Efficacy and Safety of Abrocitinib in Prurigo Nodularis and Chronic Pruritus of Unknown Origin: A Nonrandomized Controlled Trial.

Importance: Prurigo nodularis (PN) and chronic pruritus of unknown origin (CPUO) are chronic pruritic diseases that dramatically impair quality of life, but therapeutic options are limited. Abrocitinib, a Janus kinase 1 inhibitor, represents a promising therapy for both conditions. Objective: To assess the efficacy and safety of 200-mg oral abrocitinib administered once daily in adults with moderate to severe PN or CPUO. Design, Setting, and Participants: This phase 2, open-label, nonrandomized controlled trial conducted between September 2021 and July 2022 took place at a single center in the US. A total of 25 adult patients with moderate to severe PN or CPUO were screened. Ten patients with PN and 10 patients with CPUO were enrolled. All 20 patients completed the 12-week treatment period, 18 of whom completed the 4-week follow-up period. Intervention: Abrocitinib, 200 mg, by mouth once daily for 12 weeks. Main Outcomes and Measures: The primary efficacy end point was the percent change in weekly Peak Pruritus Numerical Rating Scale (PP-NRS) scores from baseline to week 12. Key secondary end points included the percentage of patients achieving at least a 4-point reduction in weekly PP-NRS score from baseline to week 12 and the percent change in Dermatology Life Quality Index (DLQI) scores. Results: A total of 10 patients with PN (mean [SD] age, 58.6 [13.1] years; all were female) and 10 patients with CPUO (mean [SD] age, 70.7 [5.6] years; 2 were female) enrolled in the study. The mean (SD) baseline PP-NRS score was 9.2 (1.0) for PN and 8.2 (1.2) for CPUO. PP-NRS scores decreased by 78.3% in PN (95% CI, -118.5 to -38.1; P < .001) and 53.7% in CPUO (95% CI, -98.8 to -8.6; P = .01) by week 12. From baseline to week 12, 8 of 10 patients with PN and 6 of 10 patients with CPUO achieved at least a 4-point improvement on the PP-NRS. Both groups experienced significant improvement in quality of life as demonstrated by percent change in DLQI scores (PN: -53.2% [95% CI, -75.3% to -31.1%]; P = .002; CPUO: -49.0% [95% CI, -89.6% to -8.0%]; P = .02). The most common adverse event among patients was acneiform eruption in 2 of 20 patients (10%). No serious adverse events occurred. Conclusions and Relevance: The results of this nonrandomized controlled trial suggest that abrocitinib monotherapy may be effective and tolerated well in adults with PN or CPUO. Randomized, double-blind, placebo-controlled trials are warranted to validate these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT05038982.

A 15% Trichloroacetic Acid + 3% Glycolic Acid Chemical Peel Series Improves Appearance of Hand Lentigines: An Evaluator-Blinded, Split-Hand Prospective Trial.

BACKGROUND: Improving the appearance of lentigines on the hands is a key component to hand rejuvenation. Soft tissue fillers revolumize hands, but do not address pigmentary changes. OBJECTIVE: This study investigated the effiacy of a 15% trichloroacetic acid (TCA) + 3% glycolic acid (GA) combination peel in improvement of appearance of hand lentigines. METHODS: A prospective evaluator-blinded, split-hand study was performed using a 15% TCA + 3% GA peel to treat patients with hand lentigines. Subjects received a total of 3 treatments at 4-week intervals on 1 hand, with the other hand serving as an untreated control. Final photographs were taken 12 weeks after the last treatment. Two blinded board-certified dermatologists graded improvement in hand lentigines using a 5-point scale. RESULTS: Eighteen of 20 patients completed the study (90%). The mean age was 64.4 years (SE 1.6, range 51-71). The mean pain scores were 3.8 (SE 0.4) on a 10-point scale (1 = no pain, 10 = extremely painful). Blinded evaluators correctly identified the after-treatment photographs in 16 patients (88%). Physician and patient-graded mean improvement of lentigines was significant for treated versus control hands ( p < .01). No adverse events were noted. CONCLUSION: A series of three 15% TCA + 3% GA peels are effective and safe in the treatment of hand lentigines.

Reduced serum pyridoxine and 25-hydroxyvitamin D levels in adults with chronic pruritic dermatoses.

Little is known about the role nutritional factors play in the pathogenesis of chronic pruritic dermatoses (CPD). In this study, we analyzed nutritional deficiencies in CPD patients compared to matched controls. We conducted a population-based study from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2006. The main outcomes of the study were laboratory data on serum vitamin levels in participants who answered affirmatively to the questionnaires on CPD as well as matched healthy controls. We identified 877 cases of CPD among 9817 adults in the US aged 20 to 59 years. These findings revealed a slightly higher percentage of females with CPD. Low vitamin B6 (OR 0.697; 95% CI: 0.696-0.699, p = 0.025) and vitamin D (OR 0.794; 95% CI: 0.789-0.799, p = 0.037) levels were associated with a higher rate of CPD compared to healthy controls. Our study suggests that low levels of Vitamin B6 and Vitamin D inversely correlates with the presence of CPD. These vitamin deficiencies suggest further studies on the effect of vitamin supplementation may help in patients with CPD.

