Background Accurately documenting pediatric atopic dermatitis (AD) severity is important, but research tools, such as Eczema Area and Severity Index (EASI), are too time-consuming for clinical settings. Product of the Physician Global Assessment and affected percentage of body surface area (PGAxBSA) is a new, rapid measure of psoriasis severity. Objective Evaluate an Investigator Global Assessment (IGA) and body surface area product (IGAxBSA) as an easy-to-use severity measure for pediatric AD. Methods Patient-reported and objective disease severity measures were collected from 195 caretaker/child dyads aged 5-17 with almost clear (validated Investigator Global Assessment, vIGA=1) to severe (vIGA=4) AD. Data was assessed using Spearman coefficients and plots. Severity strata were proposed using an anchoring approach based on EASI. Results IGAxBSA correlates better with EASI than IGA alone (r=0.924 vs. r=0.757, p<.001). Bland-Altman plot indicates high and consistent agreement between IGAxBSA and EASI. Suggested severity strata for IGAxBSA are 0-30 mild, 30.1-130 moderate, 130.1-400 severe (κ = 0.760). Limitations Patient cohort was predominantly from the Midwestern United States. Conclusions IGAxBSA (using the validated IGA/vIGA) is a simple measure that correlates well with EASI in mild-to-severe pediatric AD. Future work is needed to affirm reliability across IGA scales and responsiveness to change.

Background Tobacco smoking is implicated in psoriasis among adults. Objective To determine whether prenatal, infantile, and childhood tobacco exposure increase risk of pediatric psoriasis. Methods Data from Danish National Birth Cohort participants were collected at approximately gestational week 12 and when the children were approximately 6 months and 11 years of age. In total, 25 812 offspring with complete data from the Danish National Birth Cohort were included. We estimated the odds of pediatric psoriasis with tobacco exposure prenatally, from birth to age 6 months (early infancy), and at age 11 years (childhood). Results We observed an increased risk of pediatric psoriasis among offspring with prenatal tobacco exposure (adjusted odds ratio [OR], 1.39; 95% confidence interval [CI], 1.06-1.82). An exposure-response relationship was observed for increasing quantities of cigarettes smoked daily (≥16 cigarettes: adjusted OR, 2.92; 95% CI, 1.20-7.10; P for trend = .038). The associations with infantile (adjusted OR, 1.17; 95% CI, 0.76-1.79) and childhood (adjusted OR, 1.10; 95% CI, 0.77-1.58) tobacco exposure were attenuated after controlling for prenatal exposure. Limitations Outcome status was maternally reported. Conclusions Prenatal tobacco exposure may increase the risk of pediatric psoriasis in a monotonic fashion, indicating that smoking may play a causal role in psoriasis pathogenesis.

Background Inpatient dermatology has been shown to improve patient outcomes at a reduced cost. Few hospitals have dermatologists available. Teledermatology may allow dermatologists to assess hospitalized patients remotely. Objective To examine diagnostic concordance between hospitalist, dermatologist, and teledermatologist using store-and-forward teledermatology. Methods For 100 consecutive cases requiring inpatient dermatology consultation, a survey was conducted by all 3 raters to convey diagnostic impressions and therapeutic recommendations. Complete and partial agreements were assessed using Cohen’s kappa statistic. Results Inpatient dermatology consultation often resulted in a change in diagnosis (50.9%), and a change in systemic therapy (41.5%). Likewise, virtual teledermatology consultation would have resulted in a change in diagnosis (54.7%) and a change in systemic therapy (47.2%) at similar rates. Comparing dermatologist and teledermatologist, diagnostic complete and partial agreement were 52.8% and 84.9% respectively. Systemic therapy agreement was 77.4%. Teledermatologists recommended biopsy more often (68.5% vs 43.5%). Limitations Small sample size, tertiary academic medical center, single rater for inpatient teledermatology with specific inpatient niche. Conclusion Teledermatologists performed comparably to an in-person dermatologist for diagnosis and management of hospitalized patients with skin conditions. Teledermatology may be a suitable alternative for delivery of inpatient care if no dermatologist is available.

Background The use of artificial intelligence (AI) for skin cancer assessment has been an emerging topic in dermatology. Leadership of dermatologists is necessary in defining how these technologies fit into clinical practice. Objective To characterize the evolution of AI in skin cancer assessment and characterize the involvement of dermatologists in developing these technologies. Methods An electronic literature search was performed using PubMed searching machine learning or artificial intelligence combined with skin cancer or melanoma. Articles were included if they used AI for screening and diagnosis of skin cancer using datasets consisting of dermatoscopic images or photographs of gross lesions. Results Fifty-one articles were included, of which 41% had dermatologists included as authors. Manuscripts including dermatologists described algorithms built using more images (mean 12111 vs 660). In terms of underlying technology, AI used for skin cancer assessment has followed trends in the field of image recognition. Limitations This review focused on models described in the medical literature and did not account for those described elsewhere. Conclusions Greater involvement of dermatologists is needed in thinking through issues in data collection, dataset biases, and applications of technology. Dermatologists can provide access to large, diverse datasets that are increasingly important for building these models.

Background Patients with chronic inflammatory skin diseases (CISD) have potential risk factors for herpes zoster (HZ). Yet, little is known about HZ risk in CISD. Objectives Determine whether CISD is associated with HZ. Methods Data were analyzed from the 2002-2012 Nationwide Inpatient Sample, a representative cohort of US hospitalizations (N=68,088,221 children and adults). Results In multivariable logistic regression models including age, sex, race/ethnicity, insurance, household income, and long-term systemic corticosteroid use, hospitalization for HZ was associated with atopic dermatitis (adjusted OR [95% CI]: 1.38 [1.14-1.68]), psoriasis (4.78 [2.83-8.08]), pemphigus (1.77 [1.01-3.12]), bullous pemphigoid (1.77 [1.01-3.12]), mycosis fungoides (3.79 [2.55-5.65]), dermatomyositis (7.31 [5.27-10.12]), systemic sclerosis (1.92 [1.47-2.53]), cutaneous lupus erythematosus (1.94 [1.10-3.44]), vitiligo (2.00 [1.04-3.85]), and sarcoidosis (1.52 [1.22-1.90]). Lichen planus (crude OR [95% CI]: 3.01 [1.36-6.67]), Sézary syndrome (12.14 [5.20-28.31]), morphea (2.74 [1.36-5.51]), and pyoderma gangrenosum (2.44 [1.16-5.13]) only showed increased odds in bivariable models. Sensitivity analyses among ages <60 and <50 years showed similar results. Predictors of HZ in CISD included female sex, fewer chronic conditions, and long-term systemic corticosteroid use. Limitations Cross-sectional study. Conclusions Many CISD are associated with increased hospitalization for HZ, even below ages recommended for HZ vaccination. Additional studies are needed to establish CISD-specific vaccination guidelines.

Background Neutralizing (buffering) lidocaine 1%, epinephrine 1:100,000 solutions (Lido/Epi) with sodium hydrogen carbonate (NaHCO3) (bicarbonate) is widely used to reduce burning sensations during infiltration of Lido/Epi. Optimal mixing ratios have not been systematically investigated. Objectives To determine whether the Lido/Epi-NaHCO3 mixing ratio 3:1 (IMP1) causes less pain during infiltration than the mixing ratio 9:1 (IMP2) or unbuffered Lido/Epi (IMP3). Methods Double-blind, randomized, placebo-controlled, crossover trial (n=2x24) with 4 investigational medicinal products (IMP1-4). Results The 3:1 mixing ratio was significantly less painful than the 9:1 ratio (p = 0.044). Unbuffered Lido/Epi was more painful than the buffered Lido/Epi (p=0.001 vs IMP1; p=0.033 vs IMP2). IMP4 (NaCl 0.9%=placebo) was more painful than any of the anesthetic solutions (p=0.001 vs IMP1; p=0.001 vs IMP2; p=0.016 vs IMP3;). In all cases the anesthesia was effective for at least 3 hours. Limitations Results of this trial cannot be transferred to other local anesthetics such as prilocaine, bupivacaine, or ropivacaine which precipitate with NaHCO3 admixtures. Conclusions Lido/Epi-NaHCO3 mixtures effectively reduce burning pain during infiltration. The 3:1 mixing ratio is significantly less painful than the 9:1 ratio. Reported findings are of high practical relevance given the extensive use of local anesthesia today.

