Oral lichen planus: comparative efficacy and treatment costs-a systematic review.

OBJECTIVE: To compare the reported efficacy and costs of available interventions used for the management of oral lichen planus (OLP). MATERIALS AND METHODS: A systematic literature search was performed from database inception until March 2021 in MEDLINE via PubMed and the Cochrane library following PRISMA guidelines. Only randomized controlled trials (RCT) comparing an active intervention with placebo or different active interventions for OLP management were considered. RESULTS: Seventy (70) RCTs were included. The majority of evidence suggested efficacy of topical steroids (dexamethasone, clobetasol, fluocinonide, triamcinolone), topical calcineurin inhibitors (tacrolimus, pimecrolimus, cyclosporine), topical retinoids, intra-lesional triamcinolone, aloe-vera gel, photodynamic therapy, and low-level laser therapies for OLP management. Based on the estimated cost per month and evidence for efficacy and side-effects, topical steroids (fluocinonide > dexamethasone > clobetasol > triamcinolone) appear to be more cost-effective than topical calcineurin inhibitors (tacrolimus > pimecrolimus > cyclosporine) followed by intra-lesional triamcinolone. CONCLUSION: Of common treatment regimens for OLP, topical steroids appear to be the most economical and efficacious option followed by topical calcineurin inhibitors. Large-scale multi-modality, prospective trials in which head-to-head comparisons interventions are compared are required to definitely assess the cost-effectiveness of OLP treatments.

Hypertrophic lichenoid dermatitis immune-related adverse event during combined immune checkpoint and exportin inhibitor therapy: A diagnostic pitfall for superficially invasive squamous cell carcinoma.

Immune checkpoint inhibitors (ICIs) for cancer treatment have revolutionized the field of medicine. However, an unintended but frequent consequence of ICI therapy is the development of cutaneous immune-related adverse events (irAEs), such as lichenoid dermatitis irAEs (LD-irAEs). The hypertrophic variant of LD-irAE may be a diagnostic challenge since it can mimic superficially invasive squamous cell carcinoma (SCC). A 79-year-old woman with metastatic melanoma who began treatment with an ICI-pembrolizumab-plus exportin-1 (XPO1) inhibitor presented after 1 month of therapy with symmetrical violaceous papules coalescing into plaques and with two nodules of the bilateral dorsal hands. Biopsy of the nodules revealed an actinic keratosis and atypical epidermal proliferation concerning for SCC. However, in the ensuing 3 weeks, the patient developed multiple new erythematous, violaceous, and scaly macules and papules, some coalescing into plaques on the extremities. Biopsies of these lesions revealed exuberant irregular epidermal hyperplasia with hypermaturation and lichenoid infiltrate concentrated at the base of the elongated, broadened rete ridges, consistent with hypertrophic LD-irAE. Treatment included topical fluocinonide ointment, intralesional triamcinolone injections and oral acitretin. Distinguishing hypertrophic LD-irAE and SCC can be challenging since both entities share histopathologic features; thus, correlation with clinical presentation is essential for diagnosis and optimal patient management.

Patients preferences for different corticosteroid vehicles are highly variable.

Introduction: Topical corticosteroids, available in an array of vehicles are used to control a variety of inflammatory skin diseases. Patients preferences for different vehicles may affect their willingness to use treatment. We assess corticosteroid vehicle preference and potential impact of topical characteristics on adherence and quality of life in patients with psoriasis.Methods: Subjects with psoriasis were recruited from Wake Forest University Dermatology Clinic. Subjects sampled desoximetasone 0.25% spray, betamethasone valerate 0.1% cream, triamcinolone acetonide 0.1% ointment, fluocinonide 0.05% gel, betamethasone valerate 0.1% lotion, clobetasol propionate 0.05% foam, and fluocinonide 0.05% solution in a predetermined randomized order. Subjects completed a Vehicle Preference Measure, Determinants of Adherence Measure, and a Determinants of Quality of Life Measure.Results: Patients preferences for the various products were highly variable. Regarding Determinants of Adherence, patients perception of absorption of the medication was ranked as 'quite important/extremely important' by 85% of total subjects. A majority of patients rated medication side effects as 'quite important/extremely important' when asked to consider topical characteristics effect on quality of life.Discussion: There was wide variation in patient preference for topical medication vehicles used for treating psoriasis. Several vehicle characteristics were considered important to adherence. Given the marked variation in vehicle preference, topical treatment should be individualized according to patients preferences.

