Combination topical therapy for the treatment of psoriasis

Dermatological research continues to move toward the goal of developing an effective psoriasis treatment that would rapidly clear lesions and provide long-term freedom from visible signs and symptoms. Currently, topical corticosteroids remain a pivotal treatment due to their effective anti-inflammatory properties; however, potential adverse effects associated with chronic application limit long-term continuous therapy. Vitamin D analogues provide another mechanism of action, reducing lesions through effects on both keratinocytes and on the cytokine environment. A topical combination of corticosteroid and vitamin D derivative appears to provide a balanced approach to psoriasis treatment. The development of clobetasol propionate foam 0.05% (clobetasol propionate foam/Olux) offers a convenient topical corticosteroid that can be used concomitantly, that is, immediately followed by application of calcipotriene ointment 0.005% (Dovonex). This regimen has been shown to offer an increased short-term efficacy compared with either agent alone. Continued application of calcipotriene ointment on weekdays supplemented by long-term clobetasol propionate foam pulse therapy on weekends appears to provide an enhanced maintenance of remission compared with calcipotriene monotherapy.     

A Rare Case of Pembrolizumab‐Induced Uveitis in a Patient with Metastatic Melanoma

Pembrolizumab, a programmed cell death protein 1 (PD‐1) inhibitor, is a humanized monoclonal antibody used in the treatment of metastatic or unresectable melanoma and advanced non–small cell lung cancer (NSCLC). We hereby report a case of pembrolizumab‐induced uveitis to increase practitioner awareness. A 78‐year‐old woman presented with onset of panuveitis after initiation of pembrolizumab therapy for metastatic melanoma. The patient received three cycles of therapy every 21 days, during which her symptoms progressively worsened. She was treated with topical and systemic corticosteroids, and further pembrolizumab was discontinued despite a good response to therapy. Pembrolizumab has been associated with rapid onset of ocular inflammation and uveitis. PD‐1 inhibitors mediate a T‐cell response against cancer cells; however, autoimmune complications have been reported. Incidence of pembrolizumab‐induced uveitis is reported to be < 1%. To date, three cases have been reported since its Food and Drug Administration approval in September 2014. Uveitis, if left untreated, may lead to permanent vision loss and ocular damage. Cases of immune‐mediated uveitis have been reported with cancer immunotherapies. Oncologists and ophthalmologists should be aware of this complication. With the increasing targeted pharmaceuticals in oncology, effective management of adverse events is necessary to ensure patient safety and optimal outcomes.     

Monilethrix treated with minoxidil

In literature many different therapies are proposed to treat Monilethrix, but a definitive therapy still doe not exist. We decided to treat four patients affected by Monilethrix, with topical minoxidil 2%, 1 ml night and day for 1 year. Minoxidil led to a an increase of normal hair shaft without any side effects in all the patients. Therefore topical minoxidil 2% could be considered a good therapy to treat Monilethrix.     

Topical minoxidil therapy for hair regrowth

The pathogenesis of hair loss, the postulated mechanisms of minoxidil action on hair growth, and clinical trials, adverse reactions, experimental formulations, and percutaneous absorption of topical minoxidil preparations are reviewed. Topical minoxidil seems to normalize hair follicles and increase blood flow to the scalp. In clinical trials of various formulations, results have varied. Improved hair growth occurred after four to six months of therapy; twice-daily application seems to be indicated. The most frequently reported adverse reactions are mild scalp dryness and irritation and, rarely, allergic contact dermatitis. Current recommendations are to reserve topical minoxidil for patients with normal cardiovascular status and to routinely monitor blood pressure, heart rate, and electrocardiographic changes. A new drug application is pending with FDA for use of topical minoxidil in androgenetic alopecia (male-pattern baldness), which is genetically determined and apparently stimulated by androgens. For alopecia areata, which involves hair loss on the body or scalp, usually patchy and of sudden onset, no reliable treatment has been found, although minoxidil may be efficacious in some patients. Minoxidil has generated new interest in hair-loss research. The etiology of hair loss must be better understood before more effective treatment regimens can be designed.     