Background Current lymph node (LN) staging for Merkel cell carcinoma (MCC) does not account for number of metastatic LNs, which is a primary driver of survival in multiple cancers. Objective To determine the impact of number of positive LNs on survival in MCC. Methods Patients with MCC undergoing surgery were identified from the NCDB and SEER. The association between LN number and survival was modeled with restricted cubic splines. A novel nodal classification system was derived using recursive partitioning analysis (RPA). Results Among 3670 patients, increasing metastatic LN number was associated with decreased survival (P<0.001). Mortality risk increased continuously with each additional positive LN using multivariable, non-linear modeling. Using a novel staging system derived via RPA, the hazard ratio for death in multivariable regression in comparison to patients without LN involvement was 1.24 (P=0.049), 2.08 (P<0.001), 3.24 (P<0.001), and 6.13 (P<0.001) for the proposed N1a (1-3 LNs with microscopic detection), N1b (1-3 LNs with macroscopic detection), N2 (4-8 LNs), and N3 (≥9 LNs), respectively. This system was validated in the SEER cohort and demonstrated improved concordance compared to AJCC 8th edition. Limitations Retrospective design Conclusions Number of metastatic LNs is the dominant nodal factor driving survival in patients with MCC.

Dermatomyositis (DM) is an idiopathic inflammatory myopathy that is clinically heterogeneous and that can be difficult to diagnose. Cutaneous manifestations sometimes vary and may or may not parallel myositis and systemic involvement in time course or severity. Recent developments in our understanding of myositis-specific antibodies have the potential to change the diagnostic landscape of DM for dermatologists. Although phenotypic overlap exists, anti-Mi2, -MDA5, -NXP2, -TIF1, and -SAE antibodies may be correlated with distinct DM subtypes in terms of cutaneous manifestations, systemic involvement, and malignancy risk. This review highlights new findings on the DM-specific myositis-specific antibodies and their clinical associations in both adults and children.

The second article in this continuing medical education series reviews the initial evaluation of patients with suspected dermatomyositis (DM), the relevant work-up for malignancy and interstitial lung disease once a diagnosis of DM is made, and treatment recommendations for patients with DM based on disease severity, the presence of systemic symptoms, and myositis-specific antibody (MSA) profiles. This review emphasizes the emerging role of MSAs in the diagnosis of DM and highlights how MSAs can be used to guide the appropriate work-up for malignancy and interstitial lung disease. The treatment approach proposed by this continuing medical education series discusses both established and novel therapies for DM and highlights the importance of considering lesion type, degree of muscle involvement, presence of systemic symptoms, presence of MSAs, and patient age when determining the best treatment approach for a patient with DM.

Background The treatment response to new immunotherapy in advanced melanoma patients remains varied between individuals. Immune-related cutaneous side effects might have prognostic value. Objective To determine whether development of ≥1 of the 3 immune-mediated cutaneous events (eczema, lichenoid reaction, or vitiligo-like depigmentation) is associated with improved progression-free survival. Methods A cohort study of adults with stage IIIC-IV melanoma treated with pembrolizumab or nivolumab during May 1, 2012-February 1, 2018, at Westmead Hospital, Sydney, Australia. Treatment response was based on iRECIST version 1.1. Results In total, 82 patients of an average age of 59.9 years were included. Median follow-up was 40.7 months; 33 patients had ≥1 target skin reaction. Skin reactions developed in one-third of individuals by 6 months. At any given time, the instantaneous risk of disease progression and death was lower for individuals who had ≥1 cutaneous adverse event (CAE) develop. Compared with individuals with no CAE, the hazard ratio for disease progression and death for individuals who had ≥1 CAE develop was 0.46 (95% confidence interval 0.23-0.91; P = .025) by the time-dependent Cox proportional hazards model. Limitations Single-center study. Conclusion This study demonstrates an association between the development of ≥1 of 3 CAEs and improved progression-free survival in this cohort of patients.

Background We have limited data on the treatment of calcinosis cutis associated with systemic sclerosis and dermatomyositis. Objective To assess the efficacy and tolerance of available treatments for calcinosis cutis based on previously published studies. Methods We performed a systematic review of studies published in Medline, Embase, and the Cochrane library during 1980-July 2018. The strength of clinical data was graded according to the modified Oxford Centre for Evidence-Based Medicine levels of evidence. Results In all, 30 studies (288 patients) were included. Eleven therapeutic classes, surgery, and physical treatments were identified as potential treatment options for calcinosis cutis. On the basis of results of a small randomized controlled trial and 4 retrospective studies, low-dose warfarin should not be used for calcinosis cutis (level IB evidence). The results of several studies suggest diltiazem and bisphosphonates might be useful treatment options (level IV). Considering biologic therapies, rituximab has shown promising results in treating both dermatomyositis and systemic sclerosis, whereas tumor necrosis factor inhibitors might be useful for treating juvenile dermatomyositis (level IV). Intralesional sodium thiosulfate might be a promising alternative (level IV). Limitations Few included studies had a high level of evidence. Conclusion This study highlights the efficacy and tolerance profiles of available treatments for calcinosis cutis, with a focus on level of evidence.

Background Randomized controlled studies of combination therapies in rosacea are limited. Objective Evaluate the efficacy and safety of combining ivermectin 1% cream (IVM) and doxycycline 40-mg modified-release capsules (ie, 30-mg immediate-release and 10-mg delayed-release beads) (DMR) versus IVM and placebo for treatment of severe rosacea. Methods This 12-week, multicenter, randomized, investigator-blinded, parallel-group comparative study randomized adult subjects with severe rosacea (Investigator's Global Assessment [IGA] score, 4) to receive either IVM and DMR (combination arm) or IVM and placebo (monotherapy). Results A total of 273 subjects participated. IVM and DMR displayed superior efficacy in reduction of inflammatory lesions (–80.3% vs –73.6% for monotherapy [P = .032]) and IGA score (P = .032). Combination therapy had a faster onset of action as of week 4; it significantly increased the number of subjects achieving an IGA score of 0 (11.9% vs 5.1% [P = .043]) and 100% lesion reduction (17.8% vs 7.2% [P = .006]) at week 12. Both treatments reduced the Clinician's Erythema Assessment score, stinging/burning, flushing episodes, Dermatology Life Quality Index score, and ocular signs/symptoms and were well tolerated. Limitations The duration of the study prevented evaluation of potential recurrences or further improvements. Conclusion Combining IVM and DMR can produce faster responses, improve response rates, and increase patient satisfaction in cases of severe rosacea.

Background Several antiepileptic drugs are photosensitizing; however, it is not known whether this confers an increased risk of skin cancer. Objective To examine the association between common antiepileptic drugs and basal cell carcinoma, squamous cell carcinoma (SCC), and malignant melanoma. Methods We conducted a nested case-control study identifying skin cancer patients in Denmark from 2004 through 2015 matched 1:10 with disease-free controls. We estimated odds ratios (ORs) for skin cancer associated with high cumulative use of antiepileptic drugs (≥500 defined daily doses) compared with nonuse. Results Most antiepileptic drugs were not associated with skin cancer. SCC was associated with use of carbamazepine (OR, 1.88; 95% confidence interval, 1.42-2.49) and lamotrigine (OR, 1.57; 95% confidence interval, 1.12-2.22) with evidence of a dose-response relationship for carbamazepine. The estimated absolute risks were low; for example, 6335 person-years of high cumulative exposure to carbamazepine were required for 1 additional SCC to occur. Limitations Data on important risk factors for skin cancer, such as sun exposure, were not available. Conclusions Most antiepileptic drugs were not associated with skin cancer; however, carbamazepine and lamotrigine were associated with SCC. These findings need to be replicated and characterized further in other settings and have no direct clinical implications.

Background Antidrug antibodies (ADAs) may change pharmacokinetic or pharmacodynamic profiles of biologic therapies, potentially decreasing efficacy. Objective To evaluate the potential effects of brodalumab immunogenicity on safety, efficacy, and retreatment. Methods Data from 1 phase 2 and 3 phase 3 studies of brodalumab in psoriasis were analyzed. Results Overall, 2.7% of patients had positive test results for binding ADAs after receiving brodalumab; ADAs were transient in 1.4% of patients, and there were no neutralizing ADAs. Among ADA-positive patients, 60.0% (3/5) achieved a static physician's global assessment score of 0 or 1 at week 12 in the group receiving the brodalumab 210 mg every 2 weeks, compared with 79.1% (1131/1429) of ADA-negative patients. All patients (100%) who experienced return of disease and were retreated with brodalumab 210 mg every 2 weeks (none were ADA positive) achieved at least a 75% improvement in Psoriasis Area And Severity Index, ≥90% of whom regained response by week 8 of retreatment. Hypersensitivity reactions were less frequent with brodalumab than with placebo. Injection site reactions occurred in 1.8% of patients treated with brodalumab versus 2% of patients treated with ustekinumab. Limitations Retreatment could be assessed in only 1 phase 3 brodalumab study. Conclusion Brodalumab compares favorably with other biologics in terms of immunogenicity and high rates of efficacy recapture upon retreatment.

