Topical Immunomodulators Research Articles

Cutaneous Crohn disease without gastrointestinal involvement in a 9-year-old boy

Cutaneous Crohn disease (CCD) is a rare dermatologic manifestation of Crohn disease and is defined as noncaseating, granulomatous skin lesions noncontiguous with the gastrointestinal tract. It most commonly affects the skin of the legs, although genital CCD is the most common presentation in children. Diagnosis of CCD is made by a combination of clinical and histopathological findings. Therapeutic options include topical, intralesional, and systemic corticosteroids as well as topical and systemic immunosuppressants and immunomodulators. Surgical excision may be considered for refractory cases. We report CCD in a 9-year old boy with penile swelling, granulomatous cheilitis-like lesions, and perianal plaques.

Comparative evaluation of efficacy and safety of cyclosporine 0.1% add-on therapy with artificial tears (carboxymethylcellulose 0.5%) with artificial tears alone in post cataract surgery patients

Background: Cataract is the most common cause of preventable blindness and to surgically remove the affected lens and replace it with an artificial lens is the only effective treatment. Most patients post cataract surgery, complain of dry eye. Artificial tears are commonly used symptomatic treatment in dry eye. Since there is an underlying inflammatory cause; therefore, recently topical immunomodulator therapy is gaining acceptance. Aims and Objective: The present prospective, randomized, open-label, the study was undertaken to evaluate the efficacy of cyclosporine 0.1% as add-on therapy with artificial tears (carboxymethylcellulose 0.5%) in post cataract surgery patients suffering from moderate-to-severe dry eye symptoms. Materials and Methods: A total of 69 patients were selected after application of inclusion and exclusion criteria with 37 patients in artificial tears 0.5% group and 32 patients in cyclosporine 0.1% + artificial tears 0.5% group, respectively. Patients were followed up to 8 weeks. Grading of the severity of dry eye was done on the basis of ocular surface disease index scale (OSDI), and patients with >23 score were selected for the study. Safety and tolerability were based on adverse events reported by the participants. Results: Treatment in both the group’s cyclosporine 0.1% + artificial tears 0.5% and artificial tears 0.5% leads to a significant improvement in the OSDI score in the patients at 4 weeks and 8 weeks interval (P < 0.0001). On intergroup comparison, the effect on OSDI score was more favorably affected by combination therapy than artificial tears alone. Both treatments were well tolerated, itching/burning and redness were common adverse drug events, all the events reported were mild in nature and did not warrant any cessation of therapy or change of therapy. Conclusion: Cyclosporine 0.1% + artificial tears 0.5% and artificial tears 0.5% topical therapy caused improvement in moderate-to-severe dry eye condition. However, combination treatment was more effective than artificial tears alone, therefore, suggesting its clinical superiority in the improvement of overall symptoms of dry eye in the patients after cataract surgery.

Trends in Medicare spending on topical immunomodulators and chemotherapies

Trends in Medicare spending on topical immunomodulators and chemotherapies

Interferon alpha-2a as alternative treatment for conjunctival squamous cell carcinoma

Abstract Case report A 35 year-old male patient with a history of HIV infection characterized by progressive tumor growth in bulbar conjunctiva of the left eye, corresponding to conjunctival squamous cell carcinoma that responded to treatment with interferon alpha-2a. Discussion Interferon alpha-2b has been used at conjunctival level as a topical immunomodulator treatment, with complete remission of epithelial neoplasms being observed. However, there have not been any previous publications on the use of interferon alpha-2a, which differs from interferon alpha-2b in a single amino acid, for the treatment of conjunctival squamous cell carcinoma.

Vitiligo: An Update on Pathophysiology and Treatment Options.

