Review

The recent albuterol vs. placebo trial reported in the New England Journal of Medicine (NEJM) found that experimental subjects with asthma  experienced substantial, measured improvements in lung function after inhaling albuterol, but not after inhaling placebo, undergoing sham acupuncture, or “no treatment.” It also found that the same subjects reported having felt substantially improved after either albuterol or each of the two sham treatments, but not after “no treatment.” Anthropologist Daniel Moerman, in an accompanying editorial, wrote, “the authors conclude that the patient reports were ‘unreliable,’ since they reported improvement when there was none”—precisely as any rational clinician or biomedical scientist would have concluded.

In Part 1 of this blog we saw that Moerman took issue with that conclusion. He argued, with just a bit of hedging, that the subjects’ perceptions of improvement were more important than objective measures of their lung function. I wondered how the NEJM editors had chosen  someone whose bibliography predicted such an anti-medical opinion. I doubted that Editor-in-Chief Jeffrey Drazen, an expert in the pathophysiology of asthma, had ever heard of Moerman. I suggested, in a way that probably appeared facetious, that Ted Kaptchuk, the senior author of the asthma report, might have recommended him.

Editorial Cronyism?

I wasn’t being facetious, even if I was a bit snide. In a 2009 article Kaptchuk touted Moerman’s notion of “the meaning response,” also discussed in Part 1. In a 1998 article, one of Kaptchuk’s early forays into the placebo topic, he had thanked Moerman and others “for advice, discussion, and feedback.” In the Acknowledgments for his 2002 book Meaning, Medicine, and the “Placebo Effect,” Moerman returned the complement to Kaptchuk. In a very recent essay on “placebo studies and ritual theory,” Kaptchuk showed some serious cultural anthropology chops with a serviceable impression of Moerman:

…healing rituals are never simply enactments of plots, stories or assertions of truth. Instead, they are compelling multi-sensory dramas involving evocation, enactment, embodiment and evaluation. Rituals and their sensory, affective, moral and aesthetic components transmute the mythos into an experiential reality for participants. Metaphors and symbols, the healer’s prestige, social interactions with relatives and community members in the course of preparation and performance of the ritual, and gesture, recitation, costume, iconography, touch, ingestion and the physical ordeal—all provide vehicles for and multi-dimensional guideposts to a process that is meant to transform a patient from brokenness to intactness.

Authorship by Committee and Mixed Messages

The asthma trial authors themselves seemed ambivalent about the meaning of their results. Here is the larger passage from which Moerman culled the “unreliable” comment:

…although improvement in objective measures of lung function would be expected to correlate with subjective measures, our study suggests that in clinical trials, reliance solely on subjective outcomes may be inherently unreliable, since they may be significantly influenced by placebo effects. However, even though objective physiological measures (e.g., FEV₁) are important, other outcomes such as emergency room visits and quality-of-life metrics may be more clinically relevant to patients and physicians.

David Gorski has previously mentioned that his “jaw dropped” when he read those words; so did mine, and so, everywhere, should jaws of asthmatic patients and competent physicians drop. The two sentences are contradictory: if the first is true, the second—essentially similar to the theme in Moerman’s editorial, weasel words and all—is perverse. How could the same authors have written both? Perusing the list of authors provides some hints:

Michael E. Wechsler, M.D., John M. Kelley, Ph.D., Ingrid O.E. Boyd, M.P.H., Stefanie Dutile, B.S., Gautham Marigowda, M.B., Irving Kirsch, Ph.D., Elliot Israel, M.D., and Ted J. Kaptchuk

Thus there were eight authors, suggesting that there may not have been a unanimity of opinion. Of the eight, five—M.E.W., I.O.E.B., S.D., G.M., and E.I.—are identified as “from the Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital and Harvard Medical School” (the same Division, as I mentioned in Part 1, that spawned NEJM Editor Jeffrey Drazen). It’s a safe bet that those five subscribed to the first sentence quoted above, but not to the second.

