Chronic Inflammatory Response Syndrome (CIRS) is a term coined by mold expert Dr. Ritchie Shoemaker. Dr. Shoemaker defines as "An acute and chronic, systemic inflammatory response syndrome acquired following exposure to the interior environment of a water-damaged building with resident toxigenic organisms, including, but not limited to fungi, bacteria, actinomycetes and mycobacteria as well as inflammagens such as endotoxins, beta glucans, hemolysins, proteinases, mannans and possibly spirocyclic drimanes; as well as volatile organic compounds (VOCs).” We certainly need to consider any possible components of influence from a water damage building. Mold is a big one!
What does mold do to the human body? What symptoms does it cause?
Approximately 24% of people have a genetic polymorphism (abnormality in a gene), which prevents them from properly breaking down the toxins that mold create. Different types of molds will produce different toxins. Different toxins will cause unique changes in our body and therefore, unique symptoms. As we live in moldy environments, genetically susceptible individuals do not have the opportunity to break down the toxins.
Mold can cause a variety of symptoms including, but not limited to:
- Joint Pain (any joint, but especially smaller joints such as finger, wrists and ankles)
- Chronic Fatigue Syndrome
- Brain Fog/Memory Changes/Cognitive Dysfunction
- Post Nasal Drip and Sore Throat
- Peripheral Neuropathy (numbness/tingling)
- Nausea and digestive disturbances
- Neck pain
- Vision Changes especially at night
- Chronic Infections
- Neurological dysfunction
- Hormonal Alterations
Mold toxins will effect the ability of the white blood cells to function properly. Therefore, it is easier to begin to pick up other infections when one has mold illness. It is not uncommon to see mold illness occur with Lyme Disease, Chronic Viral Infections and gastrointestinal infections.
In addition, mycotoxins can lower a hormone known as melanocyte stimulating hormone (MSH). Since MSH is a signal for other hormona
Information About the Mold Toxins
Many different mold toxins can cause problems for people. Some people can react to mold toxins due to an IgE inflammatory condition. Others may have an IgG response to mycotoxins. Other people respond due to a genetic predisposition, which prevents them from breaking down the toxins well. The toxins that affect these people the most include ochratoxin A, aflatoxins, gliotoxins and trichothecenes.
Aflatoxins are produced by certain fungus. They are typically found in some food products such as peanuts and corn. In addition, aflatoxins are also produced by aspergillus. Aflatoxins can be cytotoxic to the liver cells and have been shown to cause liver cancer.
Gliotoxins are produced both from candida and the fungus aspergillus. Gliotoxins have the capacity of inactivating neutrophils and phagocytes. In addition gliotoxins attack astrocytes and oligodendrocytes. Therefore, nervous system symptoms are likely to be produced in individuals having a difficult time detoxing this. One study found that gliotoxins were completely broken with the use of N-Acetyl Cysteine. Gliotoxins are composed of disulfide bonds and NAC is capable of breaking disulfide bonds. Thus, this is likely the mechanism behind the ability of NAC to break down these toxins. Gliotoxin cytotoxicity has been shown to be reduced by vitamin C. In addition, gliotoxins can reduce intracellular concentrations glutathione and glutathione has been shown to reduce the cytotoxicity of gliotoxin.
Ochratoxin A toxins are produced by aspergillus and penicillum genus of fungus. Ochratoxin A has been found in contaminated wine, beer, dried fruit, pork, poultry, dairy, spices, grape juice and chocolate. Ochratoxin A binds to albumin, which serves as a mobile reserve of the toxin. In addition the intestinal microbiota break down ochratoxin A into the less toxic ochratoxin alpha. Therefore, any disruption to the gut microbiome could contribute to higher ochratoxin A levels. Research has also found that treatment with Vitamin E, Vitamin C and Vitamin A significantly reduce the effects of ochratoxin A. Ochratoxin A was also found to be more toxic when given with an NSAID in animals studies. Ochratoxin is nephrotoxic and can lead to kidney disease. It is also capable of crossing the placenta. Ochratoxin can cross the blood brain barrier, causing significant oxidative stress in the brain. In addition, it can contribute to memory problems and depression. Sweat has been shown to contain ochratoxin. Therefore, sauna is a great way of increase excretion of this toxin. Most of the metabolism of ochratoxin occurs in the gut. Therefore, maintaining a healthy gastrointestinal tract is very important. Aspartame has actually been shown to reduce the toxicity of ochratoxin, but we should avoid it for other reasons. A study on rats showed that 30 day use of licorice and melatonin completely reduced all of the biochemical and histological abnormalities that this toxin caused.1
Tricothecenes are toxins produced by the fungus Stachybotrys, fusarium, myrothecium. This toxin is so virulent it has been used as a biological warfare agent. Trichothecenes have the ability to inhibit RNA, DNA synthesis, cell division and cause mitochondrial dysfunction. The wide effects of this toxin are likely due to its ability to destroy mitochondrial function and disrupt protein synthesis. Common symptoms include emesis, diarrhea, multiple organ failure, weight loss, nervous system disorders, cardiovascular abnormalities, skin disorders, and immunodepression.
