Topical Tacrolimus Research Articles

Peripheral ulcerative keratitis associated with tralokinumab therapy: a case report and review of IL-13 inhibitor-associated ocular surface disease

BackgroundDupilumab and tralokinumab are interleukin-binding monoclonal antibodies used to treat systemic atopic disease. Use of these medications in management of atopic dermatitis (AD) is known to cause conjunctivitis. Dupilumab therapy has also been associated with more severe ocular surface disease, which has not previously been described in association with tralokinumab. This report describes a case of tralokinumab-associated conjunctivitis and peripheral ulcerative keratitis and reviews the spectrum and proposed mechanisms of ocular surface disease triggered by these medications.Case presentationA 61-year-old male with no rheumatologic or ocular history presented with bilateral papillary conjunctivitis and right eye peripheral ulcerative keratitis (PUK). PUK was arrested using oral corticosteroids and doxycycline, and long-term control of papillary conjunctivitis was achieved using topical tacrolimus ointment, allowing continuation of effective AD management with tralokinumab.ConclusionThis case report documents ulcerative keratitis occurring in association with tralokinumab therapy for AD, which has previously been described with dupilumab but not tralokinumab. This report demonstrates the need for vigilant ocular surface monitoring for patients on tralokinumab and illustrates successful management and long-term control of adverse ocular events associated with this medication.

Vernal Keratoconjunctivitis: Immunopathological Insights and Therapeutic Applications of Immunomodulators.

Vernal keratoconjunctivitis (VKC) is a complex and multifactorial disease process that employs Th2 cell-mediated immunologic processes, which involves the overexpression of interleukin 4 (IL-4), IL-5, IL-9, IL-13, and IL-31, and the activation of mast cells that release IL-5 and CCL-11, recruiting eosinophils to the site of inflammation. The disease primarily affects young males and is more common in regions with warm climates. VKC is characterized by persistent and recurrent conjunctival inflammation that can adversely affect the patient's quality of life, and, when inadequately treated, may lead to a host of ocular complications, such as corneal shield ulcers and scarring. The major distinct forms of VKC include limbal or palpebral, which may occur in combination. The clinicopathological features of VKC include the presence of pseudogerontoxon, limbal gelatinous hyperplasia, and perilimbal hyperpigmentation. Topical immunomodulators are effective anti-steroidal options for controlling severe and chronic cases of VKC. This review will provide a brief overview of topical immunomodulators, including cyclosporin and tacrolimus, and will highlight the clinical manifestations, pathological mechanisms, and fibroproliferative changes in the conjunctiva that can result from recurrent disease.

Comparative Study Between Tacrolimus 0.1% Ointment Versus Topical White Soft Petrolatum Jelly in the Treatment of Oral Retinoid-Induced Cheilitis

Retinoids are used topically as well as orally, and the most commonly used oral retinoids are isotretinoin and acitretin. Mucocutaneous adverse effects are frequently seen with the use of systemic retinoids, the most common being cheilitis, which is dose-dependent and seen in almost all patients using it. To study the comparative effect of topical tacrolimus 0.1% ointment versus topical white soft petrolatum jelly in the treatment of cheilitis due to retinoids. A total of 26 patients with cheilitis post-treatment with isotretinoin were enrolled in this cross-sectional study conducted over a period of 6 months. They were randomized into two groups of 13 patients each to receive topical tacrolimus 0.1% ointment and soft petrolatum jelly twice daily, respectively. Patients were followed up weekly with clinical photographs. Resolution of cheilitis was assessed on the basis of photograph and ICGS score. About 84.6% of patients of group A and 53.8% of patients of group B showed resolution of symptoms within 1 week of treatment. A significant difference was seen in duration for complete cheilitis resolution and relapse rate in the two groups. Our study concludes that oral retinoid-induced cheilitis shows faster and more significant resolution with twice-daily topical tacrolimus 0.1% ointment application compared to twice-daily topical petrolatum jelly.

Comparison of the clinical efficacy of topical tretinoin(0.05%) cream and tacrolimus(0.1%) ointment using iontophoresis in the management of palmar/plantar psoriasis.

