Experts respond to questions about autoinflammatory diseases

An expert panel with physicians, psychiatrist, and a parent of a child with an autoinflammatory disease respond to audience questions during the “Managing your Autoinflammatory Disease: Lifestyle and Wellness Workshop,” which took place on April 28, 2018, at Boston Children’s Hospital in Waltham, MA. 

Watch the video or read the transcript below. Take a look at other videos from this workshop. 

The transcript has been edited for clarity.

Audience 1: What do you see in the future? Our son right now is suffering from CAPS and is on Ilaris…it works, but is there research on types of other medications or are we stuck with this for now?

Moderator: The question is on medication future. I want to be respectful of people who need amplification. That’s why we’re using a microphone.

Dr. Fatma Dedeoglu: Definitely. There’s a lot of research going on trying to figure out even better ways of doing IL-1 inhibition. It’s not just IL-1 involvement in the different types of diseases… even though it works, it may not be the full answer. We’re assuming that there are other cytokines involved.  Anytime there is inflammation in the body, there are so many proteins that are involved. If we block one, sometimes it may tip the balance on the rest. Another type of IL-1 inhibition is called rilonacept and it’s also been used in some patients with autoinflammatory diseases.

Dr. Jonathan Hausmann: The future is bright in terms of medication. The last 20 years, we’ve seen a revolution in the development of the biologics. I have no doubt that that’s just going to accelerate in the future. Now we’re experimenting with medications–small molecules that are actually able to silence genes. Basically, like a switch that turns the gene on or off.

To my knowledge, it hasn’t been studied in an autoinflammatory disease just yet, but it’s been studied in other diseases, and it’s been very successful in some diseases. I have no doubt that in the next 10 years, we’ll have these small molecules and other ways at targeting inflammation, which may be as good as or even better than the medicines we have today.

Dr. Dedeoglu: There’s also work to try to get these medications by mouth. We know that injections a major problem.

Audience 2: Are you seeing an increasing diagnosis of very rare diseases such as HIDS or CAPS?

Moderator: Question on the frequency of diagnosis.

Dr. Dedeoglu: Yes. That’s a very good question. Yes because if you look at FMF diagnosis, it used to be diagnosed in the teen years. We certainly now diagnose FMF much earlier. Also, there are new diseases becoming known. Over the past year,  five or six new diseases have been discovered,

Having said that, in our autoinflammatory clinic, probably 60% of our patients we call “undefined” because they do not match any of the known conditions. I know most of you don’t want to hear that, but as long as we can place the patient under the umbrella called “autoinflammatory diseases,” it is acceptable for now.

Our hope is that over time when we see our patients, we may be able to relate their symptoms to one of these new diseases and arrive at a diagnosis.

Dr. Ezra Cohen: There’s always that question about whether it’s incidence that’s actually changing or whether it’s recognition that’s changing.  Most autoinflammatory diseases are genetic.  I don’t think the incidence may be changing as much as new diagnoses are being made because of increased recognition and new genes being identified.

Dr. Hausmann:  I can see it in my adult patients that have had recurring fevers for years and years and years and years and years. They’ve gone through the workup. It’s not an infection. It’s not cancer. They just kind of deal with it. Eventually, they land in either our autoinflammatory clinic or with another rheumatologist that’s able to recognize, “Hey. That’s probably an autoinflammatory disease.” Then that’s when the workup and treatment starts.

We’re getting better at recognizing them, although I would probably venture to say that most people out there that have autoinflammatory diseases are undiagnosed.

I think there are a lot of patients with autoinflammatory diseases that are being told they have recurrent infections because doctors are unable to recognize these rare diseases. Fortunately, now there are chapters about autoinflammatory diseases in medical textbooks. Medical students are learning about them. We’re educating our students and residents about them. I think it certainly takes time, but I think physicians are getting better at recognizing autoinflammatory diseases.

I can’t tell you how many patients have come to me who diagnosed themselves or their children with these rare syndromes! They told their pediatrician, “I was looking online and I think my child has PFAPA.” Or, “I was looking online and I think I have FMF because it matches the symptoms.” And, lo and behold, they’re right. I think there’s been more awareness from patients and from doctors. I think we’re heading in the right direction.

Audience 3: At what point, as a doctor, do you decide to do genetic testing? How has genetic testing change over the years?

Moderator: Question about genetic testing.

Dr. Dedeoglu: There’s no one right answer. The genetic testing is not perfect. All the dogma we learned about genetics seems to be changing–especially Mendelian rules. Autoinflammatory diseases don’t seem to follow them.

Just an example, for familial Mediterranean fever, is a recessive condition so you need to have two mutations. However, about 30% of patients with FMF have one mutation and still have symptoms. There are also patients with these mutations who have no symptoms.

We need to decide ahead of time what we’re going to do with genetic test information. If it’s going to change our management. For some, knowing the answer it’s going to increase the stress level.

If clinically you don’t match one of the known genetic syndromes, then genetic testing is unlikely to be very helpful–it’s likely to reveal mutations of unknown significance.  For some, that creates a lot of stress.  For others, they feel better with that answer. They would prefer that over not knowing anything.

The utility of genetic testing can change over time. I had patients who had genetic testing 10 years ago and it was negative.  Now they come to me and I say  “You seem to be fitting into this new disease” and we can check genetic testing for mutations in these new genes.

Dr. Cohen: Part of the issue is, historically, they are very expensive tests.  Over time, our mapping of the genome has improved a lot and the expense is coming down.

A lot of our genetic tests are like asking a person to find objects in a dark room…you have to know where to look.

Now with whole exome sequencing, looking at the whole genome at once, you may not need to know where to look–it helps–but it’s basically just like turning on the light and then looking at the room.