I don’t know about the other two authors, but Ted Kaptchuk would appear to agree with the second sentence. Here he’s quoted in the Brigham and Women’s Hospital press release:

“We chose to study patients with asthma because earlier evidence had suggested that placebos would change the underlying medical problem,” explains senior author Ted Kaptchuk, Director of the Program in Placebo Studies at BIDMC and Associate Professor of Medicine at HMS. “While I was initially surprised that there was no placebo effect in this experiment [after looking at the objective air flow measures] once I saw patients’ subjective descriptions of how they felt following both the active treatment and the placebo treatments, it was apparent that the placebos were as effective as the active drug in helping people feel better.”

…adds Kaptchuk, the study results imply that placebo treatment is just as effective as active medication in improving patient-centered outcomes.”It’s clear that for the patient, the ritual of treatment can be very powerful,” notes Kaptchuk. “This study suggests that in addition to active therapies for fixing diseases, the idea of receiving care is a critical component of what patients value in health care. In a climate of patient dissatisfaction, this may be an important lesson.”

Let’s see: “patient-centered outcomes” are now defined as feeling better but not being better? (I wonder if Don Berwick, the nation’s most influential exponent of patient-centered care, would agree). According to whom? Other press reports were even worse:

Treatment, not medicine, helps asthma patients feel better

NEW YORK, July 15 (Reuters Life!) – Inhaling albuterol helps asthmatic lungs work better, but patients who get it don’t feel much better than those treated with a placebo inhaler or phony acupuncture, according to a U.S. study.

The results, which appeared in the New England Journal of Medicine, demonstrate the importance of, literally, caring for patients and not just providing drugs, said co-author Ted Kaptchuk of Harvard Medical School.

The findings also demonstrate the impact of the so-called “placebo effect,” or the phenomenon seen in clinical trials when people given inactive, fake “treatments,” such as a sugar pill or saline, show improvements.

“My honest opinion is that a lot of medicine is the doctor-patient relationship,” Kaptchuk told Reuters Health.

“A lot of doctors don’t know that, they think it’s their drugs. Our study demonstrates that the interaction between the two is actually a very strong component of healthcare.”

…

Treatment of Asthma now Possible with Placebo Treatments

A New study says, “Placebo treatments are equally effective in the treatment of asthma like [sic] any asthma medications.”

According to the researchers, the main reason behind proposition of this study is that several asthma patients have reported that they felt improvement in their asthma symptoms after they received placebo treatments. These treatments also include inhaler treatments and fake acupuncture. The improvement is similar to what they feel after taking asthma medication such as albuterol.

But the researchers also mentioned that unlike asthma medications, the placebo treatments are not capable of affecting the functioning of the lung.

The researcher of the study, Mr. Ted Kaptchuk said, “The practice of treatment can be highly effective for the patients”. “The study also recommends that patients should value not only the treatments for improving diseases but also the intensive care they receive from their healthcare providers” he added.

Mr. Ted Kaptchuk also said, “In the initial stage of the experiment, placebo treatments fail to make any impact. But later, when I observed that patient’s subjective descriptions about what they felt after receiving the two treatments then I concluded that placebo treatments work as well as other asthma treatments”.

At least one blog, citing the Reuters report quoted above, reported that “placebos were just as effective as real therapy” without even mentioning the trial’s having found a discrepancy between objective findings and subjective reports.

I am aware that authors of journal articles can’t be expected to control how every reporter characterizes those articles, but it’s fair to say that the emphasis of the various quotations attributed to Kaptchuk—which, as far as can be gleaned from the web, are accurate—was essentially the opposite of the study’s most important finding.

From Campus Radical to AltMed Superstar

You might have noticed that Kaptchuk’s is the only name on the list of authors that is not accompanied by the mark of an advanced degree, as I will eventually discuss. Like Moerman, Kaptchuk lacks formal training in either modern medicine or biomedical science, although he has learned a lot about the history and methods of clinical trials. How did he get to be Senior Author of an article published in the New England Journal of Medicine, and how did he become Associate Professor at the Harvard Medical School?

Here is the short version:

I was interested in science for a long time. In college, I studied religion and philosophy. Then I studied Chinese medicine in China and I came back and was a practitioner of Chinese medicine. When people became interested in alternative medicines, they asked me to help out at Harvard Medical School. I realized that in order to survive there, one had to become a scientist. So I became a scientist.