Palmoplantar psoriasis is a localised variant of psoriasis that maybe resistant to topical therapy, owing to poor penetrability of topical agents at this anatomical site. Modalities enhancing localised cutaneous delivery of drugs could help in solving this problem. Iontophoresis is one such procedure that augments transdermal drug delivery; thus enabling achievement of better, and expeditious therapeutic outcomes. To compare the therapeutic efficacy and safety of iontophoresis with tretinoin (0.05%) cream and tacrolimus (0.1%) ointment in treating patients with palmar/plantar psoriasis. In total, 60 patients with palmoplantar psoriasis (28 males, 32 females, age range 8-76 years) were enrolled and randomly assigned to one of the 2 groups, consisting of 30 patients each. Group A (12 males, 18 females) received iontophoresis treatment with tretinoin (0.05%) cream, and group B (16 males, 14 females) received iontophoresis treatment with tacrolimus (0.1%) ointment, once every week from baseline till 4 weeks and then fortnightly at 6 and 8 weeks.Clinical images were taken at each visit and improvement of psoriasis was evaluated using the erythema, scaling, induration and fissuring (ESIF) score. Percentage reduction of ESIF score was also assessed on completion of treatment, and the grade of improvement was accordingly outlined for each patient. Study was completed by 27 patients in group A, and 29 patients in group B. In group A, the ESIF score reduced significantly from 8.7±2(baseline) to 3.2±1.7(end point), (p value:<0.001). Similarly in group B, there was a substantial reduction in the ESIF score from 8.2±1.9 (baseline) to 3.3±1.1(end point), (p value:<0.001). No significant adverse effects were encountered in both treatment arms. Iontophoresis using tretinoin and tacrolimus was found to be effective and safe for palmoplantar psoriasis. Although iontophoresis with tretinoin was slightly better than tacrolimus, results were not significant statistically.

571 - Case series of topical 1.5% ruxolitinib cream for pediatric vitiligo

Abstract Introduction/Background Pediatric Vitiligo affects 1.52% of 4-11-year-olds within the United States and 2.16% of 12-17-year-olds with non-segmental disease affecting 65% and 69% respectively (1). The FDA has not approved any medications for vitiligo for children younger than 12 years of age. Additionally, about one-third of pediatric vitiligo is segmental (1), and there is no FDA-approved topical agent for segmental vitiligo in any pediatric age group (2). Objectives To identify the efficacy of 1.5% ruxolitinib cream for pediatric vitiligo in clinical practice. Methods An IRB-exempted pediatric chart review was conducted addressing the usage of 1.5% ruxolitinib cream, currently FDA-approved for non-segmental vitiligo affecting 10% of body surface area or less for 12 years of age or older. All children and adolescents using topical 1.5% ruxolitinib cream including segmental, non-segmental, and mixed vitiligo including individuals up to age 17 years. Results Twelve children were identified with topical usage of 1.5% ruxolitinib cream for vitiligo ages 3-16 years (average age: 10.75 years). Demographics included 9 males, 3 females and race/ ethnicity included Black (n=1), Hispanic/ Latin X (n=4), Indian (n=1), and White (n=6). Vitiligo subtype included: Non-segmental vitiligo (n=7), Mixed type vitiligo (n=1), and segmental vitiligo (n=4). Regarding treatment subgroup of Non-segmental vitiligo and the non-segmental component of the Mixed type included 8 children, average age of 10.4 years (range 3-15 years), including 5 children under the age of 12 years (one 3-year-old, two 9 year-olds, and two 10 year-olds). Treatment was once daily in 1 child and twice daily in 7 children. One was lost to follow-up. Of the 6 children with documented response, average maximum repigmentation occurred at 6.14 months (range 3-12 months), with five achieving complete repigmentation, one partial repigmentation with only a three-month trial. The average length of disease before treatment began was 1.25 years (1 month to 6 years). The onset of response was 1.57 months on average (range 1-3 months). The initial location of response was the face (n=3), arms (n=2), and abdomen (n=1). No adverse events were reported. Four children had a complete blood count while on medication, with no laboratory abnormalities, including the 3-year-old. Two had a parent with vitiligo. Four patients previously failed tacrolimus topically, two patients failed topical class 2 corticosteroids, and one previously failed narrowband UVB, with no notable difference in response in these patients. Regarding treatment subgroup of Segmental vitiligo including five SV patients average age 11.2 years (range 5-16 years). One had facial segmental, one face and neck lesion (solitary stripe), one chest/back, and one on the lower abdomen. The five year-old did not repigment after 6 months of neck application, but never developed poliosis. The ten-year-old with segmental disease for 6 years had no response. The eleven-year-old SV of the chest/ back failed topical tacrolimus and responded with 40% repigmentation over 3 months, increasing to 90% after 5 months and 12 concurrent sessions of 308-nm laser. The 14-year-old developed slight poliosis, but started repigmenting within 3 weeks, with continuous usage and subtotal repigmentation at 14 months. The 16-year-old began to repigment after 1 month, with a concurrent weekly 308-nm laser, and subtotal repigmentation after 5 months. Repigmentation was One facial SV (12 treatments), one chest/back SV (12 treatments), and one NSV had concurrent 308-nm laser (24 treatments) with pulsed dexamethasone, without any notable adverse events. Two teenage males (ages 15 and 16 years) developed acne on sites of application on the face. Laboratory screening including complete blood count was normal during treatment for 2 patients evaluated. Conclusions NSV responds to 1.5% topical ruxolitinib consistently, with a solitary patient responding to once daily, and efficacy in children as young as three years of age with no notable lab abnormalities in screened patients. Topical 1.5% ruxolitinib cream appears very effective in repigmenting SV in children if used twice-daily and in combination with 308-nm laser sessions in the first 6 months. Topical ruxolitinib can cause acne in teenagers with facial segmental vitiligo. Early institution of topical 1.5% ruxolitinib cream appears to have a rapid onset of repigmentation (average 1.57 months) and rapid complete response (6.14 months). Clinical trials of 1.5% topical ruxolitinib in children are needed to identify outliers and long term outcomes. Early institution of therapy appears to speed up the response. Adjunctive 308-nm laser is promising but requires placebo-controlled trials.

