New Developments in Hormonal Therapy for Acne

J. K. L. Tan, MD, FRCPC

Abstract
Oral contraceptives (OCs) are a valuable option for the treatment of women with acne. The use of OCs can be considered across the spectrum of acne disease severity in women. In Canada, three preparations are approved for mild-to-moderate acne, and a fourth is indicated for severe acne. These formulations contain estrogen in the form of ethinyl estradiol and a progestin. In Canada, the most recently approved OC is ethinyl estradiol 0.03mg and drospirenone 3mg (Yasmin, Bayer). With the accumulating evidence on the efficacy and safety of drospirenone-containing hormonal preparations, this formulation provides dermatologists with a new treatment option for acne and other hyperandrogenic disorders.

For many years, oral contraceptives (OCs) have been used by dermatologists as a treatment option for women with acne. OCs that are indicated for use in acne are effective across the spectrum of disease severity :

1. in mild acne as an adjunct to topical therapy for female patients desiring contraception

1. in moderate acne as a form of systemic therapy

1. in severe acne

1. as a primary form of therapy

1. as one of two preferred forms of contraception in women treated with systemic isotretinoin.

From their inception, these preparations have evolved to include less estrogen and incorporate progestins with less intrinsic androgenicity. These modifications were undertaken to reduce the potential risk of thromboembolic events, hepatic tumors, hypertension, altered glucose metabolism, and androgenic side-effects.

OCs for the Treatment of Acne
In Canada, four hormonal preparations are presently indicated for the treatment of acne. These preparations all contain estrogen and progestins with either minimal androgenicity (i.e., ethinyl estradiol/ norgestimate, and ethinyl estradiol/ levonorgestrel) or antiandrogenic potential (i.e., ethinyl estradiol/ cyproterone acetate, and most recently, ethinyl estradiol/ drospirenone). Their demonstrated efficacy and long-term safety profile advocate their use in various grades of acne in women. Evidence supporting the use of these agents in acne was recently reviewed in the Journal of Cutaneous Medicine and Surgery, and is summarized briefly here.

Ethinyl Estradiol/ Norgestimate (Ortho Tri-Cyclen
Ethinyl estradiol 0.035mg with norgestimate in increasing doses, 0.180mg/ 0.215mg/ 0.250mg (Ortho Tri-Cyclen, Ortho- McNeil), was shown to be efficacious in moderate facial acne in two randomized placebo-controlled trials involving 324 subjects who were treated for 6 cycles. Significant improvements in lesion counts and investigator global assessment scores were observed. Inflammatory lesions were reduced by 56%, noninflammatory lesions by 41%, and 32% achieved excellent improvement. Norgestimate has low intrinsic androgenicity with low binding affinity for androgen receptors, whereas it is strongly selective and avidly bound to progesterone receptor sites.

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Management and Treatment of Pruritus

P. Lovell, RN, BScN; R. B. Vender, MD, FRCPC

Abstract
Pruritus, or itch, is a common sensation that causes a person to want to scratch. It is a complex process that may negatively impact quality of life and commonly occurs with skin disorders such as atopic dermatitis and urticaria. It could also be a symptom related to an underlying disease process such as cholestasis or hyperthyroidism, or simply be caused by dry skin, especially in the cold, winter months. Therapy is often aimed at eliminating the underlying cause first, followed by the management of the itchy sensation. Treatment may include prescription and over-the-counter (OTC) medications, herbal remedies, hydrotherapy, phototherapy, and ultraviolet therapy. This overview provides information regarding the various management and treatment options for pruritus.

Pathophysiology of Pruritus
Pruritus is a complex process that involves the stimulation of free nerve endings found superficially in the skin. Thesensation of pruritus is transmitted through the C-fibers in the skin to the dorsal horn of the spinal cord, and then, via the spinothalamic tract to the cerebral cortex for processing. Many chemicals have been found to be pruritogenic, therefore causing the itch sensation, including histamine, serotonin, cytokines, and opioids. There are six categories of pruritus: dermatologic, systemic, neurogenic, psychogenic, mixed, and other. Various treatment and management options exist depending on the category or cause.

Treatment
Treatment of pruritus can be categorized in several ways. A common method of grouping the various options is causativevs. symptomatic treatment. Causative treatment involves finding the underlying disorder and then correcting it, thereby eliminating the itch sensation. Symptomatic treatment involves substituting another sensation for the itch, using methods such as cooling, heating, or counter irritation (e.g., scratching). Symptomatic treatment can be used in addition to treating the underlying disease process in order to provide earlier relief. Most of the available treatment options are categorized under symptomatic therapy and management.

