There’s no denying that celiac disease (CD) is more prevalent now than ever. In the US, rates of CD have increased at least 5-fold over the past few decades, and prevalence in Finland has doubled. (1, 2, 3) The incidence of CD has also increased four-fold in the UK and three-fold in the Netherlands in the past 20 years, and the incidence of pediatric CD in Scotland has increased 6.4-fold. (4, 5, 6)
So naturally, everyone is wondering – why? We know that there’s a strong genetic component to celiac disease (and our ability to detect the disease has vastly improved), but the rising rates have occurred too quickly to be explained by a genetic shift in the population.
Besides, the genes that predispose an individual to CD are actually relatively common in the population, but only a very small percentage of those people actually develop the disease. In other words, genetics appear to be necessary – but not sufficient – for someone to develop CD.
Can the overuse of #antibiotics trigger celiac disease?
Antibiotics Can Cause Intestinal Dysbiosis and Infection
Clearly, something has changed in the environment to trigger celiac disease in a higher proportion of genetically susceptible people. Multiple factors probably play a role, but evidence indicates that one big factor is the intestinal microbiota. And a major contributor to disordered intestinal microbiota is antibiotic overuse.
In my previous article on the effects of antibiotics, I reviewed several studies that demonstrate how drastically antibiotics can alter the gut microbiome. Just a single course of antibiotics can reduce the richness and diversity of the intestinal microbiota, and in many cases, people never completely regain the diversity they lost.
Even if a person doesn’t develop an overt, clinically-diagnosable infection such as C. difficile, imbalances in the types of bacteria that colonize the gut can still cause serious problems. But to understand how antibiotic-induced gut dysbiosis could trigger celiac disease in genetically-susceptible individuals, it helps to first understand some of the basic mechanisms behind celiac disease.
Celiac Disease Involves an Immune Reaction to Both Gliadin and Tissue Transglutaminase
The biological mechanisms behind celiac disease are complicated and still not fully understood, but the general idea is that gluten – a group of proteins found in wheat, rye, and barley – triggers an autoimmune response that results in severe damage to the epithelial lining of the intestine.
Gliadins and glutenins are the two main components of gluten, with gliadins being the primary trigger for celiac disease. These proteins are very difficult for the body to digest fully, but in most people, this isn’t a problem. However, in people with celiac disease, certain cells (known as “antigen-presenting cells”) get a hold of these large, undigested fragments of protein and present them to T-cells, triggering an immune response. (7, 8)
An enzyme called tissue transglutaminase (TG2) is also important in the development of CD. This is because antigen-presenting cells only bind certain types of proteins, and they don’t usually bind normal gliadin fragments. (9) On the other hand, TG2 readily binds gliadin, and actually modifies it to make the gliadin much more attractive to antigen-presenting cells. This vastly increases the likelihood of an immune response.
Once this happens, the body starts creating antibodies against gliadin. But because the gliadin is usually bound to TG2, the body also creates antibodies against TG2, its own enzyme. This attack of “self” is what earns CD the classification of “autoimmune.”
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Intestinal Dysbiosis and Infection Can Lead to Up-Regulation of Tissue Transglutaminase
In healthy individuals, TG2 plays a role in tissue repair, as well as in other processes such as regulation of cell death; it’s not an enzyme that’s “supposed” to interact with gluten. (Interestingly, TG2 also plays a role in other diseases, such as Parkinson’s and Huntington’s, by modifying proteins that it isn’t supposed to modify.) (10)
Most TG2 appears to be either stored safely inside cells or inactive under normal conditions, and is only activated in the event of tissue injury, bacterial or viral infection, or another source of inflammation. (11, 12) This indicates that tissue damage or inflammation in the intestine (and subsequent TG2 up-regulation) might actually be necessary for the development of CD.
Without substantial TG2 activity, it’s unlikely that the antigen-presenting cells would bind and present enough gluten fragments to provoke a major immune response. But a bacterial or viral infection could create inflammation and tissue damage that would activate TG2, and thus trigger the cascade of events eventually leading to celiac disease.
