Hyper IgM Syndrome is a primary immunodeficiency (PID) which should be managed and followed closely by an immunologist with experience treating PID’s. Although there are several treatments that can help maintain a generally healthy status quo, the comorbidity and general outcomes vary within the patient population. As one expert put it in a recent study, “effective management of [Hyper IgM Syndrome] requires a comprehensive individualized look to each patient regarding his/her course of disease and various manifestations. In this view, each efficiently managed patient is an individual piece of art.”
Treatments for Hyper IgM:
Treatment for Hyper IgM will include, at a minimum: (i) immunoglobulin replacement therapy, (ii) long-term antibiotic prophylaxis to prevent pneumocystis jirovecii pneumonia (PJP or PCP), (iii) in some cases, G-CSF to treat neutropenia (where neutropenia is present), and (iv) a series of lifestyle changes. In addition, although Hyper IgM patients do not respond to vaccines, some immunologists recommend getting the flu shot every year as there may be some benefit.
I. Immunoglobulin Replacement Therapy:
Early diagnosis and use of immunoglobulin replacement therapy is associated with better outcomes, a lower rate of infections, and decreased complications associated with neutropenia and high IgM levels. There are currently two types of available immunoglobulin replacement therapies that are recommended: Intravenous Immunoglobulin (IVIG) or Subcutaneous Immunoglobulin (SCIG). Human immunoglobulin (IgG) is a blood product extracted from the plasma donations of thousands of blood donors. It is essentially a sample of the thousands of antibodies that the general population has running through their bloodstream, and provides Hyper IgM patients with essential protection from infection as they are not able to produce these antibodies on their own. Generally, IVIG and SCIG are similar and patients should discuss with their physician the pros and cons of each treatment (assuming both are available to them – in some countries only one type of treatment may be included in the government sponsored health plans and in the U.S some insurance might cover one type but not the other). It is important to understand what to expect from each type of immunoglobulin therapy. It is also important to know that one can always change the method they receive IgG.
a. Intravenous Immunoglobulin (IVIG):
IVIG has been around for longer and can be administered in a hospital setting, outpatient clinic or at home by an authorized healthcare professional (usually a registered nurse). The IVIG is infused through the vein over several hours and is administered like other blood products in a monitored setting.
Each dose of IVIG is effective for an average of 3-4 weeks, so it is recommended that the patient receives a dose of IVIG every 3-4 weeks, depending on their immunoglobulin levels. The most important distinction between IVIG and SCIG is that, for IVIG, there is a high boost of antibodies right after treatment. The IgG level then decreases over the course of the next few weeks. The amount of IgG’s in the patient’s bloodstream at the end of the month where the IgG is lowest is called the “trough.” Trough levels should be measured at the three week spot. Since the level of protection that IVIG provides is directly related to the amount of antibodies in the bloodstream, for Hyper IgM patients on IVIG, it is generally advised to keep the trough level over 800 (mg/dL) to lower the risk of infection.
Common side effects of IVIG can include headaches, chills, flushing, wheezing, myalgia, lower back pain, nausea and hypotension. Headaches and migraines tend to be more common.
b. Subcutaneous Immunoglobulin (SCIG):
Subcutaneous Immunoglobulin, or SCIG, is an infusion of immunoglobulins just below the first layer of the skin. This type of treatment can be administered by the patient, or, if a minor, by their caregiver, at home. It is recommended that the patient receive a dose of SCIG once each week. Unlike IVIG, it does not need to be administered by a nurse or in a clinic setting, but rather the patient or their caregiver is taught to administer the infusions. This type of therapy takes significantly shorter time to infuse (depending on dosage, it can be anywhere from 45-90 minutes). Before choosing this type of immunoglobulin therapy one must feel comfortable learning to administer the infusion on their own. A healthcare professional will teach you how to infuse the SCIG over several weeks until you are ready to do so on your own. The benefit of the SCIG weekly infusions (besides the comfort of schedule control and comfort of one’s own home) is that there is no trough level. Rather, the level of protection provided by SCIG is consistent from one weekly infusion to the next. For SCIG, and especially for Hyper IgM patients who are more susceptible than most PID patients, it is recommended to keep the levels above 1000 (mg/dL) . There are several pharmaceutical companies making different types of SCIG, and together with your immunologist, and home therapy speciality pharmacy through your health plan, you will choose the best product for you. The home therapy specialty pharmacy will supply all the drugs, supplies and equipment needed for the weekly infusions.
