A Comparison of Hidradenitis Suppurativa Characteristics Among Israeli Arabs and Jews: Analysis of Two Cohorts.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease involving apocrine gland-bearing regions. There is an under-representation of non-Caucasians in epidemiologic studies of HS. The characteristics of HS in Israeli Arabs have not yet been studied. OBJECTIVES: To investigate the demographic and clinical profile of HS in the Israeli Arab population. METHODS: A retrospective analysis was conducted in two cohorts of patients with HS in Israel. The patients were derived from the database of a large health management organization (n=4191, 639 Arabs; population-based) and a major tertiary medical center (n=372, 49 Arabs). Demographic and clinical data were compared between ethnic groups. RESULTS: The prevalence of HS in Israeli Arabs was found to be 0.5%, fivefold higher than in Jews. Arab patients were younger (35.3 vs. 40.5 years, P < 0.001) and mostly male (52% vs. 35.7%, P < 0.001), with lower rates of co-morbidities, including smoking (40.8% vs. 55.7%, P < 0.001), hyperlipidemia, and depression as well as a higher rate of dissecting cellulitis (10.2% vs. 1.9%, P = 0.008). HS was more severe in Arabs, but of shorter duration, with mainly axillary involvement (79.6% vs. 57.9%, P = 0.004). Treatment with hormones was more common in Jews, and with biologic agents in Arabs. CONCLUSIONS: The findings suggest a different phenotype of HS in Arabs, warranting further study.

Biological treatment for bullous pemphigoid.

Background: Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease. Topical or systemic corticosteroids are often used as the first-line treatment. However, long-term corticosteroid use may lead to significant side effects. Therefore, various adjuvant immunosuppressant therapies are used as steroid-sparing agents, with accumulating reports of biological treatments for severely recalcitrant BP. Objective: To describe the clinical and immunological features of a series of patients with recalcitrant BP treated with immunobiological therapies. To assess the efficacy and safety of their therapies. Methods: Patients receiving biological treatment for BP from two centers were assessed. Here, we described the clinical, immunopathological, and immunofluorescence findings of adult patients with BP and analyzed the clinical response and adverse events associated with various biological therapies. Results: We identified nine eligible patients treated with rituximab (seven), omalizumab (three), or dupilumab (one). The mean age at diagnosis was 60.4 years, the average BP duration before biologic initiation was 1.9 years, and the average previous treatment failure was 2.11 therapies. The mean follow-up period from the first biological treatment to the last visit was 29.3 months. Satisfactory response, defined as clinical improvement, was achieved in 78% (7) of the patients, and total BP clearance was achieved in 55% (5) of the patients at the last follow-up visit. Additional rituximab courses improved the disease outcomes. No adverse events were reported. Conclusions: Efficient and safe novel therapies can be considered in recalcitrant steroid-dependent BP non-responsive to conventional immunosuppressant therapies.

How Do Experts Treat Patients with Bullous Pemphigoid around the World? An International Survey.

Many treatments are currently proposed for treating patients with bullous pemphigoid (BP). We assessed treatment modalities of BP depending on the different countries, BP extent, and patients' comorbidities. We surveyed worldwide experts about how they treat patients with BP. A total of 61 experts from 27 countries completed the survey. Severe and moderate BP were treated with oral prednisone (61.4 and 53.7%, respectively) or superpotent topical corticosteroids (CSs) (38.6 and 46.3%, respectively). Conventional immunosuppressants were more frequently combined with oral prednisone (74.5%) than with superpotent topical CS (37.5%) in severe BP. Topical CSs were mainly used in Europe in mild (81.1%), moderate (55.3%), and severe (54.3%) BP. In the United States of America and Asia, systemic CSs were mainly proposed for treating severe (77.8 and 100%, respectively), moderate (70 and 77.8%, respectively), and also mild (47.1 and 33.3%, respectively) BP. Most experts reduced the initial dose of oral CS in patients with diabetes mellitus (48.1%) or cardiac insufficiency (40.2%) but rarely changed BP treatment in patients with neurological disorders or neoplasia. This survey showed major differences in the way patients with BP are treated between AmeriPac countries (United State of America, Latin America, and Australia) and Asia on the one hand and Europe and the Middle East on the other hand.

Facial demodicosis in the immunosuppressed state: a retrospective case series from a tertiary referral center.