Central serous retinopathy associated with topical oral corticosteroid use: a case report.

BACKGROUND: Oral topical corticosteroid gels are widely used in dental medicine. Case studies of central serous retinopathy have been reported following administration of corticosteroids, but none so far coinciding with the use of topical fluocinonide gel. This case report further contributes to the database of potential risks of corticosteroid use. CASE PRESENTATION: A 40-year-old South Asian woman presented with decreased vision, pigment epithelial detachments, and serous retinal detachments in both eyes 1 month after starting treatment with topical fluocinonide 0.05%, a topical oral corticosteroid gel. Her condition resolved 6 months after discontinuing the use of the steroid. CONCLUSIONS: To the best of our knowledge, this is the first case of idiopathic central serous retinopathy associated with the use of oral fluocinonide gel. Discontinuing the use of the steroid may result in resolution of the serous retinal detachment and improvement of visual symptoms. Patients and their doctors who prescribe this medication should be aware of this association.

Successful management of pediatric oral pemphigus vulgaris with topical corticosteroid monotherapy.

Pemphigus vulgaris (PV) is an autoimmune intraepithelial bullous disease that affects the skin and mucous membranes. Typically, the management of PV is challenging, with systemic corticosteroids being the mainstay of treatment. We describe the case of a 14-year-old girl who was diagnosed with oral PV and successfully treated with topical corticosteroids alone. This case details a pediatric mucosal PV case successfully managed solely with topical corticosteroids.

A Pilot Study Characterizing Factors in Adherence to Cutaneous Lupus Treatment.

Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease that manifests as scarring, dyspigmentation, erythema, and pain. Topical corticosteroids are a mainstay of treatment. Irritation, messiness, and tediousness may deter use. Thus, nonadherence, rather than nonresponse, can result in treatment failure. Prior adherence studies were limited to systemic lupus erythematosus. We performed a single-center, open-label pilot study to assess adherence to topical medication in patients with CLE. CLE adherence to topical medications is suboptimal and declines over time. Shorter treatment duration and greater patient perception of disease severity may contribute to higher adherence. Improving adherence to existing treatments could be as or more valuable than new therapies for the disease.

Molluscum Contagiosum-Like Presentation of Langerhans Cell Histiocytosis: A Case and Review.

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by clonal proliferation of Langerhans cells in the skin. A molluscum-like presentation of cutaneous LCH is rare but important to consider for examination and management. We present an atypical molluscum-like LCH case and review the literature for common features of this unusual presentation.

Drugs for discoid lupus erythematosus.

