Hypergammaglobulinemic purpura of Waldenström in children.

BACKGROUND: Hypergammaglobulinemic purpura of Waldenström (HGPW), a rare cutaneous eruption characterized by the triad of recurrent episodes of lower extremity petechiae, symptoms of stinging and burning, and lower extremity edema, is poorly described in children. Some children have been reported to follow a benign course, while others are eventually diagnosed with fulminant rheumatologic disease. OBJECTIVES: To determine the distinguishing features of HGPW including the spectrum of disease manifestations and clinical outcomes. METHODS: This is a multicenter, retrospective case series of six children with HGPW combined with a literature review of 45 previously published pediatric cases. RESULTS: Most children were eventually diagnosed with systemic disease (63%) or developed autoantibody accumulation suggestive of evolving disease (71%). The most common diagnoses were Sjogren's syndrome and systemic lupus erythematosus. The mean duration between onset of cutaneous eruption and diagnosis of systemic disease was 5.6 years, underscoring that HPGW patients often present with a rash that precedes the development of systemic symptoms. CONCLUSIONS: Diagnosis of HGPW should prompt initial screening for rheumatologic disease with long-term rheumatology follow-up, as the majority of patients present with evolving manifestations of systemic disease.

Current and emerging therapies for hand eczema.

Although hand eczema (HE) and chronic hand eczema (CHE) are common conditions with significant disease burden, they traditionally have had limited treatment options beyond topical and short-term systemic corticosteroids. We reviewed published and preliminary evidence on the current and emerging topical and systemic therapeutic agents for HE and CHE. The etiologies of various HE subtypes are discussed, and remaining knowledge and practice gaps are highlighted to encourage further investigations. A comprehensive search of ClinicalTrials.gov and PubMed was completed for clinical trials that utilized known and emerging treatment options for HE and CHE. Several agents that target IL-4 and IL-13 signaling, keratinocyte proliferation, inflammatory cytokine production, bacterial protein synthesis, and inflammatory mediator (TNF-α, JAK1, JAK2, and JAK3) proliferation are shown to be involved in the pathogenesis of CHE. Systemic agents include dupilumab, alitretinoin, acitretin, cyclosporine, azathioprine, and probiotics. Topical agents include delgocitinib, retapamulin, halometasone/triclosan, calcipotriol/betamethasone, tacrolimus, and pimecrolimus. These modalities have demonstrated varying degrees of clinical efficacy, evaluated by subjective assessments and scoring indexes. Targeted therapies are emerging for HE, but options are still limited, partially due to our narrow understanding of this heterogeneous condition. Additional and targeted therapeutic options are needed to match the rising prevalence and burden of HE. KEYPOINTS: Hand eczema (HE) is a heterogenous dermatosis with limited therapeutic options due to a lack of international guidelines regarding classification of HE subtypes and treatment. This review discusses current and emerging topical and systemic agents and their efficacies in the treatment of different types of hand eczema.

A comparison of international management guidelines for atopic dermatitis.

BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) is a chronic condition that is predominantly found in pediatric patients and commonly presents therapeutic challenges. The management of AD encompasses a variety of factors, and the pillars of optimal management revolve around skin barrier repair and antiinflammatory, antimicrobial, and antipruritic treatment. AD management guidelines exist in various geographic regions globally. The purpose of this review was to compare international guidelines to highlight the similarities and variances among populations and skin types. Comparisons were made for recommendations regarding moisturization, bathing, wet wrap therapy, topical corticosteroids, topical calcineurin inhibitors, antihistamines, antipruritics, antibiotics, systemic immunosuppressants, and biologics. METHODS: A literature search of the PubMed, EMBASE, and MEDLINE databases was performed for published guidelines in each geographic region. Inclusion criteria included publications available in English that were established by a dermatological association or group including dermatologists, pertained to the treatment of AD in humans, were the most recent guidelines available that were published between 2007 and 2018, and included comprehensive treatment recommendations. RESULTS: Publications from Europe, North America, Asia, the Asia-Pacific region, Australia, and Africa were reviewed, encompassing 14 guidelines. Notable diversity exists across these guidelines regarding recommendations for moisturization and bathing, as well as topical and systemic therapies for AD. CONCLUSIONS: Due to the heterogeneity of the disease and regional treatment accessibility, complete standardization of AD management guidelines may be difficult. Nevertheless, more consensus on management guidelines is needed, and recommendations should be updated as new treatment modalities become available.

Topical probiotics: the unknowns behind their rising popularity.

OBJECTIVE: Topical probiotics have been used for skin care and treatment since the early 20th century. Over the past decade, there has been a dramatic surge of commercially-available topical probiotic products. We conducted a systematic search of clinical data relating to the use of topical probiotics and identified relevant clinical and regulatory gaps. METHODS: PubMed and Google Scholar searches were conducted for trials and reviews of probiotics. FDA definitions of cosmetics, drugs, and regulation of topical probiotics were reviewed. RESULTS: Topical probiotics have shown efficacy in a number of limited trials, particularly those involving the treatment of acne, atopic dermatitis, and rosacea. However, there is a paucity of literature on the safety profiles, mechanistic action, and therapeutic potential of topical probiotic products. Several regulatory gaps exist, including approval and classification of topical probiotic products by the FDA; currently there are no topical probiotic products the FDA has approved as drugs. CONCLUSION: With increasing popularity among the general public, but insufficient clinical data to demonstrate large-scale effectiveness and a thorough understanding of side effects, there is a need for further mechanistic and clinical investigation, as well as improved regulation and standardization of topical probiotic products.

Temozolomide-induced inflammation of disseminated superficial actinic porokeratosis.