Background Randomized controlled trials have shown the efficacy and safety of brodalumab in patients with moderate to severe plaque psoriasis. Objective To evaluate the efficacy and safety of brodalumab through 120 weeks of treatment in the AMAGINE-2 trial. Methods Patients received ustekinumab through week 52 followed by brodalumab 210 mg every 2 weeks, continuous brodalumab 210 mg every 2 weeks, or any dose of brodalumab. Efficacy data were reported through 120 weeks by using observed data, last observation carried forward, and nonresponder imputation analyses. Results Of patients who received brodalumab 210 mg every 2 weeks, 84.4%, 75.6%, and 61.1% achieved 75%, 90%, and 100% improvement from baseline in Psoriasis Area and Severity Index at 120 weeks (observed data analysis), respectively. Patients who received brodalumab 210 mg every 2 weeks after receiving ustekinumab through 52 weeks achieved a similar skin clearance response as patients who received continuous brodalumab 210 mg every 2 weeks. Safety through 120 weeks was comparable to that of the blinded study periods. Limitations A large number of discontinuations toward the end of the study (31% in the final 6 months) were due to early termination and led to differences between observed data and nonresponder imputation results. Conclusions Brodalumab is well tolerated and showed robust efficacy for more than 2 years.

Background Psoriasis of the intertriginous, anogenital, and facial regions remains a therapeutic challenge, with current algorithms lacking a topical agent that exhibits both high efficacy and minimal side effects. Objective To assess the safety and efficacy of crisaborole 2% ointment—a nonsteroidal phosphodiesterase 4 inhibitor—in the treatment of intertriginous, anogenital, and facial psoriasis. Methods A double-blind, randomized, vehicle-controlled trial was conducted in 21 participants. Participants were randomized 2:1 to receive 4 weeks of twice-daily treatment with either crisaborole 2% ointment (n = 14) or vehicle ointment (n = 7), followed by 4 weeks of open-label treatment with crisaborole 2% ointment. Disease severity was measured by using the Target Lesion Severity Scale (TLSS). Results After 4 weeks, participants in the crisaborole group demonstrated 66% improvement compared with 9% in the vehicle group (P = .0011). Participants in the crisaborole group continued to experience improvement through the open-label phase, demonstrating 81% lesional improvement by week 8, with 71% of these participants achieving clinical clearance. There were no adverse events. Limitations The study was limited to a single tertiary care center and small sample size. Conclusion Treatment with crisaborole 2% ointment was well-tolerated and led to clinical improvement in participants with intertriginous, anogenital, or facial psoriasis.

Background A needs assessment for patients with hidradenitis suppurativa (HS) will support advancements in multidisciplinary care, treatment, research, advocacy, and philanthropy. Objective To evaluate unmet needs from the perspective of HS patients. Methods Prospective multinational survey of patients between October 2017 and July 2018. Results Before receiving a formal HS diagnosis, 63.7% (n = 827) of patients visited a physician ≥5 times. Mean delay in diagnosis was 10.2 ± 8.9 years. Patients experienced flare daily, weekly, or monthly in 23.0%, 29.8%, and 31.1%, respectively. Most (61.4% [n = 798]) rated recent HS-related pain as moderate or higher, and 4.5% described recent pain to be the worst possible. Access to dermatology was rated as difficult by 37.0% (n = 481). Patients reported visiting the emergency department and hospital ≥5 times for symptoms in 18.3% and 12.5%, respectively. An extreme impact on life was reported by 43.3% (n = 563), and 14.5% were disabled due to disease. Patients reported a high frequency of comorbidities, most commonly mood disorders. Patients were dissatisfied with medical or procedural treatments in 45.9% and 34.6%, respectively. Limitations Data were self-reported. Patients with more severe disease may have been selected. Conclusion HS patients have identified several critical unmet needs that will require stakeholder collaboration to meaningfully address.

Background Though the National Comprehensive Cancer Network recommends consideration of localized adjuvant radiation after clear-margin surgery for cutaneous squamous cell carcinoma (cSCC) with large-caliber (≥0.1-mm) nerve invasion (LCNI) and other high-risk features, only a single small study has compared surgery plus adjuvant radiation therapy (S+ART) to surgical monotherapy (SM) for cSCC. Objective Compare S+ART to SM for primary cSCCs with LCNI and other risk factors. Methods Matched retrospective cohort study of primary cSCCs (matched on sex, age, immune status, type of surgery, diameter, differentiation, depth, and LCNI) treated with S+ART versus SM. A subgroup analysis of cSCCs with LCNI was performed. Results In total, 62 cSCCs were included in matched analysis (31 S+ART and 31 SM) and 33 cSCCs in the LCNI analysis (16 S+ART and 17 SM). There were no significant differences in local recurrence, metastasis, or death from disease in either analysis. Risk of local recurrence was low (8%, 7/89), with 3 of the local recurrences being effectively treated upon recurrence. Limitations Single academic center and nonrandomized design. Conclusion Adjuvant radiation did not improve outcomes compared with SM due to a low baseline risk of recurrence, although adjuvant radiation for named nerve invasion and LCNI of ≥3 nerves has been shown to improve outcomes in a prior study. Randomized studies are needed to define the subset of cSCC for whom adjuvant radiation has utility.

Background Immunotherapy using programmed cell death 1 protein (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors has been increasingly reported in a variety of nonmelanoma skin cancers (NMSCs). Objective To analyze the evidence of PD-1 and PD-L1 inhibitors in the treatment of NMSC. Methods A primary literature search was conducted with the PubMed, Cochrane Library, EMBASE, Web of Science, and CINAHL databases through October 28, 2018, to include studies on the use of PD-1 or PD-L1 inhibitors in patients for NMSC. Two reviewers independently performed study selection, data extraction, and critical appraisal. Results This systematic review included 51 articles. The most robust evidence was in the treatment of Merkel cell carcinoma and cutaneous squamous cell carcinomas, as supported by phase 1 and 2 clinical trials. Treatment of basal cell carcinoma, cutaneous sarcoma, sebaceous carcinoma, and malignant peripheral nerve sheath tumor also showed benefit with PD-1/PD-L1 inhibitors, but data are limited. There does not appear to be efficacy for PD-1/PD-L1 inhibitors in cutaneous lymphomas. Limitations More investigation is needed to determine the efficacy, tumor responsiveness, and the safety profile of PD-1 and PD-L1 inhibitors in NMSC. Conclusion PD-1 and PD-L1 inhibitors exhibit treatment efficacy in a variety of NMSCs.

Chronic nodular prurigo (CNPG) is a subtype of chronic prurigo, also called prurigo nodularis, and a chronic skin condition characterized by intensely pruritic nodular lesions. Although the exact cause of CNPG is unknown, it appears to result from a repetitive itch-scratch cycle induced by neuronal sensitization to chronic pruritus. CNPG is associated with an underlying dermatologic condition in about half of patients, and it can also be attributed to systemic, neurologic, psychogenic, or unknown causes. For most patients, multiple underlying causes are identified. Patients with CNPG often experience impaired quality of life, sleep disturbance, anxiety, and depression. To encourage consistent and accurate diagnosis and treatment of CNPG across regions, we are proposing a diagnostic and treatment algorithm that includes initial assessment of core symptoms, detailed dermatologic history and clinical examination, patient-reported outcomes, diagnostic workup, and recommended therapies. This information is supplemented with photographs to illustrate clinical appearance and disease severity. Because CNPG is often multifactorial and it can take months to years for lesions to heal, interdisciplinary cooperation and long-term management are important.

Background Severe Hurley stage 1 Hidradenitis suppurativa (HS1) is a difficult to treat form of the disease. Objective To assess the efficacy and tolerance of the oral combination of rifampin (10 mg/kg once daily) – moxifloxacin (400 mg once daily) – metronidazole (250 to 500 mg t.i.d) (RMoM) treatment strategy in severe HS1 patients. Methods Prospective, open-label, non-comparative cohort study in 28 consecutive patients. 19 patients were treated for 6 weeks by RMoM, followed by 4 weeks of RMo alone, then by cotrimoxazole after remission. Moxifloxacin was replaced by pristinamycin (1g t.i.d) in 9 cases because of contra-indications or intolerance. Primary endpoint was a Sartorius score of 0 (clinical remission, CR) at week 12. Results The median Sartorius score dropped from 14 to 0 (p= 6 x 10-6) at week 12, 75% of patients reaching CR. A low initial Sartorius score was a prognosis factor for CR (p = 0.049). Main side-effects were mild gastro-intestinal discomfort, mucosal candidiasis and asthenia. At one year of follow-up, the median [IQR] number of flares dropped from 21/year to 1 (p = 10-5). Limitations: small monocentric non-controlled study. Conclusion: complete and prolonged remission can be obtained in severe HS1 using targeted antimicrobial treatments.

