Physician do no harm.  This simple statement is the crux of medical therapy, but it can be complicated to weigh the risk/benefit ratio of many treatments.  Too much aspirin causes tinnitus (ringing ears) and bleeding stomach ulcers, yet low dose aspirin is a nearly ubiquitous recommendation as a way to reduce the risk of heart attacks and stroke.  More problematic is when a drug is shown to cause unexpected side effects.  This was the case with Raptiva, or efalizumab, a medication used to treat psoriasis.  Raptiva was pulled from the market June 8 after 3 cases of a deadly brain infection called progressive multifocal leukoencelphalopaty (PML) occured in 1,900 patients who had received the drug for more then 3 years.  I was sad to see Raptive go, because it was a life-changing drug for many of my patients who were using it, but there was no way I would have continued prescribing it anyway; we had already contacted our patients on the drug and begun transitioning them to something new before the drug was pulled.  Genentech, the maker of Raptive, pulled the drug from the market voluntarily, and had maintained a running dialogue as the problem unfolded, so they were in no way the evil corporation out for profit above safety.  What this does show, however, is the difficulty in finding rare side effects that occur only after prolonged use.  Certainly we should all look at any new drug askance while experience with it accumulates, but when the disease is severe and options are limited, sometimes the benefits outweigh the unknown risks.

On a different note, recently Botox received a dreaded “black box” warning label from the FDA.  Black box warnings are given to drugs with potentially fatal side effects, but this is another example of the FDA using a broad brush to deal with an unlikely problem.  Botox is based on a protein, botulinum toxin type A, produced by a bacteria called Clostridium botulinum.  The protein prevents muscles from contracting.  A person who eats a damaged can of food that has been contaminated with Clostridium botulinum will lose muscle control and be unable to breath.  When using this protein as Botox, the dose that will be fatal to 50% of adults is about 3,000 units.  When I inject Botox, however, the maximum dose needed is 100 units and most people receive between 25 and 50 units.  That is a broad margin of safety, equal to or greater then most drugs including aspirin.  So what is the problem?  Botox is also used to relieve the painful muscle spasms of children with cerebral palsy, and the dose used is much larger.  In that group there have been problems with generalized muscle weakness.  To date, I have never read of a documented serious side effect from Botox used for cosmetic purposes, and I have never had one in my practice.  This then is an example of the FDA lumping instead of splitting; the black box warning should have been limited to the medical use of Botox and reflected the risk from using large doses.

Separately, there is a competitor to Botox finally approved by the FDA for use in the United States:  Dysport.  I am glad Botox finally has some competition, which should slow down price increases on this already very expensive drug.  Dysport and Botox have been used in Europe for 17 years, however, and yet Botox has 90% of the market share overseas.  The reason is the difference in the protein itself; botulinum toxin type A is a biologic drug, produced in factories by culturing Clostridium botulinum, and the two drugs use different strains.  Accordingly the two drugs are different in potency and effect; Dysport is more likely to spread further from the point of injection, which is not good for the small areas we treat on the face.  I don’t intend to use Dysport anytime soon, except for the armpits where I use it to treat excessive sweating (hyperhidrosis) and the increased spread of the medication would be a good thing.  Still, I  hope Dysport achieves enough market share to keep the makers of Botox honest about pricing.

Methicillin-resistant Staphylococcus aureus (MRSA) is not a new bacterial problem.  Despite the recent media attention to extremely bad infections, we have had to deal with antibiotic resistant Staphylococcus (staph) since the 1950’s, soon after the introduction of penicillin.  So what makes MRSA so scary?  Let’s separate the facts from the media hyperbole.

After staph became resistant to penicillin, methicillin was created.  This antibiotic was the fallback drug, yet before long methicillin-resistance was encountered.  Initially this occurred in hospitalized patients, but a different genetic type of methicillin-resistant staph then developed in the general community.  Methicillin-resistance became the marker for multiple-drug resistant staph, and in the last few years it has become more common.  However, community acquired MRSA (CA-MRSA) is resistant to fewer antibiotics and is generally less aggressive then hospital acquired MRSA.  CA-MRSA creates the same general problems as non-resistant staph:  boils, infected hair follicles, surgical wound infections, and impetigo are common types of staph infections.   There are still commonly used antibiotics that will treat community-acquired MRSA (CA-MRSA) well. 

So why the hysteria over CA-MRSA?  Well, it tends to infect young, healthy people like athletes, military personnel, and others who are in close contact with other people.  That would be the same group that is infected with any type of staph.  Rarely, the bacteria will cause a more serious infection, like pneumonia, infected heart valves, or a deep skin infection.  That too is the same as regular staph.  CA-MRSA is also mercifully rare.  In one study the incidence of CA-MRSA in an outpatient clinic was 7.5% of infections over 6 years.

Clearly any bacterial infection can be serious.  Jim Henson, the creator of the Muppets, died of streptococcal pneumonia in 1990.  Streptococcus generally causes a sore throat.  Mariana Bridi, a 20 year-old Brazilian model recently died of a Pseudomonas infection, a bacteria that generally causes urinary tract infections.  Similarly, staph and CA-MRSA occasionally cause overwhelming infections. 

Luckily, CA-MRSA and other bacteria are easily removed by daily bathing and, important point here, hand washing.  If you or someone you know develops CA-MRSA or regular staph, there is no need to panic, but pay attention to things like a fever, increasing pain and redness in a skin infection, or signs of other organ systems becoming infected.  There is no need to close schools or businesses, but good hygiene is important.

A recent article in Journal of Drugs in Dermatology (December 2008, Volume 7, Issue 12, page 1153-1157) compared two common medications used in atopic dermatitis:  Protopic and Elidel.  These are both nonsteroidal, topical calcineurin inhibitors used for mild to severe atopic dermatitis.  They are useful as steroid-sparing agents, but have their own risk profile.  Despite that, they are generally considered safer then long-term, medium strength topical steroids.  The problem has been to decide which is better.  Since Protopic has an official indication for moderate to severe atopic dermatitis, but Elidel’s indication has been for mild to moderate atopic dermatitis, I have assumed that Protopic is more effective.  Well, it has been proven true.  In this randomized, comparative 6 week study of 98 patients, patients treated with Protopic achieved a 59% improvement in the signs and symptoms of atopic dermatitis, versus a 43% improvement in patients treated with Elidel.  The patients treated with Protopic also cleared faster.  Notice that both groups of patients improved, and within the study some Elidel patients probably improved more then some Protopic patients.  That is what I notice in my practice, and which makes some patients swear Protopic is ineffective. This study, however, demonstrates the importance of a real trial with an adequate number of participants; overall Protopic is a better treatment.  I will use this study to guide my therapeutic choices.