Here is the beginning of the longer version. Kaptchuk graduated from Columbia University in 1968, having majored in Asian philosophy. While there he was Chairman of the radical group Students for a Democratic Society (SDS), just prior to the emergence of its more famous chairman, Mark Rudd. I mention this not to commie-bash, but because it helps to elucidate some of Kaptchuk’s later opinions (hint: he has no trouble agreeing with both sentences in the jaw-dropping paragraph quoted above) and to demonstrate some of the ironies of his later choices.

After graduation, in Kaptchuk’s own words, ”I worked in the welfare and social services trying to help people.” During this time “I decided that I wanted to learn a healing art but was disillusioned with some of the aspects of Western allopathy and decided to learn acupuncture.” Kaptchuk pursued training with Asian practitioners in California and “studied every book in English on the subject,” but by 1972 had decided that this would not be sufficient:

Because of the relative unknowness [sic] among non-Chinese Americans of acupuncture and Dr. Hong’s limited practice, I cannot get enough experience to adequately master this healing art. In addition, there is a greater reluctance among other Chinese doctors who have more patients to have a student observe because of legal restrictions concerning their practice in the United States.

Kaptchuk reports having next spent a year in Taiwan, followed by 2.5 years in Macau (click on the image to enlarge):

Within a few years of his return to the United States, Ted Kaptchuk published the book that made him an alt-med superstar:

It is this book that I will discuss in the next part of this series.

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Online discussions on the merits of alternative medicine can get quite heated. And its proponents, given enough time, will inevitably cite the same drug as “evidence” of the failings of science. Call it Gavura’s Law, with apologies to Mike Godwin:

As an online discussion on the effectiveness of alternative medicine grows longer,  the probability that thalidomide will be cited approaches one.

A recent comment on my own blog, regarding the homeopathic product Traumeel, is typical:

If the scientific method is all that separates an accepted claim, ie Thalidomide, Vioxx, Bextra, Darvon, from mere anecdote, of what benefit is the Science?

As a non-scientist consumer, I’ll take the anecdotes and my own experience. Thank you.

If scientists want to be taken seriously, they must stop selling themselves to the highest bidder becoming corporate whores without a shred of decency. To my mind, that’s how the claims for Thalidomide, Vioxx, Bextra, Darvon were accepted, making the scientific method utterly worthless.

To this commenter, “science has been wrong before.” And that invalidates science, and apparently validates homeopathy. It’s a fallacious argument. But does thalidomide actually represent a failing of science-based medicine? No, not even close. It’s so wrong, it’s not even wrong. Thalidomide is good example of the importance of science-based medicine and why allowing alternative medicine to be sold in the absence of good science is a concern.

The broad strokes of thalidomide causing thousands of birth defects are well known. But the details are important to understand the implications to regulation, and to science-based medicine, today.

Thalidomide was first marketed in 1958 in Germany by Chemie Grünenthal. While its developmental origins are somewhat unclear, it was initially marketed as a treatment for seizures, and later as an anti-nauseant and sedative. At the time, barbiturates were frequently used as sedatives. And compared to barbiturates, which were highly toxic in overdose, thalidomide was well tolerated, even in overdose. Based on its apparent safety, no prescription was required. Eventually its attractiveness as an anti-nauseant led to its use in pregnancy for morning sickness.

It wasn’t known at the time, but fetal exposure to thalidomide between days 35 and 48 was causing severe limb and organ defects in 20-30% of children. In the 1950′s it wasn’t even recognized that drugs could cross the placenta and cause adverse effects to the fetus. Thalidomide hadn’t been tested on pregnant animals prior to marketing for use in pregnancy. Regulators didn’t require it. And the consequences were horrific.

Thalidomide became a popular drug because of its apparent safety and effectiveness, and it was marketed alone and in combination with other drugs in Germany, the UK, Canada, and other countries. But within a few years, babies started being born with characteristic limb and organ deformities. In 1961, two independent researchers identified thalidomide as the likely causal agent. The manufacturer sought to undermine and discredit the findings, but it was clear – the drug had caused catastrophic harm to thousands of fetuses. Subsequent animal testing confirmed this.

The USA largely escaped the thalidomide tragedy – due to stronger regulations, and the action of a single employee.