Topical Tacrolimus and Mycophenolic Acid Therapy Synergizes with Low Dose Systemic Immunosuppression to Sustain Vascularized Composite Allograft Survival

AimThe goal of this study was to evaluate whether topical administration of tacrolimus (TAC) and mycophenolic acid (MPA) at the transplant site enables vascularized composite allograft (VCA) survival with significant minimization of the dose and adverse effects of systemic TAC (STAC) immunosuppression. Materials and methodsLewis (Lew) rats received orthotopic hind limb allotransplants from fully mismatched Brown Norway (BN) donors. Group 1 (Controls) received no treatment. Other groups were treated with STAC at a dose of 1 mg/kg/day for 7 days. On post-operative day (POD) 8, the STAC dose was dropped to 0.1 mg/kg/day for Group 2 and maintained at 1 mg/kg for Group 3. Group 4 received topical application of TAC and MPA on the transplanted (Tx) limb starting POD 8 without STAC. Group 5 received topical TAC and MPA on the contralateral non-Tx limb and Group 6 received topical TAC and MPA on the Tx limb starting POD 8 along with low dose STAC (0.1 mg/kg/day). Treatment was continued until the study end point was reached, defined as either grade 3 rejection or allograft survival exceeding 100 days. .We conducted sequential LC-MS/MS measurements to assess TAC and MPA concentrations in both blood/plasma and allograft tissues. Additionally, we evaluated markers indicative of organ toxicity associated with STAC immunosuppression. ResultsCompared to controls, topical therapy with TAC+MPA significantly prolonged allograft survival beyond 100 daysat very low dose STAC (0.1 mg/kg/day) (Group 6). The histopathological assessment of the grafts was consistent with the clinical outcomes. .Drug levels in blood/plasma remained low or undetectable, while allograft tissues showed higher drug concentrations compared to contralateral limb tissues (P<0.05). . Urinary creatinine clearance remained within the normal range at 2.5 mL/min. ConclusionCombination therapy with topical TAC and MPA synergizes with a very low dose, corticosteroid- free-STAC regimen and facilitates rejection-free, prolonged VCA survival without morbidity.

Efficacy and Safety of Topical Tacrolimus Microemulsion Applied Twice Daily in Patients with Mild to Moderate Scalp Psoriasis.

Involvement of the scalp is common in psoriasis and severely affects the quality of life of those affected. It is difficult to treat and places special demands on the galenics of a drug formulation. Tacrolimus is a calcineurin inhibitor and is approved as an ointment formulation for the treatment of atopic dermatitis. The efficacy and safety of topically applied tacrolimus have also been studied and proven for psoriasis. However, no proprietary pharmaceutical product is currently approved for this indication. A multicenter, double-blind, vehicle-controlled phase3 study was conducted to evaluate the efficacy and safety of 0.1% tacrolimus microemulsion when applied topically twice daily in 128 patients independentlyofsex with scalp psoriasis. The primary efficacy analysis showed a scalp Investigator Global Assessment (s-IGA) of 0 (absence of disease) or 1 (very mild disease) at 8weeks in 28.6% of subjects in the tacrolimus group, indicating a significantly better response (p = 0.0476, chi-square test) versus 12.7% of subjects in the placebo group (difference of 15.9%-points). The Dermatology Life Quality Index (DLQI) improved over time and was more pronounced in the group treated with tacrolimus-containing microemulsion than in the placebo group, but showed no statistically significant difference after 8weeks of use (p = 0.193, ANCOVA). The safety analysis revealed no evidence of cutaneous side effects other than those known. Toxicologically relevant serum levels of tacrolimus could be excluded. The study data show that 0.1% tacrolimus microemulsion has good efficacy and safety in the treatment of scalp psoriasis.

