High IgD in Periodic Fever Syndromes

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"Recent research shows that IgD is an important immunomodulator that orchestrates an ancestral surveillance system at the interface between immunity and inflammation." 1*

“Recent research shows that IgD is an important immunomodulator that orchestrates an ancestral surveillance system at the interface between immunity and inflammation.” 1 Photo by designua/Bigstockphoto.com

In 1984, Dr. Jos van der Meer published a study describing a newly recognized periodic fever syndrome. All six  patients in this study had similar symptoms of periodic fevers with other inflammatory symptoms. They also all had elevated immunoglobulin D. This led to naming this new fever syndrome, hyperimmunoglobulinamia D and periodic fever syndrome, or HIDS for short. This study led to a better diagnosis for many because now a test for elevated IgD could be performed to help confirm a diagnosis of HIDS. But advancements in genetic testing has shown that elevated IgD is not diagnostic to HIDS.

In 1999, the gene responsible for HIDS was found. HIDS and MA (mevalonate aciduria) are caused by mutations in the mevalonate kinase gene (MVK), giving rise to the new classification for these conditions–mevalonate kinase deficiencies (MKD). This discovery led to great advances in understanding HIDS and MA.

By using genetic testing as part of the diagnosis and research into HIDS, studies now show that elevated IgD levels are not the best diagnostic method for HIDS. About 20% of patients with HIDS, confirmed by genetic testing, do not have elevated IgD. Children with HIDS under age three almost never have elevated IgD. Plus some patients with other fever syndromes, such as PFAPA, TRAPS, and FMF can also have elevated IgD. Some with undifferentiated autoinflammatory disease may also have elevated IgD levels.

In addition, according to Toro et al in this study, elevated or high IgD levels can be found in other conditions, including, “multiple myeloma, Hodgkin disease, cigarette smoking, pregnancy, immunodeficiency syndromes, and recurrent infections.”

While it’s true that most with mevalonate kinase deficiencies (MKD) have elevated or high IgD, and it’s less common or rarely  elevated in other fever syndromes, basing a diagnosis on IgD results becomes problematic when evaluating individual patients, especially considering that PFAPA, TRAPS, and FMF also have symptoms that are similar to HIDS.

Below is a collection of studies and quotations from the research related to IgD in periodic fever syndromes.

PFAPA (Periodic Fevers with Aphthous Stomatitis, Pharyngitis, and Adenitis)

Elevated immunoglobulin D levels in children with PFAPA syndrome – In this study, PFAPA patients that did not have mutations in the MVK gene (HIDS/MA) and met the clinical diagnosis for PFAPA had high IgD in the range of about 300 to 350 U/I. Elevated IgD was found in all the PFAPA patients in this study. “Raised IgD levels may represent a non-specific epiphenomenon, which frequently accompanies PFAPA syndrome as well as MKD. Because of the overlapping clinical and laboratory features, genetic testing of the MVK gene is indicated to differentiate these two conditions.”

HIDS and MA

Autoinflammatory diseases in childhood – “Increased plasma levels of IgD (>100 UI/ml) during fever episodes and in basal conditions have been considered in the past as a hallmark of the disease. However, the specificity of this finding is low. The polyclonal elevation of serum IgD is found mostly in patients older than 3 years, but this is not exclusive for MKD, while in 20% of patients there is no increase of serum IgD.”

MVK mutations and associated clinical features in Italian patients affected with autoinflammatory disorders and recurrent fever – “IgD plasma level was found increased or minimally increased (>100 UI/ml) in only 10/15 patients, five of whom showed also increased IgA levels (>400 mg/dl)… Two cases…showed a remarkable increase of only IgA, a condition already reported in MKD and, finally, in three patients both IgD and IgA levels resulted in the normal range.”

“This latter definition does not comply any longer with this disease, because of the increasing evidences of patients showing normal IgD levels, as confirmed by the finding of normal or minimally elevated serum IgD in nearly half (seven out of 15) of the MKD patients reported here. Consequently, IgD level cannot be considered a sensitive marker for clinical MKD diagnosis.” 

Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) in a child with normal serum IgD, but increased serum IgA concentration – “This report describes a boy with hyperimmunoglobulinemia D and periodic fever syndrome (HIDS). The serum IgD level was normal, but the serum IgA concentration was markedly elevated. In addition, he had a history of orchitis on two occasions, a previously unreported manifestation of HIDS. This report expands the clinical and laboratory features associated with HIDS and serves to emphasize that a normal serum IgD level does not exclude the diagnosis of HIDS.”

