Clinical Facts & Curios

Q 

A 17-year-old young lady is in your office for an annual checkup. Her only real complaint is that she is soon off to college and fears that she will be embarrassed by a lifelong problem she has had with blushing. The blushing begins on her neck and spreads up to her face and occurs in situations in which she feels awkward, such as having to speak before the class and when meeting new people. She recognizes that she may have a mild case of social phobia, but nonetheless, the blushing is her principal concern.

What might you do to assist her with this problem?

A 

There is not much written in the pediatric literature about blushing, which is usually characterized by episodic attacks of redness of the face, ears, and often the neck, often accompanied by tingling or a burning sensation in these areas. An involuntary process, it is uncontrollable and cannot be inhibited and is usually triggered in susceptible individuals by the mildest of emotions. Darwin, in fact, characterized blushing as “the most peculiar and most human of all expressions,” since no other animal species has been described with the phenomenon. Blushing is seen in all races and, although those with darker skin do not find it as much of a problem because of the visible changes are less striking, it still may be associated with a tingling and burning sensation of the skin.

For those with severe blushing induced purely by emotion and for those with social phobia, several treatment options have recently been reviewed (Nicolaou M, Paes T, Wakelin S. Blushing: an embarrassing condition, but treatable. Lancet 2006;367:1297-99). Adolescent girls and women may choose simply to use camouflaging makeup or high-neck clothing. Others might benefit from cognitive behavioral treatment and task-concentration training (Mulken S, Bögels SM, de Jong PJ, et al. You’re blushing: effects of task-concentration training versus exposure in vivo on fear and physiology. J Anxiety Disord 2001;15:413-32; Scholing A, Emmelkamp PM. Treatment of fear of blushing, sweating, or trembling. Results at long-term follow-up. Behav Modif 1996;20:338-56). Medical treatment with drugs such as beta-blockers might reduce blushing, although clinical studies have yet to have been reported. Clonidine is licensed for use in postmenopausal flushing, but no one knows whether this would be effective in the usual type of flushing that most have. Anxiolytics and antidepressants can help alleviate the anxiety associated with blushing, but no published studies show that it actually affects the intensity of the blushing itself. There have been isolated reports on the use of intradermal botulinum toxin-A injection to treat neck and facial blushing, but this type of treatment is obviously temporary and can be fairly expensive in the long run. This indication is not a licensed use of botulinum toxin-A.

The only highly effective treatment for blushing when absolutely needed is bilateral endoscopic transthoracic sympathectomy. It is the option of choice for blushing when nonsurgical treatments have failed and if the consequences of blushing are severe. The success rate with this surgical approach approaches 90% with documented substantial improvement in quality of life (Drott C, Claes G, Olsson-Rex L, et al. Successful treatment of facial blushing by endoscopic transthoracic sympathicectomy. Br J Dermatol 1998;138:639-43). Complications of surgery are rare, but the most common drawback is a compensatory sweating on other parts of the body, the cause of which is uncertain. As many as 80% of individuals will experience this side effect with somewhere between 1 and 2% of individuals being so significantly affected that they regret having had the operation.

If all this sounds a bit over the top in terms of treatment of such a common problem as blushing, one alternative might be to go on the Internet. There are a number of sites that are designed to help those with this problem shy of the need for medicines or surgery. Just Google “blushing” and you will see the array of sites available for affected individuals to peruse.

Q 

You are called to the emergency room to consult on a 12-year-old who has deep-green macules coalescing into diffuse patches that are mainly located on the volar and lateral side of the fingers and on the palms of the hands. The question is, what is the differential diagnosis of green sweating spots on the hands and the feet?

A 

Recently, a middle-aged man presented with the above signs. He also had recurrent fever, mild jaundice, and epigastric pain. The most startling aspects of the physical examination, however, besides mild jaundice, were deep green macules that were coalescing over his fingers, palms of the hands, and soles of the feet. A biopsy of the lesions showed the staining to be due to degradation of bilirubin products in the skin, presumably laid down by the sweating of bilirubin. Serum bilirubin was 8 mg/dL. Cholelithiasis was diagnosed by endoscopic retrograde cholangiopancreatography. A surgical cholecystectomy corrected the problem and the green discoloration of the skin cleared over a 3-week period (DiStefani A, Bianchi L, Orlandi A, et al. Green sweating spots on the hands and feet: unusual expression of hyperbilirubinemia. Ann Intern Med 2006;145:710-11).

