San Francisco Monday, October 4th

No everyone believes that just because the words "fun" and "run" rhyme they should appear together. But some of us have a running problem, and the Academy accommodates us each year with a 5K somewhere scenic. This year our reward for standing on the sidewalk jumping up and down blowing on our hands waiting for a shuttle bus was to stand in Golden Gate Park jumping up and down blowing on our hands, looking at the bridge. You might think the public bathrooms would be warmer than the parking lot. You would be wrong, and more exposed. This year budget constraints kept the organizers from hiring a perky trainer to lead us in deep lunges to a disco soundtrack before the race. Budget cuts are not all bad. The academy has some truly gifted athletes, my term for the hoards who crossed the finish line ahead of me.

By the time I got back, showered, fed, and caffeinated I walked in to the plenary a little late. Enough running for one day. Here's what I did catch.

Neil Risch, PhD

Ancestry Matters: Ethnicity And Disease Risk

• Genetics divide the human population into about 6 groups based on continent of origin
• Different Asian populations have different genetics, meaning calling Asian a race is genetically nonsensical
• So how does self-reported race/ethnicity correlate with genetics? Actually almost perfectly!
• Because race and culture are linked it's almost impossible to tease out what group differences are genetic and which ones are cultural, from a statistical standpoint.
• You can look at populations of mixed race and see if certain outcomes track with what percent of markers come from a given genetic cluster, but this still doesn't rule out confounders that are not purely genetic, like skin color
• Another strategy is to look at ancestry-based polymorphism affecting a single gene. One such study showed a gene from African populations that codes for FSGS susceptibility but also confers protection against Trypanosomiasis.
• Race, ethnicity, and ancestry do matter from a genetic and medical standpoint
• Gene environment interactions are key

Russell Chesney, MD

Vitamin D, it's not just for bones anymore

• Not so much a vitamin as a hormone!
• It resembles other steroid hormones
• It serves as a gene transcription promotors
• Receptors are present in more than 30 tissues
• It promotes transcription of more than 300 proteins and peptides
• It has multiple immune mediation functions
• Sources are local, mainly sun exposure, influenced by diet and obesity
• Measured by circulating OH-D1,25
• Impacts rates of ovarian cancers, MS, RA, IBD, wheezing, DM, HTN, multiple common cancers
• Suddenly it seems we think vitamin D does everything!
• Why are we deficient? Not enough sunshine.
• NHANES study gave us accurate population based values of vitamin D levels, data from 2000-2004
• Concentrations fall off with age, worse in women, African Americans
• In children and in pregnant women we see large percentages of the population with levels below the deficiency cutoff
• Tuberculosis is more prominent where vitamin D is lowest
• Vitamin D may provide large scale protection against influenza, that may be why flu spreads in the winter!
• Per 2008 recommendations all kids and babies need 400 IU a day.
• That's a teaspoon of cod liver oil
• 400 IU seems to be at the effective threshold
• Side effects probably occur way over the recommended upper limit of 1000 IU a day
• Supplements should be given to all ethnic groups
• There will be a revised recommendation 11/30/2010!

Dr. Wesley Burks

Food Allergy: oral desensitization therapy, closer to a cure?

• 6-8% of young children are food allergic, but parents think it's more like 30%
• Milk, soy, wheat' shellfish, and nuts account for the bulk of food allergies
• Food allergies have doubled over the last decade
• Reactions occur within two hours of ingestion
• Peanut IgE levels do not predict severity of clinical reaction
• About 1/3 of reactions are ton accidental exposures
• Deaths usually occur in people who know they are allergic
• About 20% of children will eventually outgrow their peanut allergy
• It's the protein, not the oil that causes peanut allergy
• For peanuts it's ingesting the protein that causes severe symptoms, although as little as 1/1000th of a peanut can do it
• There are some promising therapies, including anti-IgE, Chinese herbal medicine.
• Engineered recombinant protein may reduce IgE binding, but not effective
• Goals of therapy are clinical desensitization, clinical tolerance
• Two types of ingested therapy are oral and sublingual (OIT, SLIT)
• OIT starts with daily increased doses from 6 to 4000 mg over about ten months, followed by a food challenge
• Hopefully tolerance will continue after treatment ends, that's the definition of tolerance
• In a small study of 25 patients the difference between treatment and placebo was enormous
• Almost half children had prolonged tolerance off treatment
• But about 20% of children cannot tolerate this type of therapy
• SLIT is better tolerated, only 5% of children cannot tolerate it
• Again the early numbers are showing dramatic success at achieving desensitization
• Whether either therapy will lead to prolonged tolerance remains unknown

