Arash Akhavan

Topical acne drugs: review of clinical properties, systemic exposure, and safety.

AbstractThis review examines the commonly available topical acne agents and factors that determine their percutaneous absorption. Reported and theoretical adverse effects from systemic exposure are detailed.The topical retinoid class, which includes tretinoin, adapalene and tazarotene, and the topical antibacterials, clindamycin and erythromycin, are regulated by prescription in most countries. Used appropriately, the above-mentioned drugs deliver, at most, miniscule amounts of active ingredient into the circulation. Clear-cut links to systemic toxicity in humans are practically nonexistent, except in the case of topical clindamycin, which has been associated with diarrhea rarely, and there have been 2 cases of pseudomembranous colitis reported. Birth defects have occurred in two patients treated with tretinoin and one patient treated with adapalene, but causation was not proven. Another prescription drug, 20% azelaic acid, is associated with relatively high systemic exposure, which is presumed innocuous because it is a normal dietary constituent whose endogenous levels are not altered by topical use.Benzoyl peroxide, salicylic acid, sulfur, and sodium sulfacetamide are available in concentrations of 2% or more in over-the-counter acne treatments and some prescription products. All of these agents are known to exhibit some degree of percutaneous absorption. They remain largely unregulated because, other than skin irritation, only local allergic contact dermatitis from benzoyl peroxide in about 2.5% of patients and rare local and systemic hypersensitivity reactions from sodium sulfacetamide have been reported. Salicylism has occurred using methyl salicylate ointments and high concentrations of salicylic acid on widespread areas of hyperkeratotic skin, but there are no known cases resulting from salicylic acid acne products.Caution is advised in special circumstances, such as during childhood, pregnancy, lactation and concomitant therapy with other drugs, because relevant studies are lacking. Animal data support avoidance of many topical agents, particularly known teratogens such as retinoids and salicylic acid, in pregnant women. Salicylate avoidance is advised during lactation, because aspirin use carries the risk of bleeding disorders in nursing infants.

Differential metabolic rates in prefrontal and temporal Brodmann areas in schizophrenia and schizotypal personality disorder.

In an exploration of the schizophrenia spectrum, we compared cortical metabolic rates in unmedicated patients with schizophrenia and schizotypal personality disorder (SPD) with findings in age- and sex-matched normal volunteers. Coregistered magnetic resonance imaging (MRI) and positron emission tomography (PET) scans were obtained in 27 schizophrenic, 13 SPD, and 32 normal volunteers who performed a serial verbal learning test during tracer uptake. A template of Brodmann areas derived from a whole brain histological section atlas was used to analyze PET findings. Significantly lower metabolic rates were found in prefrontal areas 44-46 in schizophrenic patients than in normal volunteers. SPD patients did not differ from normal volunteers in most lateral frontal regions, but they had values intermediate between those of normal volunteers and schizophrenic patients in lateral temporal regions. SPD patients showed higher than normal metabolic rates in both medial frontal and medial temporal areas. Metabolic rates in Brodmann area 10 were distinctly higher in SPD patients than in either normal volunteers or schizophrenic patients.