If you ever see a patient with green pigmentation of the skin, the differential diagnosis is fairly short. Green skin has been reported with Pseudomonas aeruginosa infection (particularly of the nails), during resolution of ecchymosis, cutaneous absorption of exogenous pigments, copper deposition into the skin, certain poisonings, sweat gland chromhidrosis, or pseudochromhidrosis, acute pancreatitis, intraabdominal hemorrhagic diseases, and eosinophilic cellulitis (Kanzaki T, Tsuda J: Biopigment deposition at sweat pores of patients with liver disease. J Am Acad Dermatol 1992;26:655-6). An increased level of bilirubin may cause a transient green discoloration when it is excreted through eccrine sweat glands. The green color observed is attributable to the change from brown-colored bilirubin to green-colored biliverdin by oxidative processes. If you are not familiar with chromidiosis, it can involve eccrine or apocrine forms and is an uncommon condition characterized by production of variously colored sweat that can be yellow, green, blue, or black. Chromhidrosis may follow the ingestion of certain dyes or drugs. Pseudochromhidrosis refers to the coloring of sweat when exogenous chemicals, such as extrinsic dyes or paints, or chromogenic bacteria react on the skin’s surface.

Remember the differential diagnosis of green skin. There is an old saying that if you live long enough, you might just see just about everything there is that presents clinically.

Q 

Is having a sweet tooth potentially harmful to your health?

A 

Besides causing dental caries, the ingestion of sweets in excess has been associated with one problem in particular. A prospective population cohort study from Sweden that began in 1997 has identified that consuming added sugar, soft drinks, sweetened soups, and stewed fruits is positively associated with the risk of developing pancreatic cancer. There were 137 new cases of pancreatic cancer among some 78,000 adults in this study, a number far in excess than would be normally anticipated (Larsson SC, Bergkvist L, Wolk A: Consumption of sugar and sugar-sweetened foods and the risk of pancreatic cancer in a prospective study. Am J Clin Nutr 2006;84:1171-6).

Q 

What is the latest in home therapies for hirsutism?

A 

Obviously men are not that worried about hirsutism, but teens and adult women are. It turns out that drinking spearmint tea can reduce mild hirsutism in affected women. Previous reports have suggested that extracts of the spearmint plant can lower male libido, probably by reducing levels of androgens. Studies in rats have confirmed this effect. More recently, a study of 21 hirsute women has found that drinking two cups of spearmint tea a day for 5 days significantly reduces their androgen levels, suggesting that this might become a more palatable alternative to hormone treatment to suppress androgen production (Phytotherapy Res 2007, doi:10.1002/ptr.2074).

There are no data on the use of spearmint Tic-Tacs or spearmint-flavored Wrigley’s chewing gum.

Q 

More and more reports are appearing these days regarding allergic reactions to the use of hair-coloring dyes. What is the latest and a cause of allergy in terms of a popular fad that may increase the risk of sensitization to hair dyes?

A 

Temporary henna tattoos are commonly applied during holidays, at country fairs, and other merry-making functions. Unfortunately, henna tattoos can also cause sensitization to paraphenylenediamine in color hair dyes, causing allergic contact dermatitis. A series of similar cases was recently reported describing stories of young people developing erythema, edema, and pruritus of the scalp, hairline, eyelids, or cheeks a couple of days after having their hair dyed. All of them had at least one henna tattoo applied in the recent past (Editorial comment. Henna tattoos. BMJ 2007;334:482).

While henna tattoos may be temporary, the lingering effect in terms of allergic reactions may not.

Q 

While on the topic to allergy to hair dyes, how bad is the problem and is the incidence of hair dye use rising?

A 

For more than 100 years paraphenylenediamine (PPD) and other related members of the aromatic amine family have been the main agents used in permanent hair dyes, and more than two-thirds of hair dyes currently contain PPD. This compound is an effective hair dye owing to its low molecular weight, its ability to penetrate the hair shaft and follicle, its strong protein binding capacity, and its rapid polymerization in the presence of a coupler (a kind of catalyst) and an oxidizing agent. However, these properties also make PPD an ideal contact allergen and PPD is among the most potent contact allergens out there. Reactions to PPD have become such a serious problem that it has been banned from hair dyes in at least three European countries but still makes its way into many of the common hair dyes elsewhere. Contact allergy to PPD and related aromatic amine dyes is detected by patch testing using 1% PPD and petroleum jelly.