BACKGROUND: Discoid lupus erythematosus (DLE) is a chronic form of cutaneous lupus, which can cause scarring. Many drugs have been used to treat this disease and some (such as thalidomide, cyclophosphamide and azathioprine) are potentially toxic. This is an update of a Cochrane Review first published in 2000, and previously updated in 2009. We wanted to update the review to assess whether any new information was available to treat DLE, as we were still unsure of the effectiveness of available drugs and how to select the most appropriate treatment for an individual with DLE. OBJECTIVES: To assess the effects of drugs for discoid lupus erythematosus. SEARCH METHODS: We updated our searches of the following databases to 22 September 2016: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We also searched five trials databases, and checked the reference lists of included studies for further references to relevant trials. Index Medicus (1956 to 1966) was handsearched and we approached authors for information about unpublished trials. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) of drugs to treat people with DLE in any population group and of either gender. Comparisons included any drug used for DLE against either another drug or against placebo cream. We excluded laser treatment, surgery, phototherapy, other forms of physical therapy, and photoprotection as we did not consider them drug treatments. DATA COLLECTION AND ANALYSIS: At least two reviewers independently extracted data onto a data extraction sheet, resolving disagreements by discussion. We used standard methods to assess risk of bias, as expected by Cochrane. MAIN RESULTS: Five trials involving 197 participants were included. Three new trials were included in this update. None of the five trials were of high quality.'Risk of bias' assessments identified potential sources of bias in each study. One study used an inappropriate randomisation method, and incomplete outcome data were a concern in another as 15 people did not complete the trial. We found most of the trials to be at low risk in terms of blinding, but three of the five did not describe allocation concealment.The included trials inadequately addressed the primary outcome measures of this review (percentage with complete resolution of skin lesions, percentage with clearing of erythema in at least 50% of lesions, and improvement in patient satisfaction/quality of life measures).One study of fluocinonide cream 0.05% (potent steroid) compared with hydrocortisone cream 1% (low-potency steroid) in 78 people reported complete resolution of skin lesions in 27% (10/37) of participants in the fluocinonide cream group and in 10% (4/41) in the hydrocortisone group, giving a 17% absolute benefit in favour of fluocinonide (risk ratio (RR) 2.77, 95% CI 0.95 to 8.08, 1 study, n = 78, low-quality evidence). The other primary outcome measures were not reported. Adverse events did not require discontinuation of the drug. Skin irritation occurred in three people using hydrocortisone, and one person developed acne. Burning occurred in two people using fluocinonide (moderate-quality evidence).A comparative trial of two oral agents, acitretin (50 mg daily) and hydroxychloroquine (400 mg daily), reported two of the outcomes of interest: complete resolution was seen in 13 of 28 participants (46%) on acitretin and 15 of 30 participants (50%) on hydoxychloroquine (RR 0.93, 95% CI 0.54 to 1.59, 1 study, n = 58, low-quality evidence). Clearing of erythema in at least 50% of lesions was reported in 10 of 24 participants (42%) on acitretin and 17 of 25 (68%) on hydroxychloroquine (RR 0.61, 95% CI 0.36 to 1.06, 1 study, n = 49, low-quality evidence). This comparison did not assess improvement in patient satisfaction/quality of life measures. Participants taking acitretin showed a small increase in serum triglyceride, not sufficient to require withdrawal of the drug. The main adverse effects were dry lips (93% of the acitretin group and 20% of the hydroxychloroquine group) and gastrointestinal disturbance (11% of the acitretin group and 17% of the hydroxychloroquine group). Four participants on acitretin withdrew due to gastrointestinal events or dry lips (moderate-quality evidence).One trial randomised 10 people with DLE to apply a calcineurin inhibitor, pimecrolimus 1% cream, or a potent steroid, betamethasone 17-valerate 0.1% cream, for eight weeks. The study reported none of the primary outcome measures, nor did it present data on adverse events.A trial of calcineurin inhibitors compared tacrolimus cream 0.1% with placebo (vehicle) over 12 weeks in 14 people, but reported none of our primary outcome measures. In the tacrolimus group, five participants complained of slight burning and itching, and for one participant, a herpes simplex infection was reactivated (moderate-quality evidence).Topical R-salbutamol 0.5% cream was compared with placebo (vehicle) over eight weeks in one trial of 37 people with DLE. There was a significant improvement in pain and itch in the salbutamol group at two, four, six, and eight weeks compared to placebo, but the trial did not record a formal measure of quality of life. None of the primary outcome measures were reported. Changes in erythema did not show benefit of salbutamol over placebo, but we could not obtain from the trial report the number of participants with clearing of erythema in at least 50% of lesions. There were 15 events in the placebo group (experienced by 12 participants) and 24 in the salbutamol group (experienced by nine participants). None of the adverse events were considered serious (moderate-quality evidence). AUTHORS' CONCLUSIONS: Fluocinonide cream may be more effective than hydrocortisone in clearing DLE skin lesions. Hydroxychloroquine and acitretin appear to be of equal efficacy in terms of complete resolution, although adverse effects might be more frequent with acitretin, and clearing of erythema in at least 50% of lesions occurred less often in participants applying acitretin. Moderate-quality evidence found adverse events were minor on the whole. There is not enough reliable evidence about other drugs used to treat DLE. Overall, the quality of the trials and levels of uncertainty were such that there is a need for further trials of sufficient duration comparing, in particular, topical steroids with other agents.

