids, topical therapy, and immunomodulators other than methotrexate). Conclusions: Exposure to ustekinumab, TNF-α inhibitors, and methotrexate was not associated with a statistically significant increased risk of HZ. However, HRs were elevated for ustekinumab and TNF-α inhibitors; a larger number of HZ events would be needed to assess the presence or absence of risk.

Evaluation of Risk of Major Adverse Cardiovascular Events With Biologic Therapy in Patients With Psoriasis.

BACKGROUND: Psoriasis is associated with increased risk of major adverse cardiovascular events (MACE). OBJECTIVES: Compare MACE risk with biologics vs topical/phototherapy use. METHODS: Psoriasis Longitudinal Assessment Registry (PSOLAR) is an international psoriasis registry of patients eligible to receive biologic/systemic treatments prospectively. MACE is defined as myocardial infarction, stroke, or cardiovascular death. Biologic cohorts, including tumor necrosis factor-alpha (TNF-α) inhibitors (ie, adalimumab, etanercept, and infliximab) and ustekinumab, combined and by class, were compared with a topical/phototherapy cohort. Incidence rates of MACE per 100-patient-years (100PY) with 95% confidence intervals (95% CI) are reported. Multivariate analyses were performed to evaluate the effect of treatment on the risk of MACE adjusting for confounders. RESULTS: Analyses included 7550 patients: 6767 in the combined biologics cohort (3949 and 2818 in the TNF-α inhibitors and ustekinumab cohorts, respectively) and 783 in the topical/phototherapy cohort. Mean duration of exposure was approximately 2.8 years (combined biologics) and 4.1 years (topical/phototherapy). A total of 52 MACE were reported; MACE incidence rates were 0.22/100PY (95% CI: 0.16, 0.30) for the combined biologics cohort (TNF-α inhibitors [0.20/100PY (0.12, 0.31)] and ustekinumab [0.24/100PY (0.15, 0.37]) and 0.34/100PY (0.17, 0.61) for the topical/phototherapy cohort. For the combined biologics (hazard ratio=0.92; 95% CI [0.426, 1.988]), TNF-α inhibitor (0.85 [0.373, 1.928]), and ustekinumab (1.03[0.440, 2.402]) cohorts, treatment was not associated with increased risk of MACE versus the topical/phototherapy cohort. CONCLUSION: Based on data accumulated to date in PSOLAR, treatment with biologics did not have an impact on the risk of MACE in patients with moderate-to-severe psoriasis.

J Drugs Dermatol. 2017;16 (10):1002-1013.

Double phase treatment with flashlamp-pumped pulsed-dye laser and long pulsed Nd:YAG laser for resistant port wine stains in adults. Preliminary reports.

BACKGROUND: Flashlamp-pumped pulsed (FLPP) dye laser still represents the standard treatment for the majority of port wine stains (PWSs), but the results on thick PWSs remain unpredictable, and many of these lesions fail to completely respond. Our aim was to report on the results obtained on unresponsive PWSs to standard laser treatments, by using a double phase laser treatment strategy using two laser passes in the same session. METHODS: Eleven adult patients with facial PWS resistant to dye laser were enrolled. Laser sessions were scheduled every 8 weeks, and each of them consisting of two laser passes. In phase one, two different laser wavelengths (595 nm and 1064 nm) were delivered consecutively to each affected area. In the second phase, the PWS was treated using a pulse stacking technique with the 1064 nm Nd:YAG. RESULTS: One patient was lost to follow-up. Among the remaining ten, 5 (50%) patients showed an excellent improvement (>75%), 3 (30%) patients showed a good improvement (51-75%), and 2 (20%) patients had no or minimal improvement (0-25%). CONCLUSIONS: Our results suggest that the combination of different wavelengths in the same session can be helpful for PWSs resistant to standard laser treatments. However, in most patients two treatment phases were necessary.

Double-blind placebo-controlled randomized clinical trial on the efficacy of Aerosal in the treatment of sub-obstructive adenotonsillar hypertrophy and related diseases.

BACKGROUND: Adenotonsillar hypertrophy (ATH) is a frequent cause of upper airways obstructive syndromes associated to middle ear and paranasal sinuses disorders, swallowing and voice disorders, sleep quality disorders, and occasionally facial dysmorphisms. ATH treatment is essentially based on a number of medical-surgical aids including nasal irrigation with topical antibiotics and corticosteroids and/or treatment with systemic corticosteroids, immunoregulators, thermal treatments, adenotonsillectomy, etc. OBJECTIVES: The aim of the present study is to assess the efficacy of Aerosal halotherapy in the treatment of sub-obstructive adenotonsillar disease and correlated conditions compared to placebo treatment. METHODS: A total of 45 patients with sub-obstructive adenotonsillar hypertrophy were randomized to receive either Aerosal halotherapy or placebo for 10 treatment sessions. The main outcome was a reduction greater than or equal to 25% from the baseline of the degree of adenoid and/or tonsillar hypertrophy. RESULTS: In the intention-to-treat analysis, a reduction of the degree of adenoid and/or tonsillar hypertrophy ≥25% from baseline after 10 therapy sessions was found in 44.4% of the patients in the halotherapy arm and in 22.2% of the patients in the placebo arm (P=0.204). Among the secondary outcomes, the reduction of hearing loss after 10 treatment sessions in the halotherapy arm was higher than the placebo arm (P=0.018) as well as the time-dependent analysis showed significantly improved peak pressure in the Aerosal group (P=0.038). No side effects were reported during the trial. In addition, the therapy was well accepted by the young patients who considered it as a time for play rather than a therapy. CONCLUSIONS: Aerosal halotherapy can be considered a viable adjunct, albeit not a replacement, to conventional medical treatment of sub-obstructive adenotonsillar syndrome and related conditions. Further research is however needed to improve ATH treatment.

