Systemic Autoinflammatory Disease (SAID) Support - Page 25 of 33 - Welcome to the Autoinflammatory Alliance blog for discussing all things involving awareness, advocacy, care and thriving with SAID

The Debut of “Healthier Ever After,” Our Injection Tips Book for Autoinflammatory Diseases

Posted on March 23, 2014 by Karen Durrant RN

We are very excited to share our newest publication, the “Healthier Ever After” book to help families with young children thrive and cope with frequent (and often very painful) injectable medications to help treat autoinflammatory diseases.

This book was printed in March 2014, and will be available for patients to request a copy in late April 2014. You can take a peek at the book, and download it now to use with your family at this link: 1202 3_HealthierEverAfter_Web ready

It was written by the Autoinflammatory Alliance board, which includes a pediatric RN, an LPN, a kindergarten teacher, and a professional writer. This book was developed by our board, thanks to an unrestricted educational grant from Sobi through The Cement Bloc, that also designed and produced the book for us. We are so thankful for this grant from Sobi, and for all the hard work by the team at The Cement Bloc to create this beautiful book with us.

Suggestions from parents of children with autoinflammatory diseases were also a big inspiration for some of the information in this book. Topics include, how to help young children cope with their injections, traveling, distraction techniques, and more.

One of the key features of the book is a guide to discuss various things related to their injection, so you can help develop a custom injection plan for your child.

This plan will be used to fill in the page for promises (what the child will and will not do during the injection) and what awards they can earn for fulfilling these goals. This page (shown below), and the page with the chart to track progress towards earning the rewards are made of dry-erase paper. A set of reusable, vinyl cling star stickers, and a dry erase pen come with the book.

Click here to download a copy.

The printed book kit includes a reusable, dry erase chart and vinyl cling stickers to track your child’s progress.

To order a copy, please do so through our Autoinflammatory Alliance online shop. This book costs a lot more to produce than the requested $5 for US orders (higher cost for outside the US). This fee covers packing, shipping, plus the vinyl cling stickers and pen that come with the book, that are all being paid for by our org. The educational grant to produce and print this first version was provided by Sobi, through The Cement Bloc, so our costs were greatly reduced. Note that you can download a copy for free anytime. If you are having challenges with being able to afford this nominal fee, and need a printed copy of this book, please email me at karen@autoinflammatory.org.

If you are willing to donate more to the Autoinflammatory Alliance, we would greatly appreciate it anytime, by mail, or online on our site. We are a tax exempt public charity in the US, so all donations are tax deductible. Your support will help us to do even more things for patients, and increase awareness about these diseases.

We try to provide our other printed materials at no cost to people, but we do share a donation form when we send our materials, so anyone can give back, if they are able to do so. This book is our most expensive product that we have had produced, plus it costs more for shipping than our standard materials, so we are asking for a little help to cover the costs. Thank you.

We hope that you like it! We would love to hear feedback on how this has helped your child and what we can do to improve it for future editions.

For more injection tips read How to Reduce the Pain of a Kineret® (Anakinra) Injection and Distraction Techniques to Reduce Pain and Anxiety for Your Child When Giving an Injection.

Click here for Tips and Resources for Patients on Biological Medications.

Research and Information About FMF Patients with Only One Mutation

Posted on March 21, 2014 by Brian Goff

Below are links to Familial Mediterranean Fever (FMF) studies regarding symptomatic patients who only have one mutation found for FMF. These are not all the studies available however. For more search Pubmed.gov. You can also find links to more FMF research and information here.

Booty et al, “Familial Mediterranean Fever with a Single MEFV Mutation: Where Is the Second Hit,” Arthritis & Rheumatism, 2009: Their “data underscore the existence of a significant subset of FMF patients who are carriers of only 1 MEFV mutation and demonstrate that complete MEFV sequencing is not likely to yield a second mutation. Screening for the set of the most common mutations and detection of a single mutation appears to be sufficient in the presence of clinical symptoms for the diagnosis of FMF and the initiation of a trial of colchicine.”

Kastner et al, “Autoinlfammatory Disease: A Clinical Perspective,” Cell, 2010: “The second “frequently asked question” concerns FMF in particular and is based on the fact that many of the patients with colchicine-responsive clinical FMF have only a single demonstrable MEFV mutation, despite thorough scrutiny ( Booty et al., 2009, Marek-Yagel et al., 2009 and Ozen, 2009). Although this widely confirmed observation is based on a clinical definition of FMF that includes milder cases than were appreciated 20 years ago, it suggests a more complex pattern of inheritance than the simple recessive model of the textbooks. It also argues that solitary MEFV mutations may confer a biochemical or clinical phenotype by mechanisms yet to be elucidated, perhaps in the presence of as yet unidentified modifier loci.”