American drug regulations have evolved over time. The Pure Food and Drugs Act (1906) did not require that drugs be tested for safety and efficacy before sale. It was the regulator’s responsibility to demonstrate a product was unsafe. In 1938, the S.E. Massengill company manufactured a liquid version antibiotic sulfanilamide, mixing it with diethylene glycol -a poison more commonly used as antifreeze. When patients started dying, a massive recall was implemented – but not before over 100 people died. The tragedy brought about significant reforms to drug regulations in the form of the Food, Drugs and Cosmetics Act (1938) that required manufacturers to obtain FDA approval for any drug sold, prior to any sale.

Frances Oldham Kelsey was a reviewer with the FDA in 1960, and was responsible for evaluating the thalidomide marketing application. Kelsey refused to approve the drug in the absence of safety data. Her concern was peripheral neuropathy – not teratogenicity, which wasn’t even considered at the time. She described the application process in a paper she published in 1965:

The New Drug Application for thalidomide was presented in September, 1960. The drug had been marketed in Germany since 1957 where it was available without prescription, and in Great Britain since 1958. However, it was felt that the evidence submitted in the application was not adequate to indicate the safety of the drug. In particular, although this drug appeared to be remarkably nontoxic in animals and human beings, little or no information was available concerning its absorption, distribution in the body, or its excretion. Since the possibility existed that the low toxicity of the drug in certain species might be related to poor absorption in those species, and that under certain conditions the absorption in other species might be increased, further work was requested relative to the metabolism of the drug.

As the FDA studied the side effect profile, the teratogenicity of the drug became clear as and the application for licensure was discontinued. Kelsey was hailed as hero. Yet despite the refusal to formally approve the product for sale, millions of doses had been administered as part of “clinical trials” (in name only). Yet due to Kelsey’s refusal to approve the drug, the drug was not widely used, and only 17 children were born in the USA with thaldomide-induced effects.

Regulators worldwide acted to ensure another thalidomide tragedy would not occur. In 1962 the Kefauver-Harris Drug Amendments were passed, increasing the rigor of the drug approval process, requiring the demonstration of safety and effectiveness via objectively designed and executed clinical trials. These amendments also implemented the requirement for adequate preclinical trials before any human studies, including animal studies to evaluate fetal risks. Marketing requirements were also implemented, restricting manufacturers from making unfounded, unsubstantiated claims of safety and efficacy. Finally, the amendments ushered in the requirement for manufacturers to collect and report all adverse events associated with drug use – measures designed to capture any events not otherwise identified in pre-marketing clinical trials. Similar actions occurred in other countries. Today, over 100 countries now collaborate with the World Health Organization to pool adverse event reporting and look for signals of drug harms.

Lessons Learned
The worldwide disaster of thalidomide led to most of the current framework we have in place today to evaluate the safety and efficacy of drug products. Ironically, these are the same requirements that manufacturers of supplements and other “alternative” medicine products have been largely successful in circumventing. In the USA, it’s DSHEA, which (as blogged about regularly at SBM) removed the onus of demonstrating safety and efficacy from the manufacturer and put the requirement to demonstrate harm on the FDA – exactly the same scenario as drugs in the early 1900′s. In Canada, the Natural Health Product regulations has introduced a lowered bar for non-drug supplements: Today even homeopathic remedies are deemed safe and effective and approved with unique recommended uses.

The Resurrection of Thalidomide
Almost 30 years after thalidomide was withdrawn, it’s back on the market in the United States, Canada and many other countries. It’s been found to be effective for a number of conditions including erythema nodosum leprosum, multiple myeloma, and is being investigated for efficacy in an array of other conditions. There’s an analog of thalidomide now marketed, lenalidomide, also used to treat cancer. To minimize the teratogenicity risk,  intensive programs are in place to minimize any possibility of use in pregnancy. So while the drug has known harms, it seems to be highly effective for some medical conditions where few effective alternatives exist. Access, therefore, is based on a careful evaluation of the risks and benefits.

Does Thalidomide Invalidate Science-Based Medicine?
Cases like thalidomide provide a good example of why SBM authors argue against regulatory double-standards, and advocate for a single, science-based standard for evaluating all products: drugs as well as supplements.  There is no intrinsic reason to think any product, regardless of its source, is safe or effective – we must evaluate it, objectively. Thalidomide’s history is a cautionary tale reminding us that assumptions without good evidence can lead to terrible consequences.

