Diagnosis and Management of Dermatitis, Including Atopic, Contact, and Hand Eczemas.

This is a comprehensive and current guide for the diagnosis, differential diagnosis, treatment, and management of eczematous dermatitis, with a focus on atopic dermatitis, irritant and allergic contact dermatitis, hand dermatitis including recurrent vesicular and hyperkeratotic types, asteatotic dermatitis, and nummular or discoid dermatitis. Diagnostic options highlighted are clinical history, physical examination, and patch testing. Therapeutic options highlighted are moisturizers, topical corticosteroids, topical calcineurin inhibitors, crisaborole, phototherapy, and systemic medications including biologics.

Approach to the Patient with Chronic Pruritus.

Chronic pruritus (itch lasting ≥6 weeks) is a bothersome chief complaint that may present in a broad variety of diseases. Most itch-causing diagnoses fit into 1 of 5 categories (inflammatory, secondary to systemic disease, neuropathic, chronic pruritus of undetermined origin, and psychogenic itch) and this broad differential can be narrowed using key findings in the history and physical. In this article, we discuss which key findings are most pertinent for narrowing this differential and guiding further workup and treatment, as well as how to treat many itchy conditions.

The long-term risk of lymphoma and skin cancer did not increase after topical calcineurin inhibitor use and phototherapy in a cohort of 25,694 patients with vitiligo.

BACKGROUND: Topical calcineurin inhibitors have been used to treat vitiligo, either alone or in combination with phototherapy; however, the long-term safety of these agents remains controversial. OBJECTIVE: To investigate the risk of lymphoma and skin cancer in vitiligo patients who received topical calcineurin inhibitors or phototherapy. METHODS: A multicenter retrospective cohort study of 25,694 vitiligo patients who received topical calcineurin inhibitors or phototherapy for 6 weeks or more between 2001 and 2019 was performed. Cumulative doses of topical calcineurin inhibitors and total phototherapy sessions were determined. Outcomes were the development of lymphoma or skin cancer after enrollment, confirmed through chart review and pathology reports. RESULTS: During 95,203 person-years, 13 cases of lymphoma, 22 of actinic keratosis, 15 of nonmelanoma skin cancer, and 5 of melanoma were observed. The risk of lymphoma and skin cancer was not significantly increased by topical calcineurin inhibitor dose or phototherapy sessions. The interaction between the topical calcineurin inhibitors and phototherapy was not associated with an increased risk of skin cancer. LIMITATIONS: Retrospective study, individual follow-up duration less than 4 years, and no adjustment for comorbidities and medication history. Not generalizable to other races. CONCLUSION: The long-term risk of skin cancer or lymphoma was not associated with the use of topical calcineurin inhibitors, phototherapy, and both treatments in combination in patients with vitiligo.

Vitiligo: an update on systemic treatments.

Vitiligo is an autoimmune skin condition characterized by depigmented macules and patches, and has a huge psychosocial impact on patients. Treatment of vitiligo aims to prevent the spread of disease and facilitate repigmentation of affected lesions. The mainstay of treatment for unstable vitiligo has been topical agents (corticosteroids, calcineurin inhibitors) and phototherapy. However, systemic treatments are increasingly being shown to have a significant impact on the course of the disease as monotherapy or adjunctive therapy. Of note, oral mini-pulsed corticosteroid therapy, methotrexate, minocycline, ciclosporin, Janus kinase inhibitors and certain supplements have been used in the systemic treatment of vitiligo. We review the underlying evidence supporting the use of each of these systemic treatments.

Inhibition effect of epigallocatechin-3-gallate on the pharmacokinetics of calcineurin inhibitors, tacrolimus, and cyclosporine A, in rats.