Background The number needed to treat or excise (NNT) is commonly used to measure the number of skin biopsies performed to detect one melanoma. The NNT for melanoma varies widely between clinical settings. Objective To provide a formal statistical comparison of the efficacy of melanoma detection between different clinical settings. Methods A systematic review and meta-analysis of all relevant observational studies on NNT in relation to melanoma was performed on MEDLINE. We performed a random effects model meta-analysis and reported NNTs with 95% confidence intervals (CIs). The subgroup analysis was related to clinical setting. Results In all, 29 papers including a total of 398,549 biopsies/excisions were analyzed. The overall NNT was 9.71 (95% CI, 7.72-12.29): 22.62 (95% CI, 12.95-40.10) for primary care, 9.60 (95% CI, 6.97-13.41) for dermatologist, and 5.85 (95% CI, 4.24-8.27) for pigmented lesion specialists. Limitations There is heterogeneity in data reporting and possibility of missing studies. In addition, the incidence of melanoma varies among clinical settings and could affect NNT calculations. Conclusion Specialists have the lowest NNT, followed by dermatologists, suggesting involving specialists in the diagnosis and treatment of pigmented skin lesions can likely improve patient outcomes.

Background Tumor necrosis factor-α inhibitor-induced psoriasis (TNFI-psoriasis) is a paradoxical reaction characterized by development of a psoriasiform rash that mimics idiopathic psoriasis subtypes both clinically and histologically. Few studies have investigated histologic features of TNFI-induced psoriasis skin lesions, and most of these are limited by inclusion of few specimens. Objective We aimed to characterize histologic features of TNFI-psoriasis and identify histological differences between TNFI-psoriasis and idiopathic psoriasis. Methods We characterized 60 biopsies obtained from 47 unique patients at a single tertiary care referral center between 2004-2016 who developed TNFI-psoriasis, and compared histologic features to those in 85 biopsy specimens from a control group of 85 patients with idiopathic psoriasis. Results The most common histologic reaction pattern in TNFI-psoriasis biopsies was psoriasiform (80.0%). Five histological parameters were significantly different in TNFI-psoriasis biopsies compared to idiopathic psoriasis biopsies: ≥3 dermal eosinophils per histologic section, neutrophils in the stratum corneum, neutrophils in the epidermis, papillary plate thinning, and absence of parakeratosis. Limitations Inability to exclude lesion selection bias as a potential reason for some significant histologic differences. Conclusion This study supports that histological differences exist between TNFI-psoriasis and idiopathic psoriasis that may help distinguish between these conditions, especially dermal eosinophil counts ≥3.

Pyoderma gangrenosum (PG) classically presents with an acute inflammatory stage, characterized by rapid evolution of painful ulcerations. The pathergy associated with PG lesions complicates disease management. Although PG is commonly treated with immunosuppression, some patients have refractory non-inflammatory ulcers. In this sub-population, there are case reports of successful surgical treatment. However, there is no consensus on optimal perioperative treatment for patients with PG undergoing surgery of any kind, PG-related or otherwise. Therefore, we conducted a comprehensive literature review describing perioperative management practices and risk factors that may predict response to surgical intervention. We identified 126 cases of surgical intervention in patients with active PG. Among these, only 16.7% experienced post-operative disease progression. No perioperative treatments or clinical risk factors were identified as statistically significant predictors of disease recurrence. Although limited by case series design and publication bias, this study is a valuable means of hypothesis generation for this rare condition.

Background/Objectives Fibrosing alopecia in a pattern distribution (FAPD) is a newly recognized form of scarring alopecia sharing characteristics of both androgenetic alopecia (AGA) and lichen planopilaris (LPP). The existing literature on FAPD and current understanding of the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of this disease are reviewed. Methods PubMed searches were performed to identify all articles discussing FAPD. The references of articles were used to identify additional articles. Results A total of 15 articles were found describing FAPD in a total of 188 patients (164 female, 24 male, average age 53.8). Conclusion FAPD affects the androgen dependent scalp and is typically associated with hair follicle miniaturization. The scalp affected by FAPD shows features of both LPP and AGA, and FAPD may possibly represent an exaggerated inflammatory response to damaged hair follicles, triggered by AGA. Physical exam and trichoscopic evidence of follicular inflammation and occasionally fibrosis are important to identify the condition and a dermoscopy-guided biopsy can confirm the diagnosis. Unless recognized, clinicians may misdiagnose FAPD as AGA associated with seborrheic dermatitis. Data on treatment modalities is limited, however based on pathogenesis, combined therapy with anti-inflammatory and hair growth promoting agents is warranted.

Background Measuring patient-centered outcomes in clinical practice is valuable for monitoring patients and advancing real-world research. A new initiative from the Harmonising Outcome Measures for Eczema (HOME) group aims to recommend what might be recorded for atopic eczema (AE) patients in routine clinical care. Objectives Prioritize outcome domains to measure AE in clinical practice and select valid and practical outcome measurement instruments for the highest-priority domain. Methods An online survey of HOME members identified and ranked 21 possible health-domains. Suitable instruments were then selected for the top-prioritized domain at the HOME VI meeting, using established consensus processes informed by systematic reviews of instrument quality. Results Patient-reported symptoms was the top-prioritized domain. Based on psychometric properties and feasibility, there was consensus that the recommended instruments to measure AE symptoms in clinical practice are the Patient-Oriented Eczema Measure (POEM) and/or the Patient-Oriented SCORing Atopic Dermatitis index (PO-SCORAD). The Numerical Rating Scale for itch received support pending definition and validation in AE. Conclusion Following the first step of the HOME Clinical Practice initiative, we endorse using the POEM, the PO-SCORAD, or both for measuring AE symptoms in clinical practice. Additional high-priority domains for clinical practice will be assessed at subsequent HOME meetings.

Background Large studies that examine risk factors for first occurrence of venous leg ulcerations (fVLU) are needed to guide management. Objective To investigate factors associated with fVLU development. Methods A retrospective cohort study utilizing a validated national commercial claims database of patients with venous insufficiency (VI). Subjects were followed to determine if they developed fVLU and risk and protective factors were analyzed. Results Adjusted hazard ratio (AHR) for comorbidities demonstrated an increased risk in men (AHR:1.838, 95% CI:1.798-1.880), older age (age 45-54 AHR:1.316, 95% CI:1.276-1.358) (age 55-64 AHR:1.596 95% CI:1.546-1.648), history of non-VLU ulceration (AHR:3.923, 95% CI:3.699-4.161), anticoagulant use (AHR:1.199, 95% CI:1.152-1.249), antihypertensive use (AHR:1.067 95% CI:1.040-1.093), and pre-exiting VI including CVI (AHR:1.244, 95% CI:1.193-1.298), edema (AHR:1.224, 95% CI:1.193-1.256), and chronic venous hypertension (AHR:1.671, 95% CI:1.440-1.939). Possible protective factors are having venous surgery (AHR:0.454, 95% CI:0.442-0.467), using compression stockings (AHR:0.728, 95% CI:0.705-0.753), prescribed statin medications (AHR:0.721, 95% CI:0.700-0.743) and pain medications (AHR:0.779, 95% CI:0.757-0.777). Limitations Risk of misclassification given the use of ICD9 codes. Possible confounding factors such as BMI could not be adequately controlled using ICD9 codes. Conclusions The new evidence presented supports paradigm shift towards VLU prevention.

Background Brigham and Women’s Hospital (BWH) stage T2a squamous cell carcinoma (SCC), demonstrating a single high-risk feature, have a low risk for metastasis and death but an increased risk of local recurrence. Little evidence exists for the best treatment modality and associated outcomes in T2a SCC. Objective We aimed to compare outcomes for T2a SCC treated by Mohs micrographic surgery (MMS) compared to wide local excision (WLE) with permanent sections. Methods Retrospective review of IRB-approved single institution registry of T2a SCC. Results 366 primary T2a tumors were identified including 240 SCC (65.6%) treated with MMS and 126 SCC (34.4%) treated with WLE. 32.5% of patients were immunosuppressed and mean oncologic follow-up was 2.8 years. Local recurrence was significantly more likely after WLE (4.0%) than after MMS (1.2%) (p=0.03). Multiple logistic regression demonstrated immunocompromised state (OR 5.1, 95% CI 1.1-23.3, p = 0.03) and WLE (OR 4.8, 95% CI 1.1-21.6, p=0.04) associated with local recurrence; and WLE (OR 7.8, 95% CI 2.4-25.4, p=0.0007), high-risk head and neck location (OR 8.3, 95% CI 1.8-38.7, p=0.004), poor histologic differentiation (OR 4.7, 95% CI 1.4-15.4, p = 0.03) associated with poor outcomes (overall recurrence or disease specific death). Conclusion MMS provides improved outcomes in BWH T2a SCC.

