Immunodeficiency–does my child get too many infections? How can I tell? Read on in the following journal article. Author information and citation listed at the end. I’ll summarize for you. Before I begin, take a look at this 3 minute (yes really) video on immunodeficiency; it will help with background information.
April 11, 2011 — Three main warning signs may help identify children with underlying primary immunodeficiency diseases (PID), according to the results of a retrospective survey reported online April 11 and will appear in the May print issue of Pediatrics. “Children with severe, recurrent, or unusual infections may have an underlying …PID,” write Anbezhil Subbarayan, MBBS, from the Department of Paediatric Allergy and Immunology, University of Manchester, Royal Manchester Children’s Hospital in Manchester, United Kingdom, and colleagues.
“Ten warning signs have been promoted by patient support groups to help identify children with PID, but the signs have never been tested in a rigorous scientific study.”
The objective of the study was to examine the efficacy of these 10 warning signs in the prediction of defined PID among 563 children evaluated at 2 tertiary PID centers in northern England. Medical records were reviewed for 430 children with a defined PID and 133 children for whom thorough workup did not result in a diagnosis of a specific PID.
Factors most predictive of PID were
A family history of immunodeficiency disease
Sepsis treated with intravenous antibiotics in patients with neutrophil PID (primary immunodeficiency)
Failure to thrive in children with T-lymphocyte PID. In simple terms, this means you just don’t grow.
When these 3 signs were present, PID was correctly identified in 96% of patients with neutrophil and complement deficiencies and in 89% of children with T-lymphocyte immunodeficiencies.
The only warning sign that correctly identified patients with B-lymphocyte PID was a positive family history. These are patients with NO antibody production–the “bubble boy”
“PID awareness initiatives should be targeted at hospital pediatricians and families with a history of PID rather than the general public,” the study authors write. “Our results provide the general pediatrician with a simple refinement of 10 warning signs for identifying children with underlying immunodeficiency diseases.”
“Delayed diagnosis of PID may be associated with increased morbidity and mortality,” the study authors conclude. “In children presenting with infection, pediatricians should always inquire about a family history of PID, as this is the best predictor that the patient may also have an underlying immunodeficiency….In those with recurrent or severe infections, clinical features other than family history are often not helpful and a lower threshold is required for requesting antibody testing in which the diagnosis of a B-cell immunodeficiency is suspected.”
Selective antibody deficiency shows up a little bit differently in that children will often have recurrent ear infections or sinus disease. A different disease altogether!
Pediatrics. Published online April 11, 2011.
Laurie Barclay, MD
Freelance writer and reviewer, Medscape, LLC
Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.
If you’re like most doctors, who doesn’t spend the winter months prescribing antibiotics and treating upper respiratory infections? But when is it serious enough to pull the trigger on a detailed work-up for immunodeficiency?
As with everything in medicine, when symptoms are outside of the “norm,” it’s time to intervene and start your work-up. Consider the following:
1. Severe infections such as sepsis or recurrent pneumonia are a no-brainer. Do the work-up!
2. The average number of yearly upper respiratory infections in a toddler is 8 to 12, so monthly episodes of a snotty nose aren’t that unusual. I would be suspicious if fluid accumulates behind the ears, or antibiotics are required with every upper respiratory infection.
3. Parental or patient anxiety should be included in your evaluation. Remember, checking for antibodies as a screen will go a long way in relieving that nagging question, “is my child normal?”
4. Remember, our job as physicians is to screen for immunodeficiency, not order every test available after the first encounter. Signs & symptoms of immunodeficiency evolve and change our outlook as to how much testing is appropriate.
Some suggestions for your consideration:
Categorize immunodeficiency into 5 subsets. The appropriate tests to order follow in a logical pattern thereafter.
1. Antibody deficiency. Labs for this diagnosis should include not only IgG, IgA, and IgM, but also specific antibody titers to Strep Pneumoniae. Most children now receive PCV-7 or PCV-13 and a subset of kids with chronic infections won’t demonstrate a vigorous antibody response to these immunizations. Interestingly, many of these children will respond to the adult Pneumovax™ and a good diagnostic test for antibody deficiency is to challenge with Pneumovax™ and repeat titers in one month. Want more info? This pocket guide is the best!
