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.

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.

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.

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.

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.

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.

Effects of a novel formulation of fluocinonide 0.1% cream on skin barrier function in atopic dermatitis.

OBJECTIVE: To determine the effect a novel formulation of fluocinonide cream on skin barrier function in subjects with atopic dermatitis. DESIGN: The authors performed an open-label, investigator-blinded, side-by-side, controlled trial examining skin barrier function before and after a two-week course of a class I, super-potent topical steroid. SETTING: Outpatient university-based dermatology clinic in Portland, OR. SUBJECTS: Twenty-five subjects aged 12 or older with a diagnosis of moderate, severe, or very severe AD were recruited for this study. INTERVENTION: Fluocinonide 0.1% cream, a novel formulation of a class I super-potent topical steroid was applied to all affected areas, except a control site, once daily for two weeks or until clear. The control target site was treated with the vehicle once daily. MAIN OUTCOME MEASURE(S): The study's primary outcome was change in skin barrier function as measured by basal transepidermal water loss (TEWL) in acute lesional skin from baseline as measured at two weeks. RESULTS: TEWL readings significantly decreased (reflecting improved barrier function) in both the active and control target sites. The active target site decreased 14.35+/-16 mg/cm2 per hour; 95 percent confidence interval, P<0.001. The control target site decreased 8.75+/-11.80 mg/cm2 per hour in 25 subjects; 95 percent confidence interval, P<0.001. Skin electrical capacitance also improved significantly, reflecting improved stratum corneum hydration with therapy. Pruritus, clinical severity, and quality of life scores all showed significant improvement by the end of the study. CONCLUSION: The authors have shown that short-term treatment with a novel formulation of 0.1% fluocinonide led to significantly improved barrier function as measured by basal TEWL in subjects with active moderate to severe AD. These data suggest short-term treatment with AD with a super-potent corticosteroid improves skin barrier function.

Improvement in treatment adherence with a 3-day course of fluocinonide cream 0.1% for atopic dermatitis.

Variations in adherence may cause variations in treatment outcomes with topical corticosteroid therapy for atopic dermatitis. An intensive short course of outpatient treatment may promote good adherence and provide a high level of efficacy. The purpose of this study was to assess the efficacy, tolerability, and adherence to short-term treatment with fluocinonide cream 0.1% in the treatment of atopic dermatitis. Twenty participants with mild to severe atopic dermatitis were instructed to use fluocinonide cream 0.1% twice daily for 3 consecutive days for a total of 6 doses. Disease severity was assessed at baseline, day 3, day 7, and day 14. Electronic monitoring was used to measure adherence to treatment. Median adherence to treatment over the 3-day period was 100%. By day 14, the median visual analog scale (VAS) of pruritus and eczema area and severity index (EASI) scores improved from baseline by 79% and 76%, respectively. By the end of the study period, 11 participants had investigator global assessment (IGA) scores of clear or almost clear. The absolute degree of improvement was proportional to baseline disease severity. Short-term treatment with fluocinonide cream 0.1% for atopic dermatitis was well-tolerated and resulted in significant disease improvement (P < .001). Participants were highly adherent to the 3-day treatment regimen. Efforts to improve adherence may be valuable approaches for treating recalcitrant atopic dermatitis.

Urticarial hypersensitivity reaction caused by temozolomide.

Temozolomide is an oral alkylating agent approved for the treatment of glioblastoma and anaplastic astrocytoma, and is currently under clinical investigation for the treatment of brain metastases from a variety of cancers. Temozolomide is well tolerated, and the reported dermatologic side effects of this medication are limited. Here, the authors report the first case of an urticarial hypersensitivity reaction induced by temozolomide. As this drug will likely be increasingly utilized in the near future, it is important to be aware of its potential to cause adverse cutaneous manifestations.

The efficacy of three class I topical synthetic corticosteroids, fluocinonide 0.1% cream, clobetasol 0.05% cream and halobetasol 0.05% cream: a Scholtz-Dumas bioassay comparison.