Intestinal Dysbiosis and Infection Can Contribute to Leaky Gut
Another factor to consider is the location of tissue transglutaminase. Nearly all TG2 is found in the sub-epithelial region of the intestine, a place that gluten shouldn’t have access to. This means the intestinal barrier would need to be compromised in some way for gluten proteins to significantly interact with TG2. (13)
This fits with previous work done by researchers such as Alessio Fasano, who have hypothesized that a person cannot develop an autoimmune condition such as CD if they don’t have leaky gut. If the intestinal barrier is intact, the immune system will never “see” the antigens, so it won’t mount an immune response.
But one big risk factor for developing leaky gut is intestinal dysbiosis or infection. Bacterial components such as lipopolysaccharides can induce inflammation and increase intestinal permeability, which would allow gluten into the sub-epithelial region of the intestine where it could be modified by TG2 and trigger CD. (14)
Candida Infection May Trigger Celiac Disease through Cross-Reactivity
So far, we’ve been talking about dysbiosis in a general sense, but there’s evidence that specific microbes could trigger celiac disease as well. A recent study (hat tip to Questioning Answers for the find) found that an overabundance of the yeast Candida albicans could contribute to the development of CD, and unfortunately, antibiotic use is a big risk factor for developing a candida infection. (15)
Candida is a normal part of the intestinal microbiome of healthy individuals, but problems can arise when it overgrows relative to other inhabitants of the intestine. Remember how tissue transglutaminase (TG2) readily binds gliadin? Well, it turns out that candida expresses a protein named Hwp1 that also binds TG2, potentially leading to immune activation and cross-reactivity with gluten.
The study found that people without CD who had candida infections produced anti-gliadin antibodies, as well as the expected anti-Hwp1 antibodies. People with CD produced antibodies to both proteins as well. This means that in theory, a person who is genetically susceptible to CD but who doesn’t have the disease could develop the disease in response to a candida infection.
So, What Does This Mean for You?
As you can see, there are several ways in which antibiotic overuse and subsequent intestinal dysbiosis or infection could lead to the development of celiac disease. As I’ve said before, antibiotics can be lifesaving and are necessary in some situations, but that doesn’t mean they’re free of consequences.
It’s becoming more and more clear how vitally important it is to use antibiotics responsibly, whether that’s not using them at all, or properly rehabilitating the gut during and after a course when they’re deemed necessary.
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Hi. Your information seems spot on. My 17 year old son-just diagnosed with CD a week ago. After almost 20 months of misery. Random infections. Losing 30 pounds with zero explanation. Stomach pains. Bladder Spasms. Oral Thrush that persisted despite three rounds of treatment. ALL of this began after he was diagnosed with gastroenteritis in April 2015 . Soon after, Bladder spasms. Told the virus settled in his bladder. The 30 pounds of weight and summer of inexplicable stomach pain began. Sometimes nauseous, feeling full after eating a little bit, hurts too much to eat, stabbing pain, then just ashiness. etc. fatigued much more than usual. Then tested for mono, ultrasound of abdomen done, all normal. Shortly he had several allergic reactions to unknown substances. Patch testing revealed nothing abnormal. Pain in ankles and legs… shortly after, referred for exam by a pediatric ortho dr… He suspected auto immune disorder and sent him for blood work to look for RA. But it returned normal… Acne spiraled out of control — leading to more antibiotics.. prescribed prevacid for reflux..
and daily Zyrtec to thwart allergy attack. still not normal… but managing ok… august of 2016 — more infections– first groin pain.. epididimitis was diagnosis.. bactrim for ten days.. then resume doxy antibiotic for acne… then he gets white coating on tongue and bumps in throat… diagnosis oral thrush normally seen in babies.. goes goes through three rounds of treatments.. ultimately taken off the doxy… and the thrush seemed to improve.. stomach pain worsens in upper abdomen.. sent for ultrasound, x ray of spleen area, blood work of mono.. has enlarged spleen but blood work good. My son is the one who saId he noticed if he did not eat bread or pasta he felt better.. that his father has a gluten intolerance he had been dealing with so my son decided to try to not eat bread or pasta.
He still complaining of stomach not being right.. school intense.. is it stress???? Has ADD as well. We go to see an ADHD specialist in NY after Christmas to have brain mapping done to help with medication analysis… FIRST MOST GLARING ISSUE with this specialist.. HIS G I issues… Sent us back to Florida with orders to get gLUTEN TESTING DONE !!! Back home, got back to local drs… Son was immediately given an upper GI and all the blood work was taken in the IV the NY dr requested… JUST found out my son has Celiacs. 95 percent accurate full blown Celiacs.