Topical minoxidil. A preliminary review of its pharmacodynamic properties and therapeutic efficacy in alopecia areata and alopecia androgenetica

When minoxidil is administered orally for periods in excess of 1 month, hypertrichosis occurs as a side effect in a majority of patients. Consequently, topical minoxidil has been developed to try to improve hair growth in patients with alopecia areata and alopecia androgenetica. Preliminary studies have shown that topical minoxidil promotes cosmetically acceptable hair regrowth in a variable proportion of patients with alopecia areata. Data from a large multicentre trial indicate that cosmetically worthwhile results are achieved in about one-third of subjects with alopecia androgenetica after 1 year of treatment. A much higher proportion (about 80%) of patients with alopecia androgenetica exhibited some non-vellus hair regrowth after 1 year, and whether more of these patients would develop a cosmetically acceptable result with a longer treatment period is an important area of future investigation. Initial indications suggest that less severe disease is a predictor of likely response. Thus, topical minoxidil would seem to be a useful treatment modality for patients with alopecia androgenetica--a disease for which no other safe and effective drug therapy exists. Results from treating patients with alopecia areata with topical minoxidil, although encouraging, have been more variable and require further evaluation. Even though a number of questions remain to be answered about topical minoxidil (as would be expected at this stage in its development), it would seem to be the first available drug with the potential to promote substantial hair regrowth in these divergent diseases.     

Treatment of pyoderma gangrenosum with etanercept

We describe a patient with pyoderma gangrenosum (PG) whose lesions responded to etanercept therapy. This disease has been recognized for diverse underlying pathology and associated immune disturbances. Although the role of cytokines in pathogenesis is not fully understood, tumor necrosis factor alpha (TNF-alpha) may facilitate induction and maintenance of the disease. This is supported by the successful use of infliximab, a recombinant anti-TNF-alpha monoclonal antibody, in cases of PG associated with inflammatory bowel disease (IBD). Etanercept is a divalent recombinant fusion protein that binds soluble TNF-alpha. To our knowledge, the utility of etanercept for PG has not been reported. A patient with recalcitrant and widespread PG that was unresponsive to systemic corticosteroids was treated with etanercept. Rapid and complete clearing of the skin lesions was observed, and steroid taper to 5 mg/day was sustained for two months. Treatment was well-tolerated with no adverse reactions reported. CONCLUSIONS: Etanercept therapy offered rapid and complete resolution of all PG lesions. Such response supports the use of etanercept as a steroid-sparing agent in recalcitrant disease and suggests the role of TNF-alpha in pathogenesis of PG.     

Overdose of Rogaine Extra Strength for Men topical minoxidil preparation

CASE REPORT: Minoxidil is a potent arterial vasodilator used in the treatment of hypertension. A side effect, hypertrichosis, has prompted the marketing of a topical preparation, Rogaine, for the treatment of male-pattern baldness. Recently, a 5% solution of minoxidil became available over-the-counter as Rogaine Extra Strength For Men Hair Regrowth Treatment. We describe an oral overdose of minoxidil 3 g as the Rogaine Extra Strength preparation. Toxicity manifested as profound hypotension, requiring vasopressor support, intubation, prolonged tachycardia, and fluid overload with pleural effusions, requiring several days of therapy with furosemide. This is the largest reported ingestion of minoxidil and the first reported overdose of the extra strength 5% solution.     

Topical minoxidil: cardiac effects in bald man.

Systemic cardiovascular effects during chronic treatment with topical minoxidil vs placebo were evaluated using a double-blind, randomized design for two parallel groups (n = 20 for minoxidil, n = 15 for placebo). During 6 months of follow-up, blood pressure did not change, whereas minoxidil increased heart rate by 3-5 beats min-1. Compared with placebo, topical minoxidil caused significant increases in LV end-diastolic volume, in cardiac output (by 0.751 min-1) and in LV mass (by 5 g m-2). We conclude that in healthy subjects short-term use of topical minoxidil is likely not to be detrimental. However, safety needs to be established regarding ischaemic symptoms in patients with coronary artery disease as well as for the possible development of LV hypertrophy in healthy subjects during years of therapy.     