The issue has been that our ability to interpret the results is lagging behind our ability to obtain the sequences.

Moderator: Person in the back.

Audience 4: My daughter has periodic fever syndrome and started her fevers from age one and is now three and a half. As a parent, I’m trying to figure out, what makes it easier to do your job? What is the best thing that you need me to do? As a doctor, when you see families come through, what are the families that seem to have this together and able to manage this well? What are their key traits? What is the information that I should be bringing to my medical providers?

Dr. Hausmann: I think that’s a great question. We peak into your lives for 20 or 30 minutes at a time. We don’t know what’s going on for those months between visits. Something that really helps me is for families to keep a log about the symptoms, about the fevers, about medicines that they’re giving, what seems to be helping and not. Seeing if they recognize triggers for their flares. We’ve spoken a lot about triggers, including good stress. I always ask the patients if vacations and birthday parties and travel, seem to trigger flares?

Our decisions that we make in the clinic in those 20 minutes is: is the patient doing okay, or do we need to change medicines? A lot of that is going to depend on how they have been doing for the past month, or past three months. Having this data available is very helpful to me.

Moderator: I’m going to interject a bit too. We have a lovely parting gift for everybody who came today. That’s going to be a binder with materials dedicated to organizing yourself for medical visits.

Dr. Dedeoglu: I think one of the reasons we wanted to do this kind of workshop is to get connected and share all your experiences.  You need to look at the body as a whole to figure out what works. It’s also important to work as a team, and not saying, “Do this or do that.” I’ve learned a lot from the patients that I’m caring for, and then I share this information with another patient to see if it may also be helpful to them.

Moderator: Thank you. We’ll entertain these last two questions and then we’re going to go to lunch. We’ll have time for more questions later.

Audience 5:  I’m curious about mindfulness, and I’m wondering if there’s scientific evidence that mindfulness actually affects the immune system.

Moderator: Question about the effect of mindfulness on the immune system.

Dr. Cohen: Most of the studies have been functional MRIs. That’s looking at areas of the brain that light up in response to different practices. One study that recently came out, six years ago, suggesting that patients who practice meditation regularly (with programs such as mindfulness-based stress reduction) have less brain activity in areas that register pain and anxiety.

They’ve also looked at long-term practitioners where they have seen that the neocortex, the surface of the brain where a lot of the cognitive processes take place, is larger. At the same time, in the limbic system, where a lot of anxiety and worry occurs,  gets smaller. I think that effects on anxiety and worry have the strongest evidence behind the usefulness of mindfulness.

There were a couple of studies suggesting that immune cells are longer-lived in patients who practice regularly based on having longer telomeres (part of the gene that protects the cell from aging).

My own personal experience, I do think it probably has an impact on the immune system. Obviously, it varies from person to person.  I don’t think it’s a cure-all. I think it’s a really important part of your life in the same way that exercise would be. I think I found that it works maybe less directly and less effectively for chronic pain as a single solution, but it can help as part of a lifestyle. I can recite a lot of other recent studies, but that’s the one that comes to mind.

Dr. Carolyn Snell: One thing that I just wanted to add. A psychiatrist who had been with our department had done some research on inflammatory bowel disease, looking at the immune response. They were able to actually see that with cognitive behavioral therapy there was less of an immune response, with lowering of cytokines. I think it all just speaks to the fact that there can be direct physiological effects of some of these mental health approaches and stress reduction techniques.

Dr. Dedeoglu:  One of my patients with Raynaud’s who used biofeedback, she was actually able to hold an ice cube on her leg and keep the temperature 90 degrees on her leg. I was skeptical initially. But with sensors when can show that these techniques are actually effective.

Moderator: Last question in the back.

Audience 6: I have a four-year-old with PFAPA. I just want to ask if the researchers are looking into alternative medicines like Vitamin D, extra Vitamin D, or cranberries and cherries. Those are really helping my daughter. I just wanted to ask if someone who is really into research, real actual research going on those alternate medicines.

Dr. Cohen: It’s a question about research alternative and complementary medicines.

Dr. Snell: There’s definitely a lot of active research into the complementary medicine. I think there are a couple of issues with research in general. As you can imagine, the most money goes towards studying medicines because of the relationship with pharmaceutical companies and studies. There isn’t much of a financial incentive, necessarily, to study alternative or herbal treatments.

There are also some very complicated things about studying these compounds because they’re not standardized. Every company will make a different formulation and it will have a different amount of the active ingredient. As a result, it’s very difficult to answer a question when there’s so much variation in what you’re trying to study.

Cherries have been studied in gout and I actually had a patient who developed gout at a very young age, which is a form of arthritis that’s autoinflammatory as well.  I had an amazing amount of success just with dietary changes, and his mother basically forced him to consume a pound of cherries and it had a really big impact.

I think there is a lot of potential for herbal treatments, but there is so much complexity and messiness in the study of the nutrition because of the tens of thousands of ingredients. It’s basically a clash between the reductionist approach of typical western science, which tries to identify a single molecule, and the wealth of complexity that actually exists in herbal medicines and in other herbal traditions like Ayurvedic medicine and traditional Chinese medicine.

Dr. Dedeoglu: All of us are different, our cases are different, so different diets may affect us differently.  What I personally found, I just watch what I eat and notice that certain things made me uncomfortable, and so I stopped eating them. I don’t follow a specific diet, but I eat food that makes me feel good.

Obviously, it’s not that easy with kids. We recommend a healthy diet, but that’s not sufficient. Sleep is important. Exercise is important. NIH is certainly looking into different herbal products, trying to study them better so that we can understand them.

Moderator: I want to thank you all of our panelists today.