2. T and B cell deficiency. Infections in this category are viral infections that cause sepsis or meningitis, not self-limited colds. AIDS falls into this category, although there are many T & B cell deficiencies in addition to AIDS. Most labs will now provide panels that count the T/B and NK cell populations without having to remember each individual test. As you can imagine, this saves time and headaches. Don’t forget to order mitogen and antigen stimulation…determines how well lymphocytes respond to infection. Often the absolute cell number fails to tell the entire story.
3. Neutrophils. The PacMan of the immune system. Usually infections due to chronic granulomatous disease (CGD) involve recurrent cellulitis or persistent abscesses. You can order screens that measure the oxidative burst when a neutrophil is confronted with bacteria!
There are several prototypes of CGD depending on the missing enzyme, but most of them can’t produce superoxide anions when needed to kill the invading bug.
4. Complement deficiencies are rare, but easy to measure. Recurrent infections with Neisseria should raise the red flag. CH50, C4, and C3 will tell you if further investigation is needed.
5. Last but not least, is the INNATE arm of immunity. When I was a fellow 20 years ago, I was not taught about innate immunity because we didn’t know it existed. How else does your body recognize a “new” infection without having to wait 7-10 days to mount an antibody response first? Toll-like receptors are found on most surveillance cells that recognize nucleic components (DNA, RNA & other repeating sequences) found only on foreign invaders like bacteria, viruses, and fungi. Believe me, you don’t want to memorize the list of Toll-like receptors (TLRs), but it’s a great cure for insomnia. Labs can measure Mannose-binding protein, but other TLRs will have to wait their turn.
If you examine a patient (young or old) with chronic infections and at least think of immunodeficiency, that’s a great start and you’ve come a long way! Have fun with it–you can give someone their life back with the correct treatment. (Sounds like another post to me!)
I have just returned from the Annual Meeting of the American College of Allergy, Asthma, and Immunology held in Boston from Nov 3-8. Sure the meeting was good, but the food was even better. Consider the oldest “active” restaurant in America, Union Oyster House–the stew was delightful and if you’re bored with allergies, peruse the menu on-line and dream of dining with JFK (he has a booth in his name there).
Smoking bans in Tulsa have stirred some vigorous debate this year (see link). Most importantly, do they work? Information presented last week would suggest a resounding YES! In the U.S. more than 200,000 asthma admissions per year are attributed to Environmental Tobacco Smoke (ETS). Smoking bans can prevent this complication! The Scottish health system has the database to measure the effects of a community-wide smoking ban and their intervention was associated with an 18% reduction in hospital admissions for asthma (NEJM 2010). Wow
If you have to smoke inside, HEPA filters reduced asthma visits in 6-12-year-old children by 18%.
I have a post on this blog describing VCD or paradoxical vocal cord motion. Our terminology is now changing and instead of VCD, I like the term” irritable larnyx syndrome (WILS).” The vocal cords are “housed” in the larynx and many structures and muscles have to work correctly in order for the vocal cords to allow air in and out of the lungs. This implies that multiple triggers will cause an attack and patients with difficult asthma may have a laryngeal dysfunction not just VCD. If you don’t believe me, look at this study. World-wide recognition (AJRCCM, a study from Australia).
Way too many choices in the treatment of asthma! Why would you consider Tiotropium or Spiriva for asthma?
1. Tiotropium works as step-up therapy in adult asthma. Some patients just can’t tolerate albuterol or Xopenex™ because of tremor and other side effects. Now you have an alternative: There were similar improvements in lung function and symptom-free days with Spiriva as adding long acting bronchodilator (NEJM 2011).
2. Tiotropium does fit into the Asthma Guidelines (2007) and works better than increasing the dose of inhaled steroids (yea, less steroids) and is equal to salmeterol (Serevent).
3. This report is from England, so BEWARE! The Respimat inhaler isn’t used in the United States and should you read about this study, it doesn’t apply to patients in the US. (Recent BMJ meta-analysis showed increased cardiovascular mortality with that formulation in COPD) (BMJ, 2011).Anti IL-13 (lebrikuzumab)–Did you say leprechaun?