Acute generalized exanthematous pustulosis: clinical characteristics, etiologic associations, treatments, and outcomes in a series of 28 patients at Mayo Clinic, 1996-2013.

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a rare skin condition typically caused by medications. The objective of this study was to examine the clinical features, causes, and outcomes of AGEP at a sole tertiary care center. METHODS: A retrospective review of patients with AGEP (European Study of Severe Cutaneous Adverse Reactions score of ≥ 5) seen at Mayo Clinic (Rochester, MN, USA) between January 1, 1996, and December 31, 2013, was conducted. RESULTS: Of 28 patients (mean age at onset: 56 years), 17 (61%) were women. The development of AGEP was attributed to medications in 25 patients (89%), with clindamycin the most common culprit (six patients). Three patients (11%) had mucous membrane involvement, and 21 (75%) showed systemic involvement. Ten patients (36%) received systemic corticosteroids for treatment of AGEP. Skin findings resolved within 15 days in 26 patients (93%) (mean time to resolution: 7.6 days). In three patients (11%), generalized skin eruptions or dermatitis developed weeks to months after the resolution of AGEP. Twenty-four patients (86%) had a personal history of drug reactions before the development of AGEP. CONCLUSIONS: A previous history of drug reactions and clindamycin causation were more common in the present cohort than in prior reports. A small subset of patients experienced new-onset non-AGEP skin eruptions within a few months of the resolution of AGEP.

Long-term adherence to topical psoriasis treatment can be abysmal: a 1-year randomized intervention study using objective electronic adherence monitoring.

BACKGROUND: Most people with psoriasis have limited disease that could be treated with topicals, but topical efficacy is limited by low short-term adherence. Psoriasis is a chronic disease, and long-term adherence is an even bigger problem. OBJECTIVES: To determine how well medication is used in the long-term topical treatment of psoriasis and to assess the potential of an internet-based reporting intervention to improve treatment adherence and outcomes. METHODS: An investigator-blinded, prospective study evaluated topical fluocinonide adherence in 40 patients with mild-to-moderate psoriasis over 12 months. Subjects were randomized in a 1 : 1 ratio to standard-of-care or internet-based reporting group. Adherence was objectively monitored with Medication Event Monitoring System® caps. RESULTS: Fifty per cent of subjects discontinued the treatment. Greater adherence was seen in the intervention group compared with the standard-of-care group (50% vs. 35%, P = 0·08). Psoriasis Area and Severity Index improved more in the intervention group at month 1 (1·61 vs. -0·12, P = 0·003), month 3 (2·50 vs. 0·79, P = 0·025) and month 12 (3·32 vs. 0·34, P = 0·038) than in the standard-of-care group. CONCLUSIONS: This study likely underestimates the challenge of long-term adherence, as adherence tends to be better in research studies than in clinical practice. This study also did not fully account for primary nonadherence. Adherence to topical treatment is low in the short term and decreased further in the long term, a considerable challenge for dermatologists to address. A reporting intervention may be one of the ways we can improve our patients' treatment outcomes.