BACKGROUND: Data on Demodex in the immunosuppressed state is limited, focusing mainly on patients with human immunodeficiency virus and hematological malignancies. The aim of this study was to describe the manifestations of facial demodicosis in diverse immunosuppressive states. METHODS: The medical records of all patients followed at a Demodex outpatient clinic of a tertiary medical center from January 2008 to November 2020 were retrospectively reviewed. Data on patients who were immunosuppressed while with demodicosis were retrieved. RESULTS: The cohort included 28 patients (17 women and 11 men; median age, 58 years). Types of immunosuppression included treatments with hydroxyurea for polycythemia vera/essential thrombocytosis, mycophenolic acid, tacrolimus, and prednisone for liver and/or kidney transplantation, prednisone with cyclosporine/methotrexate/azathioprine/rituximab mainly for autoimmune diseases, mercaptopurine with/without anti-tumor necrosis factor alpha (TNF-α) for Crohn's disease, chemotherapy for neoplasms, anti-TNF-α for psoriasis, and Cushing's syndrome. The clinical types of demodicosis included: papulopustular, erythematotelangiectatic and fulminant rosacea, hyperpigmented, pityriasis folliculorum, pustular folliculitis, and dermatitis. The diverse clinical presentations led to various differential diagnoses. Topical treatment with ivermectin (monotherapy/combination with other treatments) was effective. CONCLUSION: Clinicians treating immunosuppressed patients should be familiar with the different forms of demodicosis and include them in the differential diagnosis of facial eruptions.

Efficacy and safety of a thermal fractional skin rejuvenation system (Tixel) for the treatment of facial and/or scalp actinic keratoses.

Actinic keratoses are common cutaneous lesions with a potential to progress to invasive squamous cell carcinoma. Therefore, treatment is crucial. The Tixel® is a noninvasive thermomechanical device designed to transfer heat to the upper dermis in a controlled manner according to a predetermined setting. This study aimed to evaluate the safety and efficacy of a thermomechanical fractional skin resurfacing technology for the treatment of facial and scalp actinic keratoses. A prospective, open-label, before-after study was conducted in a tertiary medical centre from May 2020 to April 2021. Patients presenting with facial/scalp actinic keratoses of mild-to-moderate thickness underwent 2 or 3 Tixel treatments (depending on clinical improvement), 3-4 weeks apart. The reduction in lesion count and overall improvement in appearance were assessed by clinical examination and digital photography. Findings were compared between baseline and follow-up at 3 months after the last treatment session. Patient satisfaction was evaluated by questionnaire, and adverse effects were documented. A total of 20 patients participated in the study. All completed 2-3 treatments and follow-up visits. Assessment of digital photographs was performed by 2 assessors blinded to the timepoint at which each photo was taken (before or after treatment). The average number of lesions at baseline was 9.8 (± 4.8) and the mean reduction in lesion count was 7.9 (± 4.4) (80.6%). Complete clearance was observed in 31.6% of patients. No adverse effects were noted during treatment and follow-up. Most patients reported being "very satisfied" or "satisfied" with the treatment results (85%) and experience (95%). Treating facial and scalp actinic keratoses with the Tixel device was found to be effective and safe.

A Combination of Non-ablative Laser and Hyaluronic Acid Injectable for Postacne Scars: A Novel Treatment Protocol.

Background: Postacne facial scars are often associated with significant patient distress. Energy-based devices, including non-ablative lasers, are commonly used for the treatment of postacne scarring. There is relatively limited data regarding the combination of non-ablative lasers with hyaluronic acid injections for postacne scarring. Objective: We aimed to evaluate the efficacy of a non-ablative 1,540-nm erbium:glass laser combined with a hyaluronic acid injectable for the treatment of postacne scars. Methods: This was a retrospective analysis of 12 patients who underwent the full treatment protocol. A before and after blinded clinical evaluation was performed independently by two dermatologists and graded on a scale from 0 (indicating a worsening of scarring) to 4 (indicating a 76-100% improvement in scarring). Pain perception, adverse effects, and patient satisfaction were evaluated. Results: A mean correct blinded before and after evaluation by two dermatologists was 96 percent. Patients demonstrated mild to moderate improvement as assessed by a quartile scale of improvement (25-50%). Mild transient pain was reported by most patients. The satisfaction level of the patients was high (4 out of 5). Limitations: The limitations of our study include the small cohort, retrospective design, and lack of a histological correlation. Conclusion: Our results suggest that this combination treatment using 1,540-nm fractional erbium:glass laser and hyaluronic acid injections is both safe and effective for patients with postacne facial scars.