Gail Pearson, MD

Avoiding Hand Me Down Information: Why Children Need Pediatric Studies

• First of all, they have diseases adults don't have
• Example of polio vaccine, involved 8 million US children
• Second example, hypoplastic left ventricle repair
• Second, they get diseases adults do get, but with different manifestations
• Example pediatric heart failure does not respond to enalapril the way adult CHF does, in fact not at all
• Example, we still are not sure how and when to check children's cholesterol levels
• Third, children develop and adults don't
• Fourth, expert opinion is fallible
• Example, blood letting in the 1600's. Earliest randomized controlled trial, six times as many people died in the control group (the ones who had blood letting)
• Children's research has led to dramatic improvements in survival for preterm births, leukemia, HIb
• First recommendations for Children's research were promulgated in1978, with first legal guidelines in 1983
• Example of horror: willow brook school for the mentally handicapped in the 1960's infected children with hepatitis on purpose
• Children are diverse, vulnerable, require more protection, cannot take pills, don't represent a lucrative market, don't vote
• National Heart Lung and Blood Institute has a program to promote clinical studies in children and address parental fears
• Children And Clinical Studies Campaign

Paul Offitt, MD

America's Anti-Vaccine Movement, A Perspective

• There're have been incidents that probably should have sparked vaccine resistance and didn't
• Examples are early polio vaccine that caused ten deaths, 200 cases of parlysis. Also a yellow fever vaccine contaminated wi hepatitis, given to US soldiers. Children infected with TB in 1929 instead of BCG
• The birth of fear: April 19, 1982. Locally produced documentary on DPT vaccine causing children to get seizures, mental retardation. Entitled DPT, Vaccine Roulette.
• That show was disseminated nationally, made big news. This spawned a grass roots movement, the National Vaccine Information Center, a flood of lawsuits
• Pharmaceutical companies abandoned the business, so the government stepped in to establish the compensation fund
• The NVIC perpetuates the message that there vaccines have supplanted infectious diseases with chronic diseases. They have come out against every new vaccine with claims they would cause diabetes, seizures, SIDS, MS, all false claims
• The autism scare has had several phases, starting in 1998 with Andrew Wakefield's claim about MMR.
• Doing the research to absolve vaccines takes many years, never makes news.
• Next idea was thimerosol causes autism, 1999. Now we have enormous studies ton disprove that idea, have spent many millions
• Now Dr. Robert Sears scares parents that children just get too many vaccines, The Vaccine Book
• We are now seeing breakdown in herd immunity involving whole communities: mumps, measles, HIb, pertussis
• We are faced with a difficult choice. We want to keep parents in the practice and do the best we can for those patients. That said, that delay does put children at risk as herd immunity has broken down. Our waiting rooms become dangerous.
• The measles outbreak provides a model of this problem, where young children who got the disease were infected in the waiting room
• Now we need studies to see what is the best approach to help bring parents back on board

Annual business luncheon

• Dr. Palfrey stands to introduce everyone on the dais
• John Almquist, MD
• Marion Burton accepts the presidency
• The Affordable Care Act is a downpayment on children's care. But it is endangered, and the children may get thrown out with the bathwater
• Stay in contact with the Advocacy arm of the AAP and be involved in making sure children get the care they need
• We hope to establish a Cabinet level Office For Children

The Child With Recurrent Infection

Sarah Long, MD

• Case history: a fatigued 15 year old girl with positive review of systems
• In history get details of vague symptoms. What kind of sore throat? Is weakness focal? Does fatigue mean increased sleep hours? Does poor appetite mean weight loss? Is there true pallor? Cyanosis? Do shooting pains follow a neurological distribution?
• Are there big time social stressors?
• Does the exam suggest illness, or is it inconsistent with complaints? Check eye grounds when headache is a complaint.
• How are CBC, CMP, CRP, and UA?
• In adolescent girls remember pregnancy is a possibility
• Sexual abuse may present with diffuse physical complaints
• Certainly depression is a possibility
• Many of these patients just have primary fatigue
• It appears this syndrome affects Caucasians, girls, children of educated patients
• Onset seems acute always
• NIH defined chronic fatigue syndrome in adults in the 1990's
• This diagnosis probably does not apply to teens
• Depression does suppress immune function to some extent
• EBV titers are not to be followed for disease progression, EBV is not the cause of chronic fatigue syndrome
• When EBNA turns positive the infection is over
• Lyme disease is not the cause of chronic fatigue in children
• Hypoadrenalism is not the cause of chronic fatigue in children
• Orthostatic hypotension is not the cause of chronic fatigue in children
• Joint laxity may be present in these kids, but significance is unclear
• Orthostatic intolerance is probably really just de-conditioning, and it improves with exercise
• These kids seem to have had very high expectations of them prior to disease onset. Have not lost weight. Age over 12 years. Tend to cooperate with exam enthusiastically.
• Validate symptoms.
• Force return to school on a graduated basis.
• Advise graduated exercise, ideally with a physical trainer.
• Let the patient know she'll feel worse to begin with, and there are no expectations of performance.
• Advise parents to stop asking child how she feels
• Change focus to health, not illness.
• As primary care provider stay in charge of the illness. Discourage more and more consults.
• If child cannot go to school she needs to be seen in the office. This cuts down on missing school. When the child gets a tutor, game over!
• Might code Adolescent Sleep And Stress Disorder