Topical minoxidil in the treatment of male pattern alopecia

Male pattern hair loss (androgenetic alopecia) is a common problem. In fact, it affects nearly all males to some degree. Expression of the disorder is variable, and while it is never life-threatening, it often becomes a major source of consternation. The biology of the process is poorly understood, and no current therapy can halt or reverse the process. Only cosmetic surgery, which is painful, time consuming, and expensive, has been effective. In the past 7 years, since it was noted that a patient taking minoxidil for hypertension had reversal of male pattern hair loss, awareness of a possible therapeutic role for topical minoxidil in the management of this disorder has grown among physicians, scientists, and the general public. It can be concluded from available data that topical application of minoxidil is effective in providing cosmetically satisfying thickening of hair in a select group of individuals with male pattern hair loss. The drug's mechanism of action remains obscure. No serious side effects have been demonstrated with its use, however, and it is therefore advised in selected patients.     

Hydrofluoric acid dermal exposure

A retrospective review of 237 consecutive cases of dermal exposure to dilute (6-11%) hydrofluoric acid (HF)- containing rust stain remover consumer products reported to the Rocky Mountain Poison and Drug Center during 1986 was done to evaluate the toxicity of these agents and the efficacy of topical treatment with calcium gluconate gel. In 148 cases (62%), failure to follow manufacturers' recommended safety procedures was the likely cause of exposure. 219 patients developed the following symptoms: dermal swelling, redness, or both (131, 55%); blistering (12, 5%); black discoloration under fingernails (12, 5%); or pain without reported dermal changes (64, 27%). Local complications were noted in 7 cases (3%) (infection, 4 cases; fingertip dermal necrosis, 3 cases). No systemic toxicity was noted. 116 patients (49%) received treatment with topical calcium gluconate gel; 53 were followed until complete resolution of symptoms. There appeared to be a relationship between earlier initial gel application and more rapid resolution of signs and symptoms. Some degree of dermal injury may be quite common following exposure to dilute (6-11%) HF-containing rust stain remover consumer products. Failure to follow manufacturers' recommended safety procedures may be responsible for many exposures. Treatment with topical calcium gluconate gel may be effective, and more rapid resolution of signs and symptoms may occur with earlier initiation of this therapy.     

Fatal Toxic Epidermal Necrolysis Associated with Minoxidil

Minoxidil is a direct-acting peripheral vasodilator for the treatment of symptomatic hypertension, or refractory hypertension associated with target organ damage, that is not manageable with a diuretic and two other antihypertensive drugs. The most frequent adverse events associated with minoxidil include hypertrichosis and cardiovascular events related to its powerful antihypertensive effect, and less frequently, rashes, bullous eruptions, and Stevens-Johnson syndrome (SJS). Evidence suggests that SJS and toxic epidermal necrolysis (TEN) are variants of a single disease with common causes and mechanisms, but differing severities. Epidermal detachment is mild in SJS, moderate in overlap SJS-TEN, and severe (> 30% of body surface area) in TEN. We describe a case of minoxidil-associated SJS that evolved into fatal TEN. A 69-year-old African-American woman with a history of chronic kidney disease was admitted to the hospital for a cerebrovascular accident and uncontrolled hypertension. On hospital day 12, oral minoxidil was added to her drug regimen. On day 23, she developed a maculopapular rash on her face that gradually diffused to her chest and back. Vesicles and papular lesions extended to her extremities and mucosal membranes; results of a skin biopsy revealed SJS. A positive Nikolsky's sign (blisters spread on application of pressure) was detected. On days 27–31, diffuse bullae developed with rash exacerbation. Skin detachment exceeded 30% and was consistent with TEN. The patient died on day 39. An evaluation of the causality and time course suggested that minoxidil was the most likely culpable drug, with a Naranjo adverse drug reaction probability scale score indicating that the likelihood of the association was possible (score of 3). The mechanism of this reaction has not been well elucidated. It may be related to an impaired clearance of the minoxidil metabolite, or an immune stimulation resulting in apoptosis and epidermis destruction. To our knowledge, this is the first case report of fatal TEN associated with minoxidil. This case report emphasizes the importance of monitoring for serious dermatologic reactions in patients receiving minoxidil therapy.     