Biological father seems to have this as well. I am getting bloodwork tomorrow. It appears to me that all of his random health issues, seemed to begin after his stomach infection with a high fever in April of 2015 and he had to miss 6 days of his junior year because of this… and is on line his senior year now.. it was just too much . Thank you for your blog. I am in the process of finding out as much as I can. I feel so bad my son suffered so long during such formative and important years feeling so poorly. It leads to doubt, worry, depression, feeling like a hypochondriac and a failure. And it appears it mostly is due to Celiacs. We are praying that with a diligent gluten free diet his energy, spark, and health will return.
Have you ever tested for intestinal candidias? I have read a lot that antibiotic use create candida albicans growh. Unfortunately most doctors don’t believe on theory but a simple stool test can diagnose whether this is an issue or not. I am not sure why their ego gets hurt in getting this tested but please don’t ignore it and discuss about it with your doctor.
Don’t stop at just gluten- follow up checking for other “allergens/sensitivities”. Dairy(casein), peanuts, and soy can be very problematic too. It is crazy where they sneak soy into things!!
HI, recommended to your site. I have CD, none of my reactions or immune responses happened until I had a C Section last year. Since then, my body seems to react to everything- gluten, dairy, sugars, you name it. I can’t help but claim this may be primarily caused by my c section and an infection. No doctor has been able to explain how this may have occurred, only that it is genetic. Do you think I may have an infection that caused CD
My son, age 5, has Celiac. He only had one round of antibiotics in his first few days of life due to complications after birth. After that he was exclusively breastfedas and infant and continued to breast feed until 22 months. I don’t think the antibiotics where the main trigger of his disease but wonder if it was the traumatic birth experience. Otherwise he is a very healthy kid and it took us a long time to even notice his Celiac symptoms since is was so healthy. We found out due to iron deficient anemia despite being on an iron rich diet.
I was on DAILY antibiotics for bladder reflux from 6mo of age until I was 10. I now (in my 30’s) have several autoimmune diseases one of which is Celiac. I often wondered if all of my autoimmune issues were related to prolonged antibiotic use. Still not sure if this is the csse, or if I will ever get an answer , but it’s definitely something to think about!
My fiancé has been taking antibiotics daily 250 mg a day morning and night since she was 11, for rheumatic fever, she is now 27, shortly after the birth of our child three years ago she developed signs of celiac disease or possibly chrohms, she’s been on a gluten free diet for almost three years now, and her symptoms are better except for one thing, she gets ulcers in her mouth, like 3-5 at a time, is this related to cd or her antibiotics?
Chris,
While working in the southern Philippines (age 38) I had an onset of severe diarrhea after eating some locally prepared food. After 7 days of GI distress I began a 30 day battery of antibiotics (US licensed physician treated and US supplied meds). The battery of antibiotics consisted of 10 days of amoxicillin (no improvement) followed by 10 days of ciprofloxacin (no improvement) followed by 10 days of flagyl and a simple diet of rice bananas and apples with improvements. The diarrhea along with abdominal distress bloating and brain fog would return upon gluten ingestion. After 3 x GI physicians diagnosis of celiac disease I finally accepted that my days of wheat barely and rye ingestion were over. Learning to manage my diet to avoid inadvertent gluten ingestion was another interesting journey…
Hopes this helps,
John
http://www.mdpi.com/2072-6643/7/3/1565
My son was born in 1969 and screamed from birth. He was 8 lb. and 22 in. long, so well developed. He was a difficult baby to carry,…kicked constantly in the womb, day and night, so much so that he caused me a hernia,!….(.I now think it was because of the Gluten I was eating). Finally, at 8 months of age, and equal number of doctors, I noticed puss on his nappy, and we were finally believed. The diagnosis was that he had caught a urinary infection in the hospital nursery at birth, and as a result they put him in hospital to check his kidneys etc. and feed him large doses of antibiotics. Not only that, but when we took him home, we were presented with a pint sized bottle of phenobarb and other sleep medications, (adult dose I was told), to quiet him down.
We were told he was going to be ‘retarded’. From that time forward, ( I never gave him the meds.) but he was on antibiotics, he had dreadful nightmares and mood swings.