There are some natural supplements that will help tricothecene toxicity. In cells that were administered tricothecenes, coadministration with Vitamin C increased cell survival by 62%. In cells treated with vitamin E, survival increased to 97%. Glutathione has also been shown to provide some defense against this toxin.
Mold and The NRF2 Gene
The NRF2 gene is a gene that codes for the NRF2 protein. The NRF2 protein works by binding to something known as the antioxidant response element. The antioxidant response element is responsible for anti-inflammatory reactions in the body. In addition, it is responsible for creation of glutathione. Glutathione is necessary for the detoxification of mycotoxins. Part of why mycotoxins can be so pathogenic is that they will bind to the NRF2 gene and prevent it from creating the corresponding protein. When this occurs, detoxification is greatly altered. Ochratoxin A, which is the toxin secreted by the mold types aspergillus and penicillin. In addition, the NRF2 pathway regulates another detoxification pathway in the liver. This pathway is known as glucuronidation. Glucuronidation helps us break down and recycle estrogen. When glucuronidation is not working well, we can get higher levels of estrogen. This could lead to symptoms such as PMS, PMDD and endometriosis. This is the mechanism through which mold can create female hormone imbalances.
Mold and the MRP2 Protein
The MRP2 protein is located in the liver and helps to stimulate bile flow. We see that certain metals and mycotoxins can alter this protein's function and therefore impact bile flow. You will read in the "all about detoxification" section that when this bile process is altered, The can back up. Therefore, in addition to treating the mycotoxins, we should work to eliminated any toxic metals allowing this pathway to work correctly.
All About Detoxification
There are several routes of detoxification that will help to eliminate mold. The biggest one is by upregulating (increasing) liver detoxification. You see, toxins are fat soluble. Therefore, they get stored in our fat cells. The blood is a watery fluid. Just like oil and vinegar (fat and water) do not mix, we cannot get toxins out easily because they will not travel in the watery blood. Therefore, the big point of detoxification is to create a chemical reaction that alters the toxins in order to get them out. This occurs in three phases. Phase one occurs as enzymes change the toxin slightly. This begins to make the toxin a bit more soluble in water. Phase two occurs as more enzymes change the toxin again. At this point, the toxin is soluble in water and can be excreted. Phase three involves the actual secretion of toxins from the cells.
The overall pathway involves the liver breaking down toxins and then putting the toxins in the bile and the gallbladder. When we eat a fatty meal, the gallbladder contracts, essentially releasing the bile into the small intestine. Once this happens, the toxins will make their way out of the body through the stool. If the gallbladder is not contracting correctly and there is bile stasis, we will not detoxify correctly. In addition, if we are constipated, toxins can sit in our intestinal tract and be reabsorbed in which case we will also not detoxify correctly. In situations such as leaky gut, there are wide "gaps" between our intestinal cells. This will cause toxins to absorb from the gastrointestinal tract into the blood stream instead of leaving through our stool. Therefore, to detoxify correctly, we should make sure we are working with any causes of leaky gut such as gluten, parasites, bacteria or fungal infections. In addition, we should help the gallbladder to contract correctly and proper bile flow to occur.
What is interesting is that often times the molecule that is created at the end of phase I detoxification is more toxic that the original molecule. Therefore, proper phase II and III functioning is essential in order to lower the toxic load. This is where things can get hairy if we do not know what we are doing. Many natural products will increase phase I without increasing phase II. This can cause that intermediate toxin to buildup and not get out of the body. This will be MORE inflammatory than the original toxin. It is important that we are working to increase phase II and III before phase one. It is also important that we are increasing activity of the MRP2 and the NRF2 proteins. Therefore, we strongly recommend working with a practitioner that understands mycotoxin illness and how to work with the toxins and detoxification pathways.
