The Monster Mash – Diseases That May Have Spawned Monster Legends

We’ve all been there. Sick with the flu, we stagger around the house in a feverish state. With our baked minds marinating in a cauldron of cytokines, we can hardly formulate a complete sentence. Droopy-eyed and disheveled, we nearly scare ourselves to death when gazing at the reflection of our barely recognizable self. Terrified out of her diaper, your toddler may even run away from you with a frightful scream. As you’ll learn from the list below, there are several diseases that produce symptoms that mimic characteristics associated with legendary monsters.

Vampires

These blood-sucking creatures of the night are believed to have been inspired by the Romanian Prince Vlad, born in Transylvania in 1431. His father was named Dracul, and Dracula means “son of Dracul”. Dracula was a “defender of the Christian faith” who, ironically, gained notoriety by impaling his victims and dipping his bread in their blood before consuming it.

 

Prince Vlad before dinner (left) and after dinner (right).

 

However, the symptoms of porphyria (yes…it is pronounced poor-FEAR-e-uh!) are likely to have contributed to several aspects of vampire lore. While it sounds like a lost Def Leppard album, porphyria is actually a blood disorder that arises when patients cannot make and regulate heme properly (heme is a critical part of hemoglobin in the blood).

Porphyria can cause excessive nail growth and receding gums, the latter of which may make the canine teeth look more like fangs. Moreover, porphyria can cause skin to bubble and blister just minutes following exposure to sunlight. Look no further than 1985’s cult classic, Fright Night, to witness the awesome power of sunlight destroying a vampire.
 

 

Finally, to make up for the compromised hemoglobin production, the treatment for porphyria involves injecting patients with blood. Despite this parallel with vampirism, people with the disease do not “thirst for blood” or bite others.

Pluto from The Hills Have Eyes

Michael Berryman, best known for his portrayal of Pluto in the 1977 cult classic, The Hills Have Eyes, has an unforgettable appearance. While his role as a deranged desert cannibal haunted the dreams of millions, his character did not require hours in the make-up chair. Rather, his appearance is attributable to a rare genetic condition known as hypohidrotic ectodermal dysplasia. People with this syndrome have fewer sweat glands, sparse body hair, and missing or abnormal teeth. In addition, facial features of these individuals tend to be consistent with those seen in Berryman’s photo below. Other than heat intolerance due to a reduced ability to sweat, people with hypohidrotic ectodermal dysplasia are otherwise healthy.

 

Instantly recognizable on screen, Berryman has appeared in dozens of subsequent roles, including multiple appearances in Star Trek episodes and films.

Werewolves

On the opposite end of the spectrum, people with excessive hair, especially when it appears on the face, have long been attractions at circus sideshows. Perhaps the most famous is Julia Pastrana, also known as “the bearded lady” or “ape woman”, who caught the attention of many onlookers during her travels with “the freak show” in the 1800s. There is a name for this condition, which often resembles the classic appearance of a werewolf:  congenital hypertrichosis lanuginosa, or CHL. Babies born with CHL are usually covered in hair right out of the womb. Today, people afflicted with CHL can elect to have that hair removed with lasers.

“Don’t worry, it’s just a little hypertrichosis flare-up!”

Demonic Possession

Schizophrenia or multiple personality disorders are often cited as likely explanations for people exhibiting unusual behaviors. But an autoimmune disease called “anti-NMDA receptor encephalitis” has been recently described that also produces striking symptoms of demonic possession. A first-hand account of this ailment was written by Susannah Cahalan called, Brain on Fire: My Month of Madness.

 

Incidentally, anti-NMDA receptor encephalitis does not induce the green projectile vomiting made famous in The Exorcist. You have to go to Taco-Bell for that.