Diagnostic value of serum immunoglobulinaemia D level in patients with a clinical suspicion of hyper IgD syndrome – This study found that patients with confirmed mutations on the MVK gene had normal IgD test results. The authors concluded, “The clinical relevance of the IgD measurement for the diagnosis of MKD in our population appears as poor…”

FMF (Familial Mediterranean Fever)

Extensive Thrombosis in a Patient with Familial Mediterranean Fever, Despite Hyperimmunoglobulin D State in Serum – First Adult Case in Korea – This is a case report of a patient with FMF who had elevated IgD.

Familial Mediterranean Fever: association of elevated IgD plasma levels with specific MEFV mutations – This study evaluated 21 FMF patients that had elevated IgD. It was determined that, “homozygotic status for M694V, and to a lesser extent V726A, is associated with increased risk for higher IgD plasma levels, regardless of colchicine use.”

Familial Mediterranean Fever (FMF): from diagnosis to treatment – 13% of FMF patients have elevated IgD and 23% have elevated IgA.

TRAPS (Tumor Necrosis Factor (TNF) Receptor-associated Periodic Syndrome)

The enlarging clinical, genetic, and population spectrum of tumor necrosis factor receptor-associated periodic syndrome – This study mentions that elevated IgD in a TRAPS patient led to a misdiagnosis of HIDS. “The finding of high IgD levels in one of the families with the T50M mutation contributed to an erroneous diagnosis of HIDS. The same error can probably be found retrospectively in the original description of HIDS by Van der Meer et al. In fact, in the current series, a patient who had recurrent inflammatory attacks but no enlarged lymph nodes had a family history (both parents) of autosomal-dominant disease complicated by amyloidosis, all of which suggests a diagnosis of TRAPS rather than HIDS. High IgD levels have been reported in other inflammatory conditions, including FMF; elevated levels were reported in 13% of a group of 80 FMF patients. This highlights the fact that even in the context of hereditary recurrent inflammatory syndromes, an increase in the serum IgD level is not specific for HIDS.”

Falling into TRAPS – receptor misfolding in the TNF receptor 1-associated periodic fever syndrome – “Laboratory findings in TRAPS are in accordance with a typical inflammatory episode: high levels of C-reactive protein, neutrophilia, moderate complement activation, raised mean erythrocyte sedimentation rate, and, in some cases, marginally raised IgA and IgD levels.”

A nephrotic patient with tumour necrosis factor receptor-associated periodic syndrome, IgA nephropathy and CNS involvement – Another TRAPS patient with elevated IgD. “Furthermore, between the fever attacks, the man had elevated IgD (511 IU/ml; normal value: <100 IU/ml), IgA (8.5 g/l; normal value: <4 g/l) and IgG values (18.1 g/l; normal value: <16 g/l). This prompted us to search for genetic variations in the TNFRSF1A and MVK genes. The genetic analyses disclosed a heterozygous T→C nucleotide substitution (c.250T>C) within exon 3 of the TNFRSF1A gene, resulting in the substitution of cysteine (TGT) at amino acid position 55 by arginine (CGT; C55R). In contrast, no pathogenic mutation was detected in the coding exons and in the neighbouring intronic sequences of the MVK gene.”

Tumor Necrosis Factor Receptor–Associated Periodic Syndrome A Novel Syndrome With Cutaneous Manifestations –“Before the identification of MVK as the gene that causes HIDS, the diagnostic criteria of HIDS required IgD levels exceeding 140 mg/L (14 mg/dL) on 2 occasions at least a month apart. However, elevated IgD levels are not specific for HIDS. Approximately 10% to 13% of patients with TRAPS and FMF have elevated serum IgD levels. In addition, a number of other conditions have been associated with elevated serum IgD levels, including IgD multiple myeloma, Hodgkin disease, cigarette smoking, pregnancy, immunodeficiency syndromes, and recurrent infections.9,47,48 Furthermore, some individuals with typical findings of HIDS and mutations in MVK do not have elevated serum IgD levels.”

Recently Identified IgD Related Autoinflammatory Diseases

As researchers continue to identify new autoinflammatory diseases, it’s being discovered that IgD can be in involved in more syndromes that are less understood. These studies below report on two separate families with two novel autoinflammatory disorders. Both presented with high levels of IgD, but did not have mutations in the MVK gene.