Although typically associated with less side effects than IVIG, there can be side effects of SCIG, including swelling, pain, redness, heat or itching at the site of injection, headache, back pain, diarrhea, tiredness, cough, rash, itching, nausea and vomiting. Click here for some examples and videos of SCIG administration.
c. Trough Levels
An important note about trough levels: Some physicians who are not very familiar with Hyper IgM might aim for a lower level of immunoglobulins mg/dL than is recommended above. Furthermore, physicians that are more familiar with IVIG administration (like transplant teams) might confuse the levels recommended for SCIG. It is important to understand that, for Hyper IgM patients who produce no antibodies on their own and are at significant risk of infection, the recommended levels are as follows:
SCIG – above 1000 mg/dL
IVIG – Trough level above 800 mg/dL
II. PJP/PCP Prophylactic:
Whether or not the patient had PJP, it is advised that they take Bactrim (also known as trimethoprim or sulfamethoxazole) as a prophylactic (e.g., preventative precaution) as soon as a Hyper IgM diagnosis is suspected. PJP is a serious and life-threatening respiratory illness caused by the fungus Pneumocystis jirovecii. PJP is one of the most frequent and severe opportunistic infections in people with weakened immune systems. Many CD40 Ligand Deficiency patients (X-Linked Hyper IgM) are first diagnosed after having PJP in their first year of life. The fungus is very common and is present in over 70% of healthy people’s lungs; however, Hyper IgM patients are not able to fight it off without the administration of Bactrim (or its equivalent). PJP is often not diagnosed until it is too late as it can be easily mistaken for a mild but persistent respiratory virus. Therefore, it is strongly recommended that patients, especially those with X-Linked Hyper IgM, regularly take Bactrim to prevent the occurrence of PJP. There is some disagreement as to what age, if at all, one can stop treatment with prophylactic Bactrim and we recommend that you discuss this with your immunologist.
III. Granulocyte-colony stimulating factor (G-CSF or GCSF)
A large percentage of Hyper IgM patients suffer from transient or consistent neutropenia and may need to be treated with G-CSF. G-CSF stimulates the production of granulocytes, a type of white blood cell. G-CSF is also used to increase the number of hematopoietic stem cells in the blood of the donor before collection by leukapheresis for use in hematopoietic stem cell transplantation.
IV. Lifestyle Changes:
Changes to lifestyle vary in approach and severity. Mostly, it will come down to the comfort level of parents, the severity of the presentation of Hyper IgM related manifestations, and overall risk tolerance. We recommend adopting the following lifestyle changes, but encourage patients to discuss with their physician:
a. Boiled or Filtered Water Only:
There is little argument about the need to avoid intake of most water sources that have not been boiled or filtered with reverse osmosis filtration. The risk, and potential morbidity of waterborne Cryptosporidium infection justify avoidance of water sources that may become contaminated. People with functioning immune systems can generally recover from cryptosporidium. Patients with Hyper IgM, however, are not protected against cryptosporidium and the parasite will continue to grow un-checked. There is currently no effective treatment for cryptosporidium, and without any defenses against this parasite, it can cause permanent damage to the liver and lead to death. Accordingly, even in municipalities that have good water sources that are tested for Crypto, the general approach is still to avoid any intake of water sources that are not boiled or filtered with reverse osmosis filtration.
Lakes and communal pools should be avoided. The CDC recently found that “The majority of Cryptosporidium outbreaks were associated with treated recreational water such as swimming pools and hot tubs and involved Cryptosporidium. The parasite can survive for 10 days or more even in water that’s chlorinated to kill germs” . . . as cryptosporidium is “extremely chlorine resistant.” See CDC Website. The CDC further instructs that Cryptosporidium is one of the leading causes of waterborne disease, or disease caused by contaminated drinking water or recreational water. Recreational water is water from swimming pools, hot tubs, fountains, lakes, rivers, springs, ponds, or streams that can be contaminated with sewage or feces from humans or animals. Crypto is not spread by contact with blood. Crypto can be spread by:
- Swallowing recreational water contaminated with Crypto. You share the water—and the germs in it—with every person who enters the pool. This means that just one person with diarrhea can easily contaminate the water. Swallowing even a small amount of pool water that has been contaminated with the Crypto germ can make you sick.
- Putting something in your mouth or swallowing something (such as food) that has come in contact with the feces of a person or animal infected with Crypto.
- Swallowing Crypto picked up from surfaces (such as lounge chairs, picnic tables, bathroom fixtures, changing tables) contaminated with feces from an infected person.
Many common brands of bottled water are safe for consumption because they undergo reverse osmosis filtration. These brands include, but are not limited to, Nestle Pure, Dasani, and Kirkland (but always check the label before drinking).
Note: Although it is recommended to avoid drinking non-purified or sterilized water, it is considered safe to shower, bathe and brush teeth with tap water depending on (a) the quality of water in your municipality, (b) the age of the patient, and (c) your comfort level. Discuss this with your physician.
b. Crowds, People and Germs:
This is one area where the approach will vary the most. We recommend sitting down for a discussion with your immunologist and finding the best balanced approach. While it makes perfect sense to feel the need to retreat into isolation after first diagnosis, every family will learn as time goes by how to best protect themselves from the germs and viruses that people carry without living in a bubble.
It is mostly recommended that Hyper IgM children avoid daycare and early preschool, a time where the other children are very often sick (part of a normal child’s immune system’s process of learning and training their adaptive immune system to fight off pathogens, which is done through exposure and creating antibodies to every germ they encounter). For Hyper IgM kids, it makes more sense to try to avoid this stage. Still, with good levels of IgG on board and overall low numbers of infections, parents can generally send their children to kindergarten and school. Many of our parents report that their kids are well protected from common illnesses with IgG therapy and may only pull their kids from school if a nasty flu epidemic or unknown virus is going around.