We report a case of temozolomide (TMZ)-induced inflammation of disseminated superficial actinic porokeratosis (DSAP), an uncommon and pre-malignant cutaneous disorder. Dermatologists and oncologists should be aware of this cutaneous eruption of DSAP associated with TMZ to prevent the discontinuation of effective medical therapy in cancer patients.

Hidradenitis Suppurativa: Disease Burden and Etiology in Skin of Color.

Hidradenitis suppurativa (HS) is a chronic, debilitating skin disease. Although most studies on HS are conducted in largely Caucasian populations, evidence demonstrates a higher prevalence in patients with skin of color, including African and Hispanic populations. These racial subgroups are likely at risk for greater disease burden due to a higher prevalence of components of the metabolic syndrome, comorbid depression, and low socioeconomic status; however, there is a paucity of research in these populations. Additionally, studies examining the genetic and anatomical basis for HS, as well as the response to HS therapies, are lacking for patients with skin of color. Complicating this issue is the limited access to effective medical care, including dermatologists, for African and Hispanic populations as well as other minority groups. In this review, we identify gaps in the knowledge base, highlight the association between HS and patients with skin of color, and provide direction for much needed research into this condition.

Efficacy and safety of noncultured melanocyte-keratinocyte transplant procedure for vitiligo and other leukodermas: a critical analysis of the evidence.

Vitiligo is an acquired pigmentary skin of depigmentation occurring secondary to melanocyte destruction. Vitiligo and other leukodermas have a profound impact on quality of life. Current therapies include medical options, such as phototherapy, topical and systemic corticosteroids, topical calcineurin inhibitors, immunomodulators, and antioxidiants, and surgical options. Surgical options provide melanocytic cells to previously depigmented areas and use either tissue grafting or cellular grafting methods. Topical treatments are often insufficient, and many of the current surgical procedures have shown variable response rates. In this review, we discuss the process of the cellular grafting melanocyte-keratinocyte transplantation procedure (MKTP) and critically analyze its efficacy and safety in the treatment of vitiligo and other leukodermas. PubMed was searched for studies (2001-2017) describing the use of MKTP in patients with vitiligo or other leukodermas. Articles or trials discussing the use of MKTP for these patients were selected for in-depth review. Clinically relevant results regarding efficacy and safety of MKTP in vitiligo and leukoderma patients were analyzed. Numerous trials and case series/reports have demonstrated tolerability and efficacy of MKTP with repigmentation for patients with refractory, stable vitiligo. However, the response rates have been variable, likely influenced by vitiligo type and affected areas. Future research and clinical reporting will provide more insight on which phenotypes may benefit from MKTP.

New and emerging targeted systemic therapies: a new era for atopic dermatitis.

PURPOSE: This is a review of emerging targeted, systemic therapies for atopic dermatitis (AD). The information presented aims to provide dermatologists with updated therapeutic options, stimulate academic interest, and spark future research. MATERIAL AND METHODS: Extensive search of ClinicalTrials.gov, the National Eczema Association, and PubMed was performed for clinical trials examining the effect of emerging targeted, systemic therapies in patients with AD. Results were included if they demonstrated efficacy in reversing AD symptoms. Studies that did not demonstrate clinical benefit were excluded. RESULTS: A number of emerging systemic agents targeting specific mediators involved in the pathogenesis of AD were found. These targets include IL-4, IL-13, IgE, B-cells, IL-5, IL-31, JAK-STAT, SYK, IL-6, PDE-4, IL-12, IL-17, IL-23, IL-22, H4R, NKR1, κOR, TSLP, PPAR-γ, and DGLA. Treatment of AD patients with these therapies has, in many cases, led to statistically significant improvements in clinical severity scores and patient-reported outcomes. CONCLUSIONS: While multiple agents have demonstrated efficacy, only dupilumab is currently approved for adults with AD. Large-scale, randomized, placebo-controlled, double-blind trials, especially in children, are needed. As we enter the dawn of targeted therapy for AD, a comprehensive clinical trial registry is needed to facilitate data pooling and comparison among international registries.

Targeted treatments for hidradenitis suppurativa: a review of the current literature and ongoing clinical trials.

PURPOSE: Targeted, immune-modulating drugs are at the forefront of therapy for HS, and a comprehensive clinical trial registry is needed to facilitate data pooling and clinical efficacy comparison. MATERIALS AND METHODS: A systematic review of the ClinicalTrials.gov database was searched for planned, in-progress, completed, or terminated trials investigating the effect of targeted biologic therapies for hidradenitis suppurativa (HS). When results of RCTs were not available, case reports or series were included. RESULTS: Inflammatory mediators that are targeted by biologic agents include tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), IL-17, IL-12, IL-23, phosphodiesterase 4 (PDE4), lymphocyte function-associated antigen 1 (LFA-1), and complement component 5a (C5a). Clinical efficacy was measured by reduction in Sartorius score, Hidradenitis Suppurativa Clinical Response (HiSCR), Dermatology Life Quality Index (DLQI), or pain Visual Analog Scale (VAS). TNF inhibitors (adalimumab, etanercept, and infliximab), IL-1 receptor antagonist (Anakinra), IL-17A inhibitor (secukinumab), IL-12/23 inhibitor (ustekinumab), and PDE4 inhibitor (apremilast) show promise due to statistically significant improvements in disease severity. CONCLUSIONS: Currently, adalimumab is the only FDA-approved biologic available for the treatment of HS. However, results from trials of other biologic agents targeting downstream mediators are promising. Large-scale, randomized, placebo-controlled trials in patients with skin of color, as well as weight-based dosing trials, are needed.