BACKGROUND: Epigallocatechin-3-gallate (EGCG) is the most biologically active catechin of green tea. Tacrolimus (TAC) and cyclosporine A (CsA) are immunosuppressive agents commonly used in clinical organ transplantation. The present study investigated the effect of EGCG on the pharmacokinetics of TAC and CsA in rats and its underlying mechanisms. RESEARCH DESIGN AND METHODS: Either TAC or CsA was administered to rats intravenously or orally with or without concomitant EGCG. Polymerase Chain Reaction and Western Blot were used to determine the effect of EGCG on drug-metabolizing enzymes (DMEs), drug transporters (DTs) and nuclear receptors (NRs). RESULTS: The Cmax and AUC of TAC were reduced, and V/F and CL/F of TAC were enhanced after co-administration of EGCG. EGCG increased the Cmax, AUC of CsA at 3 ~ 30 mg∙kg-1 dosages, while decreased those parameters at the dosage of 100 mg∙kg-1. EGCG inhibited the mRNA and protein expressions of DMEs and DTs, such as CYP3A1, A2, UGT1A1, Mdr1 and Mrp2, but upregulated the expressions of Car, Pxr and Fxr. CONCLUSIONS: These results revealed consumption of high dose EGCG may cause a significant alteration in pharmacokinetics of TAC and distribution/elimination profiles of CsA through the regulation of DMEs, DTs and NRs.

Association Between Topical Calcineurin Inhibitor Use and Keratinocyte Carcinoma Risk Among Adults With Atopic Dermatitis.

Importance: Topical calcineurin inhibitors (TCIs), primarily used to treat atopic dermatitis (AD), carry a black box label warning users about the potential for increased skin cancer risk. The risk associated with keratinocyte carcinoma (KC), the most common cancer, defined as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), remains poorly defined because findings from large-scale postmarketing surveillance studies have not been reported. Objectives: To examine KC risk overall and by subtype (BCC and SCC) among adults with AD exposed to TCIs compared with those exposed to topical corticosteroids (primary comparator group) and those unexposed to TCIs or topical corticosteroids (alternative comparator group) as well as alterations in risk with TCI dose, frequency, and duration of exposure. Design, Setting, and Participants: A retrospective cohort study was conducted at Kaiser Permanente Northern California, a large, integrated health care delivery system, of adults 40 years or older (n = 93 746) with a physician-rendered diagnosis of AD or dermatitis. Patients who were diagnosed from January 1, 2002, to December 31, 2013, were included, with follow-up through December 31, 2017. Data analysis was conducted from June 1, 2016, to October 1, 2018. Exposures: Time-varying pharmacy-dispensed TCI exposure (n = 7033) over the study period was compared with topical corticosteroids (n = 73 674) and no TCI or topical corticosteroid exposure (n = 46 141). Main Outcomes and Measures: Electronic pathologic testing-validated incident KCs (n = 7744). Results: Among a cohort of 93 746 members, the mean (SD) age was 58.5 (12.7) years, and 55 023 patients (58.7%) were women. Multivariable Cox proportional hazards regression revealed no association between TCI exposure and KC risk (adjusted hazard ratio [aHR], 1.02; 95% CI, 0.93-1.13) compared with topical corticosteroid exposure. Similarly, there were no significant differences in BCC risk (aHR, 1.01; 95% CI, 0.90-1.14, TCI vs topical corticosteroids) or SCC risk (aHR, 0.94; 95% CI, 0.82-1.08, TCI vs topical corticosteroids). Changing the comparator group to unexposed individuals yielded similar findings (aHR, 1.04; 95% CI, 0.91-1.19, TCI vs unexposed for basal cell carcinoma). There were no associations between TCI dose, frequency, and duration of use and BCC, SCC, or overall KC risk. Conclusions and Relevance: The results of this postmarketing surveillance study of adult health plan members with AD revealed no apparent association between TCI exposure and overall KC, BCC, or SCC risk. Secondary analyses examining dose, frequency, and duration of TCI exposure revealed no associations. These findings suggest that use of TCIs may be safe with respect to KC risk among adults with AD.

Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review.