Prescription Medications
Prescription medications include topical and systemic antihistamines, corticosteroids, local anesthetics, and topical immunomodulators, among others. Some lower concentration preparations of these medications are available OTC.

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Dermatological Management of Human Immunodeficiency Virus (HIV)

B. L. Bartlett, MD, M. Khambaty, MD, N. Mendoza, MSc; A. M. Tremaine, MD, A. Gewirtzman, MD,S. K. Tyring, MD, PhD, MBA.

Abstract
Atypical presentations of typical dermatological conditions are common in human immunodeficiency virus (HIV). This article will focus on three specific topics: eosinophilic folliculitis, psoriasis, and cutaneous mycoses. Their unique presentations in HIV and treatments are discussed.

Introduction
Despite attempts at increasing awareness of HIV and its transmission, this infection continues to spread and remains asignificant cause of morbidity and mortality worldwide. As of 2003, there were an estimated 1 million people living in the US with HIV infection, and nearly 40,000 cases were diagnosed in 2005. HIV infection affects nearly every organ system in the body, including the skin. HIV-infected patients can pose diagnostic challenges, as their altered immune status may lead to atypical presentations of common cutaneous diseases, as well as the occurrence of uncommon or opportunistic skin disorders.

Management of cutaneous disease in sero-positive patients can also be challenging, as the dermatological manifestations may be more severe, may recur with greater frequency, and may be refractory to standard treatment. The addition of highly active antiretroviral therapy (HAART) further complicates the picture as other dermatologic manifestations may arise as part of the immune reconstitution phenomenon. The scope of issues encountered in HIV-positive patients is too broad to discuss in its entirety. This article will focus on three diseases and their management: eosinophilic folliculitis, psoriasis, and cutaneous mycoses.

Eosinophilic Folliculitis
Eosinophilic folliculitis (EF) is seen commonly in HIV with CD4 cell counts of less than 250-300/mm3. It presents as recurrent, pruritic, erythematous papules and pustules that are usually distributed on the face, shoulders, upper back, and upper extremities. The pruritus associated with EF can be severe and debilitating. Its etiology is not well elucidated, but some theories propose an infectious derivation. EF is an example of a dermatosis that is associated with immunereconstitution. It is described as a phenomenon wherein HAART triggers a generalized immune activation as viral loads decrease and CD4 lymphocytes increase. Studies have shown that EF typically flares shortly after starting antiretroviral therapy, but will resolve from 3 weeks to several months later. Clinicians should warn patients with EF that after starting HAART, their skin will likely worsen initially, then improve. EF can be difficult to manage, as response to treatment is variable and it tends to recur once treatment is discontinued. Various treatments have been employed, including: isotretinoin, UVB phototherapy, itraconazole, and metronidazole, among others, with contrasting results. The treatment of EF with potent topical corticosteroids is reportedly effective, but is accompanied by skin atrophy and hypopigmentation.

This can be a problem given the distribution of EF on the face, and can be especially challenging in dark-skinned individuals. A relatively recent case study showed promising results with topical tacrolimus. Subjects who applied daily topical tacrolimus 0.1% to the face had an average lesion clearance time of 2.6 months with an absence of residual scarring. The average remission of 12.3 months was seen in subjects with well controlled viremia on HAART. The associated pruritus subsided within days. Given these promising results and the relative safety of topical tacrolimus, clinicians may want to consider this as an alternative to corticosteroids, which can cause hypopigmentation and scarring in darkskinned patients, resulting in potential disfigurement.

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Current Concepts in the Treatment of Recurrent Aphthous Stomatitis

Altenburg, MD; C.C. Zouboulis, MD

Abstract
The treatment of recurrent aphthous stomatitis (RAS) still remains nonspecific and is based primarily on empirical data. The goals of therapy include the management of pain and functional impairment by suppressing inflammatory responses, as well as reducing the frequency of recurrences or avoiding the onset of new aphthae. For common forms of RAS, standard topical treatment options that provide symptomatic relief include analgesics, anesthetics, antiseptics, anti-inflammatory agents, steroids, sucralfate, tetracycline suspension, and silver nitrate. Dietary modifications may also support therapeutic measures. In resistant cases of benign aphthosis or aphthosis with systemic involvement, appropriate systemic treatment can be selected from a wide spectrum of immunomodulators that include colchicine, prednisolone, cyclosporine A, interferon-á, tumor necrosis factor-áantagonists, antimetabolites, and alkylating agents.