BACKGROUND: This study compared the efficacy of a novel, topical class I synthetic, 0.10% fluocinonide corticosteroid with two other class I corticosteroids and placebo for the treatment of plaque psoriasis. METHODS: A 0.5 gram dose of fluocinonide 0.1% cream, clobetasol propionate 0.05% cream, halobetasol propionate 0.05% cream, and placebo ointment were applied to test sites on one psoriatic plaque per patient (n=5). Test sites were outlined according to the Scholtz-Dumas bioassay. Test sites were assessed by a blinded evaluator (1 = psoriasis worsened to 5 = psoriasis clear or almost clear), cleaned and medications were reapplied on days 3, 5, 7, 10 and 12. RESULTS & CONCLUSION: The three class I corticosteroid products were comparably effective, numerically and statistically, in clearing the psoriatic plaques. Upon completion of treatment, 60-80% of active-treated sites were clear or almost clear of psoriasis compared to zero with the placebo.

Case report: Fluocinonide-induced perioral dermatitis in a patient with psoriasis.

Topical corticosteroids are the primary treatment for psoriasis. A patient with psoriasis being treated with topical fluocinonide for lesions on the extremities developed an erythematous facial eruption consistent with perioral dermatitis. When topical agents are applied, they often end up in unintended areas. The potential for drug-induced perioral dermatitis should be considered in psoriasis patients treated with potent topical corticosteroids.

A case of disseminate and recurrent infundibulofolliculitis responsive to treatment with topical steroids.

Disseminate and recurrent infundibulofolliculitis (DRIF) is an uncommon pruritic follicular eruption of unknown etiology that is predominantly seen in black men. This condition tends to affect the trunk and upper extremities and is usually unresponsive to local and systemic treatment. Recently, several investigators have reported successful treatment with isotretinoin. Herein, we report a case of a patient with disseminate and recurrent infundibulofolliculitis who was successfully treated with potent topical corticosteroids.

A single-center, double-blind, randomized trial of the atrophogenic effects of fluocinonide cream 0.1% versus clobetasol propionate cream 0.05% in participants with corticosteroid-responsive dermatoses.

To compare the atrophogenic effects of fluocinonide cream 0.1% versus clobetasol propionate cream 0.05%, 20 participants with corticosteroid-responsive dermatoses were randomly assigned to receive fluocinonide cream 0.1% on one arm and clobetasol propionate cream 0.05% on the other arm. Study medications were applied to disease-free target areas on the inner arms twice daily for 2 weeks. The epidermal thickness of pretreatment and posttreatment punch biopsy specimens was measured. Skin examinations were performed evaluating clinical signs of atrophy. No significant reduction in epidermal thickness was observed in the fluocinonide-treated sites (mean, -0.0318 mm; standard deviation, 0.0239; P=.1991). A significant reduction in epidermal thickness was seen in the clobetasol-treated sites (mean, -0.1825 mm; standard deviation, 0.0239; P<.0001). This reduction was significantly greater than results from sites treated with fluocinonide cream 0.1% (difference, -0.1507; standard deviation, 0.0131; P<.0001). Although topical corticosteroids often are the first-line treatment for patients with various dermatoses, a side effect of continuous use is cutaneous atrophy. Our study demonstrated that clobetasol propionate cream 0.05% caused a significantly greater reduction in epidermal thickness compared with fluocinonide cream 0.1% when used twice daily for 2 weeks (P<.001). However, neither drug caused significant clinical signs of atrophy.

Reticulated phototoxic eruption in a patient on long-term diltiazem therapy.

Diltiazem hydrochloride is a commonly prescribed medication in the treatment of cardiovascular disease. A case of diltiazem-induced hyperpigmentation in a patient after significant sun exposure is reported. The morphological appearance was reticulated and slate-gray to blue in color. The pathogenesis of the hyperpigmentation is discussed and possible treatment options are reviewed.