Acne Scars: An Update on Management

Acne vulgaris is a troubling skin disease known to have both physiologic and psychological effects on patients. Acne scars, a frequent complication, can further impact patients' quality of life. Scars result from an impairment in the healing process. Acne scars can be categorized as follows: atrophic scars (including ice pick, rolling, boxcar subtypes) and trophic (including hypertrophic and keloid scars), the latter being less common. Though various treatment approaches have been suggested, there is a lack of high-quality evidence on effective, type-specific acne scar approaches. Herein, we aim to review the current evidence for treating various acne scars.

Oral Nystatin Prophylaxis for the Prevention of Fungal Colonization in Very Low Birth Weight Infants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

We conducted this systematic review and meta-analysis of randomized controlled trials (RCTs) to investigate the prophylactic role of oral nystatin in the prevention of fungal colonization in very low birth weight (VLBW) infants compared with placebo or no treatment intervention. From inception until June 2022, we screened four major databases for pertinent RCTs and examined their risk of bias. The main outcomes were the rate of fungal colonization, rate of invasive fungal infection, rate of mortality, mean length of stay in the neonatal intensive care unit (NICU), and mean duration of antibiotic treatment. We summarized data as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI), using the fixed-effects model. Five RCTs met our inclusion criteria. One RCT was evaluated as having "high risk," one RCT was evaluated as having "some concerns," and three RCTs were evaluated as having "low risk" of bias. Compared with the control group, oral nystatin prophylaxis was correlated with substantial decrease in the frequency of fungal colonization (n=4 RCTs, RR=0.34, 95% CI {0.24, 0.48}, p<0.0001), the rate of invasive fungal infection (n=4 RCTs, RR=0.15, 95% CI {0.12, 0.19}, p<0.0001), and the mean duration of antibiotic treatment (n=3 RCTs, MD=-2.79 days, 95% CI {-5.01, -0.56}, p=0.01). However, there was no significant difference between both groups regarding the rate of mortality (n=4 RCTs, RR=0.87, 95% CI {0.64, 1.18}, p=0.37) and mean length of stay in NICU (n=3 RCTs, MD=-2.85 days, 95% CI {-6.52, 0.82}, p=0.13). In conclusion, among VLBW infants, the prophylactic use of oral nystatin was correlated with favorable antifungal benefits compared with placebo or no treatment intervention.

Risk of Hematologic Cancer in Patients With Undifferentiated Pruritus.

Importance: Although pruritus is common in patients with hematologic cancers, it is unknown whether patients with undifferentiated pruritus have higher risk of developing hematologic cancer. Furthermore, it is unclear whether serum lactate dehydrogenase (LDH) level, commonly ordered for cancer workup, has diagnostic utility in patients with pruritus. Objective: To assess the risk of hematologic cancer and the diagnostic utility of LDH level in patients with undifferentiated pruritus. Design, Setting, and Participants: This retrospective population-level cohort analysis was conducted using the TriNetX Research Network, a global health records database encompassing more than 69 million patients, from 2002 to 2020. The study included 327 502 eligible patients diagnosed with unspecified pruritus, excluding those with existing chronic pruritic dermatoses or systemic diseases known to cause pruritus, along with 327 502 matched controls. Exposures: Development of hematologic cancer within 1 year, 5 years, and 10 years following unspecified pruritus diagnosis. Main Outcomes and Measures: Primary study outcomes were 1-year, 5-year, and 10-year relative risks (RRs) for development of 9 hematologic cancers in patients with pruritus compared with control patients. Secondary outcomes were 1-year, 5-year, and 10-year RRs for any hematologic cancer at different LDH cutoffs (250 U/L and 500 U/L). Results: After matching, the pruritus and control cohorts each had 327 502 patients (68.1% female patients; 0.4% American Indian or Alaska Native patients; 3.5% Asian patients; 22.2% Black patients; 0.1% Native Hawaiian or Pacific Islander patients; 59.3% White patients; mean [SD] age, 42.2 [22] years). Patients with pruritus had increased 1-year risk of Hodgkin lymphoma (RR, 4.42; 95% CI, 2.83-6.88), myeloid leukemia (RR, 2.56; 95% CI, 1.79-3.67), multiple myeloma (RR, 2.38; 95% CI, 1.66-3.41), non-Hodgkin lymphoma (RR, 2.35; 95% CI, 1.96-2.82), monoclonal gammopathy (RR, 1.90; 95% CI, 1.55-2.32), myelodysplastic syndrome (RR, 1.74; 95% CI, 1.14-2.64), and lymphocytic leukemia (RR, 1.47; 95% CI, 1.07-2.02). After 12 months, the cancer risk was comparable with that of controls. Patients with pruritus had increased LDH levels, which were not associated with increased hematologic cancer risk. Conclusions and Relevance: In this cohort study, the RR of hematologic cancer in patients with undifferentiated pruritus was highest in the first 12 months, and LDH level had limited diagnostic utility in these patients. Clinicians should consider a thorough review of symptoms and assessment of cancer risk factors when deciding on workup for patients presenting with undifferentiated pruritus.