And that leads to the logical fallacies that the thalidomide retort represents.  Thalidomide is an effective drug for some conditions – but it is a teratogen. It’s not alone in this regard – other drugs have been identified as teratogens. The sale of any drug is based on an evaluation of the known benefits and risks.And getting back to the comment I received at the top, those that support alternative medicine will reject the science-based approach: This is the system that gave us thalidomide (and Vioxx, etc). Therefore, it’s a failure, and we should reject it. This is the perfect solution fallacy.

Admittedly, medicine is not perfect. Regulators don’t identify all the harms before a drug is licensed. Drug manufacturers can behave badly. And drugs don’t always work the way we want them to, and they can cause harms. They commenter I cite above took objection to an evaluation of homeopathy.  Yes, homeopathy has no toxic side effects (usually) and causes no teratogenicity – but it also has no demonstrated efficacy beyond placebo effects. The harms and problems of science-based approaches add no support to the efficacy claims of any alternative medicine system.  Homeopathy, acupuncture, and reiki don’t become effective because drugs can have side effects. SBM may not be perfect, but it delivers the goods.

More generally, comparing science-based medicine to any alternative medical system a is false dichotomy. Unlike the different alternative medicine systems (homeopathy, naturopathy, reiki, etc) which are typically based around a fixed set of rules, the only thing that science-based medicine interventions have is common is that they work. SBM is not immutable to change – treatment shown to be safe and effective become medicine, and those that are not, are discarded.  So although thalidomide causes birth defects, it is also an effective medication when used properly. We don’t have to make a choice between a system that produced drugs that cause birth defects, and alternative medicine. We choose to use treatments where the expected benefits outweigh the known risks.

Citing thalidomide as an argument against science-based approaches is also a straw man argument. The way drugs are regulated today bears little resemblance today to when thalidomide was licensed and sold. Safety standards are far more rigorous, in part because of the lesson of thalidomide. Today, the only products that are not subject to these same strict safety and efficacy standards are usually the alternative medicine treatments.

Citing thalidomide is also an appeal to fear. We hear the word and we immediately think of children born with birth defects. We don’t want that to happen. But like the perfect solution fallacy, the catastrophic side effects of thalidomide in pregnancy add no merit to to claims of efficacy of any alternative medicine treatment or system. We still need the evidence.

Conclusion
Thalidomide was a very real tragedy with a huge human cost. It’s most important lesson is that assumptions of safety and efficacy, in the absence of evidence, can be catastrophic.  Citing thalidomide as a a reason to reject science-based medicine is not only fallacious, it reflects a fundamental lack of understanding of the lessons learned.

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There have been many cases now of big companies or organizations, or wealthy individuals, threatening to sue or actually suing a blogger for libel. The most famous case is that of Simon Singh who was sued by the British Chiropractic Association over comments he made in an article. Simon braved through the expensive and exhaustive legal process (which is especially onerous in England), but he is not just a lone blogger. He is a successful author and was writing for the Guardian. Eventually the BCA was forced to drop the case – but only after the blogging community rallied behind Simon, magnifying his criticisms of the BCA by orders of magnitude. By all accounts it was a PR disaster.

The blogging community as a whole is rather passionate about this issue. We exist on the premise of free and open public discourse about important issues. At SBM we take on many controversial issues and we don’t pull our punches when criticizing what we see as pseudoscience in medicine. So of course we take notice when a large company tries to bully a blogger to silence their legitimate criticism.

According to the BMJ this has happened yet again – this time the international homeopathy producer, Boiron, is threatening a lone Italian blogger because he dared to criticize their product, Oscillococcinum. The blogger, Samuele Riva, wrote two articles on his blog, blogzero.it, criticizing what our own Mark Crislip has called “oh-so-silly-coccinum.”  The blog is entirely in Italian, but he is maintaining a page in English with updates on the Boiron vs Blogzero affair.

Criticizing homeopathy is always fun, because it is at the extreme absurd end of the silly pseudoscience spectrum, even among some stiff competition. But now homeopathy has a corporate face in Boiron – a large multinational corporation based in France. Boiron is the largest manufacturer of homeopathic products in the world and the second largest manufacturer of over-the-counter products in France.

What they are doing to this small blogger, in my opinion, is nothing less than corporate thuggery. They are using their resources and their corporate lawyers to try to silence completely legitimate criticism of their pseudoscientific products. Of course, they will only succeed in magnifying that criticism.