Temperature-responsive molecular recognition chromatography using phenylalanine and tryptophan derived polymer modified silica beads.

Temperature-responsive polymers incorporating molecular-recognition sites were developed as stationary phases for high-performance liquid chromatography (HPLC). The grafted stationary phases consisted of functional copolymers composed of N-isopropylacrylamide (NIPAAm) and N-acryloyl aromatic amino acid methyl esters, i.e., phenylalanine and tryptophan methyl esters (Phe-OMe and Trp-OMe). Three novel temperature-responsive polymers, P(NIPAAm-co-Phe-OMe5), P(NIPAAm-co-Phe-OMe10), and P(NIPAAm-co-Trp-OMe5), were synthesized. These copolymers exhibited a reversible hydrophilic/hydrophobic phase transition at their lower critical solution temperatures (LCSTs). The polymers were grafted onto aminopropyl silica using an activated ester-amine coupling method, and were packed into a stainless steel column, which was connected to an HPLC system. Temperature-responsive chromatography was conducted using water as the sole mobile phase. More hydrophobic analytes were retained longer, and the retention times of aromatic steroids and aromatic amino acids were dramatically increased. This indicated that π-π interactions occurred between the phenyl or indole moieties of phenylalanine or tryptophan, respectively, and the aromatic compounds. Furthermore, the retention times of compounds with hydrogen bond acceptors were higher with P(NIPAAm-co-Trp-OMe5), which contained indole as a hydrogen bond donor, than with P(NIPAAm-co-Phe-OMe5). This indicated that hydrogen bonding occurred between the stationary phase and the analytes. These results indicate that hydrophobic, π-π, and hydrogen bonding interactions all affected the separation mode of the temperature-responsive chromatography, and led to selective separation with molecular recognition. Both temperature-response and molecular recognition characteristics are present in the proposed separation system that utilizes a temperature-responsive polymer bearing aromatic amino acid derivatives.

Oral candidiasis following steroid therapy for oral lichen planus.

OBJECTIVES: The purpose of this multicentre study was to determine the incidence of oral candidiasis in patients treated with topical steroids for oral lichen planus (OLP) and to determine whether the application of a concurrent antifungal therapy prevented the development of an oral candidiasis in these patients. MATERIALS AND METHODS: Records of 315 patients with OLP seen at four Oral Medicine practices treated for at least 2 weeks with steroids with and without the use of an antifungal regimen were retrospectively reviewed. RESULTS: The overall incidence of oral fungal infection in those treated with steroid therapy for OLP was 13.6%. There was no statistically significant difference in the rate of oral candidiasis development in those treated with an antifungal regimen vs those not treated prophylactically (14.3% vs 12.6%) (P = 0.68). CONCLUSIONS: Despite the use of various regimens, none of the preventive antifungal strategies used in this study resulted in a significant difference in the rate of development of an oral candidiasis in patients with OLP treated with steroids.

Beware of the Beetle: A Case Report of Severe Vesicating Dermatitis.

INTRODUCTION: Outbreaks of Paederus dermatitis have been documented worldwide. A case of Paederus dermatitis from Ethiopia is presented to highlight the importance of this clinical entity in the deployed setting. CASE PRESENTATION: A 31-year-old male presented with a 3- day history of scattered areas of a purulent, vesicating erythematous rash to his mid-back and neck. The largest of these measured 5 × 7 cm with erythematous borders and an erosive center. One to 2 days prior, 15 troops reported similar and less severe vesicating lesions to their extremities and backs. All patients participated in the same outdoor recreational event. A survey of the event's location revealed signs of the Paederus beetle. DISCUSSION: Although a known phenomenon, there are no literature reports of Paederus dermatitis within AFRICOM. Crushing the Paederus beetle against the skin causes an intense rash because of paederin in the hemolymph. Most present with typical linear lesions likely caused by brushing off the beetle from the skin. Fortunately, patients respond favorably to topical steroid treatment. CONCLUSION: Paederus beetle exposure in the deployed setting can impact force health. Increased awareness among providers and personnel should mitigate potential exposure and limit the morbidity associated with this beetle.