The pathophysiology of vitiligo is becoming increasingly clarified. In non-segmental vitiligo, early factors include activation of innate immunity, inflammasome activation, oxidative stress, and loss of melanocyte adhesion. Nonetheless, the main mechanism leading to non-segmental vitiligo involves an immune-mediated destruction of melanocytes. Anti-melanocyte-specific cytotoxic T cells exert a central role in the final effector stage. Genetic research revealed a multi-genetic inheritance displaying an overlap with other autoimmune disorders. However, some melanocyte-specific genes were also affected. Segmental vitiligo carries a different pathogenesis with most evidence indicating a mosaic skin disorder. Current management includes topical corticosteroids and immunomodulators. Narrow-band ultraviolet B can be used in patients not responding to topical treatment or in patients with extensive disease. Pigment cell transplantation offers an alternative for the treatment of segmental vitiligo or stable non-segmental lesions. Recent findings have revealed new targets for treatment that could lead to more efficient therapies. Targeted immunotherapy may halt the active immune pathways, although combination therapy may still be required to induce satisfying repigmentation. A recently established core set of outcome measures, new measurement instruments, and biomarker research pave the way for future standardized clinical trials.

Interferón alfa-2a como tratamiento alternativo para el carcinoma conjuntival de células escamosas

Case reportA 35 year-old male patient with a history of HIV infection characterized by progressive tumour growth in bulbar conjunctiva of the left eye, corresponding to conjunctival squamous cell carcinoma that responded to treatment with interferon alpha-2a. DiscussionInterferon alpha-2b has been used at conjunctival level as a topical immunomodulator treatment, with complete remission of epithelial neoplasms being observed. However, there have not been any previous publications on the use of interferon alpha-2a, which differs from interferon alpha-2b in a single amino acid, for the treatment of conjunctival squamous cell carcinoma.

Individualize treatment for vernal keratoconjunctivitis based on clinical features and personal preferences

Due to the lack of clarity regarding the pathogenesis of vernal keratoconjunctivitis, the treatment of this condition is challenging. The therapeutic regimen should be selected from among the many options (e.g. oral and/or topical mast-cell stabilizers, antihistamines, corticosteroids, and immunomodulators) based on the clinical features of the disease, personal preferences of the patient and clinical experience of the prescriber. Moderate-to-severe vernal keratoconjunctivitis may require topical corticosteroid treatment during the acute phase, followed by topical ciclosporin or tacrolimus for long-term management.

The cost of topical immunomodulator therapy in Medicare patients varies by prescriber specialty

Topical immunomodulators (TI)-including corticosteroids, calcineurin inhibitors, and vitamin D analogues-are commonly prescribed in multiple specialties, but cost comparisons are lacking. To evaluate differences in costs of TI across specialties and determine associated variables. A cross-sectional study was performed using the Centers for Medicare & Medicaid Services 2008 and 2010 Prescription Drug Public Use Profiles, which contain 100% of drug claims made by Medicare beneficiaries. Branded drugs cost an average of $174.02 more than generics per 30-day supply (P<.001). Differences in health insurance benefit phase, drug choice, brand name, and coverage type were the greatest determinants of patient cost (P<.001). Prescriptions for low-, medium-, and high-potency TI from specialists (mostly dermatologists) cost more than those from family medicine, internal medicine, and psychiatry/neurology physicians; total costs of a 30-day supply from a specialist differed from family and internal medicine physicians by $7.36-$14.57, and patient costs were higher for specialists by $1.69-$3.16 (P<.01). Brand names were prescribed 8% of the time by specialists and 1.4%-3.1% by nonspecialists. We were unable to adjust for some confounders of cost, such as medication weight or treated body area, and the data does not reflect previous treatment failures or use by non-Medicare patients. The costs of TIs prescribed by specialists (primarily dermatologists) are higher than those prescribed by primary care physicians and could be reduced by choosing more generics within the respective potency classes.

Clinico-epidemiological study of tinea incognito with microbiological correlation.

Tinea incognito is a dermatophytic infection with a clinical presentation that is modified due to previous treatment with topical or systemic steroids, as well as topical immunomodulators. It tends to mimic other dermatological conditions. To evaluate the various clinical manifestations, sites, predisposing factors and causative agents of tinea incognito. A prospective observational study was done on one hundred clinically suspected cases of tinea incognito, with a history of topical or systemic steroid use for a period of at least six weeks. They were subject to direct microscopy and fungal culture, and re-evaluated at the end of the third and sixth week. Eczema-like conditions were the most common clinical manifestation, followed by inflammatory, autoimmune and infective conditions. The face was the most commonly affected site. Direct microscopy was positive in 85% of cases, and fungal culture was positive in 63% of cases. Trichophyton rubrum was the most common species isolated. Pharmacists were responsible for 78% of tinea incognito cases, and betamethasone dipropionate was the most common drug used. As this was a hospital outpatient-based study, cases with severe systemic problems could have attended other departments. Cases involving the hair and nails were negligible. Tinea incognito is a commonly encountered, yet poorly reported entity in the study population. An increased level of awareness and vigilance on the sale of steroid containing compounds will help control this dermatological condition.