Malignancy concerns with psoriasis treatments using phototherapy, methotrexate, cyclosporin, and biologics: facts and controversies.

Cancer is one of the several comorbidities that have been linked with psoriasis. Not surprisingly, tumors associated with well-documented risk factors for the dermatosis, such as smoking and obesity, have been found with increased incidence in psoriatic patients. They include lung, kidney, and colon cancers. For unknown reasons, the risk of lymphoma is also increased in psoriatic patients. Despite several difficulties with documenting risks, some systemic treatments for psoriasis have been linked with an increased risk of selected cancers. The best-documented association is nonmelanoma skin cancer with psoralen plus ultraviolet A therapy and cyclosporin. More recently, an increased risk of cancer has been a concern with newly introduced biologic agents. The documentation of such a purported increased risk requires long-term follow-up of treated patients.

Prediction of clinical response to excimer laser treatment in vitiligo by using neural network models.

BACKGROUND: A predictive model may help to select likely responders and to anticipate treatment duration in vitiligo. METHODS: We aimed to develop a predictive rule based on data from a randomized trial of excimer laser in vitiligo. Information on 325 treated patches was available. The degree of repigmentation was assessed by digital image analysis of UVB-reflected photographs. Since no strong relationship between any single predictive parameter and outcome was initially documented, we relied on artificial neural networks. RESULTS: Using a time-response optimal threshold model, data were divided into 2 groups of responders and nonresponders. A discriminant network was trained in order to detect responders versus nonresponders. A regression network was subsequently used to compute repigmentation time in responders. The neural network discriminator achieved 66.46 +/- 5.37% (95% CI) overall accuracy. The mean absolute error of the neural network regressor was 19.5843 +/- 2.0930 with a root mean square error of 23.7156 +/- 2.2225. CONCLUSION: Our study offers insight into the difficulty of clinical prediction in vitiligo and presents a way to develop an instrument with which to predict the clinical time response in patients treated by excimer laser.

Psoriasis (chronic plaque).

INTRODUCTION: Psoriasis affects 1-3% of the population, in some people causing changes to the nails and joints in addition to skin lesions. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of systemic drug treatments, topical drug treatments, and non-drug treatments (other than ultraviolet light) for chronic plaque psoriasis? What are the effects of ultraviolet light treatments for chronic plaque psoriasis? What are the effects of combined treatment with drugs plus ultraviolet light on chronic plaque psoriasis? What are the effects of combined systemic plus topical drug treatments for chronic plaque psoriasis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 122 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, adding calcipotriol (topical) to psoralen plus ultraviolet light A or ultraviolet light B, adding oral retinoids to psoralen plus ultraviolet A (PUVA), alefacept, balneotherapy, ciclosporin, dithranol, T cell-targeted therapies, cytokine blocking agents, emollients (alone or plus ultraviolet light B), etanercept, fish oil supplementation, fumaric acid derivatives, Goeckerman treatment, heliotherapy, infliximab, Ingram regimen, keratolytics (salicylic acid, urea), leflunomide, methotrexate, oral pimecrolimus, phototherapy plus balneotherapy, psoralen plus ultraviolet A, psychotherapy, oral retinoids (alone or with ultraviolet light B), systemic drug treatments plus topical vitamin D derivatives, tars, tazarotene, topical corticosteroids (alone or plus oral retinoids), topical Vitamin D derivatives, ultraviolet light A, and ultraviolet light B.

The clinical spectrum of psoriasis.

The clinical picture of psoriasis is not uniform. Being one of the most common chronic inflammatory skin disorders, psoriasis may present in many different forms and may include extracutaneous manifestations. Classifications have been proposed based on disease onset or the clinical course of psoriasis. Chronic plaque psoriasis occurs in a variety of clinical forms primarily distinguished by size, distribution, and dynamics of psoriatic plaques. In addition, psoriasis inversa, localized and generalized pustular forms, erythrodermic psoriasis, as well as a number of more uncommon forms have been recognized, a distinction on clinical grounds that is relevant for the overall prognosis and impact on the patients' quality of life as well as for the choice of therapy. The broad and rather colorful clinical spectrum of psoriasis as well as implications for clinical practice will be comprehensively reviewed in this article.