Introduction
Idiopathic aphthae are the most frequently occurring inflammatory lesions of the oral mucous membrane. Nosologically,the condition is clearly defined, but the sores are often difficult to differentiate from heterogeneously similar aphthoid ulcerations and mucosal erosions. Episodic aphthous attacks are characterized by painful lesions that range from the size of a pinhead up to several centimeters. Fibrin covered ulcerations with a hyperemic halo are typically visible on the oral mucous membrane, but they rarely appear in the genital region. Spontaneous healing is possible after many years. Common simple aphthae, with 3-6 attacks per year, heal rapidly, are not very painful, and are restricted to the oral mucosa.

They can be differentiated from complex aphthae (less than 5% of aphthosis cases), which are recurrent, present with few to unusual multiple lesions, are extremely painful, heal slowly, and can also occur in the genital region. Complex aphthosis requires the accurate diagnosis of a possible causal or associated condition, such as anemia, cyclic neutropenia, folic acid or iron deficiency, ulcus vulvae acutum, aphthous-like ulcerations in HIV positive patients, gastrointestinal diseases, such as Crohn's disease and ulcerative colitis, and Adamantiades-Behcet Disease (ABD). In ABD, which represents a malignant form of aphthosis, there is an increase in both the frequency of occurrence and severity of lesions. The diagnosis of ABD is based on several clinical criteria sets, of which the International Study Group Criteria are the most frequently used and the New International Criteria are the most recent.

Topical Therapy
Dietary and General Measures
Certain foods should be avoided as they appear to trigger the eruption of new aphthae and prolong the course of the lesions (e.g., foods that are hard, acidic, salty, or spicy, as well as nuts, chocolate, citrus fruits, and alcoholic or carbonated beverages). In addition, because surfactants and detergents can cause irritation, dental care products containing sodium lauryl sulphate should be avoided.

Local Anesthetics
Pain relief can be attained using topical lidocaine 2% gel or spray, polidocanol adhesive dental paste, or benzocainelozenges. Available combination preparations include a pump spray with tetracaine and polidocanol, and a mouth rinsesolution that uses benzocaine and cetylpyridinium chloride as the active ingredients. As well, anesthetic-containingsolutions, e.g., a viscous lidocaine 2% solution, can be applied carefully on the lesions.

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An Update on New and Emerging Options for the Treatment of Vitiligo

B. H. Mahmoud, MD, PhD; C. L. Hexsel, MD; I. H. Hamzavi, MD

Abstract
Vitiligo is an acquired leukoderma that results from the loss of epidermal melanocytes, and is characterized by macules and patches of depigmented skin. With a relatively high rate of prevalence, vitiligo occurs in localized, generalized, or segmental patterns; it can run a rapidly progressive course or remain stationary. The pathogenesis of vitiligo is not yet fully understood, but the autoimmune hypothesis is the most commonly accepted one, based on which, many treatment modalities have been described. Although many therapeutic options exist and new modalities are still emerging, treatment challenges persist, as not all patients respond to available therapies. Variables that affect the choice of treatment include the extent, distribution, and progression rate of the lesions. Another challenge is the lack of a standardized scoring system, which hampers the production of level 1a evidence studies for the treatment of this condition.

Introduction
The worldwide prevalence of vitiligo is estimated to range between 0.5% and 4%. These depigmented macules were first described more than 3,000 years ago in pre-Hindu Vedic and ancient Egyptian texts. The pathogenesis of vitiligo is complex and not yet fully understood, but it is believed to involve a combination of autoimmune, genetic, and environmental factors. The autoimmune hypothesis suggests that antibodies develop against melanocyte surface antigens. Gauthier, et al. recently proposed the melanocytorrhagy hypothesis, which is based on an in vivo observation of melanocyte detachment from the basal layer, followed by transepidermal migration, which in turn triggers melanocyte death. In addition, the neural, self-destruct, and biochemical hypotheses have also been proposed.

Evaluation of Therapeutic Options Based on Strength of Evidence
This review will primarily discuss the more recent studies on vitiligo with a high level of evidence. Reference will be made throughout the discussion regarding the strength of evidence as defined in Table 1 .

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