Zombies

There are a number of conditions that give people a zombie persona, such as that window of time from waking up till you get some coffee in you. While there is no disease that allows you to persist as an undead, brain-hungry zombie, there is a famous one that can drive animals to bite others:  rabies. Rabies is caused by a virus, and, thanks to Stephen King’s Cujo, most of us are familiar with how rabies can transform a puppy into a hellhound. The virus is plentiful in the salvia of infected animals and is transmitted through a bite or scratch. Many pathogens change the behavior of their host in order to spread. The rabies virus infects the brain in such a way that its host organism becomes overly aggressive, increasing the odds that the virus will be transmitted to a new victim through a bite.

Another type of disorder can lead to an eerie change in behavior with shades of zombification. A rare mental illness called Cotard delusion, or walking corpse syndrome, occurs when the afflicted no longer believe they are alive. First described in 1880 by neurologist Jules Cotard, this “delirium of negation” can run from mild self-loathing to severe depression. In the most extreme cases, the afflicted will deny the existence of certain body parts or their entire body. Consequently, they will stop taking care of themselves, even to the point of starving to death.

 

Marilyn Manson or ‘Cotard delusion’ support group?

 

For some interesting examples of zombification in wildlife, be sure to read Mark’s recent post, “Zombies And The Loss Of Free Will”.

Contributed by:  Bill Sullivan

Follow Bill on Twitter: @wjsullivan

 

Schulenburg-Brand D, Katugampola R, Anstey AV, & Badminton MN (2014). The cutaneous porphyrias. Dermatologic clinics, 32 (3) PMID: 24891059

Deshmukh S, & Prashanth S (2012). Ectodermal dysplasia: a genetic review. International journal of clinical pediatric dentistry, 5 (3), 197-202 PMID: 25206167

Kaur S, Juneja M, Mishra D, & Jain S (2014). Anti-N-methyl-D-aspartate receptor encephalitis: A case report and review of the literature. Journal of pediatric neurosciences, 9 (2), 145-7 PMID: 25250071

Ramirez-Bermudez J, Aguilar-Venegas LC, Crail-Melendez D, Espinola-Nadurille M, Nente F, & Mendez MF (2010). Cotard syndrome in neurological and psychiatric patients. The Journal of neuropsychiatry and clinical neurosciences, 22 (4), 409-16 PMID: 21037126

The Witches In The Rye

The Salem Witch trials remain one of the most haunting chapters in colonial American history. In the winter of 1692, the Puritans in Salem, Massachusetts were facing a terrifying conundrum. For no apparent reason, several young girls started behaving out of sorts.

Contrary to what you might see in the movies, the Salem witches
were not green and they failed miserably at broom flying.

These girls were having unusual fits. One minute they would be ranting incoherently and the next they would regress into a trance-like state (not unlike some candidates in political debates). After the doctor could find nothing wrong with the girls, the obvious conclusion was…witchcraft. 

The finger-pointing quickly commenced - who was responsible for bewitching these girls? But it wasn't easy to spot the guilty parties - it's not like they parked a broom outside the general store or asked for help getting a big black cauldron through their front door. 

The town was whipped up into an historic frenzy and, within a few short months, nearly 200 people were accused of being a witch and 19 of them tragically hanged. The mysterious events disappeared almost as quickly as they came and did not return.

The winter in Salem, 1692, was particularly grim. In addition to battling the cold and hunger, one had to be careful to avoid being accused of witchcraft.

While many people are quick to attribute a mystery to supernatural forces, Linnda Caporael was not content with this explanation. In the 1970s, as Caporael studied the firsthand accounts of Salem’s citizens, she hypothesized that a neurological toxin may be at play.

Caporael recalled that in 1951, the denizens of a small town in France suffered an outbreak of unusual behavior that was linked to ergot poisoning. Ergot is a fungus that grows on rye grain and contains alkaloids such as lysergic acid, the precursor of the psychoactive drug LSD. The strange behavior of the young girls may have looked like witchcraft to someone under the influence of ergot. 

No, “ergot on rye” is not the name of a sandwich you can order at the local deli. These dark areas on the grain are a fungus that may have initiated the Salem Witch trials.

There is little debate that ergot poisoning can cause hallucinations, but is it plausible that the terrible events in Salem had something to do with this fungus? We can’t know for sure, but several lines of evidence are consistent with Caporael’s theory.

