Treatment drawbacks can outweigh disease risks

April 1, 2011

I am challenged every day by children with skin disease that has no evidenced-based approach to evaluation or treatment. The trickiest issue is that my medical recommendations seldom have enough specific evidence to prove safety and efficacy, so I have to be very familiar with the wide range of potential risks and weigh them carefully against the potential benefit in each case.

Key Points

I have a large collection of tools and parts, well-organized enough to find what I need for most jobs. Last week I fixed my favorite rolling carry-on by replacing a broken wheel with one from an old pair of roller blades that my kids had outgrown.

I don't know whether this hobby evolved from my professional trials or vice versa. I do know that I am challenged every day by children with skin disease that has no evidenced-based approach to evaluation or treatment.

However, in our current medicolegal climate, the balance is tipped, emphasizing the risks of treatment more than the risks of disease. Adverse events are assumed to be a treatment-related side effect rather than pharmacogenetic or disease-associated events. This is especially true for newer treatments. Medications that have been used for decades (or even centuries) in millions (or countless numbers) of people for a variety of conditions enjoy a higher comfort level.

I recently ruminated over several of these treatments with a degree of scrutiny similar to that of today's Food and Drug Administration (FDA). Although these treatments are widely used without mandated MediGuide information or black box branding, the potential for adverse effects may be greater than for newer drugs that carry these warnings.

Water

I recommend frequent bathing and wet wraps on a daily basis. But water can be dangerous - or even fatal - if used incorrectly. The risks of excessive topical application include maceration followed by asteatotic eczema or intertrigo with superinfection. Overingestion can cause headache, behavioral changes and even lethal hyponatremia.

Hot water can accidentally cause severe burns or be used to inflict abusive injury on innocent children. Excessive exposure to cold water can also be fatal. Frozen water carries a high risk of slips, falls and serious fractures. And sustained environmental alteration in water content will result in profound changes beginning at the bottom of the food chain.

Wet wraps may pose another hazard, if plastic wrap is used for occlusion. The Consumer Product Safety Commission gets about 25 reports a year of infants suffocating due to plastic bags.

Aspirin

Acetylated salicylate was introduced by Bayer in 1899. After many decades of use, the most likely mechanism of action was proposed: irreversible acetylation of a cyclooxygenase serine. The drug has several seemingly unrelated therapeutic effects: analgesia, antipyretic and antiplatelet. But status as an over-the-counter medication would not be the likely outcome of a New Drug Application submitted for aspirin in 2011.

Acute aspirin overdose kills 2 percent of adults who take 20 gm to 30 gm (60 to 90 325 mg tablets), while chronic overdose is lethal in 25 percent. Mild drug-related adverse effects include gastritis, dizziness, lethargy and tinnitus, while severe reactions include respiratory alkalosis and metabolic acidosis, seizures and cerebral edema. Reye's syndrome was first described in 1963, but the association between aspirin and viral infection was not made for another 20 years.

The risks of aspirin are rivaled by those of other NSAIDs and acetaminophen. The FDA finally addressed some of these risks in 2009 with a final rule requiring warning labels about some of the potential safety risks. Clearly, inertia and market forces play a major role in allowing these drugs to be sold without a prescription, while Elidel (pimecrolimus, Novartis) bears a black box that bars third-party payment to use this drug for many of my youngest patients.