Pediatric and adult dermatologists anecdotally have reported that the frequency of positive reactions to PPD on patch testing is increasing. Allergic reactions seem to be doubling in frequency every 6 years or so. This rise is not attributable to an increase in occupational exposure such as in hairdressers. Whether exposure to henna tattoos accounts for any significant portion of the increase is questionable as well.

Market research indicates that more people are dying their hair and are doing so at a younger age. A survey undertaken in 1992 showed that 13% of female high school students, 6% of women in their 20s, and 2% of men in their 20s reported using hair coloring products, but by 2001 the proportions using hair coloring agents had increased in these three groups to 41, 85, and 33%, respectively (Sosted H, Basketter BA, Estreda E, et al. Ranking of hair dye substances according to predicted sensitization potency. Quantitative structure—activity relationships. Contact Dermatitis 2004;51:241-54). Furthermore, high schoolers and young women were dying their hair at shorter intervals. Here in the United States, the proportion of young men dying their hair has increased by 25% in the 5 years since 1998. We are not alone in our vanity. In Denmark, 75% of women and 18% of men have used hair dye.

The “culture of youth” continues. If you have money to invest, invest it in hair dye manufacturers and botulinum spores. You cannot go wrong.

Q 

While on the topic of exposures that may affect skin, is there any potential long-term consequence of phototherapy for the management of neonatal hyperbilirubinemia?

A 

Phototherapy has been around now for some 40 years to treat neonatal hyperbilirubinemia. A study from France raises questions about its long-term safety (Matichard E, Le Henanff A, Sanders A, et al. Effect of neonatal phototherapy on melanocytic nevus count in children. Arch Dermatol 2006;142:1599-604). A group of children aged 8 to 9 years who had been treated with phototherapy as neonates were shown to have significantly more nevi in comparison to a control group. Because higher numbers of acquired benign nevi are associated with an increased risk of melanoma, the study raises the issue of whether exposure to neonatal phototherapy should require regular dermatological surveillance for the rest of an individual’s life.

As of now, there is no concrete link between phototherapy and the development of melanoma, but this does not mean that such a link will not be documented in the future.

Q 

Just how big are high school linemen these days and what is the implication for long-term health?

A 

Those who play football here in the United States have to be big, but some young players are so heavy they clearly are putting themselves at risk for future health-related problems. A survey of high school linemen (defenders) in the state of Iowa has found that 45% are clearly overweight and another 28% are almost there with a body mass index between the 85th and 95th centile for age. Almost 1 in 10 linemen have a body mass index above 35, the adult threshold for severe obesity.

If you are wondering how investigators were able to study every high school lineman in the state of Iowa, data on height and weight are publicly available on published rosters. The survey included 69% of Iowa’s high school teams and the conclusions are probably generalizable to linemen in other parts of the country as well.

When you have a body mass index above 35, someone trying to tackle you will feel like they have hit a brick wall (Laurson KR, Eisenmann JC. Prevalence of overweight among high school football linemen. JAMA 2007;297:363-4).

Q 

When this editor was growing up, he was admonished on a number of occasions to “eat your vegetables.” The question is, does eating a lot of vegetables during childhood make anyone smarter later in life?

A 

The answer to this query comes from a study of more than 8000 men and women age 30 years who have been participating in the 1970 British national birth cohort study (Gale CR, Deary J, Batty GED, et al. IQ in childhood and vegetarianism and adulthood: 1970 British cohort study. BMJ 2007;334:245-8). The bottom line is that if you are smart as a child, you are more likely to become a vegetarian as an adult (not necessarily vice versa). A higher IQ at age 10 is associated with a significantly increased likelihood of being a vegetarian at age 30. For those who have an IQ score at age 10 that is 1 standard deviation above the mean, the probability of being a vegetarian at age 30 increases 1.38×. Exactly why this link exists remains speculative, but it is possible that the association between childhood IQ and vegetarianism in later life is not a causal chain of events related to health, but rather that those with higher IQ compared with those with less brain power simply develop a different lifestyle as they age. This has been shown with respect to choice of newspapers, types of books read, and preferred types of entertainment, not just what types of food one ages with.