Rye grain was indeed the staple crop used to make the bread back then. 1691 was a very warm and wet year for Salem, which would have provided an ideal climate for ergot to flourish. The contaminated rye would have been harvested in the fall to bake bread in the winter, in line with the start of the outbreak just after the New Year.

The ergot poisoning hypothesis also explains why the witch hysteria failed to rear its ugly head again. The following season was very dry, which is not conducive to the growth of the fungus, leaving the rye untainted in 1693.

The ergot theory is not without its problems, as spelled out in this paper. In addition, many scholars highlight the tense atmosphere in Salem at the time. Accusations of witchcraft may have had more to do with rivaling families than anything else.

Contributed by: Bill Sullivan, Ph.D.

Follow Bill on Twitter.

Caporael LR (1976). Ergotism: the satan loosed in Salem? Science (New York, N.Y.), 192 (4234), 21-6 PMID: 769159

Everybody’s Free To Wear Sunscreen…And Prevent Skin Cancer

Our last article discussed using sunscreen to help protect skin against damaging UV radiation. When used properly, sunscreen prevents sunburn and sun-induced skin aging, and protects from skin cancer. Studies have shown that sunscreen use reduces the incidence rate of squamous cell carcinoma (SCC) and melanoma, but currently no evidence supports a protective role against basal cell carcinoma (BCC).

While some people, including supermodel Gisele Bundchen, believe sunscreen is dangerous (she declared “I cannot put that poison on my body”) experts such as The Skin Cancer Foundation and the American Academy of Dermatology—and even Cosmopolitan magazine—disagree with her and other skeptics.

A large, randomized controlled trial examined the effect of daily sunscreen use on the development of skin cancers. Researchers followed 1621 Australians from 1992-2006. From 1992-1996, participants were randomly placed in a group and instructed to either use the study-provided broad spectrum SPF 16 sunscreen daily on face, arms, neck and hands, or to continue personal discretionary use of sunscreen. At the 2004 follow up, researchers noted that the daily sunscreen use group had a 35% rate reduction in the incidence of SCC (considering all SCCs that appeared throughout the entire study). However, the incidence of BCC was not statistically different between the two groups. More recent studies corroborate these results.

US Senator and 2008 Republican Presidential Candidate John McCain has had multiple melanomas removed. Other political figures have battled skin cancer, including former Presidents Jimmy Carter (metastatic melanoma) and Bill Clinton (BCC), and former First Lady Laura Bush (SCC).

In 2006, researchers followed up again, this time looking for melanoma. The overall incidence rate of melanoma was 50% less in the sunscreen intervention group than the discretionary use group (out of approximately 800 people in each group, 11 people in sunscreen group and 22 in the control group developed melanoma). It should be noted that these results had borderline statistical significance, with a P value of 0.051 (P = 0.05 is the accepted cutoff for significance). This essentially translates to a 5.1% probability of these findings being due to chance, rather than to the actual sunscreen intervention. Also, there was a 73% lower rate of invasive melanoma in the sunscreen group. Although there was no significant difference in number of melanomas diagnosed at the prescribed intervention sites, it is possible that sunscreen use reduced the risk, as participants in the sunscreen intervention group reported more frequent use of sunscreen over the whole body after the intervention terminated.

Although these results are not the most compelling, they nonetheless point to a protective role of sunscreen. Many factors may contribute to a less than straightforward outcome. First, the sunscreen intervention was in adults and lasted 4.5 years. Melanoma and BCC are thought to result from both long term sun exposure and intense, intermittent episodes (sunburns), whereas SCC is mainly caused by cumulative UV exposure (both natural and indoor tanning bed). Furthermore, blistering childhood sunburns are a risk factor for melanoma. One study that examined sunscreen use in children found a significant protective benefit. Regular use (applied any time sun exposure would exceed 30 min) of a broad-spectrum SPF 30 sunscreen over a 3-year period resulted in significantly fewer newly developed moles, the number of which is a risk factor for melanoma.