By the time he was nine, the teachers at school told me that they couldn’t work him out. He was both brilliant and vague.
I asked him why this was and his answer was that ‘after lunch, a ‘little man’ pulls a blind down and he can’t think.”
He also developed dreadful tantrums where he would say that he wished he had a zip in his head to let the steam out!!
At almost ten, a family member was researching in one of the Uni. Medical libraries and came across a book called…”Good Food, Gluten Free”. The book was delivered to my door with the words,…”read the Intro”. I did, and there, I saw an outline of my son. I was considered ‘mad’ by the doctors until I found my way to a doctor educated in Western and Chinese Medicine. At last, someone listened. I had already worked out a ‘natural food’ GF diet, which my son had been on for 8 weeks. They did ‘blind studies’ on him for 6 weeks, and then wanted him to return to a ‘normal diet’.
The child refused saying that he didn’t want to be sick like that again. That little boy is now well in his forties,….married with three teenage daughters. He has university degrees and is definitely not ‘retarded’. He has never eaten gluten again.
I then researched our family. My mother-in-law had had part of her bowel removed for colitis. Her mother died of dementia, and was known for her ‘bilious attacks’ and ‘rings’ on her tongue. I recognised this immediately as something my son had. Later my strapping 6ft.2in. husband began making regular night trips to the toilet, sometimes 2 or 3 times. WE put him on the GF diet and it all stopped.
So now I was looking at my child, my husband, my mother-in-law and her mother!!! My daughter and I were not celiac, but she now has two boys who are. I think that makes about five generations! All these family members also carry MTHFR mutations. As for me,…I’m not celiac and I don’t carry MTHFR gene mutations, but I do have Hashimotos, vitiligo and various other ‘auto immune’ issues.
My daughter has Grave’s disease.
I’m taking the trouble to briefly write ‘our’ story, because I don’t think there are many who can prove the genetics for so many generations. With my son, I have NO doubt that his ‘treatment’ in hospital at 8 mths. of age, brought the problem to the fore much earlier than it otherwise would have become evident. As for previous generations, ..who knows. My son now suffers acid reflux, and sadly takes meds. for it that make me shudder. I’m very interested in the microbiome of the gut and can’t wait for more research on this. But I think we are just at the beginning, I DO know that ‘probiotics’ are NOT the answer. Specific varieties MIGHT be, but that’s going to take time to work out.
Our whole family live on fresh organic food, and watch the water we drink, plastics and all manner of household products. Some of us do not eat grains at all. It helps us to stay on our feet! My husband is 74. He’s outside concreting in 35o heat!
I hope that helps someone! Never give up, Auto immunity is a horrible thing, but it makes you ‘strong’ and disciplined in a
sense. There’s some wonderful research going on at present, and we need to support it as much as we can.
I am 56 years old and is suffering now for 2 months from a problem that is unknown at present. I was in church and suffered a hot flash accross my stomach and arms. I went to my Dr. and was put on zoloft, after five days of taking the zoloft I started hearing voices, I thought I was dying. I quickly wake my husband and asked him to call 911, before 911 came the feeling subsided and I decided not to go because of financial concerns. The next night the same feeling came back and I decided to go to the emergency room. I was given drug test, had a Police officer pat me down but no test to find out what the problem was. I was then diagnosed with psychosis and sent home. The next week I had a very rapid heart palpitation went back to the ER for being scared and again nothing was done. I then decided to call someone that practices holistic medicine. I was told to stop eating food with gluten and I did. I am feeling a lot better and I am waiting to go to my Dr. to be diagnosed.
Did you ever take a fluoroquinolone drug… cipro, avelox, levaquin etc? These will also do it to ya.. long after you’ve taken the drug. Check out Fluoroquinolone toxicity group on FB. Good luck !
Do you think the high doses of antibiotics caused worse reactions to the gluten? Did he happen to get sores in his mouth like ulcerous?
This is really interesting (as always). After 44 years of ‘perfect health’ with no digestive or other symptoms despite 20 years of developing country travel I returned from a trip to Nepal and started getting infrequent bouts of diarrhoea. Eventually I went to the GP who suspected Giardiasis and prescribed Metronidazole, the first course of anti biotics I’ve ever had. I rapidly went from bad to worse, lost 2 stone in weight and was vomiting daily. 6 months later was diagnosed with CD. My instinct has always been that the anti biotics not a gut infection triggered the condition. 6 years on I’m writing my MSc dissertation on FM approach to CD so some good came out of it!