Once phase I and II have had a chance to work, phase III and the MRP2 pathways do their job. The MRP2 pathway increases the bile flow. Phase III involves the release of toxins from the cells. Once we move through Phase I, II, III and the MRP2 pathways, toxins can be excreted from the body via the stool and skin.
Another way of understanding detoxification is through a mug analogy. Imagine that you have a mug and each toxin is one drop of water in the mug. As long as you are able to safely empty the water from the mug before the water gets to the top, it will not spill. Our body's detoxification processes are essentially working to remove the drops from the mug. We can have toxins come in, but as long as they do not come in faster than we can eliminate, we do not generally see symptoms. With mycotoxin illness, the body has more toxins than it can safely eliminate. Therefore, we should consider all areas of toxicity with mold illness. If there are toxic metals, accumulation of pesticides or toxins produced by infections (which occurs in about the case of any infection), there will be additional drops of water in that mug. We should also work to lower the overall toxic load by decreasing any non-mold toxins.
Are All Molds Bad?
Certainly not! There are many species in the fungal family that are good. Take the medicinal mushroom family for example. A component in the cell wall of mushrooms such as shiitake, lion's mane, cordyceps and other mushrooms, known as beta glucans, have been shown to help fight cancer as well as chronic viral infections such as epstein-barr (mono). In addition, the genetic makeup that predisposes someone to mold, is most problematic towards indoor molds. Outdoor molds do not affect these individuals in the same way.
How is mycotoxin illness different than a mold allergy?
Mycotoxin illness and CIRS occur due to the genetic predisposition to the inability to break down the mold toxins. The toxins therefore buildup in the body and symptoms occur. An allergy to mold can create symptoms, but in this case, symptoms occur due to a different mechanism. Allergies are created by the body creating a protein known as an IgE (immunoglobulin E). This protein will activate the immune system to release histamine. Often with histamine types of symptoms we can have difficulty breathing or rashes occur. An individual can have a reaction to mold due to this histamine mechanism, the genetic mycotoxin mechanism or both.
How do I know if it is in my house?
If we suspect that there is mold in your house we can run an ERMI test to look for the molds themselves, or a mycotoxin test to look for the toxins the mold produces. These are conducted by taking samples of dust and sending them to the lab. We have test kits in our office we can give you (or mail you if you are out of state). The collection is fairly simple. When doing this dust collection, take samples using the q tip provided from a few areas around the house. It is important to take samples from the areas where mold is most likely. If there has been any known water damage, definitely take samples from this area. In addition, if there is any discoloration (yellow or black) on any surfaces, take samples here. Bathrooms and laundry rooms are often where mold is found due to the moisture. We recommend collecting dust from these areas. You can also cut a small piece of an air sample and send this in. This is a good idea if you have central air as mold will often collect in the ducts. Once you take all of these samples, write composite on the form that you are sending in and mail it off to the lab.
Do I need to remediate?
If you find mold in your house, it is important that you get out of the house immediately. In order to help you heal from your symptoms, you will either need to get your house remediated or move. If you have mycotoxin illness, it will be pretty impossible to get you well while you are still living in an environment that made you sick.
Can I remediate myself?
We strongly recommend that you do not remediate without the help of professionals. Professionals have a lot of equipment that helps make this dirty job safer. When we attempt to use bleach or vinegar, it will likely kill any superficial mold. This sounds good at first. However, as the mold is attacked with these anti fungal agents, it will release as many spores as possible into the air. This spreads the mold and the mold toxins around the house, essentially worsening the problem. We have seen patients (or their family members) who try to do this and all of their symptoms get worse. It is extremely important that you work with someone who is trained in remediation. See below for some resources.
The remediation specialist definitely makes a difference in how successful the remediation is. We like working with companies that have a basic understanding of effects of mold illness. We feel that these people are less likely to skip steps that could be important because they understand the severity of the situation. Below are the remediation specialists we recommend.
Environmental Assessment Group, LLC
Michael Shrantz (Tucson but comes to CO sometimes)
Mike Shaan with Mold Inspection Sciences
Do I have to move?