A Novel Autoinflammatory Disorder Characterized by Ectodermal Dysplasia, Metaphyseal Chondrodysplasia, Growth Failure and Hyper-IgD in a Single Family – The symptoms included fevers, ectodermal dysplasia, short stature, and failure to thrive.

Identification of a novel monogenic autoinflammatory disease due to mutation in a mitochondrial chaperone protein in a single kindred, and cure with allogeneic haematopoietic stem cell transplantation – “Three affected children in a Pakistani family suffered from a severe and unusual autoinflammatory syndrome, presenting in the first year of life with recurrent fevers, erythema nodosum-like rash, severe oromucocutaneous ulceration, systemic inflammation, and massively elevated serum IgD, without mutation in MVK.”

For many with recurrent fevers, there is not a single test that can give a clear answer or diagnosis. IgD testing can be a piece of the puzzle to consider, but diagnosing a periodic fever syndrome requires careful consideration of all symptoms, lab results, genetic results, other diagnostic tests (hearing tests, eye exams, skin biopsies, xrays, MRI, etc) and response to treatment. Thankfully today, genetic testing is readily available, often paid for by insurance, and not an outrageous expense. The cost is comparable to many other tests and procedures patients need to get a good diagnosis. The Comparison Chart of Systemic Autoinflammatory Diseases is also a valuable tool in helping to guide testing and diagnosis for these conditions.

More References and Resources

  1. NIH.gov: New Insights into the Enigma of Immunoglobulin D
  2. American Society of Hematology: Hereditary Periodic Fever Syndromes
  3. Nature: MVK mutations and associated clinical features in Italian patients affected with autoinflammatory disorders and recurrent fever
  4. JAMA Network: Tumor Necrosis Factor Receptor–Associated Periodic SyndromeA Novel Syndrome With Cutaneous Manifestations

“Perfect” Attendance Programs Stigmatize Kids with Chronic Illnesses

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chornic illness perfect attendance awardsMany schools in many communities in the U.S. and around the world reward students who have perfect attendance. They may win a simple certificate during an assembly or much bigger prizes, such as a computer, bikes, trips to Disneyland, iPads, or yes, even a brand new car.

This may seem like a valuable reward for students, but perfect attendance awards have a dark side. Before you shower awards on kids that happened to show up to school every day, consider the entire school population, especially the students with chronic illness and medical challenges. These school attendance incentive programs are discriminating against, and alienating children with health issues and disabilities.

True Story: One Patient’s Demoralizing Experience with a Perfect Attendance School Assembly

We recently received the following message from one 14-year-old student in the U.K who wanted to share her story. The school is aware of her chronic illness. She tells of how she felt about a recent assembly that focused only attendance. This young lady has a challenging periodic fever syndrome and often cannot attend school during attacks of her disease.

Sitting through this assembly, I felt I was being singled out because I have a rare disease. On Thursdays, we usually have an assembly, just because that’s the rota. Sometimes it was the Vicar, or another time it was a talk through of upcoming events, but this time, it was an assembly on the ‘importance’ of school attendance.

I had been sitting there for around five minutes, ignoring the snickers my friends were giving me. I was well aware that everyone in my year knew I was off a lot, and some of my closer friends knew why. I’m not usually one to bother hiding things – I think it’s pointless. Although, the only people who really understood my condition were the two people sitting next to me, that were taking great delight in my irritation. They muttered about the man who was explaining that if we do not come to school every day, we will fall into a pit of destruction and get disappointing grades. In addition, he tells us, if we are successful in being healthy for the whole year, you will get a certificate.

I thought, “Congratulations kids! You don’t have something that legitimately hinders your ability to attend school!” Did I mention the chance of having this autoinflammatory disease is pretty much one in a million?

While watching him hand out some shiny, paper certificates to the people who have 100% attendance, I started to get angry. I have suffered with periodic fevers from when I was small, and now, in year ten of secondary school (9th grade or the freshmen year for Americans), I was still suffering from it. Despite being on colchicine, which has helped, I was still having flares of my disease. I had been absent from school due to my illness just  four days before this assembly. So in some ways, it’s kind of ironic that he decided to hold a school assembly on attendance right when I got back! I was angry because it was not my choice to have this one-in-a-million disease that keeps me out sick for days at a time. I am not choosing to skip school because I’m lazy! But that is exactly what this assembly is insinuating.

After the people who had managed to be in school all year had gotten their reward, we were all dismissed and sent to our lessons.