Hi Nicky,
The exact same thing happened to me. I was in Nepal last year and caught food poisoning. The doctor gave me antibiotics that I reacted badly too. After that, like you, I started having frequent episodes of diarrhea, which became worse, rash on my back, dizzy and nausea, etc. It took me a month to realise it was probably Celiac disease. I haven’t been diagnosed (as I really don’t want to eat bread for two weeks), but my symptoms and relapses are pretty clear.
Is there anything new about your state or knowledge on what could have happened to us?
Are you familiar with interstitial cystitis? It’s a chronic condition where one experiences symptoms of a bladder infection but no bacteria are found in the urine. Many acquire IC after having a bladder infection and taking antibiotics. Many have found that avoiding gluten resolves many symptoms. Perhaps there is a connection to this process. Millions of women are suffering from IC, some estimate as many as 3-7% of women in the US.
This is very interesting! In the study showing onset of celiac disease following candidal infection, this was a very specific, and somewhat rare subset of people with candidal infection, ie hospitalized patients with blood cultures positive for candida. It makes good theoretical sense that this might also apply to the much more common and less sick patients with intestinal candidal overgrowth- it would be great to see a study among this group of patients!
As of 4 hours ago I was feeling like I was losing my 8 yr old son. For years the doctors told us he has asthma, although he never had an asthma attack. At 1st it was every few months he would catch a cold. It would progress to a high fever. The doctors would send us home saying it was a virus. in 2-3 days we were back at the doctors with deep non stop cough and 102-104 temperature. Sent home with antibiotics, then they added steroids.( Which we rejected) Over the past year -years and a half we have been at the doctor every month. We were repeatedly not a food allergy. Last month they said he had ADHD….my mommy instincts have been off radar for so long I thought I was losing it. Over the past few months he has had headaches, foot pain, and an upset stomach. 2 days age we are back at the doctors with headache, stomach ache, swollen foot, and a rash. The doctor, if you want to call him that, told me the rash had an unknown cause but was unimportant , and as a mother I should ignore the complaints of foot pain( even though you could plainly see the swelling) it was for attention. That was it I was watching my son suffer And I couldnt help. Today we took him to a new doctor. By the time we got there his lips looked so red and inflamed, feet swollen, and rash all over. The years of antibiotics wiped his system and he was now fighting his own body! His lower intestine is inflamed, his is rampant with yeast( another thing I questioned the other doctor about), his foot and joint pain is inflammation, and adhd is brain fog( basically inflamed). They said he is 6 months to a year away from celiac disease. He is on a non dairy non gluten diet, heavy duty probiotic, and oregano oil. All I have to say is The title doctor means nothing if you have that feeling , that something is wrong , bad energy feeling follow it. These “doctors” should have their licenses taken and be charged with something. As a mother I should have gone with my gut. Im just so thankful my son is going to be ok and that his years of suffering will soon be over. We have to use our voices and help each other!
My younger brother use antibiotic for more than 1 year and doctor said he has celiac disease. He left wheat for last 1 year however there is no improvement and his anti ttg result still shows same result. Could you guys help …it seems he has some infection not sure candida or some other but not celiac disease…When we talk to doctor about this…they dont believe on our theory or this article…is there any test which can confirm candida yeast infection or any other thing?
Bharat, if it is celiac disease and an improvement is sought through diet, then he needs to cut out more than wheat, he needs to avoid all sources and every trace of gluten, including possibilities of cross contamination through surfaces, implements and so on. I did a similar thing, I mistakenly thought it was wheat and tried cutting that out for years. TO cut out gluten is really difficult and took me about 2 years to get fully sorted out, but this is what you have to do. Have a look at http://www.celiac.com/ or https://www.coeliac.org.uk/home/ for guidance. Good luck
I’ve had a suspicion about this for a long time. But I’ve increasingly grown concerned about the effects of regular prednisone use. My daughter had “recurrent croup due to narrowed airway” and was prescribed a 3-day course of prednisone for each episode. We followed this religiously for 2 years (I’m estimating she had more than 100 doses) because she couldn’t breathe and my husband wasn’t taking any chances with homeopathy, etc. But I’ve been worried about the unknown side effects of the steroids on her system as a whole, especially since my 38-yr-old sister has recently been diagnosed with Celiac after constant antibiotic use to control acne.