Early rituximab treatment is associated with increased and sustained remission in pemphigus patients: A retrospective cohort of 99 patients.

Rituximab is the front-line therapy for pemphigus disease. Although very effective, relapse rates are high. We assessed factors associated with disease remission and early relapse following the first rituximab cycle. A single center, retrospective cohort study of patients with pemphigus treated with rituximab (1000 mg 0, 14 days) at the Autoimmune Bullous Disease Clinic of the Division of Dermatology in Rabin Medical Center, Israel, between January 1, 1995 and March 31, 2020. The cohort included 99 patients with a median follow-up of 37 months (range 12-155). After a single rituximab cycle, 74 patients (75%) achieved remission. Increased time to rituximab was associated with decreased remission rates (OR, 0.98 per month; 95% CI, 0.97-0.998). Of patients in remission with sufficient follow-up, 15/69 (22%) experienced an early relapse (≤12 months from remission). Prolonged time to rituximab and increased baseline disease severity, were associated with early relapse (OR, 1.02 per month; 95% CI, 1.001-1.04; OR, 1.04 per point; 95% CI, 1.01-1.08, accordingly). Initiating rituximab early following diagnosis is recommended. Maintenance rituximab infusions, especially for patients with severe baseline disease, should be further investigated.

Rituximab versus Mycophenolate Mofetil in Patients with Pemphigus Vulgaris.

BACKGROUND: Rituximab and mycophenolate mofetil are used to treat pemphigus vulgaris, but they have not been adequately compared in clinical trials. METHODS: In a randomized, controlled trial, we assigned patients with moderate-to-severe pemphigus vulgaris in a 1:1 ratio to receive intravenous rituximab (1000 mg on days 1, 15, 168, and 182) or oral mycophenolate mofetil (2 g per day), in addition to an oral glucocorticoid administered on the same tapering schedule in the two groups. The primary end point was sustained complete remission at week 52, defined as the healing of lesions with no new active lesions, as reflected by a Pemphigus Disease Area Index (PDAI) activity score of 0 (on a scale of 0 to 250, with higher scores indicating greater disease severity), for at least 16 weeks without the use of glucocorticoids. Secondary end points were the cumulative dose of glucocorticoids, the number of disease flares, and the change from baseline in the score on the Dermatology Life Quality Index (DLQI; scores range from 0 to 30, with higher scores indicating greater impairment). RESULTS: Of the 135 patients who underwent randomization, 67 were assigned to receive rituximab and 68 to receive mycophenolate mofetil. The primary outcome was assessed in the modified intention-to-treat population: 62 patients in the rituximab group and 63 in the mycophenolate mofetil group. The median PDAI activity scores at baseline were 22.7 in the rituximab group and 18.3 in the mycophenolate mofetil group. At week 52, sustained complete remission was observed in 25 patients (40%) in the rituximab group and in 6 (10%) in the mycophenolate mofetil group (difference, 31 percentage points; 95% confidence interval [CI], 15 to 45; P<0.001). The mean cumulative glucocorticoid dose during the 52-week treatment period was 3545 mg in the rituximab group and 5140 mg in the mycophenolate mofetil group (difference, -1595 mg; 95% CI, -2838 to -353; P<0.001). There were 6 disease flares in the rituximab group and 44 in the mycophenolate mofetil group (adjusted rate ratio, 0.12; 95% CI, 0.05 to 0.29; P<0.001). The mean change in DLQI score was -8.87 points and -6.00 points, respectively (difference, -2.87 points; 95% CI, -4.58 to -1.17; P = 0.001). Serious adverse events occurred in 15 of 67 patients (22%) in the rituximab group and in 10 of 68 (15%) in the mycophenolate mofetil group. CONCLUSIONS: Rituximab was superior to mycophenolate mofetil in producing sustained complete remission at 52 weeks in patients with pemphigus vulgaris. Rituximab resulted in a greater reduction in glucocorticoid use than mycophenolate mofetil, but more patients in the rituximab group had serious adverse events. Further trials are needed to determine the comparative efficacy and safety of rituximab and mycophenolate mofetil beyond 52 weeks of treatment. (Funded by F. Hoffmann-La Roche; PEMPHIX ClinicalTrials.gov number, NCT02383589.).