James Jarvis, MD

• There are about three rheumatologic concerns to keep in mind with prolonged fever
• Between fevers kids may look great!
• Daily, timed fevers that make children look awful when febrile, fine when afebrile, accompanied by macular rash is classic for JRA
• Remember platelets usually rise when ESR rises. If platelets are low think Acute Lymphocytic Leukemia.
• Don't order an ANA unless you're trying to confirm lupus, because normal children have elevated ANA about 30% of the time.
• In a case where patient gets three days of fever every month start thinking about cyclic fever syndromes
• JRA fevers occur daily, at predictable times, and kids look good between fevers, unlike with Kawasaki's, when they seem irritable all the time
• Don't think JRA if WBC is under 15K or platelets are under 300K
• Dermatomyositis may present with daily, low grade fevers, fatigue with minimal activity
• Look at nail-bed capillaries
• Check CPK, CMP, aldolase
• Get these children to a pediatric rheumatologist no matter where you live!
• Parents will report fatigue more than muscle weakness

Dr. Long again, case of four year old boy with fever every thirty days, swollen nodes, no mouth ulcers

• If these are viral illnesses the symptoms tend to vary somewhat from one to the next
• Ask if fevers recur at predictable intervals.
• How many days do the fevers last?
• Do antibiotics or antipyretics help or not?
• Do immunizations trigger the fevers?
• The more URI symptoms you hear about the less you suspect cyclic fevers
• How well are they between episodes of fever?
• What is the ethnic background of the patient? There are exceptions, so don't write off a familial fever just because the ethnicity is wrong
• Does anyone in the family have amyloidosis? That's the end result of familial fever disorders
• Get a urine culture or two, CBC, CMP, immunoglobulins. Avoid imaging studies without symptoms to suggest an infectious focus
• PFAPA: periodic fever, aphthous stomatitis, pharyngitis, adenopathy. Not all elements are always present.
• PFAPA affects preschoolers, not infants. Child looks glassy eyed prior to fever occurrence. Fever is the cardinal symptom. Seems to occur in happy children, happy families!
• Disease lasts 4.5 years on average, but longer if it starts younger
• Cimetidine seems to help about a third of patients
• Prednisone, one dose, aborts the attacks but not a good long term plan.
• Tonsillectomy seems to cure the syndrome in over 90% of patients!
• If the fit for the diagnosis isn't good then don't take out the tonsils

Dr. Jarvis presents the next case, a 13 year old girl with six days of daily fever, fatigue, abdominal discomfort, hypertension, white cells and red cells in urine.

• Lupus. ANA lessnthan 1:1000 just is not exciting. If you order an ANA also check C3, C4, and urinalysis with microscopy
• Remember UTI's don't cause hematuria
• Adolescents with lupus look sick
• Next case 15 year old Native American girl with rales, fever, hypertension. IHS doc checked a C-ANCA, and it was positive, proof of Wegeners

Dr. Long discusses cyclic neutropenia.

• Look for ulcers, gingivitis, fevers every 3 weeks for 5-7 days.
• If presentation is appropriate check CBC twice a week.
• Autoinflammatory syndromes are relatively newly described, include FMF, Hyper-immunoglobulinemia D, TRAPS, all genetic. These can be successfully treated now.

From there it was on to dinner with the Pediatric News Editorial Advisory Board. Watch the exciting publication for some serious pediatric muck-raking! Also, I promise future issues will be gut-busting hilarious! I look forward to next year's Conference and Exhibition in Boston!