Certainly there are some cases where moving is the best option. This may be due to landlords that are unwilling to fix the situation. It may be that the mold remediation expert you are working with has informed you that the mold levels in your home are unrepairable to the level that a mold sensitive person need for healthy living. Whatever the reason for the move, the financial investment, the chaos of moving are worth it. This is perhaps the MOST important piece of getting you well. We cannot get you well while you are in that environment. It is therefore also important that you test any potential places that you will be moving into for mold prior to making the commitment.
Can you do the move yourself?
It will be absolute best if you can have friends, partners and movers help you move. This includes even being in the house for packing. The more time you spend there, the more you body is going to be affected by the toxins. This can sometimes be a difficult scenario depending upon how much help you have and how quickly you are trying to move. If you have to be in the house packing, it is a must that you wear a mask. Masks are labeled by how much they filter out particulate matter. Masks with the label P100 will filter out 99% of particulate matter. Masks labeled N100 will filter out 99.7%. We recommend getting a N100 mask. These can be found online and at most hardware stores.
What to do about the items in your house?
This is a complicated question. You will see many different opinions on the internet. This is because it is not clear in research yet what needs to happen to our personal items in this situation. We feel pretty strongly that your bed should be trashed. You hopefully spend a lot of hours here and this could really impact your recovery. The other consideration is that the bed is porous and may contain mycotoxins.
If you have leather furniture, this can be wiped down with a leather cleaner. It is also good to use run a hepa filter vacuum over it entirely. Other furniture should be wiped down with vinegar or a quaternary cleaner. You can find quaternary cleaners on the internet. Anything that can be washed, should be washed. We have found some evidence that some mycotoxins break down at 160 degrees. Many washers have sanitary cycles that will get the water temperature close to this. Wash items with detergent and vinegar. Other porous furniture such as particle board and non leather couches may be worth tossing. If you saw visible mold on any of your furniture, get rid of it. Do not try to clean and save.
Top Ten Things You Need to Keep Your Future House Safe
As you move into your new home (or repair your current home), it is important to take precautions so this does not happen again. Here are the top ten recommendations:
1) Buy a squeegee for every shower. Make sure to use it after every time you shower and leave the fan on for 30 minutes
2) Buy a propolis vaporizer. Propolis has been estimated to kill about 70% of mold and mycotoxins. Our personal and professional experience has shown this to work much better than diffusing essential oils (although this can be useful too) for mold specifically. Run the vaporizer initially in every room of the house for 12 hours after moving in (or remediation). After this, run it once a week for 12 hours (does not have to be exact), rotating the room it is in every week. We recommend writing this on the calendar to make sure you remember to do so. When you purchase the vaporizer, you should also purchase refill cartridges. There are five cartridges in each refill box. They will each last 21 hours. Please go to this website to order: https://beehealthyfarms.com
3) Buy a hepa air filter. We strongly recommend an IQ Air. It is more expensive than other air filters on the market, but it will filter such a small particle size that it will remove both mold and mycotoxins. This is a very good investment. If you use the code provided here, you can save 5%! Go to this website http://www.iqair.com & use this code: IQ50470
4) Buy a far infrared sauna. Studies have shown that mycotoxins have been found in sweat, indicating that sauna is a great tool. Far infrared saunas heat the body from the inside out and weekly use can be great for detoxification support. We like the relax far infrared brand because they are affordable, easily movable and incredibly small. In addition, your head is not in the sauna, and keeping the head cool while sauna-ing is the preferable thing for health. If you order from our clinic, we can help get you $95 off your order. You can check out the sauna here: https://www.momemtum98.com/relaxsauna.html. Call our office at 720-722-1143 to order one.
5) Once a month run a load of vinegar through your washing machine. Make sure to ALWAYS leave the door to your washer open between use. In addition, the compartment for putting detergent can get moldy too. This especially happens in front loaders. We recommend leaving this open between uses as well.
6) Clean all surfaces with vinegar weekly
7) Fix any water leaks immediately. If you have leaks, clean up water, use fans, spray the area with vinegar and use the propolis vaporizer in the area.
8) Make sure if you are going to move to test the house before you move in.
9) If you can install a central vacuum into your house, this will also help with keeping mold and mycotoxins eliminated.
10) Put small fans in corners of the rooms and run them once a week to help move stagnant air.