P949 Effectiveness and safety of rectal tacrolimus in patients with ulcerative colitis. TACRO-TOPIC study. A multicenter study from the young group of GETECCU

Abstract Background Few small studies have assessed the efficacy of topical therapy with tacrolimus in patients with ulcerative colitis (UC). The aim of our study was to evaluate its effectiveness and safety in a real-world setting. Methods A multicenter observational retrospective study at 25 Spanish GETECCU hospitals was performed. Adult patients with UC who received topical tacrolimus from January 2009 to January 2023 were eligible. Inclusion criteria were proctitis, left-sided, or extensive colitis with persistent distal colonic activity confirmed endoscopically during the previous 3 months. Clinical and biochemical data were collected at baseline, week 4, 8 and 54. Tacrolimus trough levels were evaluated in week 4 and 8. Primary outcome was clinical response at week 8, defined as a ≥3 points or ≥30% decrease of partial Mayo score with ≥1point reduction in the bleeding score. Mean partial mayo scores were compared using the t-test. A p&amp;lt;0.05 was considered statistically significant. Results 106 patients, 59 (55.6%) males, median age 48.7 years (IQR:39.9-59.7), received rectal tacrolimus during a median of 9.7 weeks (IQR:5-18.7). Sixty-four patients (60.4%) received suppositories, 41 (38.7%) enemas and 1 patient an ointment (0.9%). Thirty (28.3%) were patients with proctitis, 45 (42.4%) with left colitis and 31 (29.2%) with extensive colitis. At baseline, 54 patients (50.9%) received concomitant biological/small molecules therapy, while 14 patients received immunomodulators. Most common dose was 2 mg (84%) Q24H (71.7%). A significant decrease in mean partial mayo score was observed at week 4 and 8 (figure 1). Clinical response at week 8 was achieved in 63 patients (66.3%) and clinical remission in 42 (44.2%). 32 patients (33.7%) were non-responder at week 8. Clinical response and remission at week 4 were achieved in 56 (57.7%) and 33 (34.4%), respectively. Clinical response at week 8 was similar between the group with concomitant biological therapy and without (64.6.9% vs 68.1%, p=0.8). Clinical response at week 8 was similar among different extensions (proctitis: 55.6%; left colitis: 80%; extensive colitis 57.1%; p=0.052). Clinical outcomes are detailed in table 1. Median tacrolimus trough levels at week 4 was 3.4 ng/ml (IQR 1.5-6.7) and 2.9 ng/ml (IQR 1.5-6) at week 8. Adverse events were detected in 21 patients (19.8%), Thirteen were graded as mild and 8 moderate. Treatment was ceased due to adverse events in 11 (10.4%) patients. Conclusion Topical tacrolimus is effective in UC achieving clinical response in more than sixty percent at week 8 with even lower doses than reported in clinical trials. Adverse events reported in nearly 20% of patients were mostly mild.

Treatment of hypopigmented burn hypertrophic scars with short-term topical tacrolimus does not lead to repigmentation.

Dyschromia is an understudied aspect of hypertrophic scar (HTS). The use of topical tacrolimus has successfully shown repigmentation in vitiligo patients through promotion of melanogenesis and melanocyte proliferation. It was hypothesized that HTSs treated with topical tacrolimus would have increased repigmentation compared to controls. Full-thickness burns in red Duroc pigs were either treated with excision and meshed split-thickness skin grafting or excision and no grafting, and these wounds formed hypopigmented HTSs (n = 8). Half of the scars had 0.1% tacrolimus ointment applied to the scar twice a day for 21 days, while controls had no treatment. Further, each scar was bisected with half incurring fractional ablative CO2 laser treatment before topical tacrolimus application to induce laser-assisted drug delivery (LADD). Pigmentation was evaluated using a noninvasive probe to measure melanin index (MI) at Days 0 (pretreatment), 7, 14, and 21. At each timepoint, punch biopsies were obtained and fixed in formalin or were incubated in dispase. The formalin-fixed biopsies were used to evaluate melanin levels by H&E staining. The biopsies incubated in dispase were used to obtain epidermal sheets. The ESs were then flash frozen and RNA was isolated from them and used in quantitative reverse transcription polymerase chain reaction for melanogenesis-related genes: Tyrosinase (TYR), TYR-related protein-1 (TYRP1), and dopachrome tautomerase (DCT). Analysis of variance test with Šídák's multiple comparisons test was used to compare groups. Over time, within the grafted HTS and the NS group, there were no significant changes in MI, except for Week 3 in the -Tacro group. (+Tacro HTS= pre = 685.1 ± 42.0, w1 = 741.0 ± 54.16, w2 = 750.8 ± 59.0, w3 = 760.9 ± 49.8) (-Tacro HTS= pre = 700.4 ± 54.3, w1 = 722.3 ± 50.7, w2 = 739.6 ± 53.2, w3 = 722.7 ± 50.5). Over time, within the ungrafted HTS and the NS group, there were no significant changes in MI. (+Tacro HTS= pre = 644.9 ± 6.9, w1 = 661.6 ± 3.3, w2 = 650.3 ± 6.2, w3 = 636.3 ± 7.4) (-Tacro HTS= pre = 696.8 ± 8.0, w1 = 695.8 ± 12.3, w2 = 678.9 ± 14.0, w3 = 731.2 ± 50.3). LADD did not lead to any differential change in pigmentation compared to the non-LADD group. There was no evidence of increased melanogenesis within the tissue punch biopsies at any timepoint. There were no changes in TYR, TYRP1, or DCT gene expression after treatment. Hypopigmented HTSs treated with 0.1% tacrolimus ointment with or without LADD did not show significantly increased repigmentation. This study was limited by a shorter treatment interval than what is known to be required in vitiligo patients for repigmentation. The use of noninvasive, topical treatments to promote repigmentation are an appealing strategy to relieve morbidity associated with dyschromic burn scars and requires further investigation.