IMPORTANCE: Approximately 125 million people worldwide have psoriasis. Patients with psoriasis experience substantial morbidity and increased rates of inflammatory arthritis, cardiometabolic diseases, and mental health disorders. OBSERVATIONS: Plaque psoriasis is the most common variant of psoriasis. The most rapid advancements addressing plaque psoriasis have been in its pathogenesis, genetics, comorbidities, and biologic treatments. Plaque psoriasis is associated with a number of comorbidities including psoriatic arthritis, cardiometabolic diseases, and depression. For patients with mild psoriasis, topical agents remain the mainstay of treatment, and they include topical corticosteroids, vitamin D analogues, calcineurin inhibitors, and keratolytics. The American Academy of Dermatology-National Psoriasis Foundation guidelines recommend biologics as an option for first-line treatment of moderate to severe plaque psoriasis because of their efficacy in treating it and acceptable safety profiles. Specifically, inhibitors to tumor necrosis factor α (TNF-α) include etanercept, adalimumab, certolizumab, and infliximab. Other biologics inhibit cytokines such as the p40 subunit of the cytokines IL-12 and IL-13 (ustekinumab), IL-17 (secukinumab, ixekizumab, bimekizumab, and brodalumab), and the p19 subunit of IL-23 (guselkumab, tildrakizumab, risankizumab, and mirikizumab). Biologics that inhibit TNF-α, p40IL-12/23, and IL-17 are also approved for the treatment of psoriatic arthritis. Oral treatments include traditional agents such as methotrexate, acitretin, cyclosporine, and the advanced small molecule apremilast, which is a phosphodiesterase 4 inhibitor. The most commonly prescribed light therapy used to treat plaque psoriasis is narrowband UV-B phototherapy. CONCLUSIONS AND RELEVANCE: Psoriasis is an inflammatory skin disease that is associated with multiple comorbidities and substantially diminishes patients' quality of life. Topical therapies remain the cornerstone for treating mild psoriasis. Therapeutic advancements for moderate to severe plaque psoriasis include biologics that inhibit TNF-α, p40IL-12/23, IL-17, and p19IL-23, as well as an oral phosphodiesterase 4 inhibitor.

Atopic Dermatitis: Diagnosis and Treatment.

Atopic dermatitis (atopic eczema) is a chronic relapsing and remitting inflammatory skin disease affecting one in 10 people in their lifetime. Atopic dermatitis is caused by a complex interaction of immune dysregulation, epidermal gene mutations, and environmental factors that disrupts the epidermis causing intensely pruritic skin lesions. Repeated scratching triggers a self-perpetuating itch-scratch cycle, which can have a significant impact on the patient's quality of life. The American Academy of Dermatology has created simple diagnostic criteria based on symptoms and physical examination findings. Maintenance therapy consists of liberal use of emollients and daily bathing with soap-free cleansers. Use of topical corticosteroids is the first-line treatment for atopic dermatitis flare-ups. Pimecrolimus and tacrolimus are topical calcineurin inhibitors that can be used in conjunction with topical corticosteroids as first-line treatment. Ultraviolet phototherapy is a safe and effective treatment for moderate to severe atopic dermatitis when first-line treatments are not adequate. Antistaphylococcal antibiotics are effective in treating secondary skin infections. Oral antihistamines are not recommended because they do not reduce pruritus. Evidence is lacking to support the use of integrative medicine in the treatment of atopic dermatitis. Newer medications approved by the U.S Food and Drug Administration, such as crisaborole and dupilumab, are effective in treating atopic dermatitis but are currently cost prohibitive for most patients.

Clinical observation on the effect of Wuzhi soft capsule on FK506 concentration in membranous nephropathy patients.

The current research aimed to investigate the correlation between the effect of Wuzhi soft capsule (WZC) on FK506 concentration and CYP3A5 gene polymorphism in patients with membranous nephropathy (MN).Seventy-five patients with idiopathic MN were enrolled and divided according to the expression of CYP3A5 gene metabolic enzyme into group A (CP3A5 metabolic enzyme function expression types CYP3A5*1/*1 type and CYP3A5*1/*3 type), and group B (non-expression type CYP3A5*3/*3 type). All patients were given oral administration of tacrolimus capsule at the initial dose of 1 mg for twice a day 1 hour before breakfast and dinner. Afterwards, the oral administration of WZC was added at the dose of 0.5 g for 3 times a day within half an hour after 3 meals.The blood concentrations of FK506 in groups A and B were significantly higher than those before administration. Compared with that before administration, the FK506 blood concentration was increased by 3.051 ±â€Š0.774 ng/ml after adding the WZC. Besides, the blood concentrations of FK506 in group A were lower than those in group B before and after administration; meanwhile, the 24 hours total urine protein and the biochemical indexes in both groups displayed no statistically significant difference. Only 1 case of diarrhea was observed, which was relieved after the reduction of tacrolimus.Wuzhi soft capsule can significantly increase the blood concentration of FK506 in MN patients. Moreover, the CYP3A5 genotyping should be considered when WZC is used to increase the blood concentration of FK506.