Second, participants in the non-sunscreen intervention group continued their discretionary use of sunscreen. No trial in humans could ever prohibit sunscreen use or provide a placebo for ethical reasons. Therefore, perfectly delineating the protective effect of sunscreen is difficult.

Many questionnaire-based studies that rely on participants’ memory of sunscreen use suffer from recall bias. Some of these studies showed no benefit of sunscreen for melanoma prevention but memory limits the reliability of these results. The bottom line is that sunscreen protects from UV radiation, a known human carcinogen.

The skin consists of two layers, the dermis and epidermis. The epidermis contains a variety of cell types, including squamous cells, basal cells and melanocytes. These are the sources for squamous cell carcinoma, basal cell carcinoma and melanoma, respectively.

UV radiation is implicated in up to 90% of nonmelanoma skin cancers, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Mutations consistent with UV radiation were also found in the genomes of melanoma tumors; UV radiation is thought to be responsible for the majority of melanoma. Whereas SCC and BCC are more frequent, melanoma is more often fatal. While UV radiation is the single most important risk factor for skin cancer, it’s worth noting that it is not responsible for all skin cancers. Aside from environmental carcinogens, cancer can arise due to a person’s genetics (familial effect) or random mutations.

Acral melanoma is a type of skin cancer not caused by UV radiation and is genetically distinct from UV-induced cutaneous malignant melanoma. Bob Marley’s acral melanoma metastasized and ultimately claimed his life.

UVA radiation primarily damages the components of skin cells by generating reactive oxygen species, or ROS. These highly active molecules can cause single-strand breaks in the DNA or crosslink DNA to protein, resulting in mutations or improper functioning. Both UVA and UVB can cause a more significant type of DNA damage called pyrimidine dimers, where two adjacent pyrimidine nucleotides (the “C” and “T” of DNA; the “A” and “G” are purines) fuse together. Because the higher energy UVB is absorbed directly by DNA, UVB can cause other modifications that compromise the integrity of DNA, leading to instability of the genetic code.

Indeed, the cell has repair mechanisms to fix pyrimidine dimers and other errors, but sometimes the very genes encoding the repair mechanisms are mutated. UV-induced DNA damage can result in highly characteristic mutations in critical genes, for example in the tumor suppressor gene p53. As the “guardian of the genome”, the p53 protein is involved in directing the repair of mutations and guiding the cell through its controlled death pathway, called apoptosis. Mutations in p53 are thought to be among the first steps in development of non-melanoma skin cancer. Formation of malignant melanoma is more complicated and not fully understood.

Yes, p53 has its own superhero persona. That’s how cool (and significant) it is. Image by Susanne Harris.

Cells that carry mutations in p53 proliferate uncontrollably, a hallmark of cancer. In some cases, the immune system will recognize malignant cells as a threat and effectively eliminate them. However, UV radiation is also known to suppress the immune system by at least two mechanisms. One is by diminishing the production of antigen-presenting cells, which engulf foreign-looking cells and display an alert to activate the immune system). The other is by inducing the production of an immune suppressive cytokine, interleukin-10. Additionally, some skin cancer cells display proteins on their surface that prevent the immune cells from killing them. Thus, in addition to mutations in key genes, immune suppression and immune evasion contribute to the development of skin cancer.

Even the mutant Wolverine wears sunscreen! In this Instagram post, Hugh Jackman urged his fans to use sunscreen. He became a fervent sunscreen proponent after having a BCC removed from his nose.