Walking out, I told my two best friends that I was not pleased at all. I really wanted to give him a piece of my mind.

A day or so later, I was given a purple card that stated I was to visit the deputy headmaster for an interview on my attendance. Of course, they knew very well why I was off so often, as it had already been explained. 10:25 a.m. was the appointment, and I was told not to miss it.

Of course, I’m a teenager and I forgot. I’m still human, after all. A lady came to pick me up. We walked pretty much in silence to the office, where I entered and told the deputy head that I had been so engrossed in my history lesson I’d forgotten to come down. He didn’t find this particularly amusing.

So as I was staring at him, and listening to him explain to me that my attendance was pretty low, and that yes, he knew why, I was resisting the urge to roll my eyes at him. He went through how he had been aware of my condition, and how my Head of House had made the other teachers aware, so I couldn’t help wondering why the heck I was even there, if he knew why. Although, I was still waiting for my chance to speak.

Then he asked me, “Did I feel supported by the school?” Bingo!

“Well, kind of. Apart from that assembly. Personally, I found that rather patronizing. You didn’t make any reference to the fact that there may be people, like myself, who have a legitimate reason to be off school so often.”

He then told me that yes, there is that issue, but he was trying to get the message across that attendance is good. He also said that he didn’t want to single me out in front of everyone.

For some reason, this makes me furious. Could it be that by highlighting everyone that had good attendance, and publicly putting down those who didn’t, that he [the principal] pretty much did single me out? Hmm. (I’m finding it hard to work that out. Give me a minute.)

“Yes, but the fact is you made no reference to me or other people who have a rare genetic disease! Obviously, I wouldn’t want you to single me out specifically. But by doing what you did, you could have damaged the emotions and stability of someone like me, that may not be ready to tell the school about their condition.”

I have to keep repeating myself to him until he finally understands what I’m trying to tell him – that actually, I can’t help missing school. And some others might not be able to either. In no way am I endorsing people who skive off, but that leads me to another question; does he know why people aren’t at school? Could they be being bullied? Are they finding their work too difficult or easy? Or have they just given up?

That assembly, in my view, was in no way going to combat low attendance. To annoy him, I thought, “Well I’m going to decide to get ill this week.” Because that’s what I felt like he was implying–that I have some control over my illness, and I am choosing not to come in, not because I physically cannot attend when my disease is flaring.

In his defense, he did apologize and said that in hindsight, he should have included that topic in the assembly. But all I can think about was that saying sorry now is not going to change his words, or comfort who he might have hurt in that room that day.

So the same night, I went home and told my mother. Which has ended up with me writing this story.

That administrator angered me by his lack of thought, and I told him so. That’s all I did. And if you, or your children suffering with a rare disease are reading this, I suggest you do what I did. Actually, print this out and show them, and tell them that a 14-year-old girl wrote this, who has gone through it and still going through it. (Woohoo for me!) Ask the school to think their facts out and try and learn why we’re not at school.

What’s the real message we are pushing on kids with health challenges, and their peers?

While attendance reward programs are designed to motivate kids to go to school and do their best, kids living with a serious medical condition are hearing a different message. They hear that they are not good enough because they have a disease, that in many cases is due to genetic causes. Many may feel that they are being punished by the school for having their disease. With these messages from their administrators, healthy peers may think that they are better than, and have more opportunities than a classmate who has medical challenges.

There is already a lot of social stigma for children with chronic diseases to deal with on a daily basis, and missing school means that they have to spend more time catching up on school work, taking tests after school and less time to be social and interact with their peers.  And often, their friendships are affected if they are not around as much as the other children. We do not need more things that divide and isolate people with chronic illnesses! These children often do all the work, and do not want to be given exceptions, but do need to miss school at times when they are severely debilitated by their disease. They need to miss school to take care of themselves.

Note that a flare of autoinflammatory disease causes fevers, severe pain in the joints, abdomen, head and elsewhere, and many are vomiting, or having loose bowels and can barely keep fluids down when they are at their worst. They are not contagious, but suffer from their disease flares greatly.  For people that do not have these diseases, most would be rushing to the doctor and unable to manage the symptoms that these patients suffer often from their disease.  So, when a patient with an autoinflammatory disease has to miss school (or work), they are in a state that would send most healthy people to the hospital. Yet people expect these patients to just suffer through it, and carry on, and often do not believe these children are suffering as badly as they are, due to their high tolerance for pain, and resilient attitude.

Why have perfect attendance awards?

