Principles of Moisturizer Product Design

Moisturizers provide significant benefit in dermatology ­ as adjuvant therapy for many clinical conditions, as a key player in anti-aging regimens, and as a core component in maintaining healthy skin barrier function. Although they have been a mainstay for decades, lotions and creams are no longer formulated with a one-size-fits-all approach, where thickness was the primary cue for efficacy. In fact, moisturizer design today has become an art as well as a science. Product efficacy, aesthetics, and packaging are all engineered in a variety of ways, to create an expansive market of products that meet many consumer needs. The addition of specific types of functional ingredients can make a noteworthy difference as well. This article will explore the myriad approaches for moisturizer development and debunk some of the long-standing myths that have pervaded the marketplace. J Drugs Dermatol. 2019;18(1 Suppl):s89-95

A case of tinea versicolor of the eyelids.

Tinea versicolor is a commonly encountered superficial fungal infection often presenting on the chest and back with hyperpigmented or hypopigmented scaly macules and patches. We report an unusual and rare presentation of tinea versicolor affecting only the eyelids.

Alteration in the gene encoding protein tyrosine phosphatase nonreceptor type 6 (PTPN6/SHP1) may contribute to neutrophilic dermatoses.

We have found a B2 repeat insertion in the gene encoding protein tyrosine phosphatase nonreceptor type 6 (PTPN6) in a mouse that developed a skin disorder with clinical and histopathological features resembling those seen in human neutrophilic dermatoses. Neutrophilic dermatoses are a group of complex heterogeneous autoinflammatory diseases that all demonstrate excessive neutrophil infiltration of the skin. Therefore, we tested the cDNA and genomic DNA sequences of PTPN6 from patients with Sweet's syndrome (SW) and pyoderma gangrenosum and found numerous novel splice variants in different combinations. Isoforms resulting from deletions of exons 2, 5, 11, and 15 and retention of intron 1 or 5 were the most common in a patients with a familial case of SW, who had a neonatal onset of an inflammatory disorder with skin lesions and a biopsy specimen consistent with SW. These isoforms were associated with a heterozygous E441G mutation and a heterozygous 1.7-kbp deletion in the promoter region of the PTPN6 gene. Although full-length PTPN6 was detected in all other patients with either pyoderma gangrenosum or SW, it was always associated with splice variants: a partial deletion of exon 4 with the complete deletion of exon 5, alterations that were not detected in healthy controls. The defect in transcriptional regulation of the hematopoietic PTPN6 appears to be involved in the pathogenesis of certain subsets of the heterogeneous group of neutrophilic dermatoses.

Spontaneous insertion of a b2 element in the ptpn6 gene drives a systemic autoinflammatory disease in mice resembling neutrophilic dermatosis in humans.

We found a spontaneous autosomal mutation in a mouse leading to neutrophil infiltration with ulceration in the upper dermis of homozygous offspring. These animals had increased neutrophil numbers, associated with normal lymphocyte count, in peripheral blood and bone marrow, suggesting a myeloproliferative disorder; however, granulocyte precursor proliferation in bone marrow was actually reduced (because circulating neutrophils were less susceptible to apoptosis). Neutrophil infiltration of the skin and other organs and high serum levels of immunoglobulins and autoantibodies, cytokines, and acute-phase proteins were additional abnormalities, all of which could be reduced by high-dose corticosteroid treatment or neutrophil depletion by antibodies. Use of genome-wide screening localized the mutation within an 0.4-Mbp region on mouse chromosome 6. We identified insertion of a B2 element in exon 6 of the Ptpn6 gene (protein tyrosine phosphatase, non-receptor type 6; also known as Shp-1). This insertion involves amino acid substitutions that significantly reduced the enzyme activity in mice homozygous for the mutation. Disease onset was delayed, and the clinical phenotype was milder than the phenotypes of other Ptpn6-mutants described in motheaten (me, mev) mice; we designated this new genotype as Ptpn6(meB2/meB2) and the phenotype as meB2. This new phenotype encompasses an autoinflammatory disease showing similarities to many aspects of the so-called neutrophilic dermatoses, a heterogeneous group of skin diseases with unknown etiology in humans.