What happens after I move?
After you move we begin to help you detoxify from the mycotoxins. This will involve a binder. As we mentioned in the "all about detoxification section", the binders help to bind the mold so it can be eliminated from the body. In conventional medicine, pharmaceuticals such as cholestyramine or Welchol are typically used. In our clinic, we general use a certain form of chitosan, which has been researched to bind mycotoxins. Binders work through polarity mechanism. They will attract a certain polarity of molecule. Certain binders will attract certain toxins. From a natural perspective, we feel that chitosan does the best job. We have had great success with this and have been able to avoid the use of pharmaceutical agents in almost all cases. In addition to the binders, our goal will be to support your detoxification pathways through the use of supplements, herbs, lifestyle and mindfulness practices. We can start to work with some of these practices before your move, which may help slightly. We will not see much change until after you are out of the moldy environment. Therefore, we do not typically start too much of the mold treatment until you are in a safe environment.
How do we treat it?
We treat mold by using the binders as described above. We will also give you supplement suggestions that will help your body reactivate the NRF2 gene in order for your detoxification pathways to work. As we are asking your body to do a lot of work to get the toxins out, we will want to give your body antioxidants and liver support to help this process. In addition, it is usually helpful to work increase phase II of the liver detoxification pathway before phase I as described above. We will also work on giving your gallbladder support so you can get the toxins out properly.
Mold toxins can leave the body through the stool and through the skin. If there is leaky gut, as we are trying to remove mycotoxins in the stool, they can be reabsorbed into our bloodstream. This will make us feel really sick. Therefore, it can be helpful to find the cause of leaky gut, treat this and heal the gut lining before we detoxify from mold. This will help to ensure that the toxins are actually getting out. In addition, since we can detoxify through our skin, sweating and using a sauna can help. We recommend using a far infrared sauna. The far infrared type of sauna will heat the body from the inside out. As the heat is generated from the inside out, it will push the toxins out to the surface. This is why it is so great for detoxification.
When will I feel better?
Depending upon how long you were in the environment and how many cause of your symptoms are involved, will directly impact your recovery. Most people begin to feel at least some improvements within a week of being out of the moldy environment. This greatly depends upon if you have Lyme or other chronic infections in addition to the mold. It also depends upon the proper functioning of your liver. If you liver is not functioning well, it will take much longer to get you well.
Why have I never been told about this before?
Mycotoxin illness has not been studied as much as many other diseases. There has been recent research that has correlated mycotoxin illness with diseases such as multiple sclerosis and parkinson's disease. As there is more research showing that there is a link between mycotoxins and these diseases, there will likely be more money invested in research. Most physicians are not trained in mycotoxin illness, therefore, they are likely not aware of the recent research that shows the many symptoms that are caused by this illness.
Mold and Lifestyle Choices
As previously mentioned, toxins build up in our body. In working with mold illness, it is helpful to reduce overall toxic load. Therefore, we strongly recommend eating organic foods and avoiding other sources of hidden toxins. Sources to avoid include plastic water bottles, non-filtered water, dust, and allergens. If you are not at a point where you can invest in organic foods, it is helpful to follow the dirty dozen and clean fifteen list. The dirty dozen is a list of the 12 most pesticide sprayed foods. The clean fifteen shows the safest 15 non-organic foods. Choosing non-organic foods from the clean 15 and avoiding those on the dirty dozen can help eliminate unsafe produce. In addition, these lists are updated regularly so as pesticide use changes, so do the lists. In addition, choose grass-fed hormone free animal products can help eliminate the overall toxic load. Toxic metals are also a big problem. Metals are often unavoidable. There is a lot of lead that is in the environment due to all the lead based fuel. We frequently find high levels of all sorts of metals in our clients' systems despite having no known exposure.
Mold and Mindfulness
It can be intense to feel that one was attacked by his/her environment. Often times with mold illness there is a sense of the world not being safe. Our home, where we hopefully feel the safest, is no longer a sanctuary for us. Mold often creates a huge immune dysregulation. Since our internal systems do not see the world as safe, we can begin to attack ourselves leading to autoimmunity. In some people, staying the night at hotels or family's house can provoke much anxiety around safety. Part of working with mold illness also involves working with the mental/emotional aspect of the disease. We invite you to journal about the possible beliefs that you have around safety, your home environment and your world in general. We work with our clients to help teach them mindfulness around these situations. The beginning stages of working with these emotions are just to allow feelings to come up. If you feel something, just allow that feeling to be without any judgement or emotional concern. Eventually, work can be done around letting go of the situation, but in the beginning it is often easiest to rest in the sensations that arise without judgement.