For example, Riva suggested that Boiron’s oscillococcinum has no active ingredient. Well, let’s see- the company lists the active ingredient in this product as “Anas barbariae hepatis et cordis extractum 200CK HPUS.” The “200C” means that the listed ingredient was diluted with a 1:100 dilution 200 times. Serial dilution is a funny thing – a 200c dilution is the equivalent of diluting 1ml of original ingredient into a volume of water that is the size of the known universe. This is far far beyond the point where there is any reasonable chance of there being even a single molecule of original ingredient left.

So Riva was completely justified (as have many other critics) in saying that Boiron’s 200c product has no active ingredient. In fact it is deceptive to list something that has been diluted 200C as an “active ingredient.”

Not that it matters in this case, because the original ingredient is a pseudoscience unto itself. Mark Crislip gives the full details, here is his summary:

In the 1919 flu epidemic a physician who did not understand that artifacts on the slide, probably bubbles, move randomly due to Brownian motion. Looking at the tissues of flu patients with a microscope, he found what he thought was not only the cause of influenza, but the cause of all diseases: small cocci (round balls) that oscillated under the microscope. He found these wiggling bubbles in all the tissues of all the ill people he examined and thought he discovered the true cause of all disease. Sigh. Yet another cause of all illness. He is the only person, before or since, to see these oscillating cocci. Hence the name.

That’s right, oscillococcinum does not even exist – essentially Boiron takes fairy dust and then dilutes it out of (non)existence. The “anas barbariea hepatis” is basically duck liver, which is supposed to contain the most concentrated nonexistent oscillococcinum. It’s a pseudoscience trifecta.

Boiron claims that their product treats the symptoms of flu. What does the evidence show? (Yes, there is evidence – someone bothered to test whether diluted fairy dust actually works)? Well, this is yet another  interesting story. Oscillococcinum was at the center of another embarrassing controversy, this one involving the Cochrane Collaboration. They published a Cochrane review of Oscillococcinum for the flu, and the author’s concluded:

Though promising, the data were not strong enough to make a general recommendation to use Oscillococcinum for first-line treatment of influenza and influenza-like syndromes. Further research is warranted but the required sample sizes are large. Current evidence does not support a preventative effect of Oscillococcinum-like homeopathic medicines in influenza and influenza-like syndromes.

This review became the poster child for what is wrong with Cochrane’s particular application of evidence-based medicine (EBM). Notice that the evidence is essentially negative, but with some positive studies – which is what we expect when studying a fancy placebo because of researcher and publication bias. But the authors concluded that the treatment is “promising” and “further research is warranted.” An SBM review of the same data would come to a very different conclusion – the data is what we would expect from an ineffective treatment. Further, the highly implausible nature of the treatment (on several levels) warrants a conclusion that it does not work, it holds no promise, and not another dime of precious research money should be wasted chasing this fantasy.

Eventually the Cochrane review was withdrawn. We interpreted this as a minor victory for SBM, although we have no way of knowing what role, if any, our criticism played in the decision to withdraw the review.

Conclusion

I hope Boiron does draw a line in the sand over their oscillococcinum product, and that it becomes the center piece of a broader public discussion about homeopathy. Most of the public does not understand what homeopathy actually is. They think it means “natural” or “herbal” medicine. They have no idea that homeopathy is about taking fanciful ingredients with a dubious connection to the symptoms in the first place, and then diluting them into oblivion, then placing a drop of the pure water that remains and placing it on a sugar pill. The resultant pill is then supposed to contain the magic vibrations of the original substance.

This rank pseudoscience, which has no place in 21st century medicine, is the business of Boiron. Let’s see them try to defend themselves and their products. Let’s see them harass bloggers and those who are just trying to expose the public to the truth. Let’s see them argue in public how air bubbles in duck liver fantastically diluted can treat the flu.

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Common warts (verruca vulgaris) are more of a nuisance than a serious health problem, but they are interesting. There is a whole mythology surrounding their cause (touching toads?) and treatment (everything from banana peels to vitamin C).  Many people believe they can be made to vanish by suggestion or hypnosis. I used to believe that too.

Every doctor has wart stories. Here are some of mine.