Allergic manifestations of contact lens wearing.

Contact lens-induced papillary conjunctivitis (CLPC) is a common ocular allergic disease in contact lens wearers. In its more severe form, it can cause giant papillary conjunctivitis, resulting in contact lens intolerance and the need to discontinue the use of contact lenses. This review presents the pathogenesis, clinical manifestations and management guidelines of this common disorder. Different types of contact lenses are associated with differences in the severity of CLPC. Refitting patients with silicone hydrogel contact lenses or with daily disposable contact lenses may improve the signs and symptoms of CLPC. The recent introduction of the topical immunomodulatory agent tacrolimus in other severe allergic eye diseases may apply in suppressing the allergic inflammation in CLPC as well. CLPC is a common ocular disorder in contact lens wearers, with a significant impact on the quality of vision. It should be promptly recognized by healthcare practitioners and managed by modifications of the types and wearing schedules of contact lenses, as well as novel treatment options with topical immunomodulators.

Effectiveness and safety of topical tacrolimus monotherapy for repigmentation in vitiligo: a comprehensive literature review.

Thus far, several small studies and case reports on the use of topical immunomodulators in vitiligo have been published. We undertook a comprehensive literature review, searching for studies evaluating clinical response to tacrolimus topical therapy for vitiligo. A search was performed on PubMed/Medline using the term “vitiligo”, combined with “topical” and “ointment”. Our inclusion criteria were: use of tacrolimus ointment as monotherapy to treat vitiligo. We found 29 studies from 2002 to 2014. Overall, 709 patients were treated in 29 studies. Pooling the lesions, 50% repigmentation of vitiligo patches was never achieved before 2 months of treatment, with a peak after 6 months of therapy. The best results were obtained on lesions of the cephalic region, especially the face, with tacrolimus 0.1% ointment two times daily. The percentage of non-responsive patients ranged from 0% to 14%. Treatment was generally well-tolerated; only localized adverse effects were reported. Our objective was to verify the effectiveness and safety of tacrolimus ointment monotherapy. It has good efficacy and tolerability. At present, only small trials and case series are available in the literature. Further, standardized investigations on a larger number of patients are needed.

Effect of Topical Tacrolimus on Vitiligo in Children

Background: Considering safe treatment modalities for children with vitiligo, search for newer therapeutic agents continues. Hence, new immunomodulatory agents such as calcineurinantagonists, frequently referred to as topical immunomodulators (TIMs) have recently been introduced as new promising tools to treat acquired hypopigmentary disorders. Tacrolimus is safe in treating children due to lack of skin atrophy and less data are available on effect of topical tacrolimus on vitiligo.Objective: To see the effect of topical tacrolimus on vitiligo in children.Materials and Methods: This prospective study was done in outpatient department of Dermatology and Venereology, Chittagong Medical College Hospital (CMCH), Bangladesh. Clinically diagnosed vitiligo patients of up to 12 years age visiting Skin &amp; VD OPD, CMCH during study period were the study population (total 30). The study was carried out from November 2007 to April 2008.Results: A total of 30 patients, 13 (43.33%) males and 17 (56.66%) females with focal, segmental or generalized vitiligo were studied. Seventy percent of study subjects were from 7–12 years of age. Topical tacrolimus 0.03% ointment was administered twice daily for 12 weeks to each patient. Repigmentation was complete (&gt;75%) in 43.33% cases (13/30), was moderate (50–75%) in 33.33% (10/30), mild (&lt;50%) in 13.33% (4/30). Clinical adverse effects were noted in 6.67% (2/30) of cases where pruritus was in 3.33% (1/30) and burning in 3.33% (1/30). None of the reactions was severe, all were mild and well-tolerated and most occurred within the first month of initiation of treatment and resolved with continued use of drug and completely cured after the treatment completed. Nobody had to discontinue the therapy for side effects.Conclusion: In conclusion, tacrolimus ointment may be a rapidly efficacious and safe option for the treatment of vitiligo in children. The ease of topical self-administration with minimal side effects makes this novel immunomodulatory agent a promising addition to the therapeutic armamentarium for vitiligo in children.J Enam Med Col 2016; 6(1): 33-37