Isolated solar angioedema: A systematic review of the literature.

Solar urticaria is a well-recognized photodermatosis, sometimes accompanied by angioedema. However, isolated solar angioedema (ISA) is a rare and unrecognized entity. The purpose of our work was to systematically review the available data on ISA. Therefore, a systematic review of studies evaluating ISA was performed. Additionally, a case of a 21-years-old patient from our photodermatosis service is presented. The search yielded 421 publications, with 3 eligible for review. Together with our case, 5 cases were included overall. All patients were female. Four out of 5 patients first experienced ISA at childhood or early adulthood (age range 6-22 years). UVA photoprovocation was positive in the 3 out of the 4 patients who were tested. Improvement was noted following NB-UVB hardening (2 out of 5 patients) or a short course of oral prednisone (3 out of 5 patients) combined with regular sunscreen application. To conclude, ISA is an extremely rare entity, although it may be underdiagnosed due to lack of awareness. The clinician must consider ISA in the differential diagnosis of angioedema since it can have a detrimental effect on quality of life. Besides sun avoidance, there is no consensus regarding treatment.

1540-nm fractional erbium: Glass laser is a safe and effective modality for nonablative facial rejuvenation.

BACKGROUND: Laser treatments for facial rejuvenation are common, with ablative modalities being of more common use for this indication. Efficient nonablative modalities are of rising demand. AIM: Our aim was to determine the safety and efficacy of high-fluence, nonablative 1540-nm fractional Erbium:glass laser for facial rejuvenation. PATIENTS AND METHODS: A retrospective study of patients treated with 3-4 treatments using the 1540-nm fractional Erbium:glass laser for facial rejuvenation, using 2500-3000 mJ/stacked pulses (51-61 mJ per pixel). Patients were followed-up for 3 months following their last treatment. Before and after photos were independently blindly evaluated by 2 dermatologists, who graded them using a scale from 0 (exacerbation) to 4 (76%-100% improvement) for 2 different facial regions (frontal face region and lateral canthal region). Pain perception and adverse effects as well as patient satisfaction were documented throughout the study. RESULTS: Sixteen patients completed both treatment and follow-up period. At the 3-months posttreatment follow-up visit, moderate-to-significant improvement in rhytids appearance (mean grade of improvement: 2.93 for frontal face and 3 for lateral canthal region) was observed. Patients' satisfaction was high (4.25). Patients reported mild and transient erythema posttreatment with no other adverse effects. CONCLUSION: The high-fluence 1540-nm fractional Erbium:glass laser is a safe and effective nonablative modality for facial rejuvenation.

Inherited genetic late-onset erythropoietic protoporphyria: A systematic review of the literature.

BACKGROUND: Inherited genetic erythropoietic protoporphyria (EPP) is characterized by a photosensitive rash that emerges during infancy or early childhood. Acquired EPP can erupt at any age, even during adulthood, and is associated with hematological disorders. A third, less-studied type of EPP is also inherited but appears later in life (during adulthood). PURPOSE: To evaluate the characteristics of inherited genetic late-onset (IGLO) EPP. METHODS: A systematic comprehensive search of the literature was conducted using PubMed, Google Scholar, ScienceDirect, and clinicaltrials.gov databases. Studies describing patients with IGLO EPP were included. Additionally, we present an index case of a patient, treated at our clinic in whom inherited genetic EPP was diagnosed at age 21 years. RESULTS: The search yielded 1514 citations. Five publications were eligible for review. Along with our case, 7 patients (4 males) were included in the analysis. Mean age at disease onset was 34.2 years (range 18-69, median 30). Most patients presented with mild pruritus and rash in a photosensitive distribution. Mean level of free erythrocyte protoporphyrin IX (FEP) was 8.6 µmol/L. A mutant ferrochelatase gene (FECH) in trans to a hypomorphic FECH allele was found in 3 of the 4 patients who underwent genetic testing. CONCLUSION: We describe the distinct features of IGLO EPP. This work emphasizes that a diagnosis of inherited genetic EPP should not be ruled out in adults with new-onset photosensitive manifestations.

