The pathogenesis of acne is multifactorial: follicular hyperkeratinization, bacteria, sebum production, androgens and inflammation all play a role. The gram-positive microaerophilic bacteria Propionibacterium acnes promote development of acne lesions by secreting chemotactic factors that attract leukocytes to the follicle, causing inflammation.

The May 5, 2008 article (Med Lett Drugs Ther 2008; 50:34) on the approval of natalizumab (Tysabri) for treatment of Crohn's disease in the "Adverse Effects" section on page 35 included the statement: "post-marketing hepatotoxicity, sometimes fatal or requiring liver transplantation, has occurred." Actually, no fatal hepatotoxicity or liver transplantation has been reported to date. The FDA warning about post-marketing hepatotoxicity with Tysabri that was the basis for our statement said: "The combination of transaminase elevations and elevated bilirubin without evidence of obstruction is recognized as an important predictor of severe liver injury that may lead to [emphasis added] death or the need for a liver transplant in some patients." Also, in the last sentence of the Conclusion, we should have said: "Because of the risk of serious hepatic toxicity and the rare but even more serious risk of developing progressive multifocal leukoencephalopathy, it should be used only in patients who have not responded to other drugs, including a TNF inhibitor." The italicized words should be substituted for "it is FDA-approved for use."

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Natalizumab (Tysabri - Elan and Biogen) is a monoclonal antibody approved for induction and maintenance treatment of moderate to severe Crohn's disease (CD) refractory to conventional therapies and inhibitors of tumor necrosis factor (TNF). Initially approved in 2004 for the treatment of multiple sclerosis (MS), natalizumab was temporarily withdrawn from the market after 3 patients developed progressive multifocal leukoencephalopathy (PML). It is now available for treatment of both MS and CD through a restricted distribution program.

Information about empirical treatment of bacterial infections, emerging trends in antimicrobial resistance, new drugs and new data about older drugs continue to become available. Usual pathogens and empiric treatment for some common types of infections are summarized in the text and a table listing the drugs of choice and alternatives for each pathogen begins on page 40. The recommendations made here are based on the results of susceptibility studies, clinical trials and the opinions of Medical Letter consultants.

The FDA has approved a new spray formulation of the super-high-potency corticosteroid clobetasol propionate 0.05% (Clobex - Galderma) for treatment of moderate to severe plaque psoriasis in adults. Clobetasol propionate is also available as a cream, ointment, gel, solution, foam, lotion and shampoo.

Serious adverse interactions between drugs continue to be reported. Many of these are due to inhibition or induction of cytochrome P450 (CYP) enzymes, particularly CYP3A4. CYP3A is thought to be involved in the metabolism of more than 50 percent of currently prescribed drugs.2 CYP3A4, which is more abundantly expressed than CYP3A5, accounts for most CYP3A activity in vivo.

The pathogenesis of acne is multifactorial: follicular hyperkeratinization, Propionibacterium acnes bacteria, sebum production, androgens and inflammation have all been implicated. P. acnes, a gram-positive microaerophilic bacterium, plays an important role in the development of acne lesions by secreting chemotactic factors that attract leukocytes to the follicle, causing inflammation.

Dehydroepiandrosterone (DHEA), an endogenous adrenal steroid, is marketed as a dietary supplement in the US. It is widely promoted to reverse the effects of aging (loss of muscle, memory and libido) and has been used by athletes as a substitute for anabolic steroids. DHEA is banned by the International Olympic Committee, National Collegiate Athletic Association, National Football League and other sports organizations, but it was specifically exempted from becoming a controlled substance in the Anabolic Steroid Control Act of 2004.

Patients with mild, infrequent asthma symptoms may require only intermittent, asneeded use of an inhaled short-acting beta2-adrenergic agonist. Use of a short-acting beta2-agonist more than twice weekly, other than for exercise-induced bronchospasm, indicates a need for anti-inflammatory treatment. Inhaled corticosteroids are the most effective anti-inflammatory medication; leukotriene modifiers are less effective alternatives. If regular use of an inhaled corticosteroid in a low dose does not prevent symptoms, a long-acting beta2-agonist should be added; addition of a second drug is more effective than raising the dose of the inhaled steroid. A leukotriene modifier can also be used as the second drug. Omalizumab may be considered as adjunctive therapy for patients more than 12 years old who have allergic asthma not controlled by other drugs. A short course of oral corticosteroids may be useful for acute exacerbations. Treatment of acute severe asthma as a medical emergency is not included here; it has been reviewed elsewhere (ER McFadden Jr, Am J Respir Crit Care Med 2003; 168:740).

With the 2004 Olympics only weeks away, performance-enhancing drugs will once again be receiving a great deal of attention. The US Anti-Doping Agency has published a list of drugs banned in Olympic sports (www.usantidoping.org) that includes, at least for some sports, all but 2 of the drugs reviewed here.

Three types of analgesic drugs are available: non-opioids, including aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; opioids; and adjuvant drugs that are not usually thought of as analgesics, such as antidepressants, which can act as adjuvants when given with NSAIDs or opioids, or have analgesic activity of their own in some types of pain. Combining two different types of analgesics may provide an additive analgesic effect without necessarily increasing adverse effects.

New drugs for bacterial infections and new information about older drugs continue to become available. Empirical treatment of some common bacterial infections is discussed in this article. A table listing the drugs of choice and alternatives for each pathogen begins on page 18. These recommendations are based on results of susceptibility studies, clinical trials and the opinions of Medical Letter consultants. Local resistance patterns should be taken into account. Trade names are listed on page 24.

Changes caused by one drug in the absorption, distribution, metabolism or excretion of another may lead to a pharmacokinetic adverse drug interaction (DN Juurlink et al, JAMA 2003; 289:1652). Additive drug interactions, such as vasodilation caused by both sildenafil (Viagra) and nitrates, can also have adverse effects.

Many different drugs are now used to treat rheumatoid arthritis. Nonsteroidal anti-inflammatory drugs (NSAIDs), listed in the table on page 26, have analgesic and anti-inflammatory effects, but may not affect the disease process. Corticosteroids can provide rapid relief of joint symptoms and control of systemic manifestations, but chronic use is associated with many complications. The "disease-modifying" anti-rheumatic drugs (DMARDs), listed on page 29, have no immediate analgesic effects, but can control symptoms and may delay progression of the disease (American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines, Arthritis Rheum 2002; 46:328). Interactions of anti-rheumatic drugs with other drugs are listed in The Medical Letter Handbook of Adverse Drug Interactions, 2003.

New drug formulations continue to be introduced for the treatment of asthma, and new studies on older drugs continue to change our perspectives on the management of this chronic inflammatory disease. Treatment of asthma in the emergency department or hospital is not addressed here. More information on the diagnosis and treatment of asthma is available from Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma (Bethesda:NIH, 1997 and 2002 update; www.nhlbi.nih.gov).

Reports of adverse interactions between drugs continue to accumulate. Recently, the FDA has expanded the recommendations on drug interactions found in the package inserts of new drugs.