P16 Hypopigmented Mycosis Fungoides in a Caucasian child

Abstract We report a case of hypopigmented MF in an 8-year-old Caucasian boy whose skin had been managed as pityriasis alba for a number of years. On initial presentation to the emergency department, multiple non-itchy scattered hypopigmented macules were incidentally noted on the lower abdomen, groin, lateral flanks and axillae. Physical examination revealed widespread hypopigmented patches. Differential diagnoses included pityriasis alba or post inflammatory hypopigmentation secondary to atopic dermatitis. He was initially managed with mild to moderate corticosteroids and emollients, but continued to develop multiple atypical asymmetrical macules, particularly on the lower abdomen and groin. Although the skin was responsive to anti-inflammatory treatment, given the progression, a skin biopsy was requested. A lesional punch biopsy from the abdomen revealed focal lymphocyte exocytosis and interface change at the epidermis. Given the subtle findings the case was discussed at our histopathology MDT meeting. Further specialist review of the histopathology showed clinicopathological correlation in keeping with CD8+ mycosis fungoides (hypopigmented variant). He is currently managed with regular potent topical steroids, 0.1% topical tacrolimus. TL01 phototherapy has been suggested. Juvenile onset MF constitutes hypopigmented, poikilodermatosis, pityriasis lichenoides-like, folliculotropic, and pigmented purpura- like presentations1. Generally there is no disease progression beyond stage 1A or 1B disease2. Hypopigmented MF is well described in black and Asian skin types but it is also important to appreciate that multiple reoccurring atypical hypopigmented patches in Caucasian skin may also be a variant of hypopigmented MF.

P15 A Case of Juvenile Dermatomyositis in a 15-year old African-descent Girl

Abstract A 15-year-old female with skin of colour (SOC), was diagnosed with Juvenile dermatomyositis (JDM) following a presentation with muscle weakness, swallowing difficulties and rash. Investigations showed CK&amp;gt;1300, positive Mi-2 alpha, beta antibodies and bilateral myositis on MRI pelvis. Her skin features commenced 2 months prior to her rheumatological presentation. They included erythematous pruritic patches on the limbs, generalised hyperpigmentation of the face and trunk, hyperpigmentation of palmar creases and nail folds, flagellate hyperpigmentation of the hands &amp; arms, and hypopigmented macules with follicular sparing across the face. She also presented skin thickening over the interphalangeal joints and nail fold capillary dilatation and infarctions. Skin biopsy showed interface dermatitis, in keeping with dermatomyositis. She was managed with weaning prednisolone, methotrexate, topical tacrolimus and sunscreen. JDM is a small-vessel autoimmune vasculopathy leading to muscle inflammation and skin changes. Unlike adult-onset disease, JDM is not associated with malignancy. The typically described violaceous skin features of JDM including photosensitive rash periorbitally, and over the knees and knuckles (Gottron’s sign) may be hyperpigmented rather than erythematous in skin of colour. Additional skin features described in SOC are generalised hyperpigmentation and pigmentation in skin creases. A flagellate dermatitis is uncommon, but recognised in association with Mi-2 antibodies in JDM. TIF1 antibodies have been reported in association with hypopigmented patches which may mimic vitiligo postulated possibly secondary to interface inflammation perhaps leading to dyspigmnentation. Notably our patient was negative for TIF1. This presentation highlights some of the less commonly described skin features of dyspigmentation in JDM in SOC.

Immunosuppressive and immunomodulating therapy for atopic dermatitis in pregnancy: an appraisal of the literature.