The relationship between atopic dermatitis and contact dermatitis

Atopic dermatitis (AD) and contact dermatitis are common eczematous disorders mediated through inflammatory mechanisms. As with other eczematous disorders, they are both characterized by a serous accumulation in the epidermis and a dermal inflammatory infiltrate, expressed clinically as erythema, with or without concomitant edema and/or blistering. AD is a recurrent, hereditary eczematous condition that typically begins in childhood, affecting patients with a personal or family history of hayfever, asthma, and/or chronic dermatitis. Multiple genetic abnormalities render atopics susceptible to flares of disease activity in the presence of environmental triggers including various allergens, as well as climate and temperature change. Exacerbation of AD can, however, occur in the absence of a known environmental stimulus. Contact dermatitis is an inflammatory condition caused by direct skin exposure to an offending chemical with or without a requirement for ultraviolet light. There are two distinct types of contact dermatitis: irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD). ICD is an inflammatory reaction caused by a chemical insult that results in direct cellular injury upon skin contact. The majority of cases of ICD are associated with soaps, detergents, solvents, acids, and alkali. There are two categories of ICD: acute reactions that develop minutes to hours after exposure to a very strong irritant chemical, and cumulative insult reactions, which follow repeated contact with milder irritants. Since ICD is essentially an injury, all individuals will develop an eruption when certain parameters of chemical concentration and frequency of exposure are exceeded. ACD, like AD, is an eczematous disease mediated through immune mechanisms. ACD is an acquired skin disorder that occurs at sites of contact with small chemical haptens in only those individuals who have been previously exposed to, and immunologically sensitized to, a particular chemical. In contrast to ICD, only a small percentage of the population develops an eruption when exposed to chemicals causing ACD. The most common chemical allergens causing the condition in North America include nickel sulfate, found in everything from keys to buttons on clothing, as well as the pentadecylcatechols, the active moiety in plants of the Rhus family, which include poison ivy, poison oak, and poison sumac. Active skin disease, such as ICD or AD, which disturb the integrity of the body’s epidermal barrier, can be predisposing factors for ACD, allowing easier access of potential chemical allergens to the immune system. Despite differing etiologies, AD and contact dermatitis have been the focus of many studies examining the potential association of the two conditions. In the past, it was believed that patients suffering from AD were less likely to suffer from ACD. However, more recent studies indicate that ACD is equally prevalent among atopics and nonatopics. Current research also indicates that AD patients may be more prone to suffer from ICD. Understanding the potential links between AD and contact dermatitis, and the parallel aspects of their pathogenesis, diagnosis, and treatment, can be helpful to clinicians caring for patients suffering from the disorders.

The treatment of atopic dermatitis with systemic immunosuppressive agents.

Atopic dermatitis (AD) is a chronic, relapsing skin disease that typically occurs in individuals with a personal or family history of atopy ie, hay fever, asthma, or AD itself. Typically beginning in early childhood, the disease affects approximately 7 to 17% of the pediatric population. Although in many cases there is moderation of the disease with increasing age, it may persist into adulthood in up to 60% of patients. AD can be managed in many patients with topical therapies, sometimes supplemented by systemic antibiotics, but some individuals, typically those with widespread disease or recalcitrant local disease that interferes with the quality of life, require more aggressive treatment. Management should embrace measures to control environmental “flare factors” such as house dust mites or in young children, certain foods. In addition, coincident skin infection, emotional distress, xerosis from dry ambient air or excessive bathing, and high temperatures causing sweating-induced exacerbations should be addressed with allergen avoidance, antibiotic therapy, relaxation techniques, bathing and skin hydration, humidification, and air conditioning, respectively. If control of flare factors combined with aggressive topical therapy or phototherapy fail to control symptoms of AD, a number of systemic immunomodulatory agents may play a role in treatment (Table 1). Because these agents have significant side effects, utmost care should be exercised in their use. It is also crucial to realize, particularly when contemplating the use of these agents in children, that none of them is approved for the treatment of AD in the United States. Informed consent, preferably in writing, for off-label use in the treatment of AD, should be obtained. Patients should be given written documentation of possible adverse effects and the treatment regimen should be tailored to each patient to limit overall exposure to the systemic agent. Although an extensive discussion of immunopathogenesis (see Kang et al, this issue) is beyond the scope of this paper, a basic understanding of the role of various immune cells and mechanisms in the causation of AD helps to clarify the rationale for using these agents.

Atopic Dermatitis : Systemic Immunosuppressive Therapy

Atopic dermatitis (AD) is a pruritic, relapsing skin disorder that negatively impacts the quality of life of those affected and that of their families. Treatment options for AD encompass a variety of emollients, topical corticosteroids, topical immunomodulators, phototherapy, and systemic agents. Such agents as systemic corticosteroids, cyclosporine, azathioprine, interferon-gamma, methotrexate, and mycophenolate mofetil have been shown to be efficacious in the treatment of moderate-to-severe AD but are not officially approved for this purpose. In this article, we review some of the data supporting efficacy of these medications and discuss some of the adverse events associated with their use.

The sensitivity and specificity of potassium hydroxide smear and fungal culture relative to clinical assessment in the evaluation of tinea pedis: a pooled analysis.

