Role of oral antifungal agents for the treatment of superficial fungal infections in immunocompromised patients.

Superficial fungal infections or tinea infections (also known as the dermatophytoses) are commonly encountered conditions in clinical practice, affecting the skin, hair, and nails. The most commonly prescribed modality to treat these infections is topical antifungal therapy. However, this method of treating tinea infections may be less convenient and efficacious in the immunocompromised patient. In such patients, skin infections are more difficult to treat because the disease is often more extensive and severe. Tinea infections of the hair and nails usually require oral therapy. Further, topical treatment is not as efficacious as oral antifungal therapy and, with the exception of the topical antifungal agent ciclopirox, is not indicated for the treatment of tinea unguium (onychomycosis). The 2 most frequently prescribed oral antifungal agents to treat onychomycosis are itraconazole and terbinafine. In the general population, both agents are effective in treating fungal nail infections; however, differences in the agents' mechanism of action and metabolic pathways result in differences in efficacy and drug-drug interaction potential. However, limited data exist on the use of these agents in immunocompromised patients for the treatment of onychomycosis and superficial tinea infections. The available efficacy data we have are limited to case reports or small pilot studies; thus, data supporting the efficacy of these agents for the treatment of tinea infections in the immunocompromised patient must be extrapolated from the general population. For safety issues, however, some postmarketing data exist supporting the safety of these agents in the diabetic and human immunodeficiency virus (HIV) patients populations; indeed, both agents appear to be safe. However, one contrasting point between these 2 agents is drug interactions. Oral terbinafine, unlike itraconazole (a potent cytochrome P-450 [CYP] 3A4 inhibitor), has a relatively low potential for drug-drug interactions, making terbinafine a useful agent for the treatment of tinea infections in immunocompromised patients (e.g., those who are HIV positive and those with diabetes), who are likely to be receiving concomitant medications. Further, recently conducted studies of terbinafine for the treatment of tinea pedis, tinea cruris, and tinea corporis infections in these high-risk patient groups also support efficacy claims and reemphasize its relatively safe profile and low potential for drug interactions. Additional studies in other immunocompromised patient populations may be useful to confirm recent studies and expand the potential use for this agent.

Posttransplant primary cutaneous T-cell lymphoma.

A patient with posttransplant cutaneous lymphoma is described. Although most posttransplant lymphomas are of B-cell origin, this patient's lymphoma is a primary cutaneous lymphoma of T-cell origin. Another report exists of the first case of posttransplant primary cutaneous T-cell lymphoma localized to the lower extremities. Our patient's involvement was generalized with tumor nodules on the face and anterior chest. Reduced immune surveillance, chronic antigenic stimulation caused by transplant grafts, and the direct oncogenic effects of immunosuppressive drugs have all been suggested as mechanisms. Prompt recognition of this condition and initiation of appropriate therapy with reduction of high-dose immunosuppression can lead to better patient outcomes.

Pivotal clinical trials of adapalene in the treatment of acne.

Adapalene, a naphthoic-acid derivative, possesses some of the biological activities of tretinoin but has distinct physicochemical properties and binding properties for selective affinity for retinoic acid receptors. As such, adapalene is less likely to be associated with certain local tolerability problems (e.g. burning, erythema, pruritus). Over the past 5 years, numerous clinical trials have been conducted to compare the efficacy and tolerability of adapalene and tretinoin in the treatment of acne vulgaris. Three pivotal, large, well-controlled studies involving almost 900 patients showed that adapalene gel 0.1% and adapalene solution 0.1% are at least as effective as tretinoin gel 0.025%, with superior local tolerability. Adapalene cream 0.1% has proven to be significantly more effective than vehicle, with response rates comparable to those observed with the gel and solution. A meta-analysis of trials with the gel formulation confirmed these findings, showing equivalent efficacy and improved tolerability vs. tretinoin gel 0.025%. Moreover, the onset of clinical effect was shown to be significantly more rapid than that of tretinoin gel. Taken together, these studies demonstrated that adapalene has overall efficacy similar to that of topical tretinoin, but with a superior therapeutic ratio that may result in superior outcomes in clinical practice through improved compliance. This may be expected because of its lesser potential for skin irritation, especially early in treatment, and because of greater convenience in that no waiting period is required between face washing and application of the product. Therefore, 5 years of clinical experience have established that adapalene in its various formulations is a valuable addition to current treatments for acne vulgaris.

Adapalene: an update on newer comparative studies between the various retinoids.

BACKGROUND: Extensive modification of the retinoic acid molecular skeleton has resulted in the development of adapalene, a more stable, less irritating compound with receptor selectivity. Adapalene selectively targets nuclear retinoic acid receptors found primarily in the epidermis. Pharmacologic and preclinical studies have demonstrated excellent follicular penetration, comedolytic activity, and anti-inflammatory activity. METHODS: Recent comparative trials were reviewed. RESULTS: Adapalene is a useful new agent because of its tolerability and stability. It is a good therapeutic choice for combination with other topical anti-acne medications, such as antimicrobials or benzoyl peroxide. Patient compliance with either combination or single-agent adapalene regimens is likely to be enhanced because of the greater comfort and reduced skin irritation associated with the new compound. Other investigators have confirmed that adapalene gel produces consistent and significantly reduced irritation. CONCLUSIONS: Recent comparative trials on retinoids have provided new data to aid in the selection of the appropriate combination of topical agents for individual patients.