Atopic dermatitis (AD) is the most common dermatological diagnosis during pregnancy. Treatment of AD during pregnancy can be challenging, due to the unpredictable course and the fact that the therapy needs to be safe for both the mother and the fetus. Here we present an up-to-date appraisal of the literature on the treatment options available for AD in patients planning pregnancy, during pregnancy, and during breastfeeding. All patients with AD are recommended to supplement any medical treatment with daily applications of emollients. The first step in the medical treatment for AD during pregnancy are topical corticosteroids, and/or topical tacrolimus. If required, UV-light therapy can also be considered. Treatment with systemic therapy during pregnancy should always rely on a careful risk-benefit assessment and be based on shared-decision making between the treating physician and patient. The first-line systemic treatment option is cyclosporine A, whereas azathioprine may be considered in patients already receiving this treatment prior to pregnancy. Systemic glucocorticoids may also be used. Treatment with systemic JAK inhibitors is not recommended, whereas treatment with mycophenolate mofetil and methotrexate is contraindicated. Targeted therapy with dupilumab is not generally recommended, due to lack of experience in human pregnancies, yet some case-reports on their use are emerging. These recommendations are based on the authors appraisal of existing literature and the current recommendation from the European Task Force on Atopic Dermatitis. It is always the responsibility of the treating physician to stay updated on the newest guidelines and literature when treating patients with AD during pregnancy.

A Comparative Study to Examine the Effects of Topical Vinpocetine and Tacrolimus on Induced Atopic Dermatitis in Mice.

Background: Atopic dermatitis (AD) is a persistent and recurring inflammatory skin disorder distinguished by parched skin and severe itching. The pathogenesis of AD involves increased production of specific cytokines, such as Interlukin-4 (IL-4) and Interlukin-13 (IL-13), which are associated with the T helper 2 pathway. However, prolonged use of the current glucocorticoids and calcineurin inhibitors medications can lead to adverse effects. Aim of the study: To assess the efficiency of topical Vinpocetine and Tacrolimus in treating an induced atopic dermatitis mice model. Methods: Five sets of fifty male Albino mice, were randomly selected. One-chloro-2,4-dinitrobenzene (DNCB) was applied to the dorsal (back) skin of forty mice to cause atopic dermatitis. Ten control healthy mice were placed in Group I, ten mice with atopic dermatitis were placed in Group II; neither group received any treatment. Group III consists of 10 mice that received tacrolimus 0.1% ointment, group IV was administered a topical ointment comprising 5% Vinpocetine and lastly, group V underwent a vehicle ointment. Severity was assessed visually, IL-4 and IL-13 were measured by immunohistochemistry, in addition to general histopathological evaluation as well as examining WBCs. Results: The groups treated with Vinpocetine 5%, and Tacrolimus all had significantly lower levels of WBC counts, decreased IL-4 and IL-13 staining according to immunohistochemistry and lower histopathological scores. Vinpocetine 5% and tacrolimus treatment also showed a statistically significant reduction in hyperkeratosis and inflammation among the studied groups (P&lt;0.001). Conclusions Topical Vinpocetine 5% ointment, and tacrolimus 0.1% were effective in the treatment of induced AD mouse model through the improvement of histopathological changes and their ability to decrease IL-4 and IL-13, Vinpocetine were effective in the treatment of induced AD. Keywords: Atopic dermatitis, Tacrolimus, Topical, Vinpocetine.

Comparative Efficacy of Topical Tacrolimus 0.1% and Clobetasol Propionate 0.05% in the Treatment of Alopecia Areata (AA)

Alopecia areata patients can choose from a variety of therapy methods. Each method has advantages and limitations, and its suitability varies for each patient. The medical usefulness of topical corticosteroids in AA is yet debatable. Objective: To assess the effectiveness of topical tacrolimus 0.1% vs. topical clobetasol propionate 0.05% while treating alopecia areata. Methods: Randomized-controlled trial (Double blind) conducted in Dermatology Department, CMH-Abbottabad, from November 2022 to April 2023. The seventy (70) patients with alopecia areata who attended to OPD of CMH Abbottabad between the ages of 20 and 50 were included. The non-probability consecutive sampling method was used. For up to 3 months, patients in Group A used clobetasol propionate 0.05% twice daily, while patients in Group B used topical tacrolimus 0.1% twice daily. Patients were evaluated at the start of each session, four weeks later, eight weeks later, and twelve weeks later. The SALT score was used to estimate hair loss at presentation and during the 3-month follow-up. The degree of response has been characterized by following hair re-growth as excellent (&gt;75%), marked (51-75%), moderate (26-50%), or mild (25%). A p-value of &lt;0.05 was considered significant.  Results: When the efficacy was compared, 26 (74.3%) patients in group-A (mean age 35.23+7.87 years) shown excellent response, while 14 (40%) patients in group-B (mean age 34.29+7.87 years) with significant p-value was 0.028. Conclusions: Clobetasol propionate 0.05% was more efficacious as a therapy choice for stimulating hair re-growth in patients. 