Multicenter questionnaires on the current management of atopic dermatitis in Korea

Purpose: The effective management of atopic dermatitis (AD) adjusted to individual clinical courses and demands can be challenging to both patients and physicians. Understanding of actual situations, experienced and perceived by patients with AD and their caregivers, is essential to improve clinical outcomes and satisfaction in real practice.Methods: This multicenter survey was conducted in patients with AD or their caregivers from 9 centers with questionnaires on diagnosis and management of AD.Results: A total of 324 patients and caregivers participated in the study. Most of the AD cases were initially diagnosed by physicians (80.6%), followed by self-diagnosis. Patients and caregivers thought that allergic substances, such as house dust mites, food, and pollutants, are responsible for AD development; moisturization, environmental control, and improvement of the body constitution are important for AD management. Allergy tests were performed in 194 patients (59.9%), but allergen avoidance strategy was instructed in only 81 subjects (41.8%). Major topical medications were steroids (81.8%) and topical immunomodulators (34.3%), while systemic medications were steroids (42.6%), antihistamines (36.4%), and cyclosporins (2.8%). One hundred eighty-one subjects (55.9%) had received complementary alternative medicine, including Oriental medicine. Many subjects desired to receive individualized management, use of specialized institutions for AD as well as evidence-based, effective, sustainable treatment.Conclusion: Our findings suggest that there may still be an unmet need for patients with AD in real practice. Personalized, evidence-based, and multidisciplinary approaches, including patient education, should be implemented for good outcomes. (Allergy Asthma Respir Dis 2016:4:271-275)

Nonsteroidal Topical Immunomodulators in Allergology and Dermatology.

The purpose of this study was to review currently available literature data concerning pathomechanisms of action, indications, treatment efficacy, as well as side effects of nonsteroidal immunomodulators used in dermatology, primarily for the treatment of allergic dermatoses. MEDLINE search was undertaken using the key words “Topical Immunomodulators, Dermatology and Allergy”. Full articles, and nothing but full articles, were used.

Topikal %1 Pimekrolimus Tedavisine Cevap Veren Bir Alopesi Areata Olgusu

Alopecia areata is a nonscaring,autoimmune,inflammatory disease,hair loss on tha scalp,and/or body.Etiopathogenesis of alopecia areata is still unknown but it's focuses on such as emotional stress,immunologic factors,neurologic factors,infections and genetic predisposition. Topical corticosteroids,topical immunomodulators,minoxidil,tacrolimus, intralesional corticosteroids,systemic corticosteroids and cyclosporin are used in the treatment of alopecia areata. In this article,we presented a case of alopecia areata which is responded to topical 1% pimecrolimus.

Systemic Immunosuppression in High-Risk Penetrating Keratoplasty: A Systematic Review.

Cornea transplantation has a high success rate and typically only requires topical immunomodulation. However, in high-risk cases, systemic immunosuppression can be used. We conducted a systematic review on the efficacy and side effects of systemic immunosuppression for high-risk cornea transplantation. The study population was 18 years old or older with a high-risk transplant (two or more clock hours of cornea vascularization or a previous failed graft or a graft needed because of herpes simplex keratitis). A comprehensive search strategy was performed with the help of an information specialist and content experts from ophthalmology. All study designs were accepted for assessment. Level 1 and level 2 screening was performed by two reviewers followed by data abstraction. Forest plots were created whenever possible to synthesize treatment effects. Quality assessment was done with a Downs and Blacks score. From 1,150 articles, 29 were ultimately used for data abstraction. The odds ratios (ORs) for clear graft survival in cyclosporine and controls were 2.43 (95% CI: 1.00 - 5.88) and 3.64 (95% CI: 1.48 - 8.91) for rejection free episodes. Mycophenolate mofetil (MMF) significantly improved the rejection free graft survival rates at 1 year (OR: 4.05, 95% CI: 1.83 - 8.96). The overall results suggested that both systemic cyclosporine and MMF improved 1-year rejection free graft survival in high-risk keratoplasty. Cyclosporine also significantly improved clear graft survival rates at 1 year; however, there were insufficient data to analyze the same in the MMF group. Higher quality studies are needed to understand this issue better.