Many school attendance reward programs only have the one criteria–that the child attends classes every day. (Which also means some may come to school ill, and infect others, but that is another topic of discussion.) Often to earn an award, it does not matter how hard they work in class, how involved they are in school, or what their grades are – it only matters that they show up.

It doesn’t matter if a student is keeping up with schoolwork at home, while in the hospital, or waiting in the doctor’s office; but still manage to make good grades–maybe even straight A’s. (top marks in the U.S.) These things do not earn someone a perfect school attendance award. Again, the message they hear is that because they are physically unable to sit in the classroom every day, they are not worthy of such a reward. Only their healthy peers who have the ability to show up and sit in class each and every day can have a chance at winning that free car, or tickets to Disneyland.

Schools value attendance as a way to increase their graduation rate, but this is not the only reason for these programs. There’s another reason the only criteria may be that a child attends class. Often, the school district funds allotment is based on the number of students attending school each day. So, the more students in class each day, the more money the school gets. When kids are home sick and not in class, the school loses money. Sometimes, students and their parents get the impression from the school, and even their teachers that their child is just a big burden on the system because being sick looses the school money, but every student has the right to get an education, with accommodations for their medical needs.

perfect attendance chronic illnessDoes school attendance really affect success?

It’s true that studies show school attendance does correlate with better odds at achieving high school graduation, which is only one standard of academic success. Success in school does depend a lot on access to learning and teachers, and it is easy to equate perfect attendance with the best odds at a child graduating.

Kids who can’t attend school regularly often have a significant life challenge preventing them from attending school, such as a severe medical condition. That life challenge is likely to be a major factor as to how well a child does in school. The level of support from the school would be another key factor. Many would rather be at school, and are not looking for reasons to “cut class” or be truant but due to circumstances beyond their control cannot be at school.

Despite it all, these children have a level of internal motivation and desire to succeed in their learning that many of their peers have not mastered. They have developed skills that many people dream of seeing in their (healthy) children!

Where is the reward for these educational skills that are as associated with success as attendance? Many of these children grow up and push themselves to finish college and also work, despite daily challenges and health issues.

Threatening kids and families dealing with serious health issues with truancy actions, and excluding sick kids from winning a valuable reward (like a car, tickets to events, etc), but rewarding healthy kids just for showing up, regardless of actual performance with their studies does not help chronically ill children succeed in school. It does not set a child up for success, nor does it create a sense of community where the school teams up with the child and their family. Instead, it creates one more battle the child and their family must fight. A battle to just to be accepted in school. And in many cases, these children and their families have had to struggle to get their child’s educational needs met. Perfect school attendance awards only remind them that their struggles and differences are not in sync with their peers, and other children are quick to notice, as noted in the teen’s story that we featured.

One child with an autoinflammatory disease said recently,

“Nothing would make me happier than to be able to go to school every day, to see my friends, be in clubs and sports, and not be known for being the kid with the medical condition that misses a lot of school.”

This child and others like him happen to have challenging medical issues from systemic inflammation and in some cases, permanent damage from their disease. Despite these challenges, many excel in their studies, and graduate from school with good grades, all with very imperfect attendance.

Did you know?

Most fever syndromes are lifelong conditions that involve recurring systemic inflammatory symptoms such as rash, fever, and joint swelling.

More School Help

School 504 Plans for Kids with Periodic Fever Syndrome

U.K. Department for Education: Supporting pupils at school with medical conditions

U.K. Medical Conditions at School Website

Educational Resources to Help Family, Friends, and Teachers Understand Autoinflammatory Diseases

References and Resources

  1. She Knows: My kid will miss out on a reward at school because she’s seriously ill
  2. The WrightsLaw Way: When Schools Punish Sick Children Who Miss School: A Game Plan
  3. Wrights Law: Special Education Advocacy
  4. Chronic Action: Schools
  5. Today Health: Schools rethink perfect attendance awards in bad flu season
  6. WIFR.com: Rochelle Student Wins Car
  7. The Connection Between Missing School and Health: A Review of Chronic Absenteeism and Student Health in Oregon
  8. Austin Independent School District: Dropout Prevention and Reduction Initiative
  9. CNET: L.A. schools give iPads, cars for perfect attendance
  10. The New York Times: And for Perfect Attendance, Johnny Gets…a Car
  11. Cecil Elementary School: Attendance

 

*Top car photo by Kurhan/Bigstockphoto.com

*Roll call photo by photosquared/Bigstockphoto.com

Studies on Biological Medication Used in Pregnant and Breastfeeding Autoinflammatory Patients

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Updated 2/3/2022

Below are some published studies that include autoinflammatory patients. For more studies, search Pubmed.gov.