There is one take home message with the use of lebrikuzumab:
1. Personalized medicine is here! In this study, patients that improved with anti IL-13 also had elevated levels of periostin in blood tests. Periostin is a marker of airway remodelling and gives us a clue as to why and how IL-13 contributes to asthma. Lebrikizumab improved FEV1, but there was no improvement in symptoms or medication use (NEJM 2011).
This comes from the literature review at the College meeting—1 of every 6 children with asthma seen the ED are prescribed antibiotics. Don’t you think this is high for a “practice” that is supposed to be very selective in who gets antibiotics? Generally, antibiotics are not helpful in asthma anyway. More than 2 courses of antibiotics for cough in a 6-month time frame should warrant consideration of asthma as a cause (Pediatrics, 2011).
In a study in Arizona, Fernandez et al. showed skin testing to Alternaria to be surprisingly accurate. Ninety-six percent of patients with a positive skin test to this mold had a positive bronchial provocation test with Alternaria. In Arizona, Alternaria has surpassed dust mite as number one allergen in asthma (due to dry climate). I wonder what results would be in Oklahoma? Here’s what alternaria looks like:
Come on now, do allergy shots REALLY work? Shots with dust mite allowed for inhaled steroid reduction by 50% in children with asthma vs. 30% in controls. Not bad! Do I have to take my medication with shots? Adding dust mite shots to pharmacologic treatment was an effective and safe strategy to reduce corticosteroid doses while maintaining disease control in children with mite-induced allergic asthma (JACI 2011).
Which inhaled steroid to use? Does it matter? QVAR™ & Alvesco™ have said for quite some time that small particles penetrate the airways of an asthmatic better than the competition. They may be right– small particle size inhaled steroids may allow for equal efficacy (benefit) with 1/2 to 1/3 the dose of a larger size of same steroid. Marketing isn’t bad, sometimes it’s just delayed results.
SABA update: Levalbuterol (Xopenex™) may not have any real-life advantages over albuterol. Even in the Xopenex™ package insert, there is mention that there was no difference in heart rate or tremor. In patients who swear by Xopenex™, there’s no reason to change, just start out with cheaper albuterol.
Antihistamines for asthma?
Many patients take antihistamines every day like vitamins. They feel better if an antihistamine is “on-board.” Once again, learn from your patient….they will often give you clues to what medications work. Symptom scores in asthma patients show comparable improvement when given desloratadine (antihistamine) compared to montelukast. Use of antihistamine may prevent the development of asthma in some predisposed children. Well I’ll be….
Asthma in the elderly
The majority of asthma deaths are in patients older than 65.
Asthma in adults/elderly is still predominantly an atopic disease. This means, it’s still due to allergy. Don’t forget to test your older population. In a University of Michigan study, 77% of adult asthma patients were skin test positive.
Depression is definitely underdiagnosed in our loved ones who have retired (ie, grandma & grandpa). Why? They should have a carefree life during retirement, but they don’t. Depression is a significant factor for poor asthma quality of life in the elderly. You are 10x more likely to suffer from psychological dysfunction if you have more than 3 exacerbation of asthma in a single year.
Just goes to show you that allergic respiratory disease is a very complicated condition and every year I’m challenged with new treatments! I can’t ask for anything more.
Most patients never know what doctors do when they’re NOT in the office. One of those activities is attending national meetings in our chosen specialty. For me, the American College of Allergy, Asthma, and Immunology is a yearly highlight. You ask why? Who wouldn’t want to see a distinguished doctor dress up and discuss hives? Seriously, the ACAAI in Boston was a great opportunity to network and stay up to date on changing treatments for allergy & asthma! It’s posted here.
Attendees of the ACAAI Annual Meeting voted Dr. David Khan winner of “The Great Chronic Idiopathic Urticaria Raft
What we do at Allergy meetings!
Debate: After Antihistamines, What’s Best for Next In-Line Treatment” based on his discussion of Hydroxychloroquine/dapsone.
An apple a day might keep the doctor away, but what is modern hospital medicine really like? Follow Dr. Benjamin Kirkland - a Doctor working in Australia - through the pinnacles and pitfalls of everyday hospital medicine!