We personally invite you to join our Denver Area Lyme, Mold, EBV and Chronic Infections Facebook Group: https://www.facebook.com/groups/1418169648227251/
Dr. Shoemaker has put together a pathway chart that helps to explain the effects of mold. You can access this here:
This site has some good information on it: http://biotoxinjourney.com
Dirty Dozen: https://www.ewg.org/foodnews/dirty_dozen_list.php
Clean Fifteen: https://www.ewg.org/foodnews/clean_fifteen_list.php
1) Zhou, X. "Gliotoxin-Induced Cytotoxicity Proceeds via Apoptosis and Is Mediated by Caspases and Reactive Oxygen Species in LLC-PK1 Cells." Toxicological Sciences 54.1 (2000): 194-202. Web.
2) Korzybski, Tadeusz, Zuzanna Kowszyk-Gindifer, and WÅ‚odzimierz KuryÅ‚owicz. "Gliotoxin And Gliotoxin Monoacetate." Antibiotics (1967): 1339-344. Web.
3) Menard, A., R. Amouri, and Et.al. "A Gliotoxic Factor and Multiple Sclerosis." J Neurologist (1998): n. pag. Web.
4) Axelsson, V., K. Pikkarainen, and A. Forsby. "Glutathione Intensifies Gliotoxin-induced Cytotoxicity in Human Neuroblastoma SH-SY5Y Cells." Cell Biology and Toxicology 22.2 (2006): 127-36. Web
5) Goldman, Gustavo. "Faculty of 1000 Evaluation for Self-protection against Gliotoxin--a Component of the Gliotoxin Biosynthetic Cluster, GliT, Completely Protects Aspergillus Fumigatus against Exogenous Gliotoxin." F1000 - Post-publication Peer Review of the Biomedical Literature (n.d.): n. pag. Web.
6) Zhang, Zhen. "Aflatoxin B1-induced Hepatocellular Carcinoma in Developing Countries: Geographical Distribution, Mechanism of Action and Prevention (Review)." Oncology Letters (2013): n. pag. Web.
7) Hope, Janette H., and Bradley E. Hope. "A Review of the Diagnosis and Treatment of Ochratoxin A Inhalational Exposure Associated with Human Illness and Kidney Disease including Focal Segmental Glomerulosclerosis." Journal of Environmental and Public Health 2012 (2012): 1-10. Web.
8) Bin-Umer, Mohamed Anwar, John E. Mclaughlin, Debaleena Basu, Susan Mccormick, and Nilgun E. Tumer. "Trichothecene Mycotoxins Inhibit Mitochondrial Translationâ”Implication for the Mechanism of Toxicity." Toxins 3.12 (2011): 1484-501. Web.
9) Hope, Janette. "A Review of the Mechanism of Injury and Treatment Approaches for Illness Resulting from Exposure to Water-Damaged Buildings, Mold, and Mycotoxins." The Scientific World Journal 2013 (2013): 1-20. Web.
10) Bin-Umer, M. A., J. E. Mclaughlin, M. S. Butterly, S. Mccormick, and N. E. Tumer. "Elimination of Damaged Mitochondria through Mitophagy Reduces Mitochondrial Oxidative Stress and Increases Tolerance to Trichothecenes." Proceedings of the National Academy of Sciences 111.32 (2014): 11798-1803. Web
11) Mclaughlin, John E., Mohamed Anwar Bin-Umer, Thomas Widiez, Daniel Finn, Susan Mccormick, and Nilgun E. Tumer. "A Lipid Transfer Protein Increases the Glutathione Content and Enhances Arabidopsis Resistance to a Trichothecene Mycotoxin." Plos One 10.6 (2015): n. pag. Web.
12) Knatko, Elena V., Maureen Higgins, Jed W. Fahey, and Albena T. Dinkova-Kostova. "Loss of Nrf2 Abrogates the Protective Effect of Keap1 Downregulation in a Preclinical Model of Cutaneous Squamous Cell Carcinoma." Scientific Reports 6 (2016)Scientific Reports