Ozner Changing concepts in familial mediterranean fever: Is it possible to have an autosomal-recessive disease with only one mutation? Arthritis & Rheumatism, 2009: “Since the identification of the MEFV gene, the mutations have been studied extensively in affected people. Surprisingly, it has become evident that the mutation in the second allele cannot be demonstrated in ∼20–26% of the patients who have FMF (5–7). The phenotype of these patients is confirmed by the presence of typical attacks of FMF symptoms and by the response to colchicine therapy. So, how can a person carrying only 1 MEFV mutation present with this autosomal-recessive disease? Two articles published elsewhere in this issue of Arthritis & Rheumatism address some of the questions in this context.”

Marek-Yagel et al Arthritis & Rheumatism 2009: “These findings are highly consistent with the existence of a clinical phenotype among some patients who are heterozygous for FMF and could explain the vertical transmission in some families. A single mutation in the MEFV gene may be much more common than was previously thought and may include up to 25% of patients who are diagnosed as having FMF.”

Touitou J Medical Genetics 2013: “Over 15 years have passed since the discovery of the first autoinflammatory gene, MEFV, responsible for familial Mediterranean fever. The identification of another gene, TNFRSF1A, in 1999 led to the concept of autoinflammation which characterises rheumatological conditions triggered by a defective innate immunity. Substantive progress has been made since then with the identification of 18 autoinflammatory genes accounting for up to 24 disease entities showing overlapping symptoms. The accumulation of studies reporting patients with missing or excess mutations as compared with expected numbers favours the hypothesis that these diseases are distributed along a continuum ranging from monogenic to multifactorial conditions, rather than featuring only classical modes of inheritance. Moreover, the probable interactions of environmental and epigenetic factors further obscure our understanding of the mechanisms underlying the phenotypic expression of patients. This review explores the history of autoinflammatory gene discovery, discusses the nosological disparities stemming from the clinical versus pathophysiological definition of autoinflammatory diseases and summarises various inheritance patterns. This review calls for a consistent disease nomenclature and presents a reconciling hypothesis which places different sequence variants within the autoinflammatory disease continuum. Integrating these new concepts should help to facilitate communication between health professionals and promote personalised patient care.”

Kone-Paut et al (Rheumatology, 2009): Assessed clinical characteristics of 94 French patients carrying single MEFV mutation. “The clinical picture of French heterozygote patients with recurrent fevers resembles that of homozygote patients.” Most of them required colchicine treatment. Fever > 39 C (80%), duration (1-3 56%, > 3 days 36%), frequency (1-2 months 48%, > 2 months 15%), peritonitis (97%), pleuritis (25%), athralgia (53%), skin rashes (20%), apthosis (18%), lymphadenopathy (9%). MEFV mutations were MEF94 (60%), M694I (7%).

Federici (Annals of Rheumatology Disease, 2012): Comparisons of children with two MEFV mutations, one MEFV mutation, and no mutations. “This clinical observation supports recent findings contrasting the notion of FMF being a pure autosomal recessive disorder associated with recurrence of mutations leading to loss of protein function. A dosage effect could be invoked, giving rise to symptom onset even in the presence of one wild-type allele.”

Moradian et al (Journal of Human Genetics, 2010): Study of 1299 Armenian patients including 236 (18%) with definitive diagnosis of FMF. From these selected individuals with two mutations and single mutation along with non-clinical control group. Compared symptoms of double mutation individuals with other two groups. “We found extremely high probabilities for the presence of FMF symptom in heterozygous [single mutation] idnviduals and determined that symptoms were eually likely to occur in both analyzed genotypes (double and single mutation). Therefore, our study supports the rising evidence that a single MEFV mutation could be associated with mild FMF symptoms.”

Bardeli et al (Genetic Testing and Molecular Biomarkers, 2011): Using DNA sequencing …”Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disorder characterized by episodes of inflammation in the absence of high-titer autoantibodies or antigen-specific T cells. The Mediterranean fever (MEFV) gene located on chromosome 16p13.3, which encodes the 781–amino-acid protein pyrin, is the causative gene for this monogenic Mendelian disease. This study presents the molecular analysis of an MEFV gene mutation screen of 5518 Turkish individuals with clinical diagnoses of FMF. Patients were genetically diagnosed using the FMF StripAssay and DNA sequencing analysis. Contrary to the results achieved by the FMF StripAssay, DNA sequencing analysis identified large-scale coding and noncoding novel sequence variants, together with a significant group (76%) of individuals who were receiving colchicine and had a single heterozygous mutation, despite the recessive inheritance of FMF. In conclusion, sequence analysis, unlike other routine laboratory techniques, may enable screening for a broad range of nucleotide variations and may prevent less common, population-restricted, novel sequence variants from being overlooked.”