A Systematic Review of the Safety of Blocking the IL-1 System in Human Pregnancy (Jan 2022) – This is a detailed analysis of 88 pregnancies where the mothers were treated with anakinra (Kineret) or canakinumab (Ilaris) during pregnancy. Patients had various autoinflammatory diseases including CAPS, TRAPS, and SJIA/ASOD. The conclusion states, “In conclusion, this review summarizes all the pregnancy exposed to Il-1 blockage and no major obstetrical and neonatal complication was reported. Il-1 blockage during pregnancy could be safe and beneficial in cases of pregnancy with inflammatory conditions.”

IL-1-blockade with Anakinra during pregnancy : Retrospective analysis of efficacy and safety in female patients with familial Mediterranean fever – “In three pregnancies anakinra treatment was continued during the whole pregnancy, while in one pregnancy anakinra was started in the second trimester because of uncontrolled FMF activity. Fetal development was normal in all pregnancies. In two patients the fetuses were carried to term, while in one patient a primary cesarean section was carried out in week 33 because of an increased risk for complications. All children showed an unremarkable early childhood development without any signs of an existing disease.”

International multi-centre study of pregnancy outcomes with interleukin-1 inhibitors – “There were 31 maternal-exposed pregnancies from seven countries and we report the first data on paternal exposure: six to anakinra and five to canakinumab, with no negative outcomes. We also report the first data on canakinumab-exposed pregnancies: eight pregnancies that resulted in the delivery of seven healthy infants of normal gestational age and birthweight. There were 23 anakinra-exposed pregnancies resulting in the birth of 21 healthy infants, and one baby with unilateral renal agenesis and ectopic neurohypophysis. There were two first trimester miscarriages affecting a mother with active disease. There were no serious neonatal infections. Fourteen infants were breast fed with no complications. There were no reports of developmental delay, with follow-up of up to 10 years (median 18 months)….This series substantially increases the published experience of IL-1 blockade and reproduction including the first data on canakinumab and on paternal exposure to these agents. Data are generally reassuring, although the case of renal agenesis is the second reported in an anakinra-exposed pregnancy.”

Placental Transfer of Canakinumab in a Patient with Muckle-Wells Syndrome – “This is the first study to show that the canakinumab administered during pregnancy in a patient with Muckle-Wells syndrome crossed the placenta.”

Anakinra use during pregnancy: Report of a case with Familial Mediterranean Fever and infertility – Case report of a woman who used Kineret before and during pregnancy. The authors note risk concerns, previous studies, and concluded that, “Anakinra seems to be safe in pregnancy, but there are very few data for conclusive interpretation, particularly in the first trimester. Subfertility in women with FMF is mostly the result of disease-related factors. Appropriate treatment and prevention of attacks are the key steps for fertility.”

Successful outcome of two pregnancies in patients with adult-onset Still’s disease treated with IL-1 receptor antagonist (anakinra) – “So far, there are scant data available on the effects of anakinra in pregnancy. We report two patients with AOSD who successfully gave birth while treated with anakinra during pregnancy.”

Brief Report: Anakinra Use During Pregnancy in Patients With Cryopyrin-Associated Periodic Syndromes – “Anakinra was continued during pregnancy in women with CAPS and provided significant, persistent symptom relief while continuing to prevent the long-term sequelae of CAPS. Anakinra was well tolerated. Although a causal relationship between anakinra and renal agenesis seems unlikely, further safety data are needed.”

ANTI IL-1 therapies and pregnancy outcome – This studied followed 7 pregnant women with various autoinflammatory diseases such as CAPS, TRAPS, FMF, and Still’s disease. Four were on anakinra for either all or some of their pregnancy.

A patient’s wish: anakinra in pregnancy – This reports on a Still’s patient who used anakinra throughout pregnancy and while breastfeeding without any apparent problems.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk – This physician’s reference book includes a chapter on anakinra in regards to fetal risk and breastfeeding. Studies regarding anakinra and pregnancy are referenced above. The breastfeeding summary states that Il-1ra (anakinra is an Il-1ra), is naturally secreted into breastmilk in healthy individuals who are not on anakinra. It states, “Because of the presence of native Il-1ra in milk, there appears to be no risk to a nursing infant from maternal administration of anakinra.”