Mediators of Chronic Pruritus in Atopic Dermatitis: Getting the Itch Out?

For centuries, itch was categorized as a submodality of pain. Recent research over the last decade has led to the realization that itch is in fact a separate and distinct, albeit closely related, sensation. Chronic itch is a common complaint and has numerous etiologies. Various receptors (TRPA1, TRPV1, PAR2, gastrin-releasing peptide receptor (GRPR), Mas-related G proteins), secreted molecules (histamine, nerve growth factor (NGF), substance P (SP), proteases), and cytokines/chemokines (thymic stromal lymphopoietin (TSLP), IL-2, IL-4, IL-13, and IL-31) are implicated as mediators of chronic pruritus. While much remains unknown regarding the mechanisms of chronic itch, this much is certain: there is no singular cause of itch. Rather, itch is caused by a complex interface between skin, keratinocytes, cutaneous nerve fibers, pruritogenic molecules, and the peripheral and central nervous systems. Atopic dermatitis is one of the most itchy skin dermatoses and affects millions worldwide. The sensation of atopic itch is mediated by the interplay between epidermal barrier dysfunction, upregulated immune cascades, and the activation of structures in the central nervous system. Clinicians are in possession of an arsenal of different treatment options ranging from moisturizers, topical immunomodulators, topical anesthetic ion channel inhibitors, systemic immunomodulators, as well as oral drugs capable of reducing neural hypersensitization. Emerging targeted therapies on the horizon, such as dupilumab, promise to usher in a new era of highly specific and efficacious treatments. Alternative medicine, stress reduction techniques, and patient education are also important treatment modalities. This review will focus on the mediators of chronic pruritus mainly associated with atopic dermatitis (atopic itch), as well as numerous different therapeutic options.

The Clinical Efficacy of Azathioprine in Korean Patients with Atopic Dermatitis.

Dear Editor: Atopic dermatitis (AD) is a chronic, distressing disease often requiring systemic treatment for disease control1. Drug candidates for AD, however, are limited; the long-term use of systemic steroid raises concerns for metabolic adverse effects, and cyclosporine has potential nephrotoxicity and is contraindicated in uncontrolled hypertensive patients. Azathioprine, an imidazole derivative of 6-mercaptopurine, is one of the alternative choices in the treatment of recalcitrant AD. Yet, its efficacy in AD patients has not been thoroughly investigated in Asian population. From a computerized institutional database, we identified AD patients who underwent treatment with azathioprine from December 2009 to January 2011. A total of 20 patients were included (16 men, 4 women; mean age, 28.65±9.51 years; range, 13~43 years). Azathioprine was started at a dose of 100 mg/day. All patients were allowed to take antihistamine and topical steroids for symptomatic control and the management of localized lesions. The mean duration of azathioprine treatment was 22.20±19.85 weeks. Overall, compared with baseline, improvements were observed in the eczema area and severity index (EASI) score from 26.12±3.20 to 15.15±3.05 (p<0.017) (Fig. 1). On the visual analogue scale, the degree of pruritus decreased from 7.35±1.66 to 4.10±2.89 (p<0.001) along with a decrease in loss of sleep from 6.55±1.88 to 3.10±2.86 (p<0.001) (Fig. 2). Fig. 1 Change in the eczema area and severity index (EASI) score before and after azathioprine treatment (mean treatment duration, 22.20±19.84 weeks). There was a 42% reduction in the EASI score from the baseline (p<0.017). *Statistically significant ... Fig. 2 Changes in pruritus and loss of sleep (LOS) before and after azathioprine treatment (mean treatment duration, 22.20±19.84 weeks). On the visual analogue scale, the degree of pruritus decreased from 7.35±1.66 to 4.10±2.89 (p<0.001), ... When azathioprine was insufficient in controlling flare-ups, the patients were prescribed with systemic steroid as a rescue drug. In our review, 40% (8 of 20) of the patients needed a rescue drug during the course of azathioprine treatment. After the discontinuation of azathioprine, 45% (9 of 20) of the patients were able to remain on a minimal disease status with only antihistamine, topical immunomodulators, or topical steroids. In this study, we observed that after an average of 22.20±19.84 weeks of azathioprine treatment, 55% (11 of 20) of the patients reported excellent outcome according to Investigator's Global Assessment of clinical response. Our result was comparable to the 60% remission rate achieved in a study group of 37 patients treated with azathioprine during an 18-year period2. The decrease of EASI score in our study was higher than in previously reported placebo-controlled studies on azathioprine (26%3 or 37%4 reduction in severity). However, the improvement rate should take into consideration those who took rescue drugs. For the adverse effects, there were no hypersensitivity reactions. Also, regular monitoring of complete blood count and routine chemistry did not show noticeable results. Although we have treated patients tolerant to 100 mg/day azathioprine for an average period of 88 weeks, this study has major limitations as there is no control group. The absence of a control group can both over- and underestimate the judgment on the efficacy of azathioprine. Nevertheless, decrease in the EASI score and improvement in subjective symptoms should provide some credentials for the clinical efficacy of azathioprine in AD and raise a suggestion that it can be an appropriate candidate for adult Asian AD patients who cannot use or are not responsive to cyclosporine.