Background Cumulative clinical improvement and speed of improvement are important to psoriasis patients. Objective Compare cumulative benefits of biologics over 12-16 weeks in the treatment of moderate-to-severe psoriasis. Methods A systematic literature review identified phase III trial data on Psoriasis Area and Severity Index (PASI) responses for biologics during 12 and 16 weeks of treatment. Cumulative clinical benefit, measured by area-under-the-curve (AUC) for PASI 75, PASI 90, and PASI 100, was compared using the network meta-analysis (NMA) and Bayesian methodology on the relative probability of achieving percent of maximum AUC. Results Among biologics approved for psoriasis treatment, anti-IL-17 biologics demonstrated consistently greater cumulative clinical benefits on PASI 75, PASI 90, and PASI 100 over the 12- or 16-week period than anti-IL-23 and other biologics. For biologics with 12-week data, both ixekizumab and brodalumab showed greater cumulative benefits for PASI 75, PASI 90, and PASI 100 than secukinumab, followed by guselkumab, infliximab, adalimumab, ustekinumab and etanercept. Ixekizumab showed greater cumulative benefits than all other biologics reporting 16-week data . Limitations Recently approved biologics were not included. Conclusion Ixekizumab (at 12 weeks and 16 weeks) and brodalumab (at 12 weeks) had greater cumulative clinical benefit than all other biologics studied.

Conjunctivitis in patients with atopic dermatitis treated with dupilumab is associated with baseline serum levels of IgE and TARC but not subjective severity scores in a real-world setting. These objective parameters are useful as practical predictors of later development of conjunctivitis.

Background The Hidradenitis Suppurativa Clinical Response (HiSCR) is the gold standard primary outcome measure for Hidradenitis Suppurativa (HS) clinical trials, however it does not assess the presence of draining tunnels, a common finding in advanced disease. It is unclear what the effect of the presence or absence of draining tunnels has upon the efficacy of adalimumab therapy in moderate and advanced disease. Objectives We evaluated the efficacy of adalimumab versus placebo using the International Hidradenitis Suppurativa Severity Score System (IHS4). Additionally, we assessed the impact of draining tunnels upon therapeutic response as measured by both the HiSCR and change in nodule counts. Methods Re-analysis was conducted using the IHS4 and PIONEER 1 and 2 Individual Patient Data. Both binary outcomes (achieving HISCR and achieving change in IHS4 severity category) and continuous outcomes (nodule counts and IHS4 score) were calculated using R version 3.5.3. Regression modeling was undertaken to assess the impact of draining tunnels and other variables. P<0.05 was considered statistically significant. Results The significance of adalimumab therapy was dependent upon the outcome measure used. Placebo response rates were highest when binary outcome measures were used. Draining tunnels, smoking, antibiotics and BMI influence HiSCR response in Pioneer 2. Significant differences in disease severity were seen between PIONEER 1 and 2 datasets. Conclusions Elevated placebo response rates in PIONEER 1 and 2 are partially attributable to the use of binary outcome measures. Draining tunnels influence clinical response as measured by HiSCR and nodule counts in Pioneer 2. Further investigation into the effect of BMI upon clinical response is required.

Background Renal involvement in adult HSP is a major cause of morbidity and can lead to significant long-term renal impairment. The prognostic significance of normal or minimal urinary abnormalities at time of diagnosis is unknown. Objective To assess the risk of long-term renal impairment in HSP patients who present with normal or minimal urinary abnormalities. Methods Retrospective cohort study of adult HSP patients presenting with normal urinalysis, microscopic hematuria or low-grade proteinuria. Patients were followed for development of long-term renal impairment adjusting for comorbidities. Results 47 patients were included with median follow up 73.9 months (IQR 35, 98). Thirty-nine (83.0%) patients had abnormal urinalysis of whom 15 (38.5%) progressed to long-term renal impairment. In contrast, 8 (17%) patients had normal urinalysis of whom only 1 (12.5%) developed long-term renal impairment (adjusted HR 10.58 [CI 1.18, 94.73]). Renal events occurred at a median 36.1 months (IQR 17.1, 61) from diagnosis, earlier in those with comorbidities compared to those with none, and in a constant event rate over time. Limitations Small sample size Conclusions Microscopic hematuria and low-grade proteinuria at HSP diagnosis is a poor prognostic sign for the development of long-term renal impairment. This population should be targeted for prolonged surveillance.

Background Metastatic basal cell carcinoma (mBCC) is a very rare entity and diagnosis can be challenging. Therapeutic options are limited and response to targeted therapy is poor. Objective We aimed to demonstrate a clonal relationship between BCCs and their metastases and additionally, to explore which hedgehog pathway related mutations are involved in mBCC. Methods Genetic analysis was conducted in ten primary BCCs and their metastases. Genes relevant for BCC development were analyzed in tumor and metastasis material, either with small molecule molecular inversion probes (smMIPs) for PTCH1, PTCH2, SMO, SUFU, GLI2 and TP53, or with targeted next generation sequencing (tNGS) of the same genes and CDKN2A, CDKN2B, CIC, DAXX, DDX3X, FUBP1, NF1, NF2, PTEN, SETD2, TRAF7, and the TERT promoter. Results In eight of ten patients, identical gene mutations could be demonstrated in the primary tumors and their metastases. A broad spectrum of mutations was found. Four patients had SMO mutations in their tumor and/or metastasis. All SMO mutations found, were known to cause resistance to targeted therapy with vismodegib. Limitations In two patients there was insufficient qualitative DNA available for genetic analysis. Conclusions Molecular testing can help to identify the origin of a BCC metastasis and may be of prognostic and therapeutic value.

Background Despite high utilization of complementary and alternative medicine (CAM) for alopecia areata (AA), efficacy and safety remain unclear. Objective To identify all CAM therapies studied for treatment of AA. Outcomes of interest included disease course and psychological well-being. Methods PubMed and Embase were searched to identify English articles containing original data investigating CAM in human subjects with AA from 1950-2018. Quality was assessed with Oxford Centre for Evidence Based Medicine criteria. Results Of 1,015 initial citations, 16 articles met inclusion criteria: 5 randomized controlled trials, 5 prospective controlled cohorts, 4 prospective non-controlled cohorts, 1 retrospective cohort, and 1 case series. CAM therapies with best evidence and efficacy for hair growth in AA include essential oil aromatherapy, topical garlic, and oral glucosides of peony with compound glycyrrhizin. Hypnosis and mindfulness psychotherapy represent low quality evidence for improvement of psychological and quality of life outcomes. Adverse events were rare and mild for all therapies evaluated. Limitations Inconsistent or poorly reported study methodology and non-standardized outcomes limit the conclusions that can be made from these studies. Conclusions This work serves to inform physician management of patients with AA seeking CAM, while encouraging further investigation into these therapies to address some of the therapeutic challenges of AA.

Background Ibrutinib is an oral inhibitor of Bruton’s tyrosine kinase (BTK) that is FDA-approved for several lymphoproliferative disorders and chronic GVHD. Objective To characterize cutaneous eruptions arising from ibrutinib and highlight overlap with epidermal growth factor receptor inhibitor (EGFRi)-induced dermatologic adverse events (dAEs). Methods Single-center retrospective cohort of patients referred to the Skin Toxicities Program for management of cutaneous eruptions while taking ibrutinib. Results Among 19 patients, cutaneous eruptions manifested as facial-predominant papulopustular eruptions, petechiae or ecchymoses, photosensitivity, panniculitis, xerosis, and clinical staphylococcal overgrowth. The majority of patients were able to continue ibrutinib therapy with focused management of their cutaneous toxicities. Limitations This study represents cases at a single tertiary care center and is limited to patients referred for toxicity. Conclusions With the exception of petechiae, the cutaneous toxicities of ibrutinib overlap with those associated with selective EGFR inhibitors. We observed that these reactions can be successfully managed using approaches for EGFR inhibitor-induced cutaneous adverse events.

Background Granuloma annulare (GA) is an inflammatory skin disorder. While localized GA is often self-resolving, generalized GA is often recalcitrant to treatments. There are no targeted treatments for GA, largely due to lack of mechanistic understanding. Recently TNF antagonism showed promise in GA, suggesting an underlying immune pathogenesis. Objective To elucidate the immune pathogenesis and identify potential therapeutic targets for GA. Methods Lesional and non-lesional skin biopsies were obtained from GA patients and evaluated for a large array of inflammatory markers in comparison to inflammatory markers from normal skin of healthy individuals. Results We found differential expression of many inflammatory genes compared to normal skin. These genes were associated with Th1/innate immunity (TNFα, IL-1β, IL-12/23p40, STAT1, CXCL9/CXCL10), JAK-signaling, and Th2 (IL-4, IL-31, CCL17, CCL18; p<0.05). Unexpectedly, IL-4 showed significant upregulation in GA lesional skin versus control skin (15,600-fold change). Limitations Limited sample size. Conclusions Our findings shed light on the inflammatory pathways of GA, supporting the notion that immune mechanisms could be driving disease, as suggested by the promising data of TNFα inhibitors in GA. The significant JAK and particularly Th2 signaling in GA advocates for the investigation of specific JAK and Th2-targeted drug therapy.