How to Use the Comparison Chart of Systemic Autoinflammatory Diseases

Posted on March 18, 2014 by Jennifer Tousseau author, Karen Durrant RN editor

The Autoinflammatory Alliance’s Comparison Chart of Systemic Autoinflammatory Diseases had it’s debut in the poster presentations at the 7^th Congress of ISSAID 2013 in Lausanne, Switzerland to medical professionals from around the world. It was edited, and expanded for release in larger distribution at the American College of Rheumatology 2013 Meeting in San Diego, CA in October 2013, and is available in print, or online. We are working on developing an interactive, multi-lingual digital format for release in 2014. The content was written, and edited by the leading experts on autoinflammatory diseases worldwide and was co-authored by Karen Durrant, RN BSN–President of the Autoinflammatory Alliance (formerly The NOMID Alliance).

We have narrowed the focus of the chart to Systemic Autoinflammatory Diseases (SAID), because these share some similar characteristics, yet unique findings between them, and can be very hard to distringuish from each other.

Some Main features of Systemic Autoinflammatory Diseases (SAIDs) include:

Most have known genetic mutation (or in a few cases, deletions) that cause the disease, so the right genetic testing could help with diagnosis. However, there are some patients that have the clinical findings, but may not show the genetic mutation, and respond to the appropriate treatment, so clinical diagnosis, based on symptoms, labs and other tests is the most important focus. This chart allows doctors to analyze the clinical symptoms, in addition to the common lab findings and genetic mutations associated with each disease.
The majority of SAIDs feature recurrent (periodic) fevers, along with other systemic symptoms (often rashes are present in most of these diseases) during flares.
SAIDs are generally lifelong diseases, and in most cases they present in infancy or early childhood, and last throughout a patient’s lifetime. There are few adult-onset autoinflammatory diseases, and some patients that may have periods of remission, or lessened frequency of symptoms at various times in their life (and a few with PFAPA may even outgrow their condition), but in general, these are significant diseases that affect patients throughout their lifespan.

With this chart you can narrow down the possible systemic autoinflammatory diseases a patient might have and focus on what further testing is needed and best treatments to try first.

You can search symptoms on the chart by accessing the pdf, and then clicking the “command” and “F” key on your computer to bring up a small green search bar on the top of the pdf. Use the page tools to scroll through each area that has that word in your search.

Note-most of the symptoms on this chart are in medical terms, so you will need to use the medical (latin) name for a certain symptom (such as “conjunctivitis” instead of the common term “red eyes.”)

Basic Steps in Using the SAID Diagnostic Chart

Read each symptom box on the chart.
Circle the boxes with symptoms that you know the patient does have.
Cross off what you are sure the patient does not have.
If you do not know if the patient has a symptom, leave that box blank. In some cases, it may be appropriate to cross off some symptoms in a box and circle others in that same box.
Then see which ones have the most circles and fewest symptoms or boxes crosses off. Those are the autoinflammatory diseases that warrant further investigation.
Most patients will have symptoms that match more than one fever syndrome as many of these conditions share the same symptoms.

Evaluate the Patient Holistically to Obtain a Good Diagnosis

The collections of symptoms need to be evaluated as a whole.
Rarely does only one symptom or test give you the answer. Some symptoms do bear more weight and can help narrow down the possibilities.
Fever pattern and length of fevers is a prominent symptom to consider. For example, most PFAPA fevers do not last longer than 6 days. If a fever has lasted more than 10 days, PFAPA and FMF may be pushed down on the list of possibilities, but kept on the list because there are always exceptions.
The type of rash as identified by a dermatologist is also very helpful. Skin biopsies can lead to a more defined diagnosis with many of these diseases.

Other Key Considerations in Using this Chart:

Patients do not have to have every symptom on the list for a specific fever syndrome to have that syndrome.
Patients may have additional symptoms not covered on the chart.
Patients themselves, and caregivers of patients with suspected fever syndromes should also carefully read this chart, and discuss what symptoms they have from the chart with their doctor, as they know their own individual symptoms best.
Not every patient presents a typical disease progression or has textbook genetic findings or other lab results.
There are always exceptions, and there are still more unclassified conditions that will need to be added to this chart, so just because someone does not “fit” all the areas on this chart, they may still have an Undifferentiated (Unclassified) Autoinflammatory Disease, and should be cared for in the proper manner.

Keep in mind that not everyone gets every symptom on the list or has every symptom with every flare. Sometimes symptoms develop later in life. Some symptoms fade away while new ones develop. Some symptoms may have been easily missed or dismissed in infancy or early childhood when symptoms, such as rashes and fevers, are not considered unusual. Not having a certain symptom, doesn’t necessarily exclude that disease. To work towards a good diagnosis, the patient’s entire symptom or potential symptom history throughout their life needs evaluation.

