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A new topical treatment for resistant herpes simplex infections
Journal of the American Academy of Dermatology Volume 32, Number 1
Pearls of wisdom
119
Abstracts from the literature Oral azole drugs as systemic antifungal therapy Como JA, Dismukes WE. N Engl J Med 1994; 330:263-72. The oral azole drugs-ketoconazole, Auconazole, and itraconazole-are relatively new agents that have proved to be a major advance in treatment of the systemic mycases.Safe and effective and easy to administer, they are now reasonable alternatives to amphotericin B and other older drugs. This succinct but thorough review objectively compares and contrasts the pharmacologic properties of the oral azole drugs, including their chemistry, spectrum of activity and resistance, adverse effects, and drug interactions and summarizes their use and efficacy as therapy for candidiasis, cryptococcosis, endemic mycoses, and aspergillosis, including fungal infections in patients with AIDS and the need for antifungal prophylaxis in neutropenic patients. COMMENT:This article is an excellent, focused review of the oral azole drugs. It should be required reading for any physician who encounters patients with systemic fungal disease. Kenneth Tomecki, MD
A new topical treatment for resistant herpessimplex infections
Resolution of severepyoderma gangrenosumin a patient with streaking leucocyte factor disease after treatment with tacrolimus (FK 506) Abu-Elmagd K, Van Thiel DH, Jegasothy BV, et al. Ann Intern Med 1993;119:596-6. Tacrolimus (FK 506), a new macrolide antibiotic derived from the soil fungus Streptomyces tsukubaensis, inhibits the activation and proliferation of CD4+ T cells. It has proved to be effective for patients who have undergone transplantation. It is available in the United States on a limited basis, usually with approval by the Food and Drug Administration. A 31-year-old man with chronic pyoderma gangrenosum, recurrent sterile pyoarthrosis, and presence of a serum factor called “streaking leucocyte factor,” received tacrolirnus, 0.15 mg/day twice daily. Within 12 weeks of treatment, the skin disease and joint disease resolved, for the first time since childhood, and remained quiescent for another 6 months. Side effects were temporary, namely transient trembling, paresthe sias, and insomnia. COMMENT:Tacrolimus is an important new immunosuppressive agent for patients who have undergone transplantation, lessso for those with recalcitrant psoriasis and pyoderma gangrenosum. Like cyclosporine, its use as a dermatologic agent may increase in the near future, although important side effects may limit its usefulness. Kenneth Tomecki, MD
Snoeck R, Andrei G, DeClercq E, et al. N Engl J Mecl 1993;329:968-9 (Letter). HPMPC ( (s)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine), an acyclic nucleoside phosphonate, is a potent and selective inhibitor of various DNA viruses. Applied daily for 3 consecutive days a week, it was effective treatment of recurrent herpes simplex virus (HSV) infection in two patients: one with AIDS and perineal HSV type 2 infection, unresponsive to acyclovir and ineligible for foscarnet: the other, a man with a bone marrow transplant and type 1 HSV facial disease, unresponsive to either acyclovir or foscarnet. COMMENT:Acyclovir is still the drug of choice for HSV infections in immunocompromised patients. HPMPC may be a reasonable alternative for those patients unable to take or tolerate acyclovir or foscarnet. Kenneth Tomecki, MD
Nitric oxide: A physiologic messenger Lowenstein CJ, Dinerman JL, Snyder SH. Ann Intern Med 1994; 120:227-37. It has recently been determined that nitric oxide is important in several different physiologic processes,ranging from regulation of blood pressure and penile erection to neurotransmission and suppression of pathogens. In excess, it can lead to neurotoxicity during strokes and hypotension during sepsis.The molecule, NO, exists in a constitutive form in endothelial cells and in neurons as well as in an inducible form in macrophages that aids in elimination of infectious pathogens. Some of the pathogens that are targets of nitric oxide include herpes simplex virus, coxsackie virus, Francisella tularensis, Mycobac-
Pearls of wisdom
119
Abstracts from the literature Oral azole drugs as systemic antifungal therapy Como JA, Dismukes WE. N Engl J Med 1994; 330:263-72. The oral azole drugs-ketoconazole, Auconazole, and itraconazole-are relatively new agents that have proved to be a major advance in treatment of the systemic mycases.Safe and effective and easy to administer, they are now reasonable alternatives to amphotericin B and other older drugs. This succinct but thorough review objectively compares and contrasts the pharmacologic properties of the oral azole drugs, including their chemistry, spectrum of activity and resistance, adverse effects, and drug interactions and summarizes their use and efficacy as therapy for candidiasis, cryptococcosis, endemic mycoses, and aspergillosis, including fungal infections in patients with AIDS and the need for antifungal prophylaxis in neutropenic patients. COMMENT:This article is an excellent, focused review of the oral azole drugs. It should be required reading for any physician who encounters patients with systemic fungal disease. Kenneth Tomecki, MD
A new topical treatment for resistant herpessimplex infections
Resolution of severepyoderma gangrenosumin a patient with streaking leucocyte factor disease after treatment with tacrolimus (FK 506) Abu-Elmagd K, Van Thiel DH, Jegasothy BV, et al. Ann Intern Med 1993;119:596-6. Tacrolimus (FK 506), a new macrolide antibiotic derived from the soil fungus Streptomyces tsukubaensis, inhibits the activation and proliferation of CD4+ T cells. It has proved to be effective for patients who have undergone transplantation. It is available in the United States on a limited basis, usually with approval by the Food and Drug Administration. A 31-year-old man with chronic pyoderma gangrenosum, recurrent sterile pyoarthrosis, and presence of a serum factor called “streaking leucocyte factor,” received tacrolirnus, 0.15 mg/day twice daily. Within 12 weeks of treatment, the skin disease and joint disease resolved, for the first time since childhood, and remained quiescent for another 6 months. Side effects were temporary, namely transient trembling, paresthe sias, and insomnia. COMMENT:Tacrolimus is an important new immunosuppressive agent for patients who have undergone transplantation, lessso for those with recalcitrant psoriasis and pyoderma gangrenosum. Like cyclosporine, its use as a dermatologic agent may increase in the near future, although important side effects may limit its usefulness. Kenneth Tomecki, MD
Snoeck R, Andrei G, DeClercq E, et al. N Engl J Mecl 1993;329:968-9 (Letter). HPMPC ( (s)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine), an acyclic nucleoside phosphonate, is a potent and selective inhibitor of various DNA viruses. Applied daily for 3 consecutive days a week, it was effective treatment of recurrent herpes simplex virus (HSV) infection in two patients: one with AIDS and perineal HSV type 2 infection, unresponsive to acyclovir and ineligible for foscarnet: the other, a man with a bone marrow transplant and type 1 HSV facial disease, unresponsive to either acyclovir or foscarnet. COMMENT:Acyclovir is still the drug of choice for HSV infections in immunocompromised patients. HPMPC may be a reasonable alternative for those patients unable to take or tolerate acyclovir or foscarnet. Kenneth Tomecki, MD
Nitric oxide: A physiologic messenger Lowenstein CJ, Dinerman JL, Snyder SH. Ann Intern Med 1994; 120:227-37. It has recently been determined that nitric oxide is important in several different physiologic processes,ranging from regulation of blood pressure and penile erection to neurotransmission and suppression of pathogens. In excess, it can lead to neurotoxicity during strokes and hypotension during sepsis.The molecule, NO, exists in a constitutive form in endothelial cells and in neurons as well as in an inducible form in macrophages that aids in elimination of infectious pathogens. Some of the pathogens that are targets of nitric oxide include herpes simplex virus, coxsackie virus, Francisella tularensis, Mycobac-