Background Previous studies found conflicting results about whether hidradenitis suppurativa (HS) is associated with depression or anxiety. Objectives Determine the relationship of HS with depression and anxiety. Methods A systematic review was performed of published observational studies in MEDLINE, Pubmed, EMBASE, GREAT, LILACS, Cochrane, Scopus and PsychInfo that analyzed depression or anxiety in HS. Two reviewers performed title/abstract review and data extraction. Meta-analysis was performed using random-effects weighting. Results Thirty-nine studies met inclusion criteria; 27 had sufficient data for meta-analysis. The prevalences of depression (26.6% vs. 6.6%) and anxiety (18.1% vs. 7.1%) were higher in persons with vs. without HS. HS patients had higher odds of depression in 12 of 13 studies and pooled analysis (odds ratio [95% confidence interval]: 2.54 [2.15-3.01]), and anxiety in 6 of 6 studies and pooled analysis (2.00 [1.66-2.42]). Similar results were found in sensitivity analyses for different methods of HS diagnosis (physician diagnosed and chart review) and control groups (healthy and dermatologic controls). HS was associated with higher anti-depressant and anxiolytic use, and suicidality, but not mean depression and anxiety scale scores. Limitations Individual level data were unavailable. Conclusions HS patients have higher odds of depression, anxiety, and suicidality.

Background Eyebrow loss (madarosis) is a frequent sign of frontal fibrosing alopecia (FFA) and it can be the first sign of the disease. Objective To describe trichoscopic findings of FFA on the eyebrows. Methods The analysis included 151 women with histologically proven diagnosis of FFA and eyebrow loss. Trichoscopy of the eyebrow area was performed using either Fotofinder videodermatoscope or handheld dermoscope DermLite® II pro. Results The most frequent trichoscopic signs were yellow dots (92.7%), multiple pinpoint dots (79.5%), short thin hairs/vellus (76.2%), black dots (66.2%), and dystrophic hairs (60.9%). Tapering hairs were found in 21 (13.9%) and dystrophic hairs in 92 (60.9%) patients. Limitations Inner limitations of a case series (there was no comparison to normal controls or individuals with other hair disorders) and lack of histological correlation to the trichoscopic findings. Conclusion Although FFA is a scarring alopecia, the most common trichoscopic signs found in the eyebrows are usually related to non-cicatricial alopecia. Therefore, in most cases trichoscopy of eyebrows does not resemble the trichoscopy of FFA on scalp. Black dots, dystrophic hairs and broken hairs are frequent signs. Occasionally tapered hairs can be present on eyebrows of FFA leading to misdiagnosis of AA.

Background While treatment guidelines exist for melanoma in situ and invasive melanoma, guidelines for other melanocytic skin lesions do not exist. Objective To examine pathologists’ treatment suggestions for a broad spectrum of melanocytic skin lesions and in comparison with existing guidelines. Methods Pathologists (N=187) completed a survey and then provided diagnoses and treatment suggestions for 240 melanocytic skin lesions. Physician characteristics associated with treatment suggestions were evaluated using multivariable modeling. Results Treatment suggestions were concordant with National Comprehensive Cancer Network (NCCN) guidelines for the majority of cases interpreted as melanoma in situ (73%) and invasive melanoma (86%). Greater variability of treatment suggestions was seen for other lesion types without existing treatment guidelines. Characteristics associated with provision of treatment suggestions discordant with NCCN guidelines were: low caseloads (invasive melanoma), lack of fellowship training or board certification (melanoma in situ), and >10 years of experience (invasive melanoma and melanoma in situ). Limitations Pathologists could not perform immunohistochemical staining or other diagnostic tests; only one glass side provided per biopsy case. Conclusions Pathologists’ treatment suggestions vary significantly for melanocytic lesions, with lower variability for lesion types with national guidelines. Results suggest the need for standardization of treatment guidelines for all melanocytic lesion types.

Syphilis is caused by infection with the spirochetal bacterium Treponema pallidum subsp. pallidum. It was first recognized in the late 15th century. Since 2000, the incidence of sexually acquired syphilis has increased substantially in the developed world, with men who have sex with men and persons living with HIV infection disproportionately affected. Clinical manifestations of syphilis are protean and often include mucocutaneous manifestations. The first article in this continuing medical education series reviews historical aspects, microbiology, epidemiology, and clinical manifestations of sexually acquired syphilis.

The methods used for the laboratory diagnosis of syphilis include direct detection of Treponema pallidum subspecies pallidum and serologic testing. Serologic testing relies on both nontreponemal and treponemal tests. In newly developed reverse-sequence screening algorithms, treponemal tests are performed before nontreponemal tests. The management of syphilis requires appropriate staging, treatment, and follow-up of patients along with the prompt reporting of infections to public health authorities to assist with prevention and control efforts. Benzathine penicillin G remains the treatment of choice for all stages of syphilis. Screening of populations at higher risk for syphilis is recommended by the US Centers for Disease Control and Prevention, the US Preventive Services Task Force, and the World Health Organization. The second article in this continuing medical education series reviews the testing for and the management of sexually acquired syphilis.

Background Hidradenitis suppurativa (HS) is characterized by recurrent, painful nodules in flexural areas. Objective The objective of this study was to explore the placebo response in HS randomized clinical trials and to compare it briefly with the placebo response in psoriasis and atopic dermatitis. Methods A Cochrane Review on interventions in HS was used as a starting point, and a systematic review was then undertaken by using the PubMed database, yielding 7 HS randomized clinical trials for inclusion in this study. Results This review demonstrates that there is a robust placebo response in HS that is most marked in physical signs but also marked in pain responses. Limitations Multiple outcome measures utilized in these studies and reporting bias limited this review. Conclusion This large placebo response has implications for clinical trial design. This knowledge can also help deliver improved clinical care by forming the basis of nonpharmacologic treatments and help optimize current medication use to maximize the placebo effect.

Background Biologic therapy for psoriasis is effective but not always long-lasting and sometimes needs to be switched. Objective We aimed to evaluate the drug survival (ie, the time from initiation to discontinuation) of each biologic and the factors affecting survival to identify better switching strategies and improve drug survival. Methods In total, 195 psoriasis patients treated in our unit during 2006-2018 were retrospectively observed. Descriptive statistical analyses and logistic regression models were performed. Kaplan–Meier survival curves and multivariate Cox models adjusted for confounding variables were used to estimate and compare drug survival. Results Overall, 90.6% of patients achieved an ≥75% reduction in their baseline Psoriasis Area and Severity Index score. In 2018, the most frequently used biologic was ustekinumab (47/169, 27.8%). Patients with higher baseline Psoriasis Area and Severity Index scores were more likely to be switched (P = .0399, odds ratio 1.08). In naive patients, ustekinumab showed longer drug survival (>7.0 years), but in biologic-experienced patients, we found no significant differences in drug survival. Previous biologic therapies increased the need for switching (P = .014, hazard ratio 1.20). Switching between biologic classes yielded longer drug survival than switching within biologic classes (P = .003, hazard ratio 0.48). Limitations As a single-center, retrospective real-life study, the data were not perfectly homogeneous. Conclusion Switching between biologic classes might increase drug survival but retrospective studies designed ad hoc are needed to confirm this better switching strategy.

Background The International Dermatology Outcome Measures established a set of core domains to be measured in all psoriasis trials. This set requires that symptoms of psoriatic arthritis (PsA) be measured in all psoriasis studies. Objective To identify the approach to PsA screening and the most appropriate outcome measure for capturing PsA symptoms. Methods Following guidelines (ie, the COnsensus-based Standards for the selection of health Measurement INstruments, Core Outcome Measures in Effectiveness Trials Initiative, and Outcome Measures in Rheumatology Handbook), we conducted a consensus-building study that included patients, physicians, industry partners, and patient association representatives. The process consisted of a literature review and quality appraisal of measures for PsA symptoms, a pre-Delphi exercise, a Delphi survey, and a consensus meeting. Results Among the 297 expert participants in the Delphi survey, 87.5% agreed that all patients in a psoriasis trial should be screened for PsA with a validated screening tool. Regarding the measurement of PsA symptoms, the preferred instrument was the Psoriatic Arthritis Impact of Disease-9 (PsAID9), with the Routine Assessment Patient Index Data-3 (RAPID3) representing an acceptable alternative. Limitations Only International Dermatology Outcome Measures members participated in the consensus meeting. Conclusion The overwhelming majority of expert stakeholders agreed that all psoriasis trial participants should be screened for PsA, with PsA symptoms measured by using PsAID9 (or alternatively with RAPID3).