Benefits and Harms of Omalizumab Treatment in Adolescent and Adult Patients With Chronic Idiopathic (Spontaneous) Urticaria: A Meta-analysis of "Real-world" Evidence.

Importance: Omalizumab is indicated for the management of chronic idiopathic urticaria (CIU) (also known as chronic spontaneous urticaria) in adolescents and adults with persistent hives not controlled with antihistamines. The effectiveness of omalizumab in the real-world management of CIU is largely unknown. Objective: To quantitatively synthesize what is known about the benefits and harms of omalizumab in the real-world clinical management of CIU regarding urticaria activity, treatment response, and adverse events. Data Sources: Published observational studies (January 1, 2006, to January 1, 2018) and scientific abstracts on the effectiveness of omalizumab in CIU were identified using PubMed, Embase, Web of Science, and Cochrane search engines; references were searched to identify additional studies. Study Selection: Included studies were observational in design and included at least 1 outcome in common with other studies and at a concurrent time point of exposure to omalizumab. A total of 67 articles (35.2% of those screened) were included in the analysis. Data Extraction and Synthesis: PRISMA and MOOSE guidelines were followed; independent selection and data extraction were completed by 2 observers. Random-effects meta-analyses were performed. Main Outcomes and Measures: Main outcomes were change in weekly Urticaria Activity Score (UAS7; range, 0-42), change in Urticaria Activity Score (UAS; range 0-6) (higher score indicating worse outcome in both scales), complete and partial response rates (percentages), and adverse event rate (percentage). Results: Omalizumab therapy was associated with an improvement in UAS7 scores (-25.6 points, 95% CI, -28.2 to -23.0; P < .001; 15 studies, 294 patients), an improvement in UAS scores (-4.7 points, 95% CI, -5.0 to -4.4, P < .001; 10 studies, 1158 patients), an average complete response rate of 72.2% (95% CI, 66.1%-78.3%; P < .001; 45 studies, 1158 patients) with an additional average partial response rate of 17.8% (95% CI, 11.7%-23.9%; P < .001; 37 studies, 908 patients), and an average adverse event rate of 4.0% (95% CI, 1.0%-7.0%; P < .001; any level of severity, 47 studies, 1314 patients). Conclusions and Relevance: Benefits and safety of omalizumab in the real-world treatment of CIU meet or exceed results gleaned from clinical trials. These real-world data on omalizumab in CIU may help inform both clinical treatment expectations and policy decision making.

Benefits of an emollient body wash for patients with chronic winter dry skin.

This randomized 5-week study assessed the clinical benefits of a high-emollient body wash versus a regular bar cleanser in terms of improving chronic winter dry skin condition. After 4 weeks, subjects who washed daily with a high-emollient body wash exhibited a significant reduction in all dermatologist-assessed dry skin attributes and improvements in self-evaluated skin condition when compared with baseline measures. Those subjects who washed with a regular bar cleanser experienced a minimal to marked increase in dermatologist-assessed and self-assessed dry skin attributes when compared with baseline. These findings suggested that bathing with a high-emollient body wash, as opposed to a regular bar cleanser, can reduce xerosis symptoms and improve skin health and appearance without the additional use of a moisturizer.

Effectiveness of omalizumab in adolescent and adult patients with chronic idiopathic/spontaneous urticaria: a systematic review of 'real-world' evidence.