Clinical features and therapeutic approaches of genital lichen sclerosus in children: results of an observational monocentric study

BackgroundLichen sclerosus is a chronic, progressive, inflammatory skin disease that presents unique challenges, particularly in the pediatric population, where limited data exist regarding its manifestation and optimal management. This retrospective observational monocentric study aims to provide insights into the clinical characteristics and therapeutic strategies employed, in a cohort of children and adolescents with genital lichen sclerosus.MethodsA comprehensive analysis was conducted involving a cohort of 60 pediatric patients ranging from 1 to 15 years old, all diagnosed with lichen sclerosus. These cases were referred to the Pediatric Dermatology Regional Center of the University of Padua, Italy, between January 2018 and January 2022. Moreover, we propose a treatment protocol that showed beneficial outcomes in all of our patients. Specifically, the initial use of mid-potency topical corticosteroids has proven effective in addressing severe acute flares. Following this acute phase, transitioning to long-term treatment with topical calcineurin inhibitors, such as tacrolimus or pimecrolimus, has demonstrated effectiveness in maintaining remission of the disease and also shown efficacy in treating mild cases. The therapeutic effectiveness was assessed by considering various clinical aspects, including erythema, paleness, skin erosions, and specific symptoms such as itching, burning, and pain.ResultsErythema emerged as the predominant clinical sign, reported in 43 (78.3%) patients, followed by paleness, reported in 17 (28.3%) patients. Pruritus was observed in 25 girls (58.1% of females) and 2 boys (11.8% of males), while pain and burning sensations were predominantly reported in female children. Among females, we observed a higher prevalence of cutaneous comorbidities, such as atopic dermatitis, psoriasis, alopecia areata, and linear scleroderma, as opposed to autoimmune systemic diseases, that were more prevalent in males. Regarding therapeutic approaches, 21 (35.0%) patients applied topical corticosteroids, 28 (46,7%) applied topical tacrolimus and 21 (35,0%) applied topical pimecrolimus. All treated patients experienced notable benefits following the initiation of treatment proposed by our protocol.ConclusionsThis study provides further insights into the clinical presentation and management of lichen sclerosus in the pediatric population, shedding light on potential therapeutic pathways for optimizing patient outcomes in this specific demographic. The proposed protocol appears to be a promising strategy, especially when the onset of the disease occurs during childhood.

Safety of topical tacrolimus and corticosteroids in young children with atopic dermatitis: a 5-year questionnaire-based follow-up study.

We previously conducted a randomized double-blinded clinical cohort study on topical tacrolimus safety issues in 1–3-year-old children with atopic dermatitis. Five years on, the participants were contacted via a postal questionnaire to obtain long-term data. There were no significant differences regarding infections, growth parameters (height, weight, body mass index), quality of life and disease severity between use of topical tacrolimus and topical corticosteroids.

Application of the waiting time distribution in a nationwide screening of real-world dermatology drug utilization for aberrant use patterns.

Inappropriate use of medicines may have critical consequences from individual, public health, and economic perspectives. Discovering wrongful medicine use may require intentional surveillance or screening. The objectives of this study were to: (i) apply and evaluate the waiting time distribution (WTD) method as a screening tool for identifying aberrant drug use and (ii) evaluate the nationwide use of Dermatology drugs in Denmark for signals of aberrant drug use. Dermatology drug use data from the Danish nationwide healthcare registries from 2018 to 2020 were used to produce WTDs that were analyzed for drug use patterns. The method provides estimates of the prevalence and incidence and enables estimation of mean treatment duration, drug relapse, and unexpected drug prescribing. The study included 2 027 889 individual drug users and analyzed 6 141 449 prescriptions. The analysis included approximately 100 dermatology drugs and drug categories and produced 56 WTD drug curves. The WTD patterns and epidemiological estimates confirmed that most drugs are used as intended and revealed few unexpected patterns for further investigation. Three unexpected findings were identified concerning (i) short-term use that would entail suboptimal clinical efficiency for minoxidil, (ii) sub-optimal use of topical tacrolimus, and (iii) potential undesirable increase in short-course doxycycline treatments. In Denmark, dermatology drugs are predominantly used as expected, with few unexpected use patterns identified. Targeted specific follow-up on the identified signals is necessary for conclusions about inappropriate use. The findings suggest that the WTD method is applicable for screening for aberrant drug use.

Management of Pediatric Psoriasis: A U.S. Survey Based on Visits from the National Ambulatory Medical Care Survey (NAMCS).