Background As a result of concerns about hypertriglyceridemia, liver enzyme abnormalities, and leukopenia during isotretinoin therapy for acne, patients are often monitored closely with routine laboratory assessments, although the value of this practice has been questioned. Methods We conducted a cohort study of patients receiving isotretinoin for acne between January 1, 2008, and June 30, 2017, using the OptumInsights Electronic Health Record Database (Optum, Eden Prairie, MN) to evaluate the frequency of laboratory abnormalities. Poisson regression was used to evaluate for changes to the frequency of routine laboratory monitoring over time. Results Among 1863 patients treated with isotretinoin, grade 3 or greater triglyceride and liver function testing abnormalities were noted in fewer than 1% and 0.5% of patients screened, respectively. No grade 3 or greater cholesterol or complete blood count abnormalities were observed. There were no meaningful changes in the frequency of laboratory monitoring over time. Limitations Limitations include that we are unable to evaluate the clinical notes to understand the exact clinical decision making when clinicians encountered abnormal laboratory values. Conclusion Although laboratory abnormalities are rare and often do not influence management, frequent laboratory monitoring remains a common practice. There are opportunities to improve the quality of care among patients being treated with isotretinoin for acne by reducing the frequency of lipid and liver function monitoring and by eliminating complete blood count monitoring.

Background Atopic dermatitis (AD) has a variable disease course and intermittent triggers, and responses to topical therapy vary, potentially affecting the magnitude of the placebo response in AD trials. Objective To determine the predictors of increased placebo response in randomized controlled trials of AD. Methods We performed a systematic review and meta-analysis of randomized controlled trials for systemic therapy in AD published during 2007-2018. We searched the Cochrane Library, Medline, Embase, Global Resource for EczemA Trials (GREAT), Literature of the Latin American and Caribbean Health Sciences (LILACS), and Scopus. Two authors performed study selection and data extraction. Multivariable mixed models were constructed for Cohen D of Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), numeric rating scale (NRS)–itch and visual analog scale (VAS)–itch, and Dermatology Life Quality Index (DLQI). Results Overall, 64 trials were included. Use of concomitant topical therapy prescriptions, study duration ≥3 months, and fewer treatment arms were associated with an increased placebo response for EASI, NRS- and VAS-itch, and DLQI. For EASI, the placebo response was increased in studies with a higher proportion of male patients, mild-moderate mean baseline EASI scores, and no blinding. For NRS-itch, and VRS-itch, higher placebo responses were associated with higher proportions of male patients and moderate-severe mean itch scores at baseline. Conclusion Placebo responses can be reduced in clinical trials of systemic therapy in AD by incorporating double- and triple-blinding, balancing the sex distribution of patients, disallowing concomitant use of prescription topical therapy, and having shorter study durations.

Background Biopsies of dysplastic nevi processed by bread-loafing allow for limited margin assessment; however, reported biopsy margins often influence management. Objective To evaluate the negative predictive value of biopsy margins of dysplastic nevi. Methods A retrospective search of a single academic institution's pathology database was conducted to identify all biopsy specimens of dysplastic nevi between January 1, 2015, and December 31, 2017. Biopsy specimen margin assessments were compared with excision pathology reports to calculate negative predictive value and to assess the frequency of residual nevus on excision after positive biopsy margins. Results A total of 1245 dysplastic nevi from 934 patients were identified. Clear biopsy margins had a negative predictive value for the absence of residual nevus on excision of 87.3% for dysplastic nevi of moderate atypia or greater. Residual nevus was identified on excision in 29.41% of cases of dysplastic nevi of moderate atypia or greater when initial biopsy margins were positive. Limitations This was a retrospective, single-institution study. The calculations likely overestimate the true negative predictive value of biopsy margins because of processing of excision specimens by bread-loafing. Conclusions This study provides additional evidence that reported biopsy margins are not representative of true margin status.

Background Several tools can provide a reliable and accurate evaluation of pruritus, including the visual analog scale (VAS), numeric rating scale (NRS), verbal rating scale (VRS), and multidimensional questionnaires such as the Itch Severity Scale (ISS). However, no single method is considered a gold standard. Objective We evaluated the validity and reliability of VAS, NRS, VRS, and ISS and their correlation with a pruritus-specific quality of life instrument, ItchyQoL. Methods A total of 419 patients (215 men and 204 women) with chronic pruritus (mean age, 46.58 years) recorded their pruritus intensity on VAS, NRS, VRS, and ISS. Retest reliability was analyzed in a second assessment 3 hours after the initial assessment. All participants answered ItchyQoL. Results A strong correlation between VAS, NRS, and VRS was found. ISS showed a low intercorrelation validity with these tools. However, ISS was more strongly correlated with ItchyQoL. The retest reliability scores were similar for VAS, NRS, and VRS but lower than the scores obtained for ISS. Limitations Limitations include patient heterogeneity and recall bias. Conclusion The assessment of pruritus is challenging because of the subjective symptoms and the multifactorial nature. Therefore, more studies are needed to determine the best strategy to assess itch intensity.

Background Despite the availability of different therapeutic modalities, treatment of recalcitrant common warts is still challenging. Cervarix (GlaxoSmithKline, Brentford, UK), a recombinant bivalent human papillomavirus (HPV) vaccine, has shown promising efficacy in the treatment of warts. Objectives To evaluate the beneficial effects and tolerability of intramuscular versus intralesional bivalent HPV vaccine in the treatment of recalcitrant common warts. Methods The study included 44 adult patients with multiple recalcitrant common warts; 22 patients received intramuscular injection of bivalent HPV vaccine at 0, 1, and 6 months or until complete clearance of warts, and the other 22 patients received intralesional injection of 0.1 to 0.3 mL of bivalent HPV vaccine into the largest wart at 2-week intervals until complete clearance or for a maximum of 6 sessions. Results Complete clearance of warts was observed in 18 patients (81.8%) of the intralesional group and 14 patients (63.3%) of the intramuscular group; however, the difference was not statistically significant. Adverse effects were transient and insignificant, and no recurrence was reported in either group. Limitations Small study sample and different dosing schedules. Conclusions Bivalent HPV vaccine, particularly by intralesional injection, seems to be a potential therapeutic option for the treatment of multiple recalcitrant common warts.

Background Outcomes for patients with cutaneous squamous cell carcinoma (CSCC) treated with Mohs micrographic surgery (MS) in the United States have never been prospectively defined. Risk factors as they relate to outcomes are primarily derived from single-institution, retrospective data without regard for treatment modality. The American Joint Committee on Cancer Staging Manual, Eighth Edition, and the Brigham and Women's Hospital T staging systems have not been prospectively validated. Objective To prospectively quantify outcomes by T stage and verify historically high-risk features as they pertain to outcomes in MS-treated CSCC. Methods A 5-year, prospective, multicenter analysis of patients undergoing MS for invasive CSCC was conducted. Results The study enrolled 647 patients with 745 tumors. The 5-year local recurrence (LR)-free survival, nodal metastasis (NM)-free survival, and disease-specific survival were 99.3%, 99.2%, and 99.4%, respectively. Both staging systems were predictive of NM, disease-specific death, and all-cause death; neither was predictive of LR. Although Breslow depth was statistically associated with LR, NM, and disease-specific death, incidental perineural invasion was not. Limitations The Brigham and Women's Hospital and the American Joint Committee on Cancer Staging Manual, Eighth Edition T staging systems were published after study enrollment, therefore T stages were retrospectively applied using the prospectively collected data. Conclusion MS is a highly effective treatment for CSCC and may mitigate factors typically considered high risk. Uniform reporting of Breslow depth should be considered in CSCC. The American Joint Committee on Cancer Staging Manual, Eighth Edition, and the Brigham and Women's Hospital staging system are useful prognosticators but are not predictive of LR after MS.