Contributed by: Julia van Rensburg, Ph.D.
Follow Julia on Twitter.

van der Pols JC, Williams GM, Pandeya N, Logan V, & Green AC (2006). Prolonged prevention of squamous cell carcinoma of the skin by regular sunscreen use. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 15 (12), 2546-8 PMID: 17132769

Lee TK, Rivers JK, & Gallagher RP (2005). Site-specific protective effect of broad-spectrum sunscreen on nevus development among white schoolchildren in a randomized trial. Journal of the American Academy of Dermatology, 52 (5), 786-92 PMID: 15858467

Koh HK, Geller AC, Miller DR, Grossbart TA, & Lew RA (1996). Prevention and early detection strategies for melanoma and skin cancer. Current status. Archives of dermatology, 132 (4), 436-43 PMID: 8629848

Leiter U, & Garbe C (2008). Epidemiology of melanoma and nonmelanoma skin cancer--the role of sunlight. Advances in experimental medicine and biology, 624, 89-103 PMID: 18348450

Brenner M, & Hearing VJ (2008). The protective role of melanin against UV damage in human skin. Photochemistry and photobiology, 84 (3), 539-49 PMID: 18435612

Into The Fire: Sun Protection From A To B

In the last month, Jessica Alba has made splashes across media headlines, but not for her latest role in a Hollywood blockbuster. The Honest Company, which she founded in 2011, has been charged with two lawsuits filed by consumers. Both lawsuits cite ineffective sun protection by the Honest Company sunscreen, and countless online images of sunburned children and adults appear to support these allegations. The failure of the sunscreen highlights a need for better education regarding sunscreen use and sun exposure. So let’s start with the one currently under fire.

Jessica Alba’s recent role has been protecting everyday people from allegedly harmful chemicals found in standard household products and cosmetics; her Honest Company offers “all natural” substitutes.

The Honest Company sunscreen contains only one active ingredient, zinc oxide, a naturally occurring mineral known for its UV reflecting properties. (The second lawsuit cites false advertisement for claims of using only “natural” substances when apparently synthetic components were included. And although zinc oxide exists naturally as zincite, it is likely that the zinc oxide used in sunscreen is synthesized in the lab). Zinc oxide is an effective broad-spectrum sunblock, protecting against both UVA and UVB radiation, but adequate concentrations must be used. If you’ve ever felt like your sunscreen just wouldn’t rub in, you’ve likely used zinc oxide, as its large particles leave a white, opaque residue many sunscreen users dislike.

The Hoff boasted, “Beyond its entertainment values, 'Baywatch' has enriched and in many cases helped save lives.” Perhaps he was referring to the prevention of nose-specific skin cancer, as he may have inspired others to liberally, but very specifically, apply chalky zinc oxide sunscreen to this body part.

Indeed, last year, the Honest Company sunscreen contained 20% zinc oxide, and many consumers complained of the undesirable aesthetic characteristics. This year, the Honest Company more than halved the zinc oxide concentration, reducing it to 9.3%. Although this change may have improved the sunscreen’s aesthetic properties, it most certainly reduced its ability to effectively block the sun’s UV radiation.

Zinc oxide, and its cousin, titanium dioxide, comprise inorganic sunscreen components. These particles reflect most of the radiation, but can absorb some of the energy. Newer sunscreen formulations typically use the nanoparticle version of these components, reducing the pasty appearance produced by the older, larger particles. Many sunscreens mix these minerals with the other class of sunscreen components:  organic molecules. Organic in this sense means “carbon-containing”, and refers to synthetic molecules made of carbon backbones. In addition to the inorganic components, some organic sunscreen molecules also provide broad-spectrum protection. However, the chemical structure of other molecules absorbs narrower wavelengths, so these are more effective when mixed with other narrow-spectrum or broad spectrum ingredients. The goal of mixing sunscreen components is to provide a broad-spectrum, photo-stable sunscreen that has acceptable aesthetic properties and increases the safety and effectiveness of the sunscreen.

These compounds are the most commonly used sunscreen ingredients. Avobenzone, ecamsules, and anthrilates absorb UVA radiation. Homosalate, octisalate, and octinoxate (also known as octyl methoxycinnamate) absorb UVB rays. Oxybenzone, octocrylene, and the inorganic particles zinc oxide and titanium dioxide filter both UVA and UVB radiation. Most sunscreens use a combination of these components to provide adequate broad-spectrum UV protection.