Biographical Sketches of the Editorid Board Members of Cutaneous and Ocular Toxicology

Abstract

Hyperbaric oxygen has been reported to have a positive effect on the healing of radiation-induced scleral necrosis following pterygium excision. The influence of hyperbaric oxygen on healing of mitomycin C- and cautery-induced scleral necrosis was tested in a rabbit model. Scleral necrosis was induced by conjunctival excision to bare sclera, wound cauterization, and regular topical application of mitomycin C. The latter two maneuvers were made to obliterate episcleral vasculature and to prevent, as much as possible, conjunctival cell regrowth. A readily identifiable level of scleral necrosis was achieved at 45 days postconjunctival removal and oxygen therapy was begun. Six animals received hyperbaric oxygen treatment for 2 h per day at 2 atm 95% oxygen for 17 days while another six animals, with similar scleral lesions, remained at room air. Lesions were photographed at regular intervals from the initiation of oxygen therapy and assessed in a masked, independent manner by three evaluators. This evaluation indicated that hyperoxygenation was of apparent benefit in promoting healing of the necrotic lesion.     

Management of scalp psoriasis: guidelines for corticosteroid use in combination treatment

Scalp psoriasis is a frequent expression of the common skin disease psoriasis, and scaling and itching are the two major complaints. Topical treatments are the mainstay of the treatment of psoriasis of the scalp, with the vehicle as well as the active ingredient relevant to efficacy, tolerability and compliance. Vehicles can be shampoos, lotions, gels, foams, creams and more greasy ointments. Active ingredients are keratolytics, coal tar (liquor carbonis detergens), dithranol, corticosteroids and vitamin D3 analogues. Some effect has also been described from topical or systemic imidazole derivatives. Topical corticosteroids remain the mainstay in the treatment of scalp psoriasis. The effects are rapid, the formulations are patient friendly and the adverse effects seem limited, although no data are available to support safety during prolonged use (more than 4 weeks). Topical vitamin D3 analogues have been available for the treatment of psoriasis since 1992. In the lotion formulation in particular, vitamin D3 analogues are a patient friendly, tolerable and effective alternative to corticosteroids, although the effects are optimal after 8 weeks, in contrast to 2-3 weeks for topical corticosteroids. Facial irritation (often temporary) can also be a disadvantage of vitamin D3 analogues, although only a small proportion of patients stop treatment for this reason. All other treatment options for psoriasis, such as tazarotene, phototherapy and systemic treatment with methotrexate, acitretin and cyclosporin are often not indicated or not suitable for treatment of the scalp. In daily practice, to make a choice from the available therapeutic arsenal for psoriasis, each patient should be examined individually. Deteriorating factors have to be excluded. For scaling, keratolysis is the first step. Subsequently, active treatment can be chosen depending on the clinical picture. When the psoriatic lesions are mainly characterised by inflammation, anti-inflammatory drugs such as topical corticosteroids are indicated. When scaling is the more important clinical feature, vitamin D3 analogues are indicated. Generally, intermittently used topical corticosteroids alternating with vitamin D3 derivatives either combined or not with liquor carbonis detergens containing shampoo is the most suitable treatment for most patients. Because psoriasis capitis is a chronic disease, long term treatment should, in addition to medical advice, also provide patient support and motivation.     

Bexarotene gel: a new skin-directed treatment option for cutaneous T-cell lymphomas

Cutaneous T-cell lymphomas (CTCLs) are a relatively uncommon group of lymphoproliferative disorders in which a malignant population of T cells is localized to the skin at presentation. Of the 4 classic CTCL phases (patches, infiltrated plaques, tumors, Sézary syndrome), the majority of patients present with early stage patch or plaque disease, which can usually be effectively managed using skin-directed therapies. Traditional skin-directed therapies include topical corticosteroids, topical chemotherapeutic agents (mechlorethamine, carmustine), electron beam therapy (local and total skin), and phototherapy (UV-A, UV-B). Each of these has demonstrated efficacy in early stage disease; however, with the exception of topical corticosteroids, all have some disadvantages and are associated with significant adverse events, particularly secondary skin malignancies and skin damage. Bexarotene is a synthetic retinoid analog that selectively activates retinoid X receptors. In clinical trials, bexarotene gel demonstrated efficacy for the topical treatment of cutaneous lesions in patients with stage IA or IB CTCL who have refractory or persistent disease following other therapies or who cannot tolerate other therapies. Initial evidence indicates that bexarotene gel may be active as first-line therapy in early stage disease. Its role in combination with other treatments remains to be determined. Topical bexarotene gel is generally well tolerated and offers patients greater convenience compared with traditional skin-directed therapies, with a flexible administration regimen. The availability of bexarotene gel provides patients and physicians with a new skin-directed treatment option for early stage CTCL.     