For example, if the patient has never had a rash, you can cross of the rash symptom in every autoinflammatory disease. However, that does not mean that all of these diseases have now been ruled out. It only means rash is not a prominent symptom for that patient and the other symptoms need more weight.

Diarrhea is another common symptom in many fever syndromes. However, not having diarrhea during a flare does not mean it is not a fever syndrome.

Even a lack of fever does not exclude the periodic fever syndromes as a possibility. There have even been rare cases of patients with confirmed periodic fever syndromes not having the typical periodic high fevers. Familial Mediterranean Fever (FMF) can very rarely start with amyloidosis as the primary symptom rather than fevers. There are also reported cases of Tumor Necrosis Factor (TNF) receptor associated periodic syndrome (TRAPS) presenting without fever. Some of this variance can be due to the various genetics. In a few cases, some patients have somatic mosiacism, so not all their body tissues have the mutation, only some of them, which leads to an altered presentation of their disease. A good diagnosis takes careful evaluation of all the symptoms and lab tests as a whole.

Now What?

By now you should have a diagnostic chart that is well-marked with circles, X’s, question marks, and other notes. Look at the abnormal lab tests and genetic tests available for the diseases that are now high on the list of possibilities and determine if any of those tests still need to be done. Consider genetic testing for those conditions with the most circles and for conditions that have very similar symptoms. If your patient is in the U.S., The GeneDx 7-gene Periodic Fever Syndromes Panel is a good test to start with because it tests for 7 different fever syndromes that can look alike symptom-wise. This test only includes these genes: ELANE (ELA2), LPIN2, MEFV, MVK, NLRP3 (CIAS1), PSTPIP1, TNFRSF1A–which will allow for testing for FMF, TRAPS, CAPS (all 3 forms), HIDS & MA (both MVK diseases), PAPA, Majeed, and Cyclic Neutropenia (not on the chart because it is not considered in the same grouping as the other SAIDs). As of 2014, ARUP Laboratories also has a periodic fever panel genetic test available.

However, if your patient does not have characteristics for those diseases on that panel, but other conditions on the chart, you will need to send samples to be tested at another facility. One of the best resources to finding the right genetic testing facility for each disease is the GTR: Genetic Testing Registry which also lists the genetic labs worldwide. Other genetic and specialized tests available only at research facilities, such as the National Institutes of Health, may also be necessary. All these labs are on this registry, which is updated frequently.

For some diseases, such as FMF, there are many labs that can do the testing, but you do need to consider the type of test offered, and if it is the most comprehensive, since some labs may not test all the possible options for this mutation, but focus on the “most common” mutations. Look for the labs on the Genetic Testing Registry list for each disease that offers “Sequence analysis of the entire coding region.” Getting the right test is essential, so nothing is missed with the test, since they can be expensive and difficult to get approval for with insurance.

If PFAPA is a possibility, other hereditary conditions should be ruled out as part of the diagnosis, in part with the GeneDx or ARUP Laboratories fever panel. Studies have shown that 83% of patients with HIDS, 57% with TRAPS, and 8% with FMF meet the diagnostic criteria for PFAPA.

This chart was created by request of many doctors and researchers, and has quickly become an important diagnostic tool for rheumatologists, immunologists, patients, and parents of patients around the world. We have shared thousands of copies of it in print, and countless numbers have downloaded it online for reference. Our goal was to have a reference, with an easy to use comparison of symptoms, so medical professionals could consider these diseases when they were caring for patients with signs of autoinflammatory diseases.

How to Print the Autoinflammatory Diseases Diagnostic Chart on Your Home Computer

The full size Comparison Chart of Systemic Autoinflammatory Diseases (SAID) published by the Autoinflammatory Alliance is a very large poster. In PDF format if you just hit print you will need a magnifying glass to read it. Here’s how to print it full poster size on your computer.

You will need to have the latest Adobe Reader software installed on your computer.

Open the chart by clicking “Click here to download the disease comparison chart” from this page – http://www.autoinflammatory.org/compchart.php

Click the rectangular button with the arrow in it on the top right of your screen.

Choose “open with adobe reader.”

You can now highlight and even post notes on the chart with the yellow tools you see at the top menu bar. Zoom in to read it more clearly.

To print, click the printer button and choose “poster.” It will now print the entire poster full size on several pieces of paper. You will need to tape it together, but you won’t need a magnifying glass to read it.

Another option is to get an electronic copy to a local Kinko’s or other copy store and have them print it as a full size poster.

References

*Printer photo by morganlstudios/Bigstockphoto.com