A Case Report of Eyebrow Basal Cell Carcinoma Successfully Treated with 5% Imiquimod Cream

3 , Seoul, Korea Purpose: Basal cell carcinoma is the most common malignant neoplasm of the skin. Periorbital basal cell carcinoma needs to be treated for cosmetic improvement and prevention of intraorbital invasion. Although surgical excision is a standard treatment, nonsurgical treatment using imiquimod cream, a topical immunomodulator, has been attempted. The authors report the first case of periorbital basal cell carcinoma successfully treated with imiquimod cream; to the best of our knowledge, similar cases have not been published to date in the Korean ophthalmology journals. Case summary: A 73-year-old female visited our hospital for treatment of a biopsy-proven basal cell carcinoma in the right eyebrow. A flat, elevated, 1 x 1 cm-sized mass having central indentation was observed in the centromedial area of the right eyebrow. She was treated with 5% imiquimod cream once daily at night, 5 days per week for 6 weeks. Eight weeks after the treat- ment with imiquimod cream was discontinued, the mass was flattened and the cilia began to grow on the mass site. Under the impression of a partial regression, an additional 4 weeks of application was recommended. The mass disappeared more and her eyebrow became more normal. At the final follow-up 31 months after treatment, her right eyebrow appeared normal. Conclusions: Imiquimod cream may be a useful medication which can be used for complex periorbital basal cell carcinomas that are difficult to reconstruct after resection or surgical candidates with poor general condition. J Korean Ophthalmol Soc 2015;56(11):1789-1793

Topical immunomodulators in the management of allergic eye diseases.

Allergic eye diseases comprise a spectrum of diseases, with each condition being characterized by a complex immunopathology. The more severe and chronic conditions, such as vernal keratoconjunctivitis and atopic keratoconjunctivitis, involve predominantly mast cells and eosinophils, while also being associated with a preponderance of T cells. Treatment with topical antihistamines or mast cell stabilizers is often unsatisfactory, and therapy depends on topical corticosteroids. Corticosteroids have significant side-effects with long-term use; therefore, they appear to be more appropriate for short-term pulse therapy. Immunomodulatory agents can also be used to inhibit T-cell activation and show encouraging results among patients with severe allergic eye conditions. The present review is an attempt to present a coherent picture of the recent investigations of topical immunomodulatory agents' therapy in severe allergic eye diseases, especially cyclosporine A and tacrolimus, and their mechanisms of action. Immunomodulatory agents are commonly indicated for the treatment of severe and prolonged allergic conjunctivitis. This article reviews the recent studies of these drugs and the development of immunomodulatory treatments for severe allergic eye diseases. Cyclosporine A and tacrolimus are currently available for the treatment of severe allergic conjunctivitis. These agents have led to improved therapeutic results for patients with severe and chronic allergic eye diseases.