Racial differences in dysregulation of the renin-angiotensin-aldosterone system in patients with prurigo nodularis.

BACKGROUND: There are limited data characterizing the association between renal disease and prurigo nodularis (PN). OBJECTIVE: To characterize the association and describe mechanistic disease linkages between PN and renal comorbidities. METHODS: We conducted a cross-sectional analysis of renal comorbidities in PN using TriNetX, a global health research network providing access to medical records. Epidemiological findings provided the basis for translational studies on plasma and skin biopsy samples from PN patients stratified by race. RESULTS: PN was associated with stages 1-5 of chronic kidney disease (CKD), end-stage renal disease, nephritic syndrome, nephrotic syndrome, glomerular disease, and tubulointerstitial disease, but the associations were significantly stronger in black patients. Compared to controls, CKD progression was faster (HR 2.88, 95% CI: 1.01-8.26) only in black PN (10-year survival: 63.5% black vs. 85.5% white). Circulating plasma angiotensinogen levels were dysregulated (P < 0.001) only in black PN patients. Cutaneous transcriptomic analysis of genes related to the renin-angiotensin-aldosterone system (RAAS) revealed considerable dysregulation in PN lesions with greater dysregulation in black patients. CONCLUSIONS: Significant dysregulation of the cutaneous and systemic RAAS in black PN patients may explain the increased incidence and severity of renal disease.

Performance of Ultrasound for Identifying Morphological Characteristics and Thickness of Cutaneous Basal Cell Carcinoma: A Systematic Review.

Advances in ultrasound technology and non-surgical treatments of basal cell carcinomas (BCCs) have raised the need to study the performance of high-frequency ultrasound (HFUS) in BCCs. We aimed to assess the performance of HFUS in the evaluation of BCCs to formulate recommendations for its uses and conducted a systematic review of the literature to do so. A search of Central, Medline, Embase, CINHAL, and Web of Science was performed using key/MESH terms "ultrasonography" and "basal cell carcinoma" (January 2005-December 2020). We included primary studies reporting biopsy-confirmed BCCs for which the target intervention was ultrasound assessment at 15 MHz or higher frequency. Thirty articles were included, studying a total of 1,203 biopsy-confirmed BCCs. HFUS provides accurate depth measurements, especially for BCCs >1 mm. The definition of lateral margins in vivo needs further studies; however, ex vivo margin assessment seems convincing. There is a diagnostic role for HFUS in identifying higher recurrence risk BCC subtypes, which can help in risk stratification. Performance of HFUS is significant in BCC management. Pre-surgical scans may support case selection for Mohs. HFUS can improve safety when used to plan brachytherapy treatments, help with case selection and adjunct treatment choice pre-photodynamic therapy. Finally, HFUS can help follow lesions after intervention, particularly non-surgical management, and support the decision to observe or re-intervene. HFUS can enhance clinical practice by providing useful information that cannot be deducted from the clinical examination. It would be recommended to evaluate the extent, mainly depth, and detect the aggressiveness of the BCCs.

Apremilast in dermatology: A review of literature.

Apremilast is an orally administered small molecule that specifically inhibits the phosphodiesterase-4 enzyme and modulates the immune system by increasing the levels of intracellular cyclic adenosine monophosphate (cAMP) and inhibiting IL-2 & 8, interferon-γ and tumor necrosis factor (TNF) production. It is FDA approved for the treatment of psoriasis, psoriatic arthritis, and oral ulcers of Behcet's disease. More recently, apremilast has been used off-label to treat varied dermatological diseases where systemic corticosteroids or immunosuppressive agents were not effective. We review the efficacy and safety of apremilast in the treatment of aphthous stomatitis, Behçet's disease, chronic actinic dermatitis, atopic dermatitis, cutaneous sarcoidosis, hidradenitis suppurativa, lichen planus, and discoid lupus erythematosus in cases where standard treatment has failed.

Spontaneous Keloids: A Literature Review.

BACKGROUND: Keloids are benign fibroproliferative tumors that extend beyond the original wound. Spontaneous keloids are those that result without a significant history of trauma. There are multiple reported cases in the literature. OBJECTIVE: This article provides a summary and review of the cases that have been reported with spontaneous keloids and organizes them according to their associated medical conditions. METHODS: A literature review was conducted using PubMed and MEDLINE that included all English published cases and case series from May 1955 to February 2018. RESULTS: Spontaneous keloids have been reported mainly in association with syndromes such as Rubinstein-Taybi syndrome, Dubowitz syndrome, Noonan syndrome, Goeminne syndrome, Bethlem myopathy, conjunctivocorneal dystrophy, X-linked recessive polyfibromatosis and a novel X-linked syndrome with flamin A mutation. Furthermore, spontaneous keloids were reported in atopic patients and a couple of patients who are medically healthy. CONCLUSION: Spontaneous keloids are diagnosed clinically based on the patient's history, and it is challenging to confirm since they might be triggered by minimal injury or inflammation especially if it is a single lesion. Reported syndromes indicate a genetic possibility in the pathogenesis of spontaneous keloids.