• A patient made an appointment to see me because he had a wart, but when he tried to show me his wart he discovered that it had vanished! Apparently, just making the appointment cured it.
• Another patient did have obvious warts and I prescribed the “wart medicine” that our pharmacy tech compounded, based on salicylic acid. He was out of one of the ingredients and had to ask my patient to return in a week. When she returned, her warts were already gone. The wart medicine apparently worked so well that you didn’t even have to use it!
• I worked with a dermatologist who used a colorful laminated card with a picture of a toad to stroke children’s warts, telling them it was a wart remover. In his experience, this would frequently make the wart vanish over the next few days. Was this ethical? Was he lying and deliberately deceiving patients, or could this be excused as playing make-believe to distract the child and improve his attitude about the wart?

He was certainly deceiving himself in thinking that this foolishness was actually effective based on his own uncontrolled observations. Hypnotists claim success in treating warts with direct suggestion: they say that prepubertal children respond almost without exception, although it is less effective in adults.  I was taught that if a patient had multiple warts and you treated just one of them, the others would likely vanish too. This might sort of make sense if the treatment stimulated an immune response, but I haven’t seen any evidence to support it.

What can science tell us about warts?

A new review article in American Family Physician, “Treatment of Nongenital Cutaneous Warts” by Mulhem and Pinelis provides a thorough update of the current evidence.

Cutaneous warts are epidermal proliferations caused by over 100 types of human papillomavirus. They are spread person-to-person or by contact with contaminated objects. They are most common in children. Walking barefoot is a risk factor for plantar warts (warts on the sole of the foot that that have a different appearance due to being under pressure). Nail-biting, meat handling, and immunosuppression are also risk factors. 90% of renal transplant patients develop warts.

Warts are usually self-limited. Half resolve spontaneously in a year, two-thirds within two years. Watchful waiting is an option, but patients often want treatment because of discomfort or social stigma. Two treatments have been clearly proven effective by scientific studies: salicylic acid and freezing with liquid nitrogen. There is limited evidence for silver nitrate, topical fluorouracil, and topical zinc. There is little to no good evidence for cantharidin, dinitrochlorobenzene, oral cimetidine, oral zinc sulfate, podophyllin, propolis ointment, retinoids and topical garlic extract. A few years ago, duct tape was reported to work, but subsequent studies showed that it probably does not. Warts can also be surgically removed, and dermatologists can offer specialized treatments such as intralesional bleomycin and pulse dye laser.

I found it interesting that the AFP review didn’t even bother to mention hypnosis, suggestion, or CAM.

Salicylic acid preparations are available over the counter for self-treatment. They are well tolerated and produce a 73% cure rate in 6 to 12 weeks. Cryotherapy with liquid nitrogen is equally effective but is more expensive, requires multiple office visits, and can cause pain, blistering, pigment changes, and other complications (tendon or nerve damage, scarring), especially if used too aggressively. A combination of cryotherapy and salicylic acid may give the best results. If a treatment caused permanent scarring, that would be worse than the disease.

To take a page from Mark Crislip’s job description, the patient has the mindset “Me have wart. You cure wart. Me go home.” The health care provider can re-frame the issue as “You have wart. Me educate. You think. We discuss.” Since warts are benign and self-limited, the option of not treating should always be on the table.

What about CAM?

Warts provide a fertile field for CAM. Various CAM modalities (chiropractic, acupuncture, homeopathy, energy medicine, etc.) have been claimed to cure warts. Acupuncturists have claimed a 90% success rate in only 1-3 weeks. PubMed lists a recent article about treatment with “sparrow-pecking” moxibustion that sounds intriguing, but no abstract is available. When warts follow their natural history and resolve, CAM is happy to take the credit. When they fail to resolve, CAM can continue treatments and continue to generate income. It’s a cash cow and ideal CAM fodder. Since warts are so common, potential clients are plentiful.

I used to believe that warts could be wished away. Now that I am older and wiser, I think warts vanish because of the natural course of the disease, not because of suggestion. Observers have reached false conclusions due to the post hoc ergo propter hoc (correlation is not causation) fallacy. Warts that went away after suggestion didn’t go away because of suggestion. The many folk remedies, like banana peels, were perpetuated by similar errors in reasoning. No matter how much we wish mind-over-matter worked, warts can’t be wished away: that’s the truth, warts and all.

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