You can bet that there will be future studies on why bright children grow up to make healthier choices. Maybe these adults were fish eaters as smart kids. We all know that fish is brain food.

Q 

While on the topic of a possible relationship between eating vegetables and IQ, does eating a lot of vegetables slow the decline in cognitive functioning as we age?

A 

Eating lots of vegetables is indeed associated with a slowing of cognitive decline in older folks. In contrast, a high intake of fruit does not slow cognitive decline. This was the conclusion of a 6-year study of 3718 people age 65 years or older (Morris MC, Evans DA, Tangney CC, et al. Associations of vegetable and fruit consumption with age-related cognitive change. Neurology 2006;67:1370-6). Participants were taking part in the Chicago Health and Aging Project. Individuals in this project who were in the fourth of the five quintiles in terms of vegetable intake had 40% less cognitive decline than the individuals who were in the lowest quintile who ate the fewest vegetables. The former ate an average of 2.8 servings a day of vegetables, while the latter had just 0.9 servings a day of vegetables. Individuals in the top quintile who ate the most vegetables, an average of 4.1 servings of vegetables a day, had 38% less decline compared with the bottom quintile. Unfortunately, this survey did not indicate a cause-and-effect relationship between the eating of vegetables and cognitive decline. It is hard to tell whether the eating of vegetables slowed the decline or those who were already on the slippery slope, for whatever reason, had an aversion to wanting to eat their vegetables. It is said that as we enter the extreme of life, we revert back to our childhood. This sounds about right since most kids do not like vegetables either.

Q 

Is it safer to be in a prison or recently discharged from a prison?

A 

There are more inmates in prison these days than ever before. With respect to the question posed, a recent study has followed all inmates released from the Washington State Department of Corrections from 1999 through December 2003 to see how recently released inmates fare. Apparently they do not do so well. Of some 30,237 released inmates, 443 died within 2 years of release from incarceration. The overall mortality rate was 777 deaths per 100,000 person years. The adjusted risk of death among former inmates was found to be 3.5 times that of other state residents. During the first 2 weeks after release, the risk of death, however, among former inmates was 12.7 times that of other state residents, with a markedly elevated risk of death from drug overdose. The four leading causes of death among former inmates are drug overdose, cardiovascular disease, homicide, and suicide (Binswanger IA, Stern MF, Deyo RA, et al. Release from prison—a high risk of death for former inmates. N Engl J Med 2007;356:157-65).

To put these data into perspective, about 600,000 individuals are released from US prisons annually. In addition, jails in which persons awaiting trial or serving short-term sentences for misdemeanors are detained have approximately 10 million releases annually (7.2 million unique persons). If the latter are at the same risk of death as former inmates of Washington State prisons, the consequences of the excess risk of death after release becomes very substantial.

Q 

What happens to all those hormones that our body produces or the ones we artificially take and what is the effect, if any, on wildlife?

A 

This question may seem like an obscure one, and perhaps one that might be a suitable entry for Ripley’s Believe It Or Not. Nonetheless, there is a relationship between our hormones and a negative impact on wildlife. In 1997, during a routine ecological assessment of several British waterways, wildlife biologists discovered an unusually high number of abnormal fish living downstream of two sewage-treatment plants. The fish were considered intersexual because their gonads contained both ovarian and testicular tissue. Nearly two decades later, after the development of more sensitive analytical techniques, researchers have provided an explanation. They have traced the animals reproductive problems to the low concentrations of estrogens that had entered the environment in waters released by sewage plants (Cunningham A. Traces of trouble: removing the small but potent quantities of estrogens from waterways. Sci News 2007;171:152).

It seems that estrogens in concentrations as low as a few parts per trillion lead to reproductive abnormalities in fish. Evidence of reproductive harm to aquatic life chronically exposed to estrogens continues to accumulate here in the United States, Italy, and elsewhere. Naturally occurring estrogens enter the environment from not only human sources, but also from livestock urine and feces, the latter being even more significant. Synthetic estrogen from oral contraceptives also turns up in sewage. Sewage treatment does not remove trace pollutants. The main task of sewage-treatment plants is to remove organic matter from wastewater. Decomposing organic matter will rob water of oxygen and endanger aquatic life. Some treatment plants also remove nitrogen and phosphorus, nutrients that encourage growth of oxygen-depleting algae. Finally, treatment plants kill pathogens in the water before discharging it. Estrogen and estrogen-like compounds exit sewage plants unfettered.