INTRODUCTION: Chronic idiopathic/spontaneous urticaria (CIU/CSU) is a dermatological condition characterized by itchy wheals and/or angioedema of continuous or intermittent duration of ≥6 weeks with a high burden of disease and impact on quality of life. Omalizumab is a recombinant humanized monoclonal antibody that inhibits the binding of IgE to high affinity receptors, and is approved for the CIU/CSU indication. The objective of this systematic review was to evaluate and synthesize the evidence on the real-world effectiveness of omalizumab in CIU/CSU in daily clinical practice. AREAS COVERED: This review of 84 observational effectiveness studies covers treatments (dosing, medication use), clinical outcomes (treatment response, disease activity, quality of life), and safety. EXPERT OPINION: The clinical outcomes observed across studies underscore the real-world effectiveness of omalizumab in the management of CIU/CSU. Continued treatment may assist patients showing an initial response to achieve a complete treatment response. Response rates are aligned with observed changes in disease activity, symptom experience, and quality of life, and this across subtypes of CIU/CSU. The positive therapeutic profile is complemented by a positive safety profile. The real-world evidence summarized here points convincingly at the high degree of effectiveness of omalizumab in the treatment of CIU/CSU in daily clinical practice.

Validation and Banding of the ItchyQuant: A Self-Report Itch Severity Scale.

Because of the significant emotional and psychosocial impact of chronic pruritus, it is important to accurately assess and measure itch severity. This study aims to validate and apply clinically meaningful bands to the ItchyQuant, an illustrated self-report numeric rating scale (NRS) for itch severity. A total of 76 adults with chronic pruritus were recruited. Participants rated their itch on the ItchyQuant, on a traditional 11-point NRS, and with verbal categorizations (no, mild, moderate, or severe). There was a significant, high correlation between the ItchyQuant and NRS (>0.92, P < 0.0001), demonstrating concurrent validity. Significantly more patients (47.2%) preferred the ItchyQuant than the NRS (23.6%) or had no preference (29.2%), P = 0.0015. Significantly more patients found the ItchyQuant easier to use (45.8%) than the NRS (20.8%) or had no preference (33.3%), P = 0.008. The set of clinically meaningful bands with the highest weighted kappa coefficient of agreement (κ = 0.69) was as follows: 0 (no itch), 1-3 (mild itch), 4-7 (moderate itch), 8-10 (severe itch). The ItchyQuant is a clinically meaningful measure of itch severity, demonstrating face and concurrent validity, that many patients prefer and find easier to use when compared with a traditional NRS. We suggest that the ItchyQuant can be added to the existing armamentarium of itch severity scales. We plan to investigate the ItchyQuant further in cognitively challenged populations.

Nodular mastocytosis.

Mastocytosis refers to a group of disorders characterized by the pathologic proliferation of mast cells. We present a 70-year-old white man with a rare presentation of nodular mastocytosis, characterized by disseminated nodular lesions, myelodysplastic syndrome, and a c-kit V560G receptor mutation. The patient presented to the clinic after initial presentation 6 months earlier, with ear pruritus, associated hearing loss, and widespread rash.

A differential gene expression study: Ptpn6 (SHP-1)-insufficiency leads to neutrophilic dermatosis-like disease (NDLD) in mice.

BACKGROUND: Irradiated syngeneic wild-type mice developed the same neutrophilic dermatosis-like disease (NDLD) after adoptive transfer of bone marrow cells from Ptpn6(meb2/meb2) mutant mice. OBJECTIVE: To analyze differentially expressed genes in the bone marrow of mice with NDLD to gain insight into the role of Ptpn6 in myelopoietic bone marrow pathology, and the mechanisms by which Ptpn6 insufficiency in the hematopoietic cells can lead to the development of skin lesions. METHODS: As Ptpn6 is involved in a myriad of signaling pathways, we used a global approach with microarray technology for the first time to characterize changes in the bone marrow and skin of motheaten-type mice. RESULTS: A total number of 1,511 probe sets in the bone marrow showed at least two-fold changes with FDR <0.05, of which 256 probe sets had over four-fold changes. A group of 63 genes in the bone marrow of NDLD mice had more than a 4-fold change with FDR <0.0001. From 503 genes encoding proteins with ITIM motif that binds to Ptpn6, 109 were up-regulated and 83 were down-regulated. We found that genes encoding hematopoietic receptors, neutrophil chemoattractants, Toll-like receptors (Tlr1, Tlr2 and Tlr4) and C-type lectin innate immunity receptors (Clec4e, Clec4d, Clec4n, Clec4a2 and Clec4a3) were significantly up-regulated in both NDLD bone marrow and skin. The Il1b gene was also significantly overexpressed in skin samples, confirming the importance of the IL-1/TLR pathway in the development of early skin inflammation in NDLD mice. CONCLUSION: Our results suggest that innate immunity genes play a major role in development of neutrophilic dermatosis-like disease in mice.