Approximately one-third of psoriasis cases present in the first two decades of life. Many psoriasis treatments are approved by the U.S. Food and Drug Administration (FDA) for adults, including topical agents, systemic non-biologic agents, and systemic biologic agents. Only a handful of psoriasis treatments are FDA approved for children. Given the constantly evolving landscape of pediatric psoriasis management, our aim is to characterize how children with psoriasis are treated in the U.S. Data from the 2003-2016 and 2018 National Ambulatory Medical Care Survey (NAMCS) were used to evaluate patient demographics and treatment patterns for visits of children with psoriasis. Visits were stratified by those with a diagnosis of psoriasis and those for children with a diagnosis of psoriasis. Separate analyses for visits of children with a diagnosis of psoriasis were performed, including for sex, race, ethnicity, age, specialty of provider seen, and medications prescribed. Pediatric psoriasis visits accounted for 3.3% of visits with psoriasis from 2003 to 2016 and in 2018; about one-third of those visits were to primary care providers. Children with psoriasis were prescribed a variety of topical and systemic medications, of which the most frequently prescribed treatments were topical tacrolimus, followed by topical clobetasol and topical betamethasone dipropionate or betamethasone valerate. Etanercept was the only biologic prescribed to children. At least 59% of the visits for children with a diagnosis of psoriasis included a topical prescription while at least 5.3% of the visits included a systemic prescription. Use of off-label treatments was common for pediatric psoriasis. Most children with psoriasis were treated with topicals, of which tacrolimus, an unapproved treatment, was the most common. The frequent use of tacrolimus could indicate an avoidance of corticosteroids in children.

A comparative randomized clinical trial evaluating the efficacy and safety of tacrolimus versus hydrocortisone as a topical treatment of atopic dermatitis in children.

Background: Atopic dermatitis (AD) aetiology is not exactly identified, but it is characterized by pruritic skin reactions with elevation in the levels of inflammatory markers. Despite the fact that Corticosteroids are the mainstay therapy in the management of AD, they have many local and systemic adverse effects. Objective: The aim of this study is to evaluate the efficacy and safety of topical tacrolimus ointment in comparison to topical hydrocortisone cream in the management of the AD of children diagnosed with AD. Patients and Methods: This study was conducted on 200 children with AD. They were simply randomized into two groups, the tacrolimus group treated with 0.03% topical tacrolimus ointment and the hydrocortisone group treated with 1% hydrocortisone cream twice daily during the 3weeks study period. Results: At the end of the study, both the tacrolimus and hydrocortisone groups showed a significant decline in the mean serum level of IL-10, IL-17, and IL-23 (p < 0.05) when compared to their baseline levels. However, the tacrolimus group showed a more significant decrease (p < 0.05) in the mean serum level of IL-10, IL-17, and IL-23 as compared to the hydrocortisone group [Mean differences = 1.600, 95% CI: 0.9858-2.214; 1.300, 95% CI: 1.086-1.514 and 4.200, 95% CI: 3.321-5.079]. Moreover, the median mEASI decreased similarly from 32 to 21 in the tacrolimus group and from 30 to 22 in the hydrocortisone group (p > 0.05) [Median difference = -2.000, 95% CI: -2.651 to -1.349; Median difference = 1.000, 95% CI: 0.3489-1.651]. Mild to moderate transient stinging and erythema were the main adverse effects that showed higher incidence in the tacrolimus group than in the hydrocortisone group (p < 0.05). In most cases, they resolved within 3-4days. Besides, tacrolimus ointment did not cause skin atrophy as compared to the hydrocortisone group (p < 0.05). Conclusion: Tacrolimus ointment is more beneficial than hydrocortisone cream in managing AD in children in terms of lowering the inflammatory markers, however, there is no difference on the dermatitis severity scale. Moreover, tacrolimus is safer with a better side effect profile compared to hydrocortisone. Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05324618).

Desquamative gingivitis treatment with topical tacrolimus applied to a custom tray: an open trial regarding its efficacy on patients’ symptoms

To evaluate the efficacy of topical tacrolimus offered on a custom tray to treat desquamative gingivitis (DG). Eighteen patients with symptomatic DG related to oral lichen planus (OLP) or mucous membrane pemphigoid (MMP) were selected, of which 13 completed the study. Periodontal treatment was followed by the fabrication of a custom silicone tray to apply a tacrolimus gel formulation (0.1%). Clinical evaluation (complaint of pain and burning - visual analog scale from 0 to 10; and the presence of erythema, desquamation, vesicle/blister, erosion, ulcer, and bleeding) was performed by the same examiner on day 1, and every 15 days for 90 days. Total remission was found in 4 patients (30.76%). Partial remission was found in 69.24% of the patients, classified with an excellent (30.76%), good (30.76%), and regular (7.69%) recovery, respectively. There was a reduction of about 60% in pain and 65% in burning sensation complaints. Wilcoxon test revealed significant differences between pre- and post-treatment pain and burning sensation symptoms (P < .01). Topical application of 0.1% tacrolimus gel was effective in the treatment of DG in controlling pain and burning sensation, leading to the clinical remission of gingival lesions in patients with OLP and MMP.