If there is a lesson in all this, do not inhabit your local swim hole if that swim hole is downstream of a sewage plant. No one wants to turn into a hermaphrodite.

Q 

What accounts for 18% of greenhouse gas emissions, 9% of carbon dioxide released into the atmosphere, produces 37% of all methane that does not occur naturally, and consumes 8% of all fresh water?

A 

If you answered livestock raised to feed humans, you would be correct. It appears that livestock production taps 8% of all freshwater used by humanity, primarily to irrigate feed crops. Farmed animals represent 20% of all of the total mass of land animals and are edging out other species cutting biodiversity. Some 30% of the land that livestock now occupy once nurtured wildlife. Animal farming accounts for 18% of greenhouse-gas emissions, making it a bigger contributor than transportation. For instance, livestock production is responsible for 9% of carbon dioxide releases, mostly as woodlands are burned around the globe for pastures or to create fields to grow feed. Moreover, 30% of all methane in the atmosphere comes from livestock. Molecule-for-molecule, this major greenhouse gas contributes 23 times as much to global warming as carbon dioxide does (Editorial comment. Big footprints. Sci News 2007;171:30). These data ought to make some of us, at least, want to become vegetarians.

Q 

Relatively little has been written about Abraham Lincoln’s clinical depression, at least until recently. What new insights have been reported?

A 

The answer to this question comes from a book authored by Joshua Wolf Shenk (Shenk JW. Lincoln’s melancholy: how depression challenged the president and fueled his greatness. New York: Houghton Mifflin; 2006, ISBN-13 978-0-618-55116-3). Although the emotional aspects of Lincoln’s life have been minimized by prominent Lincoln historians of the 20th century, contemporary reviews of primary source material now provide ample evidence that Lincoln experienced an enduring and at times near-fatal depression. Lincoln experienced at least two major depressive episodes, as defined by the Diagnostic and Statistical Manual of Mental Disorders (4th Ed.). The first occurred in 1835, a time of intense preoccupation with his law studies and with the illness and subsequent death of Ann Rutledge, a woman for whom he had developed a strong affection. In the weeks following her death, Lincoln spoke openly of suicide and confided to a friend that he was so overcome with depression that he not dare carry a knife. Clearly unable to care for himself, neighbors took Lincoln in until he was able to live safely on his own.

The second episode of Lincoln’s depression occurred in 1841. It is likely that several events, occurring in close order, precipitated this breakdown. Lincoln had broken off his engagement to Mary Todd, possibly because of his affection for another woman. He was also undergoing devastating reversals as a representative in the Illinois State Legislature, stemming from his ill-timed support of public works projects. His law practice, while successful, was becoming increasingly hectic, and his close friend and confidant, Joshua Speed, was about to marry and move away. Speed later gave an account of the breakdown: “Lincoln went crazy—we had to remove razors from his room—take away all the knives and other dangerous things—it was terrible.” Once again it was the supportive intervention and kindness of friends that nurtured him through the episode. Fortunately this crisis proved a turning point in Lincoln’s life. He developed an “irrepressible desire” to accomplish something while he lived, some significant impact on the events of the day “that would redound to the interest of his fellowman.”

In later life, Lincoln was able to cope with his depression by this development of a sense of purpose that informed his actions and moderated his manner. He was determined to make some substantive contribution to society for which he would be remembered. He recognized the importance of social engagement and had a wide circle of friends. From an early age, he cultivated the use of humor and storytelling as a means of bonding with others. He read voraciously and found solace especially in the works of Poe and Shakespeare. Finally, he openly acknowledged the fact of his suffering and was a keen observer of his own illness. He developed a theory of depression consistent in many ways with modern views. He recognized moodiness as “a misfortune, not a fault” and recognized that he was constitutionally predisposed to his depression. He also recognized three factors that exacerbated his depression: social isolation, high stress, and periods of bleak weather, all recognized to be precipitators of the condition in others.

What is interesting about Lincoln’s depression is what would have happened had he received modern-day therapy to eliminate, or mitigate, the problem. Would Lincoln have been as great as he was? Would he have set such challenges for greatness? We will never know.