It is also recommended that the child’s teachers are informed about his vulnerability to germs. Early detection of contagious illnesses in the classroom can be essential to keeping your child safe (and keeping them home from school when a teacher reports an incidence of a contagious illness).
It is also recommended to avoid dense crowds, especially indoors.
Still, for many parents considering transplant or dealing with other complications of Hyper IgM, it may be recommended to limit exposure to people to a greater extent in the short term to minimize risks before a procedure or while recovering from illness.
c. Air Quality:
While IgG replacement therapy provides very good protection against many of the dangers Hyper IgM patients face many doctors recommend using an HEPA air filter in the home. The level of filtration and quality of the HEPA filters varies widely and every family should make their own decisions on the purchase of these filters. Here are some of the brands that our families have had some experience with and work well:
d. Household pets and other animals:
Recent Journals articles have stated that patients with Hyper IgM Syndrome should avoid household pets and live cattle. It is believed that these animals can be carrying certain pathogens that are not as common and therefore antibodies against them are not in abundance in the IgG replacement therapy. That said, many Hyper IgM families report having household pets and finding a balance between risk and the therapeutic aspects of having a pet. Every family will make a decisions on household pets together with their immunologist based on factors such as recent infection, proximity to transplant and type of pet. In general petting farms should probably be avoided, but many doctors permit zoo visits where there are barriers between the animals and visitors.
e. Parks, Playgrounds, Gymborees
As with anyone that is immune compromised, avoiding large crowds is advisable, more so during flu and RSV season. While most families do not restrict outdoor playground activities, it may be advisable to avoid indoor playgrounds and gymboree’s at young ages. Furthermore, playing in sandboxes or soil is not advisable as they can contain and serve as a breeding ground for microbia that Hyper IgM patients do not have defenses against, even with IgG replacement therapy.
f. Fresh Fruits and Vegetables, and other Food Restrictions
Fresh fruit and vegetables are generally considered safe to eat as long as they can be adequately washed. For this reason, some patients like to avoid vegetables like broccoli or lettuce, which has many crevices and can be difficult to wash. Some doctors advise washing fruits and vegetables with a drop of dish soap, others advise simply scrubbing under running water for at least 30 seconds. It is important to wash the fruit or vegetable before it is peeled or sliced. Peeling and slicing the fruit or vegetable introduces any bacteria that was living on the outside into the flesh.
Raw meat, eggs and fish should be avoided entirely as they can carry disease and bacteria that a Hyper IgM patient is not protected against.
Some immunologists also recommend avoiding unpasteurized cheese and dairy products.
g. Restaurant, Fast Food and Buffets:
While there are not clear lines what is safe when to comes to eating out one clear red flag is buffet style eateries. There is little control over what can be introduced into the food at these eateries and for children and adults with Hyper IgM who are already at risk for chronic diarrhea it is advisable to avoid. Some cities have very strict public health laws and grading systems in place and it is worth taking the time to look into the rating restaurants get before choosing a location to eat with your family.
It is generally recommended to limit airplane travel or to take certain precautions when air travel is necessary. The most common sources of germs on an airplane and at an airport are surfaces. Contrary to common belief, the air in the airplane is actually HEPA filtered. Most people get sick from touching the backs of the seats, door knobs, and faucets. Make sure to carry Purell and use before eating or touching your face. Clean your seat, seatbelt, and tray table with a clorox wipe.
And remember, when you’re traveling, be sure to drink bottled water and avoid fresh fruits and vegetables (and anything washed with tap water), and ice.
i. Hand Washing and Purell:
This is by far the most important preventative step you can take to protect yourself. Teaching a child with Hyper IgM the importance of hand-washing before and after eating, using the bathroom, and sneezing or coughing, is a critical step that every Hyper IgM patent and their entire family should follow.
There is a proper way to wash your hands. Scrubbing your hands with soap for at least 15-20 seconds under warm water and using a paper towel to turn off the faucet is the best method. The sink faucet is a source of contagion, as is the doorknob of the bathroom. When using public restrooms, make sure to carry Purell and use it immediately after exiting the restroom.
V. Vaccines and the Flu Shot
Live vaccines are very dangerous to Hyper IgM patients, both if administered and if in contact with someone who has recently had a live vaccine. Although it is highly recommended that anyone regularly in contact with Hyper IgM patients be up-to-date on all their vaccines, it is important to avoid anyone who has had a live vaccine within the past 3 days or so. The pediatrician or doctor can provide exact instructions on how long a live vaccine is dangerous to someone who is immune compromised.
Although Hyper IgM patients do not make a normal response to vaccines, it may be beneficial to get a flu shot because other parts of the adaptive immune system might be primed to recognize and fight those flu strain. The flu shot should be administered as a shot and not as a nasal spray, which has live bacteria and can be dangerous.
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