Forbes’ contributor David Korr noted that perhaps the formulation contributed to the sunscreen failure. The sunscreen label directed users to shake well before using, likely to redistribute to zinc oxide particles throughout the lotion. However, it is possible that many people skipped this step, resulting in some very heavy and greasy applications and other light and useless applications. So, formulation and proper consumer use indeed influence the effectiveness of sunscreen.

Other common misuses of sunscreen are applying too little or failing to reapply often enough. The FDA tests sunscreen at 2.0-2.2 mg of sunscreen per square centimeter of skin. To adequately cover an entire average-sized adult human body, at least 1.0 ounce (2 tablespoons or the volume of a shot glass), is needed.

In 2011, the FDA mandated higher standards for sunscreen labeling, requiring full compliance by the end of 2012. Under the new regulations, only sunscreens containing ingredients that absorb both UVA and UVB radiation can be classified as “broad-spectrum”. A sunscreen product with SPF (Sun Protection Factor) 15 or greater can state that it protects against all forms of sun damage, including sunburn, premature skin aging, and skin cancer. Those with SPF 2-14 can only state that they have been shown to prevent sunburn. Additionally, “waterproof” can no longer be used; rather if appropriate, labels can specify “water-resistant” with the length of time (either 40 or 80 minutes) before reapplication is needed. Keep in mind that these changes did not remove other sunscreens from the market, but merely mandated what they can claim.

Avoiding painful sunburns requires proper use of sunscreen—most importantly, actually using sunscreen whenever you are exposed to the sun for extended periods of time.

SPF refers to the amount of UV radiation filtered out by the sunscreen. Thus, a sunscreen user with a proper application of SPF 15 sunscreen is exposed to 1/15^th of the sun’s harmful radiation. This suggests that SPF 15 sunscreen imparts a 15-fold increase in the length of time one can spend in the sun without getting burned. However, the FDA and Mayo Clinic recommend reapplying sunscreen at least every 2 hours and more often if swimming, sweating, or toweling off. Another way SPF is explained is that SPF 15, 30, and 50 protect from 93%, 97%, and 98% of UV radiation, respectively. Keep in mind that SPF refers to protection against only UVB radiation; there is no numerical rating of UVA protection.

UV radiation is more energetic than visible light, but not as energetic as X-rays; thus, it penetrates the top layers of skin, but not beyond that.

It was previously thought that UVA radiation was harmless; however, recent evidence shows that UVA does indeed contribute to tanning/sunburn, premature skin aging, and skin cancer. UVA comprises 90-99% of the UV radiation that reaches the Earth’s surface, whereas UVB radiation accounts for 1-10%. The stratospheric ozone layer filters out most of UVB and all of UVC radiation. The longer wavelength, lower energy UVA radiation can penetrate clouds, glass, and the skin’s dermal layer. Shorter, higher energy UVB rays do not significantly penetrate glass, but penetrate the epidermis and cause the majority of sun-induced skin damage.

UVA rays can penetrate deeper into the skin, reaching the dermis layer, whereas UVB penetration is limited to the epidermis.

The recent changes in sunscreen labeling were prompted primarily by new information on UVA radiation and the increasing incidence rates of skin cancer. In a future article, I will discuss how UV radiation promotes or causes skin cancer. Until then, remember that the highest concentration of UV radiation is 10 am – 4 pm, April through October. But that doesn’t mean you shouldn’t take precautions at other times of day or other times throughout the year. Sun protection should be a year-round commitment, keeping in mind that water, snow, and concrete can reflect sunlight. In addition to properly using sunscreen, wearing protective clothing and avoiding peak sunlight will protect your skin from UV radiation.

Contributed by: Julia van Rensburg, Ph.D.

Follow Julia on Twitter.

 

 

Shah P, & He YY (2015). Molecular regulation of UV-induced DNA repair. Photochemistry and photobiology, 91 (2), 254-64 PMID: 25534312

Narayanan DL, Saladi RN, & Fox JL (2010). Ultraviolet radiation and skin cancer. International journal of dermatology, 49 (9), 978-86 PMID: 20883261