Background. There are relatively few studies published examining the sensitivity and specificity of potassium hydroxide (KOH) smear and fungal culture examination of tinea pedis. Objective. To evaluate the sensitivity and specificity of KOH smear and fungal culture for diagnosing tinea pedis. Methods. A pooled analysis of data from five similarly conducted bioequivalence trials for antifungal drugs was performed. Data from 460 patients enrolled in the vehicle arms of these studies with clinical diagnosis of tinea pedis supported by positive fungal culture were analyzed 6 weeks after initiation of the study to determine the sensitivity and specificity of KOH smear and fungal culture. Results. Using clinical assessment as the gold standard, the sensitivities for KOH smear and culture were 73.3% (95% CI: 66.3 to 79.5%) and 41.7% (34.6 to 49.1%), respectively. The respective specificities for culture and KOH smear were 77.7% (72.2 to 82.5%) and 42.5% (36.6 to 48.6%). Conclusion. KOH smear and fungal culture are complementary diagnostic tests for tinea pedis, with the former being the more sensitive test of the two, and the latter being more specific.

Intralesional Bleomycin for Warts: Patient Satisfaction and Treatment Outcomes.

Background: The treatment of warts is challenging with regards to both tolerability and efficacy. Objective: Ascertain the efficacy, tolerability, and patient satisfaction of intralesional bleomycin in the treatment of warts. Methods: Retrospective chart review followed by telephone interviews with patients from university-based dermatology referral centers. Results: Seventy-four percent (34/46) of patients had complete resolution (CR) of all warts. Of 34 patients who experienced CR, an average of 1.7 treatments were required. Pain experienced during the procedure and recovery, irrespective of outcome, was rated 5.8 out of 10 (range, 1-10; SD, 2.72; SEM, 0.40). Approximately 70% of patients had pain that lasted less than 2 days after treatment. Seventy-eight percent (36/46) of patients in the study were satisfied with treatment and would recommend it to others. Conclusion: Patients felt bleomycin to be an effective treatment modality for warts, offering high rates of CR in lesions resistant to more traditional therapies.

Color atlas: eczema

Atopic dermatitis is a chronic relapsing skin disorder often presenting in infancy and early childhood and characterized by an age-dependent distribution. Lesions may be acute, subacute, or chronic. The cardinal feature of atopic dermatitis is pruritus, and many of the lesions of atopic dermatitis result from rubbing and scratching persuant to this symptom. Patients with atopic dermatitis have alterations in cutaneous immunity and barrier function that may cause them to be more susceptible to skin infection including viruses, certain bacteria and dermatophytic fungi. Should smallpox vaccination be reinstituted in the U.S., patients with eczema or household contacts of patients with eczema should not be vaccinated because of the risk of eczema vaccinatum.

Assessing retinol stability in a hydroquinone 4%/retinol 0.3% cream in the presence of antioxidants and sunscreen under simulated-use conditions: a pilot study

BACKGROUND Retinol (ie,vitamin A) is commonly used in dermatology as an adjunct to treat rhytids, acne,and dyschromia. However, vitamin A and many of its derivatives have poor photostability and are unstable in the presence of oxygen. OBJECTIVE We aimed to assess the stability of retinol under simulated patient application conditions in a commercially available hydroquinone 4% cream containing retinol 0.3%, avobenzone (ultraviolet-A sunscreen), octinoxate (ultraviolet-B sunscreen), vitamins C and E (antioxidants), and moisturizers. METHODS One gram of the preparation was applied as a thin film to the inside base of 4 groups of four 100-mL wide-mouthed beakers, incubated in a 37+/-2 degrees C water bath. Each experimental group consisted of 4 beakers for assays at 0.5,1,2,and 4 hours. The samples were exposed to varying combinations of full spectrum light and headspace gas (air or inert nitrogen gas [N2 ]). Retinol content was assayed via high-pressure liquid chromatography using a 1:9 water:methanol solvent system. The control group (group 5) was not exposed to full-spectrum light or headspace gas but served for comparative purposes. RESULTS On exposure to light and room air, retinol stability was 94.4% at 0.5 hour, 94.8% at 1 hour, 92.4% at 2 hours, and 91.5% at 4 hours. The retinol contained in the preparation was stable for >or=4 hours. Samples exposed to light and N 2 gas demonstrated 96.5% and 91.3% stability at 0.5 hour and 4 hours exposure times, respectively. Samples that were not exposed to light had a stability of 99.2% (group 3, exposed to air) and 96.9% (group 4, exposed to N(2)) of the initial retinol present after 4 hours. CONCLUSION The retinol in the hydroquinone 4%/ retinol 0.3% cream with antioxidants and sunscreens underwent <10% degradation under simulated-use conditions, including exposure to UV light, oxygen, and body temperature.