Treatment of Pemphigus with Rituximab: Real-Life Experience in a Cohort of 117 Patients in Israel.

BACKGROUND: A combined regimen of rituximab with corticosteroids for the treatment of pemphigus was effective in a prospective randomized controlled trial. OBJECTIVE: To assess real-life response to rituximab in patients with pemphigus. METHODS: A retrospective cohort of patients with pemphigus treated with ≥1 rituximab cycles (1,000 mg on days 0 and 14). The primary outcome was remission rate after 1 cycle. For efficacy analyses, a minimal 6-month follow-up was required. Adverse events were assessed in all patients. RESULTS: The cohort included 117 patients for safety analysis, 108 for efficacy analysis (median follow-up of 33 months). All but one received concomitant corticosteroids, a third also received adjuvants. Overall, 80/108 patients (74%) achieved remission after the first rituximab cycle at a median of 5.5 months. Relapses occurred in 39 patients (49%) at a median of 18 months. Repeating treatment in relapsed patients increased remission rates to 75 and 88% after the second and third cycles, respectively. Adverse events were similar to those of previous publications. Two elderly patients died of infections attributable to rituximab combined with high-dose corticosteroids. CONCLUSION: In a large real-life long-term cohort, rituximab with corticosteroids ± adjuvants induced remission in most patients with pemphigus, with relatively favorable safety. Repeating treatment following relapse or remission failure was beneficial.

Does interval time between pulsed dye laser treatments for port-wine stains influence outcome? A systematic review and meta-analysis.

The pulsed dye laser (PDL) is the standard treatment for port-wine stains (PWS). Maximal improvement occurs after multiple treatment sessions; however, the optimal treatment interval has yet to be determined. The aim of this study was to review whether there is an association between PDL treatment interval and outcome of PWS. Six databases were searched by three reviewers for publications investigating treatment of PWS with PDL. The 75% improvement rates (75IR) were extracted for quantitative analysis. Meta-regression was used to investigate the association between treatment intervals and 75IR. The systematic review included 1 RCT and 33 cohort studies (7 prospective cohorts and 26 retrospective cohorts), with a total of 3777 patients. The pooled 75IR was 37% (95% CI 29-45%; I2 = 95%). Light Fitzpatrick skin type (p = 0.04), facial anatomic location (p = 0.01), and young age (p = 0.008) were associated with 75IR. In an unadjusted (p = 0.42) and multivariable adjusted (p = 0.98) meta-regression, no association was found between time interval between treatments and 75IR. These results persisted in a sensitivity analysis of studies with a mean patient age of ≤ 1. The majority of included studies were heterogeneous and retrospective. Based on cohort studies of low-to-moderate quality, time intervals between PDL treatments are not associated with PWS outcome.

Treatment of Pemphigus Vulgaris and Foliaceus with Adjuvant Rituximab Compared to Immunosuppression Alone: Real-Life Experience.

INTRODUCTION: In a randomized prospective trial, adjuvant rituximab was more efficacious than corticosteroids alone in the treatment of pemphigus; however, real-life data are limited. Rituximab treatment for pemphigus has only recently been introduced to the Israeli health basket. Previously, patients received rituximab if they paid out of pocket or through private insurance, separating patients into 2 treatment groups, mostly based on economic capability. METHODS: A retrospective cohort study of the 12-month clinical response of pemphigus vulgaris/foliaceus patients. We compared patients after a single cycle (1,000 mg on days 0 and 15 or weekly 375 mg/m2 for 4 weeks) of adjuvant rituximab with systemic corticosteroids ± steroid-sparing agents, to patients who were prescribed rituximab, could not obtain it, and received systemic corticosteroids ± steroid-sparing agents. RESULTS: Forty-five patients were included (adjuvant rituximab, n = 29; immunosuppression alone, n = 16). At baseline, rituximab patients had a higher mean pemphigus disease area index (PDAI) (p = 0.07) and higher mean daily dosages of prednisone (1.51 vs. 1.16 mg/kg, p = 0.39). All patients but 1 in the rituximab group continued systemic steroids, and 31% in the rituximab group versus 50% in the immunosuppression-alone group received systemic adjuvants. At 12 months, partial or complete remission rates (on or off maximum 40 mg/day prednisone equivalent) were nonsignificantly higher in the rituximab group (62 vs. 50%, p = 0.53); however, patients on rituximab showed faster remissions (3.4 ± 1.9 vs. 5.9 ± 3.6 months; p = 0.03) with a trend for a greater PDAI reduction (p = 0.051). Adverse events were comparable. CONCLUSIONS: In this real-life study, a single cycle of rituximab achieved more remissions and sooner compared to conventional immunosuppression, but the differences were not significant, probably due to a small sample size and severe baseline disease in the rituximab group. Future real-life studies on larger groups are needed.