Lichen planus: a comprehensive evidence-based analysis of medical treatment.

Lichen planus (LP) is a chronic-relapsing inflammatory skin disease. Although many drugs have been used for the management of LP, some of them lack the backup by strong therapeutic evidence, while others are not suitable for some patients due to safety profile issues. The aim of this study was to review the recent status of available medical therapies for LP to help physicians make better decisions upon best medical practice while facing patients with this condition. A review of published articles on management of LP was conducted with the MEDLINE and PubMed databases. The quality of the evidence was graded as high, moderate, low or very low. A total of 1366 articles were retrieved, and 219 (16%) were included in the final analysis. Twenty-one different treatment modalities were analysed. The quality of evidence was high for topical steroid and calcineurin inhibitor, while it was moderate for oral steroids. All the other modalities reached low or very low quality of evidence. Topical steroids and calcineurin inhibitors are the current first-line therapies, while for other therapies the strength of recommendation is not so evident. Unfortunately, larger randomized, controlled trials to support the efficacy, safety and tolerability of other therapies in LP are lacking, and many of them are recommended based on studies with small sample sizes, lack of standardized outcome measures or lack of controlled duration or even in anecdotal evidence. Thus, large-scale randomized clinical trials are still warranted to establish the exact benefits of other topical treatments, phototherapy, immunosuppressant and new immunomodulators for an optimized treatment of LP.

A systematic review of treatments for pityriasis lichenoides.

Pityriasis lichenoides (PL) represents a spectrum of inflammatory skin diseases comprising pityriasis lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica (PLC). This study aimed to provide a summary of effective treatments for PL. A systematic review was performed according to PRISMA guidelines for studies investigating PL treatment including ≥3 subjects and published in English between 1 January 1970 and 15 April 2019. A total of 441 papers were screened, and 37 original manuscripts meeting the inclusion and exclusion criteria were found, including 12 case series, 18 reviews, four prospective studies, two comparative studies and a single randomized controlled study. In most studies, ultraviolet (UV) phototherapy (narrow-band UVB, broadband UVB, UVA1 or PUVA) was used. Clearance rates with the different modalities are hardly comparable between different studies, ranging approximately between 70% and 100%. Narrow-band UVB showed an efficacy similar to PUVA as such as the combination of UVA and UVB vs. PUVA. Oral erythromycin showed clearance rates ranging between 66% and 83%, whereas methotrexate up to 100% but in small and dated studies. Evidence for other treatments is scarce. There is a lack of high level of evidence studies on PL treatment. The interpretation of the results is biased by the possible auto-resolution of the disease, the sample heterogeneity between children and adults and the short follow-up period of the studies. Only some studies investigated how results were durable after cessation of therapy. Quality of life and the impact of treatment were never assessed. According to the results of this review, we suggest narrow-band UVB phototherapy as first-line treatment. Oral erythromycin with or without topical corticosteroids and low-dose methotrexate as second-line therapies. High-powered studies and randomized controlled trials are needed to establish the optimal treatment for PL.

Childhood Vitiligo.

Vitiligo is a common acquired depigmenting skin disease characterized by a progressive loss of functional melanocytes. It may appear from the first years of life to late adulthood. Childhood vitiligo (CV), defined as vitiligo that begins before the age of 12 years, is common and may differ from post-CV in terms of epidemiology, clinical presentation, comorbidities, and treatment options. Taking into consideration the potential significant psychosocial impact of the disease on both children and their parents, all available therapeutic options must be offered to patients who desire treatment. According to the most recent guidelines, topical corticosteroids, topical calcineurin inhibitors, and narrowband ultraviolet B phototherapy are the most commonly used treatment modalities for vitiligo in children. This review presents recent data regarding the whole spectrum of CV. Differences between CV and post-CV are also discussed.