Stratum corneum absorption kinetics of 2 potent topical corticosteroid formulations: a pilot study.

Fluocinonide and halcinonide are class II topical corticosteroids that are indicated for the relief of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses and generally are applied to affected skin at least twice daily. This pilot study compared the absorption kinetics of cream formulations of fluocinonide and halcinonide in the stratum corneum within a 9-hour period following application. A dermal tape-stripping protocol was used to quantify corticosteroid concentration at 6 sequential depths in the skin of 4 sites on the forearm. Halcinonide and fluocinonide were extracted from the strips and concentrations were measured using liquid chromatography-mass spectrometry. Results demonstrated the immediate absorption of fluocinonide and halcinonide into the stratum corneum within 1 hour of application followed by a sustained release of halcinonide and a steady decline of fluocinonide after peaking.

Measure of atopic dermatitis disease severity using actigraphy.

BACKGROUND: Analyzing adherence to treatment and outcomes in atopic dermatitis is limited by methods to assess continual disease severity. Atopic dermatitis significantly impacts sleep quality, and monitoring sleep through actigraphy may capture disease burden. PURPOSE: To assess if actigraphy monitors provide continuous measures of atopic dermatitis disease severity and to preliminarily evaluate the impact of a short-course, high-potency topical corticosteroid regimen on sleep quality. METHODS: Ten patients with mild to moderate atopic dermatitis applied topical fluocinonide 0.1% cream twice daily for 5 days. Sleep data were captured over 14 days using wrist actigraphy monitors. Investigator Global Assessment (IGA) and secondary measures of disease severity were recorded. Changes in quantity of in-bed time sleep were estimated with random effects models. RESULTS: The mean daily in-bed time, total sleep time, and wake after sleep onset (WASO) were 543.7 minutes (SEM 9.4), 466.0 minutes (SEM 7.7), and 75.0 minutes (SEM 3.4), respectively. WASO, a marker of disrupted sleep, correlated with baseline (ρ  =  .75) and end of treatment IGA (ρ  =  .70). Most patients did not have marked changes in sleep. IGA scores declined by a median change of 1 point at days 7 (p  =  .02) and 14 (p  =  .008). CONCLUSIONS: Using actigraphy, atopic dermatitis disease severity positively correlated with sleep disturbances. Actigraphy monitors were well tolerated by this cohort of atopic dermatitis subjects.

Adherence to a five day treatment course of topical fluocinonide 0.1% cream in atopic dermatitis.

BACKGROUND: Adherence in the treatment of chronic inflammatory skin diseases such as atopic dermatitis is poor. Methods to improve adherence have proven difficult. PURPOSE: To determine whether a short course of treatment with a high-potency corticosteroid will improve adherence compared to longer treatment studies and if improvement in disease and itch continues after treatment. METHODS: 10 patients with mild to moderate atopic dermatitis were instructed to apply fluocinonide 0.1% cream twice daily for 5 days. Adherence was self-reported and electronically monitored. Treatment outcomes were assessed in terms of Visual Analog Scale of Itch (VAS), Eczema Area and Severity Index (EASI), and Investigator Global Assessment (IGA) scores. RESULTS: The median adherence rate was 40% (range of 0-100). The median percent change in VAS from baseline measures on days 7 and 14 were 90% (range -13, 100, p=0.02) and 52% (range 0, 100, p=0.004). On days 7 and 14, 20% and 70% patients achieved an EASI-75 and 40% and 60% an IGA of 0 or 1. LIMITATIONS: Small sample size limited subgroup analyses. CONCLUSIONS: Adherence rates with short-term treatment were similar to previously reported rates in longer term treatment studies. However, even non-adherent patients had significant improvement in itch and disease severity.