Laser Treatment for Non-Melanoma Skin Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Surgery is the mainstay of treatment for non-melanoma skin cancer. Lasers are an additional option. OBJECTIVE: The objective of this study was to review the literature on the efficacy and safety of lasers for the treatment of non-melanoma skin cancer. METHODS: A systematic review and meta-analysis of laser treatment for non-melanoma skin cancer was performed. The primary outcome was recurrence rate (RR). RESULTS: The review included 32 studies (six randomized controlled trials and 26 cohort studies): 27 evaluated basal cell carcinomas (BCCs), three squamous cell carcinomas, and two both, for a total of 4755 BCCs and 214 squamous cell carcinoas. Most BCCs were low risk. The Nd:YAG laser (seven studies, 3286 BCCs) had a 3.1% RR (95% confidence interval [CI] 1.4-6.4%) during a mean follow-up of 7.9 years, with a low rate (< 20%) of scarring and dyspigmentation. The CO2 laser (ten studies, 904 BCCs) had a 9.4% RR (95% CI 4.1-20) during a mean follow-up of 2.1 years, with a low rate of side effects. The pulsed dye laser (eight studies, 206 BCCs) had a 38% RR (95% CI 24-55). In two studies, the Nd:YAG laser demonstrated a RR of 10% (95% CI 2-31) for Bowen's disease, and in three studies, the CO2 laser demonstrated a RR of 22% (95% CI 5-61) for squamous cell carcinoma. CONCLUSIONS: Based on cohort studies, the Nd:YAG laser is a safe and efficacious modality for the treatment of low-risk BCC. Based on settings applied in prior studies in the literature, the CO2 laser is less efficacious than the Nd:YAG laser, thus it cannot be recommended for BCC treatment. Insufficient data preclude conclusions regarding laser treatment for squamous cell carcinoma. REGISTRATION: PROSPERO registration number CRD42019129717.

Topical and systemic retinoids for the treatment of cutaneous viral warts: A systematic review and meta-analysis.

Cutaneous viral warts (CVW), caused by human papillomavirus, often have a self-limited course. However, some patients experience a recalcitrant disease despite treatment. Retinoids are considered the mainstay of therapy in many dermatologic diseases. Data on their use for viral warts are limited. To systematically review the published evidence on the efficacy and safety of retinoids for the treatment of CVW. A systematic review and meta-analysis of topical or systemic retinoid treatment for CVW was performed in accordance with the PRISMA statement. The primary outcome was clinical response; secondary outcomes were recurrence rate and adverse events. Fourteen publications including 399 patients treated exclusively with retinoids (65% topical, 35% systemic) were evaluated. The complete response rate was 64% (95% CI, 46-78%; I2 =80%) for topical treatment and 61% (95% CI, 44-76%; I2 =69%) for systemic treatment. The most common side effects were irritant contact dermatitis and cheilitis, respectively. Relapse rates were 6% and 17%, respectively. The reviewed studies were considerably heterogenous and most lacked a control group. Both topical and systemic retinoids are effective and safe as monotherapy for CVW. Further studies are required to determine their exact role in this setting.

Treatment of Bullous Pemphigoid in People Aged 80 Years and Older: A Systematic Review of the Literature.