What's new in atopic eczema? An analysis of systematic reviews published in 2016. Part 1: treatment and prevention.

This review is part of a series of annual updates summarizing the evidence base for atopic eczema (AE). It provides a summary of key findings from 28 systematic reviews that were published or indexed during 2016 with a focus on treatment and prevention of AE. There is reasonable evidence of benefit for topical corticosteroids, calcineurin inhibitors, a glycyrrhetinic acid-containing preparation (Atopiclair® ), oral ciclosporin, oral azathioprine, narrowband ultraviolet B radiation and education programmes. Overall, there is evidence that topical corticosteroids and calcineurin inhibitors have similar efficacy and that both can prevent AE flares when used twice weekly as maintenance therapy. However, topical calcineurin inhibitors are costlier and have more adverse reactions, thus topical corticosteroids should remain the standard of care for patients with AE. There is no evidence that multiple applications are better than once-daily application of topical corticosteroid. There is inconsistent evidence to support omalizumab and specific allergen immunotherapy use in AE. There is some evidence that vitamin D supplementation and synbiotics reduce AE severity, although the margin of improvement may not be clinically meaningful. There is little evidence to support the use of wet wraps or of complementary/alternative medicine (including Chinese herbal medicine). There is some evidence to suggest that a diet high in fish in infancy may be preventative for AE, but other dietary interventions for the prevention of AE show little promise. This review provides a succinct guide for clinicians and patients wishing to remain up to date with the latest evidence for the treatment and prevention of AE.

Frontal Fibrosing Alopecia: An Update on Pathogenesis, Diagnosis, and Treatment.

Frontal fibrosing alopecia (FFA), first described by Kossard in the early 1990s, is a form of primary lymphocytic cicatricial alopecia characterized by selective involvement of the frontotemporal hairline and eyebrows. Since the original description, an increasing number of cases have been reported worldwide and the clinical aspects of the disease have been better characterized. However, the pathogenesis is still unknown and several hypotheses have been made about possible triggering factors, including hormones, neurogenic inflammation, smoking, UV filters, and ingredients in leave-on facial products. A genetic basis has also been hypothesized as the disease can occur in siblings and members of the same family. Besides its pathogenesis, research is also focused on treatment; FFA is a chronic condition and at present there is no validated or approved treatment for this disorder. Commonly prescribed topical treatments include corticosteroids, minoxidil, and calcineurin inhibitors. Systemic treatments include 5α-reductase inhibitors, hydroxychloroquine, and retinoids. Intralesional triamcinolone acetonide is also utilized, especially for the eyebrows. Other possible treatments include pioglitazone, naltrexone, tofacitinib, and lasers.

Traitements topiques et photothérapie dans la dermatite atopique: Topical treatments and phototherapy in atopic dermatitis.

Atopic dermatitis is a chronic disease with an alteration of the skin barrier and an abnormal immune response. The European guidelines for treatment of atopic dermatitis in children and adults recommend basic hygiene rules including daily use of emollient. Then in the first therapeutic line, for mild or acute atopic dermatitis, the prescription of local care by topical corticosteroids or topical calcineurin inhibitors is recommended. A proactive treatment is now recommended. If the atopic dermatitis is moderate or recurrent, the use of phototherapy in addition to topical treatment is recommended. Each therapeutic step can be added to improve the lesions and reduce the burden of the disease on the patient's daily life. © 2019 Elsevier Masson SAS. All rights reserved.

Lichen planus and lichenoid dermatoses: Conventional and emerging therapeutic strategies.

Having reviewed the diverse clinical subtypes of lichenoid disease and the postulated molecular basis thereof in the first article in this 2-part continuing medical education series, we discuss herein the existing and emerging treatment strategies in the most common clinical forms of lichenoid inflammation and provide an overview of their pharmacodynamics and evidence base. The scope of this review is not to exhaustively discuss treatment modalities for all lichenoid variants discussed in the previous article of this series. Instead, the focus will be on frequently encountered subtypes of lichen planus and on linking mechanisms of disease with mechanisms of drug action. Future directions and potential avenues for translational research will also be discussed.