Antihistamines and their role as antipruritics.

Antihistamines that bind to the histamine 1 receptor (H1) serve as important therapeutic agents to counter the effects of histamine in the skin. Two generations of antihistamines exist; however, second-generation agents are more advantageous because they cause less sedation, have a longer half life and are more selective for the H1 receptor. While H1 antihistamines have proven to be effective at reversing the pruritus and cutaneous lesions of chronic urticaria, their ability to treat pruritus associated with other cutaneous and systemic diseases is unproven.

A randomized, placebo-controlled trial of 5% and 2% topical minoxidil solutions in the treatment of female pattern hair loss.

BACKGROUND: To pical minoxidil solution 2% stimulates new hair growth and helps stop the loss of hair in men with androgenetic alopecia and women with female pattern hair loss. Results can be variable, and historic experience suggests that higher concentrations of topical minoxidil may enhance efficacy. OBJECTIVE: The purpose of this 48-week, double-blind, placebo-controlled, randomized, multicenter trial was to compare the efficacy and safety of 5% topical minoxidil with 2% topical minoxidil and placebo in the treatment of female pattern hair loss. METHODS: A total of 381 women (18-49 years old) with female pattern hair loss applied 5% topical minoxidil solution (n = 153), 2% topical minoxidil solution (n = 154), or placebo (vehicle for 5% solution; n = 74) twice daily. Primary efficacy variables were change in nonvellus hair count at week 48, and patient and investigator assessments of change in hair growth/scalp coverage at week 48. RESULTS: After 48 weeks of therapy, 5% topical minoxidil was superior to placebo for each of the 3 primary efficacy measures. The 2% topical minoxidil group demonstrated superiority over placebo for hair count and investigator assessment of hair growth/scalp coverage at week 48; differences in patient assessment of hair growth at week 48 were not significantly different from placebo. The 5% topical minoxidil group demonstrated statistical superiority over the 2% topical minoxidil group in the patient assessment of treatment benefit at week 48. Both 5% and 2% topical minoxidil helped improve psychosocial perceptions of hair loss in women with female pattern hair loss. An increased occurrence of pruritus, local irritation, and hypertrichosis was observed with 5% topical minoxidil versus 2% topical minoxidil and placebo. CONCLUSION: In this 48-week study of 381 women with female pattern hair loss, 5% topical minoxidil was superior to placebo on each of the 3 primary efficacy end points: promoting hair growth as measured by change in nonvellus hair count and patient/investigator assessments of hair growth and scalp coverage. Application of 2% topical minoxidil was superior to placebo for assessments of nonvellus hair counts and investigator assessment of hair growth/scalp coverage at week 48; differences in patient assessment of hair growth at week 48 were not significantly different from placebo. At week 48, the 5% topical minoxidil group demonstrated statistical superiority over the 2% topical minoxidil group in the patient assessment of treatment benefit. Both concentrations of topical minoxidil were well tolerated by the women in this trial without evidence of systemic adverse effects. With the introduction of numerous herbal remedies for hair loss, of which most have not been tested in randomized, double-blind, placebo-controlled trials, it is important to describe well-controlled trials that demonstrate the efficacy and safety of topical drugs.