Background Syphilis is often misdiagnosed clinically, and biopsies might be required. Objective To determine histopathologic features that distinguish secondary syphilis from pityriasis lichenoides (PL), pityriasis rosea (PR), and early mycosis fungoides (MF). Methods Histopathologic features of 100 cases of syphilis, 110 cases of PL, 72 cases of PR, and 101 cases of MF were compared. Results Elongated rete ridges and interstitial inflammation favor syphilis over PL (likelihood ratios 3.44 and 2.72, respectively), but no feature reliably distinguishes between them. Secondary syphilis and PR can be distinguished by neutrophils in the stratum corneum, plasma cells, interface dermatitis with lymphocytes and vacuoles, and lymphocytes with ample cytoplasm. Plasma cells and lymphocytes with ample cytoplasm are rare in early MF and can be used as distinguishing features. Conclusions Histopathologic features characteristic of syphilis can be seen in PL, PR, and early MF. Distinguishing syphilis from PL can be difficult histologically, and a high index of suspicion is required. Although elongation of rete and interstitial inflammation favor syphilis, plasma cells (historically considered a significant feature of syphilis) are often encountered in PL. Vacuolar interface dermatitis with a lymphocyte in every vacuole is considered characteristic of PL, but this feature appears to be more common in syphilis.

Background Psoriasis is a chronic inflammatory disease with clinical manifestations of the skin that affect adults and children. In adults, biologics have revolutionized the treatment of moderate to severe plaque psoriasis where clear or almost clear is a tangible goal. Research on biologics has recently been extended to children. The introduction of these new therapeutic options has outpaced the limited guidelines in this population. Objective To provide a review of current data on biologics, with a proposal for a clinically relevant treatment algorithm on the management of moderate to severe plaque psoriasis in the pediatric population. Methods A Canadian panel with expertise in psoriasis, pediatric dermatology, and experience with consensus recommendation processes was selected to review the current landscape of pediatric psoriasis and clinical data on biologics plus identify special considerations for baseline workup and monitoring. Recommendations were reviewed and edited by each expert in an iterative process. Conclusion A treatment algorithm for moderate to severe plaque psoriasis in pediatric patients is presented, incorporating approved biologics. Guidance on baseline screening and ongoing monitoring is also provided. Ultimately, treatment choice depends on the patient and his or her caregiver, with consideration of comorbidities, impact on quality of life, and relevant safety aspects.

Background Human papillomavirus (HPV) infections are associated with common dermatologic and nondermatologic diseases. Although HPV vaccines are well established as preventive measures for genital warts and cervical neoplasia, their use as therapeutic agents deserves greater attention. Objective To evaluate the use of HPV vaccine(s) as a treatment modality for cutaneous and/or mucosal disease. Methods A primary literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in January 2019 by using the PubMed and Cochrane databases. Results A total of 63 articles with 4439 patients were included. The majority of patients with cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas were successfully treated with HPV vaccination. Preliminary data on patients with pre-existing anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia is promising. Limitations This review was limited by the lack of controls, patients' previous HPV vaccination status, and publication bias. Conclusion The commercially available three-dose, quadrivalent HPV vaccine is a potential therapeutic option for the treatment of cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas. Noncommercially available HPV vaccines demonstrate therapeutic response for treating anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia. The vaccine's efficacy as an adjunct therapy for HPV-associated cutaneous and/or mucosal disease warrants further exploration.

Background T helper (Th) type 17 and Th2 cells mediate psoriasis and eczema, respectively. Some dermatoses exhibit overlapping clinicopathologic features, and their immunopathology is relatively unexplored. Objective To determine whether Th17 and Th2 subsets and interleukin (IL) 36 and β-defensin 2 (BD-2) markers of IL-17 signaling expression can discriminate between biopsy samples of psoriasis and eczematous/spongiotic dermatitis and to use those markers to immunophenotype cases with clinicopathologic overlap. Methods A retrospective study was performed on biopsy samples of psoriasis, eczema/spongiotic dermatitis, sebopsoriasis, tumor necrosis factor α inhibitor–associated psoriasiform dermatitis, and ambiguous cases diagnosed as spongiotic psoriasiform dermatitis. Dual CD4/GATA3 and CD4/RORC, IL-36, and BD-2 immunohistochemistry was performed. Results IL-36 and BD-2 were strongly expressed in biopsy samples of psoriasis compared with eczema/spongiotic dermatitis. No significant differences were observed in the percentages of Th2 and Th17 cells between disease types. Strong expression of IL-36 and BD-2 was observed in a subset of spongiotic psoriasiform dermatitis, sebopsoriasis, and tumor necrosis factor α inhibitor–associated psoriasiform dermatitis biopsy samples. Limitations This was an exploratory study with a small sample size. No multiple testing adjustment was done. Clinical follow-up was limited. Conclusions In cases with clinicopathologic overlap between psoriasis and spongiotic dermatitis, IL-36, and to a lesser extent BD-2, may be used to assess for a psoriasis-like/IL-17 phenotype, which could inform therapeutic clinical decisions.

Introduction Xeroderma pigmentosum (XP) is a rare genetic disease that is characterized by extreme photosensitivity, resulting in a higher incidence of cutaneous tumors. Reflectance confocal microscopy (RCM) is a noninvasive imaging method for diagnosing cutaneous lesions. Objective To explore the application of RCM in the follow-up of XP patients. Materials and Methods XP patients underwent RCM for suspicious lesions from January 2010 to April 2019. Lesions with malignant RCM features were excised, and the results were compared with their histopathological features. Benign lesions on RCM were monitored every 3 months. We recorded the confocal features that were related to malignancy and specifically to melanoma. Results A total of 61 suspicious lesions from 13 XP patients were included. Thirty-three lesions (54%) were malignant (14 melanomas, 15 basal cell carcinomas, and 4 squamous cell carcinomas). Nonvisible papillae (OR: 11.8 [95% CI 2.6-53.1], p:0.001) and atypical cells at the dermal-epidermal junction (OR: 11.7 [95% CI 2.7-50.3], p:0.001) were independent predictors of malignancy. Limitations The limited number of patients and lesions. Most cases were retrospectively included, and some did not undergo a histological analysis. Conclusions RCM is a valuable tool in the follow-up of XP patients, reducing the need for excisions by 35%.

Background Vismodegib demonstrated 60% response rates in the ERIVANCE trial. Basal cell carcinoma (BCC) has various histopathologies. Their impact on response is unclear. Objective To determine if BCC histopathology impacted vismodegib response. Methods This phase 2b, single center, prospective case series study, compared the efficacy of vismodegib in infiltrative, nodular, and superficial BCCs treated for 12 or 24 weeks in 27 patients. Patients had one target lesion (TL) and up to 3 non-target lesions (NTL). Results Twenty-seven patients were enrolled, with 65 tumors (27 TL/38 NTL). At 24 weeks, most BCCs achieved histologic clearance, with positive biopsies in 10.5% TLs, 30.4% NTLs and 21.4% overall. No statistical differences were seen between histopathologic subtypes. 100% of patients experienced an adverse event (AE), 94% Grade 1 or 2. The most common AEs were dysguesia/loss of taste (86%), muscle spasms (82%) and alopecia (71%). Clinically progressive disease during treatment was low (1.5%). Two patients had recurrence within 1 year of treatment. Limitations Sample size of BCC histopathologic subtypes, sampling punch biopsies, and short follow up. Conclusions Basal cell histopathologic subtype did not significantly impact response to vismodegib. Each subtype was seen to completely respond at 12 and/or 24 weeks of therapy.

Background The increasing use of biologics is accompanied by a risk of hepatitis B (HBV) and C virus (HCV) reactivation. Objective To determine the predictors of HBV and HCV reactivation in psoriasis patients receiving biologics. Methods This study screened 2060 psoriasis patients (3562 treatment episodes) who were taking biologics from 2009 to 2018. There were 359 psoriasis patients with HBV (561 treatment episodes) and 61 with HCV infection (112 treatment episodes). Results During 8809 and 1522 person-months of follow-up, 88 treatment episodes for HBV involved HBV reactivation, and 14 episodes of HCV involved reactivation. The reactivation rate was significantly higher in treatment episodes of chronic HBV infection than that of occult HBV (34.3% vs. 3.2%, p=0.001) and resolved HBV (34.3% vs. 5.0%, p < 0.001). The multivariate analysis revealed that being HBsAg-seropositive, being HBeAg-seropositive, and TNF-α inhibitor therapy were risk factors for HBVr, while antiviral prophylaxis was effective in reducing the risk of HBV reactivation. No predictors were significantly associated with HCV reactivation. Limitations Observational design and a lack of a comparison group. Conclusions Psoriasis patients on biologics have a risk of HBV and HCV reactivations, particularly those who are HBsAg-seropositive, HBeAg-seropositive, and undergoing TNF-α inhibitor therapy.

Extemporaneous compounding is a means to tailor a medication to an individual patient’s needs and may be required when no commercial product exists to meet that need. Compounded products range from buffered lidocaine to topical creams and ointments. Recent heightened regulations have made compounding more challenging for dermatologists and prompted this review of regulations, liability and safety related to compounding. With this information, providers may minimize liability and maximize safety while caring for their patients.