Pilomatrix dysplasia in an immunosuppressed patient.

Immunosuppressive drugs have been used for many years in the prevention of graft failure in transplant recipients. Although they improve morbidity and mortality after transplantation, these medications carry a significant risk of adverse mucocutaneous and systemic effects. We describe a patient receiving 4 immunosuppressive drugs who experienced persistent facial dysmorphism along with striking follicular disturbances. On histopathologic examination, the follicular structures were dilated and hyperplastic with a peculiar dysplasia of the pilar matrix. Based on a review of the clinical, microscopic, and investigational findings of the skin previously reported in association with her immunosuppressive drugs, we conclude that cyclosporine was the most likely causative agent. Moreover, hypertrichosis, dysmorphic facies, and tissue hyperplasia have all been observed in patients during cyclosporine administration.

Anecdotal therapies.

Traditionally, many advances in medicine have been serendipitous. Are serendipitous and anecdotal synonymous? Many of our materia medica today relate to initial probes and anecdotal reports that matured to full investigation and therapeutic indications. The recent situation regarding Skin Cap is one that highlights the downside of this scenario. Several drugs in the US continue usage largely related to anecdotal indications, and anecdotal extension of legend indications is a standard for American Dermatology. The situation with systemic drugs, such as Trental, zinc preparations, imidazoles for extended indications, lysine and melatonin, all will be discussed. Topical preparations such as skin cap, cantharone, Vioform, all also are included in this category. It is important to place this topic in perspective in regards to geographic variation and therapeutic need. Many diseases lacking specific therapy are important targets for anecdotal therapy, and this will foster continued approaches in this area. The growing standardization of medicine and pharmaceutical regulation, threatens the anecdotal approach, but it provides still an important link to the future for some forms of therapy in diseases that are difficult to treat. Traditionally, the anecdote has been the first step in the therapeutic chain. Withering discovery of the benefits of the common fox glove in dropsy, was followed by many other anecdotes arriving via folk-medicine in the New World. This approach of utilizing folk medicine has now reached new heights, with very active searches by major pharmaceutical companies throughout the third world for remedies that may have potential. Couched with this is the history of anecdotal "snake-oil" remedies, that clearly had no benefit to anyone except the huckster marketing same. The excesses in this area of unproven and false therapies, led to the gradual organization of therapeutic trials and the Food and Drug Administration in the US as we know it today. The biggest shot in the arm for enhancing FDA protocols was the thalidomide situation, an outgrowth of an ethically studied and used medication that perhaps had been released too soon, prior to sufficient trials to determine the total patient risk. As in many situations, the pendulum swings in both directions, and after thalidomide, the acceptance of new treatments required more and more rigorous studies, and studies from other countries often were not acceptable unless a small part of a larger, whole proposal. The AIDS crisis has prompted a swing back, away from such expensive and rigorous pre-marketing review, to more expedited processes for the relief of patients with this fatal disease. This has streamlined the FDA, and hopefully the swing of the pendulum will not go too far, to result in problems in the future. Anecdotal therapies and medications are the first step in many parts of the world to therapeutic trials. The most widely used aspects of anecdotal therapies, again, remains in the situation with diseases without good therapies at the present time. The so-called orphan drugs and orphan diseases, while a serious medical problem, do not present a significant volume for effective drug screening in many instances, and the FDA has developed some new approaches to circumvent this very expensive development process for patients suffering from these rare and unusual disorders. The most recent example of anecdotal therapy catching the public fancy in dermatology was the Skin-Cap Spray. This product, over the period of twelve months, got rave reviews in the lay press in the non-peer reviewed dermatologic periodicals, and amassed impressive sales figures in this period of time. It was extremely effective, and most dermatologists who used it have patients who consider it the most effective therapy in the last year. The formulation of a low concentration of zinc pyrithione seemed unusual, and this truly was an anecdotal approach, using a homeopathic dosage of a commonly used p

Propylthiouracil hypersensitivity: report of two patients with vasculitis and review of the literature.

Two patients with a hypersensitivity vasculitis in association with propylthiouracil (PTU) administration are described. Although both patients presented with a cutaneous eruption, our first patient suffered severe systemic manifestations and the second patient's involvement was primarily limited to the skin. Patients with a vascular hypersensitivity reaction to PTU typically present with constitutional symptoms, acral purpuric skin lesions, and variable involvement of multiple organ systems. The reaction is treated by urgent withdrawal of PTU and implementation of supportive measures and immunosuppressive agents, as necessary. Prompt recognition of this condition and initiation of appropriate therapy lead to complete recovery in most cases.

A new therapeutic approach to type II leprosy reaction.

BACKGROUND: An increase in tumor necrosis factor (TNF) has been implicated in type II leprosy reaction. Thalidomide, which inhibits TNF, is an effective drug, but has severe side-effects in pregnant women. Other therapeutic drugs are required. METHODS: Clofazimine and pentoxifylline were evaluated for their efficacy against severe type II leprosy reaction in four patients (three men and one woman). RESULTS: All four patients showed a similar fast response to treatment. CONCLUSIONS: The results obtained in this study are promising; however, clofazimine and pentoxifylline must be evaluated in a larger group of patients in order to determine their value in controlling type II leprosy reaction.