BACKGROUND: Bullous pemphigoid commonly affects older adults and has a detrimental effect on both quality of life and longevity. Systemic corticosteroids, the mainstay of therapy, may cause significant adverse effects, especially in older patients. Therefore, safer therapeutic options are being sought. OBJECTIVE: The objective of this article was to systematically review the published evidence on the efficacy and safety of different treatment modalities for bullous pemphigoid in older patients. METHODS: We performed a systematic review of all publications until May 2020 in PubMed, Google Scholar, and the ongoing trials registry of the US National Institutes of Health databases evaluating the efficacy and safety of bullous pemphigoid treatments in patients aged older than 80 years. The primary outcome was complete response. The secondary outcomes were partial response, complete remission on minimal therapy or during tapering, recurrence, adverse events, and mortality. RESULTS: Twenty-eight publications were included: 2 randomized controlled trials, 5 prospective cohort studies, 10 retrospective cohort studies, and 11 case series, with a total of 153 older patients. The overall complete response rate was 31%. Topical corticosteroids had the highest complete response rate (55%) with a low side-effect profile. Biologics (omalizumab and rituximab) were effective in achieving complete remission on minimal therapy (29%) without recurrence, although rituximab was associated with a relatively high mortality rate (29%). CONCLUSIONS: Current data suggest that topical corticosteroids are effective and safe and should remain the first line of treatment for bullous pemphigoid in older adults. However, their application is difficult and requires a high-functioning patient, third-party assistance, or a relatively mild disease. Biological agents are effective but warrant meticulous patient selection owing to the relatively high mortality rate associated with rituximab. CLINICAL TRIAL REGISTRATION: PROSPERO registration number CRD42020186686.

Topical and Systemic Retinoids for the Treatment of Genital Warts: A Systematic Review and Meta-Analysis.

BACKGROUND: Genital warts, caused by the human papillomavirus, are a common sexually transmitted disease. The warts can regress spontaneously or exhibit a persistent clinical course. Various therapeutic modalities are available, yet none is curative, and there may be recurrences. Retinoids are considered the mainstay of therapy in many dermatologic diseases. Data on their use for genital warts are limited. OBJECTIVE: To systematically review the published evidence on the efficacy and safety of retinoids for the treatment of genital warts. METHODS: A systematic review and meta-analysis of all publications evaluating topical or systemic retinoids for the treatment of genital warts was performed. The primary outcome was complete response (CR); the secondary outcomes were recurrence rate and adverse events. RESULTS: Six publications were evaluated, three randomized controlled trials and three prospective cohort studies, including a total of 141 patients with genital warts treated exclusively with retinoids (90% with isotretinoin). CR rates were 100% for systemic etretinate (3 out of 3 patients, 95% CI 28-81%) and 56% for isotretinoin (95% CI 28-81%; I2 = 84%). Topical etretinate did not induce CR. The most common side effect of topical agents was irritant contact dermatitis (36%) and that of systemic agents mucocutaneous disorders (80%). The relapse rate was 12% for oral isotretinoin and was unavailable for the other modalities. CONCLUSIONS: Current data suggest that unlike topical retinoids, systemic retinoids are an effective and safe treatment for genital warts. Further studies are required to determine their specific role and the most effective regimen for each derivative.

Nonsurgical Treatments for Extramammary Paget Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: Surgery is commonly regarded as the mainstay of treatment of extramammary Paget disease (EMPD); however, nonsurgical approaches have gained popularity in recent years. OBJECTIVES: To review the published evidence for the efficacy and safety of nonsurgical modes of therapy for EMPD. METHODS: A systematic review and meta-analysis of nonsurgical EMPD treatments was performed. The primary outcome was complete response (CR); secondary outcomes were clinical regression by ≥50%, adverse events, and recurrence rate. RESULTS: The systematic review included 43 observational studies (341 patients; 7 prospective cohort studies, 19 retrospective cohort studies, and 17 cases series) evaluating 5 treatment modalities. Imiquimod (13 studies, 110 patients) administered at variable doses ranging from daily to twice weekly for 2-56 weeks demonstrated CR of 54% (95% CI, 40-67%; I2 = 37%) and had a satisfactory safety profile. In 14 heterogeneous studies (122 patients) evaluating photodynamic therapy (PDT), only 36% (95% CI, 22-53%; I2 = 52%) of patients achieved CR. Radiotherapy (12 studies, 67 patients) showed CR of 97%, but was associated with local and systemic side effects. Ablative lasers and topical fluorouracil and calcipotriene lacked adequate evidence of efficacy. CONCLUSIONS: Imiquimod and radiotherapy are the most appropriate nonsurgical modalities for EMPD treatment given their good efficacy and safety profile. PDT has limited efficacy but may be appropriate in selected clinical settings.