Hi Chris,
I can absolutely relate to how use of antibiotics makes the gut more disposed to develop CD. Both my mom and my grandma got CD/gluten intolerance after using antibiotics.
This was a really great article who highlighted and confirmed many of my previous thoughts about how CD might be developed, and who important good bacterias is for protecting us from CD.
Thanks!
I agree with the possibility of a connection of antibiotic use and CD. I was diagnosed four years ago at age 58. I have taken antibiotics most of my adult life, for years at a time. Whenever I questioned my doctors about this long term use they just said “don’t worry we’ll keep an eye on you”. I’m not sure what that is suppose to mean since they only thing they did was write another prescription. Besides CD, I am allergic to soy and intolerant to dairy. I am continuing to react to other foods such as beans and tomatoes. Really getting tired of feeling bloated most of the time and hate that I may have contributed to my CD diagnosis by not listening to my “gut” about the excessive use of antibiotics. My new doctor is trying to say he thinks I may not have CD and wants me tested again even though I have told him I have been gluten free for four year, except for being “glutened” a few times by mistake. He said it doesn’t matter the intestinal damage will still be there. Does anyone know it this is true?
Please ask for candida infection test….it might not be celiac. If gluten level gets down after leaving gluten it may be celiac and if not chances are high that it might be candida overgrowth
Thanks Chris for laying out the many avenues to food intolerance. Heavy duty antibiotics contributed all through my childhood.
Avoiding all grains and starches as well as all sugar products has initiated an amazing outcome. Along with anti-inflammatory supplements I’ve gone down many sizes in clothing.
I look forward to your guidance, especially in how to talk with the general public.
Hi Chris,
Very interesting. I have all the signs of CD though I haven’t gone through a formal diagnosis (though have discussed the issue with my doctor) and spent many years on antibiotics as teenager for acne. From the age of 12-19 I was on a constant course of minocycline or tetracycline and it was in my early 20s that I first developed IBS. I was checked out for all sorts of things (though not CD) and it is not until now (aged 40) that the penny dropped and I adopted a fully gluten (and grain) free diet despite being mostly wheat-free for years.
That said, my sister and my partner, neither of whom received such antibiotic treatments, are both intolerant to wheat/gluten (as are several friends that I know of) so antibiotics are not the entire story where the development of intolerance never mind fully blown CD are concerned.
Hi Chris,
I found the article very interesting. There is no doubt about the relationship between antibiotic overuse and celiac disease. I agree with you about the increase in the incidence of celiac disease. I have been coming across a few number of people with this condition recently unlike before. Some have been placed on a long term course of antibiotics due to misdiagnosis which happened to have aggregated the situation. Some have been placed a very strict diet that almost left them with nothing to eat apart from drinking milk which triggers an allergic response.
A few of the patients were misdiagnosed as having duodenal ulcers and one or two with gastric ulcers. Dairy milk and natural yoghurt were recommended hoping to have antibacterial and calming effect on the G. I. system.
Personally, when dealing with patients with celiac disease, I recommend gluten free diet; I place them on a well researched Aloe Vera drinks, probiotic containing six strains of beneficial bacteria ( for two weeks), multi-minerals and anti-oxidant supplement containing beta carotene. Within 3 months, their condition is generally under control, no more leaky gut syndrome, they look better with amazing vibrant energy unlike before.
I wish Josephine had given us more information. I’ve had 7 rounds of antibiotics in the last 4 years and my digestion problems have greatly increased. I’m wondering what specific supplements she used. I’m going to my 6th gastro doctor next week and already know he will have no help.
I have celiac disease (and sjogrens) and was on tetracycline for the first 2 years of my life. I was diagnosed with celiac when I was 51. I have a daughter who has celiac disease and was on antibiotics most of her childhood due to lung infections. My son and youngest daughter cannot tolerate gluten at all but are not celiac.
I truly believe the antibiotics I had and a poor American diet is what made me prone to autoimmune disease. I am just sorry my kids are sick with autoimmune symptoms. It’s one thing to be chronically ill when you are older, but sad to have to deal with it as a young adult.