Treatment of Myasthenia Gravis With High-Dose Cholinesterase Inhibitors and Calcineurin Inhibitors Caused Spontaneous Muscle Cramps in Patients.

OBJECTIVES: The objective of this study was to investigate the influence of treatment with cholinesterase inhibitors (ChEIs) and calcineurin inhibitors (CNIs) on the occurrence of cramps in myasthenia gravis (MG) patients. METHODS: The frequency and duration of cramp and serum electrolytes were evaluated in 81 patients with MG. The patients were classified using Myasthenia Gravis Foundation of America postintervention status scores based on the treatment and the responsiveness to the treatment. Quantitative MG score, MG activities of daily living score, MG composite score, or MG quality of life 15 score was used to assess the health-related quality of life (QOL). RESULTS: Muscle cramps developed in 44 (54.3%) of 81 MG patients. The scores of MG activities of daily living, MG composite, or MG-QOL 15-item questionnaire in patients with cramp were significantly higher than those in patients without cramps (P = 0.002, P = 0.01, or P = 0.0022, respectively). The serum magnesium concentrations were lower in patients treated with CNI (n = 16) than in those not treated with CNI (n = 65) (P = 0.002). The probability of cramps was significantly higher in patients treated with ChEIs (≥180 mg/d) in addition to CNI than in patients who were treated with a low dose of ChEIs (≤60 mg/d) without concomitant CNI treatment (P = 0.017). CONCLUSIONS: Our data suggested that treatment with a high dose of ChEI and CNI accelerated the probability of cramps and reduced the QOL in MG patients.

Dose and timing of injections for effective cyclosporine A pretreatment before renal ischemia reperfusion in mice.

BACKGROUND: There is experimental evidence that lethal ischemia-reperfusion injury (IRI) is largely due to mitochondrial permeability transition pore (mPTP) opening, which can be prevented by cyclosporine A (CsA). The aim of our study is to show that a higher dose of CsA (10 mg/kg) injected just before ischemia or a lower dose of CsA (3 mg/kg) injected further in advance of ischemia (1 h) protects the kidneys and improves mitochondrial function. METHODS: All mice underwent a right unilateral nephrectomy followed by 30 min clamping of the left renal artery. Mice in the control group did not receive any pharmacological treatment. Mice in the three groups treated by CsA were injected at different times and with different doses, namely 3 mg/kg 1 h or 10 min before ischemia or 10 mg/kg 10 min before ischemia. After 24 h of reperfusion, the plasma creatinine level were measured, the histological score was assessed and mitochondria were isolated to calculate the calcium retention capacity (CRC) and level of oxidative phosphorylation. RESULTS: Mortality and renal function was significantly higher in the CsA 10 mg/kg-10 min and CsA 3mg/kg-1 h groups than in the CsA 3mg/kg-10 min group. Likewise, the CRC was significantly higher in the former two groups than in the latter, suggesting that the improved renal function was due to a longer delay in the opening of the mPTP. Oxidative phosphorylation levels were also higher 24 h after reperfusion in the protected groups. CONCLUSIONS: Our results suggest that the protection afforded by CsA is likely limited by its availability. The dose and timing of the injections are therefore crucial to ensure that the treatment is effective, but these findings may prove challenging to apply in practice.

Long-Term Treatment of Atopic Dermatitis.

Many patients with mild to moderate atopic dermatitis (AD) are managed by identifying and avoiding allergens and irritants, ensuring skin moisturization, and graded use of topical corticosteroids and/or calcineurin inhibitors. There is little consensus on the next step. Most systemic therapies are "off label" in the United States and include phototherapy, cyclosporine, mycophenolic acid precursors, azathioprine, and methotrexate. The decision to use these therapies should be based on efficacy and safety readouts from well designed, long-term trials. This article reviews the long-term randomized, controlled trials examining safety and/or efficacy of interventions recommended for patients with mild to severe AD.