Treatment options for a patient experiencing pruritic rash associated with transdermal testosterone: a review of the literature.

A 22-year-old man with hypogonadotropic hypogonadism was receiving monthly intramuscular injections of testosterone replacement therapy. The patient refused to self-administer the injections because of discomfort, so the therapy was switched to testosterone patches. He experienced a pruritic, macular, erythematous rash underneath the reservoir area of two different transdermal formulations, which did not improve after pretreatment with topical corticosteroids. Eventually, he tolerated application of a testosterone gel and his serum testosterone levels returned to normal after 1 month of therapy. Commercially available and investigational testosterone products and therapeutic monitoring guidelines for androgen replacement are reviewed.     

Simultaneous effects of tocopheryl polyethylene glycol succinate (TPGS) on local hair growth promotion and systemic absorption of topically applied minoxidil in a mouse model

In this study, topical minoxidil solutions supplemented with TPGS in cosolvent systems of various compositions consisting of water, alcohol, and polyethylene glycol 400 were designed to evaluate the efficacy of promoting hair growth after topical application and the safety in terms of the amount of minoxidil absorbed through the skin into the circulation using C57BL/6J mice as a model. The commercial product of 2% Regaine) was used as the positive control. The role, which sulfotransferase activity plays in hair growth with treatment using minoxidil, was determined as well. The results revealed that the addition of 0.5% TPGS was able to enhance the proliferation of hair, but an increase in the amount of TPGS to 2% led to deterioration in the enhancement of hair growth. At the higher added amount (2.0%) of TPGS, the promotion of hair growth was slightly reduced for both cosolvent formulations F1 (100% water) and F3 (100% PEG 400), whereas it was reduced to a greater extent for the cosolvent formulations F8-F10. In comparison, the influences of cosolvent compositions with TPGS amounts of 0.0 and 2.0% on the promotion of hair growth were similar. On the contrary, variability in the promotion of hair growth by different solvent formulations was minimal when the added amount of TPGS was 0.5%. In general, a relationship between hair growth and sulfotransferase activities after topical application of 2% Regaine and minoxidil formulations containing various amounts of TPGS was not demonstrated. Plasma concentrations of minoxidil with 2% Regaine were found to be greater than those of 2% minoxidil in those cosolvent formulations containing various amounts of TPGS, while showing insignificant differences among those 10 cosolvent formulations with a fixed amount of TPGS. A tendency for the plasma concentration of minoxidil to increase after the topical administration of minoxidil formulations containing the higher amount of TPGS (2%) was noted.     

Clinical observation on the treatment of oral lichen planus with total glucosides of paeony capsule combined with corticosteroids

IntroductionOral lichen planus (OLP) is a relatively common, chronic immune-mediated disease. The main treatment for OLP has been the administration of topical or systemic corticosteroids, but side effects have limited their use. We aimed to assess the effect and adverse reaction of total glucosides of paeony capsule (TGPC) in combination with corticosteroids for the treatment of OLP.MethodsEighty one patients with a confirmed clinical and histopathologic diagnosis of OLP (44 reticular OLP [ROLP] patients, 37 erythematous/erosive OLP [EOLP] patients) were enrolled. Patients were treated with topical or systemic corticosteroids, with or without 1200 mg TGPC in the ROLP and EOLP groups, respectively. Patients were followed for 6 months. The pain and severity of the lesions were recorded at the initial visit and monthly thereafter during the follow-up period.ResultsSeventy three of 81 patients completed the scheduled treatment period. In the ROLP patient group, combined treatment significantly reduced the visual analogue scale (VAS) at months 3, 5, and 6. The clinical signs (CS) of ROLP patients worsened during the follow-up period in control group. However, CS in the combined treatment group remained largely unchanged at months 4–6. In the EOLP patient group, the VAS decreased almost equally in patients with and without combined treatment at months 1–2, but continued to significantly decrease in the combined treatment group in months 4–6. The CS of the combined treatment group decreased gradually over time in the study period, with significantly lower scores in the treatment versus control group (which decreased slightly in the first three months, then remained almost unchanged during the following visits). The effective rates of combined treatment were statistically higher versus control groups both in ROLP and EOLP patients.ConclusionsTGPC is a safe and effective drug for OLP with rare side effects. Combined treatment of TGPC with corticosteroids shows a definite therapeutic effect. More than four months of medical treatment of TGPC is recommended to achieve the full effect.     

Preparation and in vivo evaluation of lecithin-based microparticles for topical delivery of minoxidil

Minoxidil is widely used for treatment of androgenic alopecia. Commercial products containing minoxidil are usually in solution form. Repeated applications of minoxidil solution can lead to adverse effects such as skin irritation and horniness. The aims of this study were to prepare lecithin-based microparticle in minoxidil solution for enhancement of minoxidil topical delivery and skin protection and evaluate the ability of lecithin on in vitro delivery, in vivo hair growth, and skin trouble improvement compared to commercial minoxidil solution. In in vitro skin permeation study, minoxidil solution containing lecithin microparticle showed higher skin penetration rate and higher retention of drug inside the skin compared to minoxidil solution without lecithin. After topical application of minoxidil solutions with or without lecithin to C57BL/6 mice, minoxidil 5% solution containing lecithin microparticle showed hair re-growth as efficient as commercial product of minoxidil 5% solution. It also significantly improved skin troubles while commercial product presented horny substance and crust formation. Therefore, the lecithin-based microparticle in minoxidil 5% solution has good ability to promote hair growth without adverse effects.     

Treatment strategies for recurrent oral aphthous ulcers.

The clinical features, etiology, and treatment of recurrent aphthous ulcers (RAU) are discussed. Aphthous ulcers are among the most common oral lesions in the general population, with a frequency of up to 25% and three-month recurrence rates as high as 50%. The ulcers, which usually occur on the nonkeratinized oral mucosa, can cause considerable pain and may interfere with eating, speaking, and swallowing. RAU is classified as minor, major, and herpetiform on the basis of ulcer size and number. The cause of RAU is idiopathic in most patients. The most likely precipitating factors are local trauma and stress. Other associated factors include systemic diseases and nutritional deficiencies, food allergies, genetic predisposition, immune disorders, the use of certain medications, and HIV infection. The primary goals of therapy for RAU are relief of pain, reduction of ulcer duration, and restoration of normal oral function. Secondary goals include reduction in the frequency and severity of recurrences and maintenance of remission. Topical medications, such as antimicrobial mouthwashes and topical corticosteroids, can achieve the primary goals but have not been shown to alter recurrence or remission rates. Systemic medications can be tried if topical therapy is ineffective. Levamisole has shown variable efficacy in reducing ulcer frequency and duration in patients with minor RAU. Oral corticosteroids should be reserved for severe cases of major RAU that do not respond to topical agents. Thalidomide is effective but, because of its toxicity and cost, should be used only as an alternative to oral corticosteroids. RAU can be effectively managed with a variety of topical and systemic medications.     

2%米诺地尔酊剂外用辅治斑秃的疗效观察

目的观察2%米诺地尔酊剂外用辅治斑秃的临床疗效。方法将120例斑秃患者随机分为观察组和对照组各60例。对照组给予基础对症治疗;观察组在对照组治疗基础上加用2%米诺地尔酊剂,并用生姜汁及生蒜外擦患处,每天2次,1个月为1个疗程。治疗后比较2组疗效及不良反应。结果观察组总有效率为93.3%高于对照组的75.0%,差异有统计学意义(P<0.01)。观察组出现头晕1例,对照组出现下肢水肿1例,经调整用药后均改善。结论 2%米诺地尔酊剂外用辅治斑秃可提高治疗效果,值得临床推广应用。