PRACTICE PEARLS
From Pediatric Clinical Update, presented by Lucile Packard Children’s Hospital at Stanford and Stanford University School
of Medicine
Educational Objectives
| The goal of this program is to improve management of cystic fibrosis (CF), strabismus, and warts. After hearing and
assimilating this program, the clinician will be better able to:
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 | 1. Screen for, diagnose, and manage children with CF according to current recommendations.
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| 2. Identify infants at highest risk for CF.
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| 3. List the most dangerous causes of strabismus and their signs and symptoms.
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| 4. Recognize and treat the most common cause of pediatric strabismus.
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| 5. Choose between canthardin and cryotherapy when treating a patient for warts.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning
committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest.
Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a
proprietary business or commercial interest. For this program, the faculty and planning committee reported nothing to disclose.
Acknowledgements
Drs. Witcoff, Fredrick, and Bruckner were recorded at Pediatric Clinical Update, held September 29, 2007, in Palo
Alto, CA, and sponsored by Lucile Packard Children’s Hospital at Stanford, and Stanford University School of Medicine.
The Audio-Digest Foundation thanks the speakers and the sponsor for their cooperation in the production of
this program.
| CYSTIC FIBROSIS —Lauren J. Witcoff, MD, Clinical Associate Professor of Pediatrics, Stanford University School
of Medicine, and Pediatric Pulmonologist, Lucile Packard Children’s Hospital, Palo Alto, CA
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| Background on cystic fibrosis (CF): autosomal recessive condition; both parents asymptomatic carriers; most
common life-shortening genetic disease in whites, but many patients live to adulthood; affects 1 in 3000 non-
Hispanic whites; 1 in 25 whites carry gene; occurs in 1 of every 4000 to 10,000 Hispanics; less common in
blacks and Asians; unlike bronchopulmonary dysplasia (BPD), worsens over time; chronic progressive multisystem
disorder; hallmark chronic progressive lung disease, resulting in bronchiectasis, respiratory failure, and early
death
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| Genetics: gene occurs on long arm of chromosome 7; codes for CF transmembrane conductance regulator (CFTR)
protein; regulates salt and water transport in airway epithelial cells; abnormality leads to abnormal salt and water
transport; dehydrated viscous secretions obstruct ducts in airways and other organs that have CFTR
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| Presentation: chronic pulmonary disease with obstructed airways; chronic bacterial colonization and infection; recurrent
respiratory tract infections; bronchiectasis; eventual lung destruction; early death
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| Gastrointestinal (GI) tract: second most commonly involved organ; ≈90% of patients have pancreatic insufficiency
due to obstruction of pancreatic ducts; supplemental enzymes necessary for adequate food absorption; presentation
may include malabsorption, greasy stools, and failure to thrive
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| Vas deferens: organ most sensitive to CFTR function; almost all male patients have obstructive vasospermia; most
prevalent finding, even in atypical CF patients; sometimes detected among adult men in fertility clinics
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| Diagnosis: ≥1 typical phenotypic feature, or sibling with CF, or positive newborn screening test, plus ≥1 indicator
of abnormal CFTR function (elevated sweat chloride on 2 occasions, 2 identified known CFTR mutations, or abnormal
nasal potential difference [reflects abnormal ion transport across nasal epithelium])
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| Sweat chloride testing: key to diagnosis; performed through pilocarpine iontophoresis; CF patients have 2 to 5
times more sweat sodium chloride (NaCl) than normal; Cl >60 mEq/L diagnostic of CF; <40 mEq/L (30 mEq in
neonates) considered normal; anything in between considered borderline, patient needs further work-up
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| California Newborn Screening (NBS) program: step 1—measure blood immunoreactive trypsinogen (IRT)
level (increased in CF patients); step 2—genetic analysis of blood in top 2.2% of IRT samples; step 3—patients
with one mutation (carriers) undergo focused DNA sequencing; panel created for state of California; includes mutations
found in Hispanic patients; step 4—sweat testing for infants with 2 mutations found during steps 2 or 3;
more focused evaluation and treatment; program should detect CF in 88 of the 92 cases expected annually in newborns
(so suspect possible CF in patients with signs and symptoms, even if screening results normal); screening
misses ≈1 case in every 100,000 infants
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| Pathophysiology of CF: viscous dehydrated secretions promote bacterial colonization, leading to intense neutrophilic
inflammatory response, further airway destruction, and vicious cycle of more obstruction, infection, and inflammation;
as result, gradual lung destruction seen, and early death typical; organisms most commonly seen in
younger patients include Staphylococcus aureus and Haemophilus influenzae; Pseudomonas aeruginosa most common
in older patients (associated with worse morbidity)
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| Treatment: focuses on minimizing and loosening abnormal secretions; antibiotics; anti-inflammatory agents;
azithromycin; lung transplantation for patients with irreversible lung injuries; current research now focuses on gene
therapy
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| Nonpulmonary manifestations of CF: abdominal pain (suggests distal intestinal obstructive syndrome); intussusception;
increased risk for gallstones and gastroesophageal reflux
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| Complications: diabetes; osteopenia and osteoporosis secondary to nutritional deficiencies; depression
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| Management: involves CF team and primary care physician; immunize on schedule to prevent infections; consider
pneumonia vaccine for older patients and respiratory syncytial virus prophylaxis for infants; institute liberal use of
antibiotics, since viral infections increase risk for bacterial colonization; cough suppressants contraindicated
(coughing clears airways); exercise improves pulmonary function and prolongs survival; advise school that children
with CF require unlimited bathroom privileges and many medications; also warn school that patients cough
frequently but are not infectious to other students; counsel patients to avoid passive as well as active smoking and
to maintain healthy weight (associated with better survival); median lifespan for CF patients today is nearly 40 yr
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| STRABISMUS IN CHILDREN: WHEN TO WORRY —Douglas Fredrick, MD, Clinical Professor of Ophthalmology
and Pediatrics, and Vice Chair for Clinical Affairs, Stanford University School of Medicine, and Lucile Packard
Children’s Hospital, Palo Alto
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| Worrisome signs: sudden-onset strabismus or nystagmus; distinguish between sudden onset and sudden discovery;
new complaint of double vision should be investigated (infants with strabismus do not have double vision because
they ignore the affected eye); oscillopsia—perception that world moving back and forth or shaking; may
be sign of posterior fossa disease; not complaint among children with longstanding nystagmus
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| Associated ocular or visual signs and symptoms: inability to see out of turned-in eye or other vision loss; severe
headache; proptosis; leukocoria
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| Associated neurologic signs and symptoms: cranial nerve palsy; sixth (abducent) nerve resides near fifth and seventh
nerves, which govern facial sensation and movement; asking child to smile may reveal weakness ipsilateral
to strabismus; head bobbing or turning (consider posterior fossa disease; may be sign of diplopia in preverbal
child); ataxia
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| Lethal causes of strabismus
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| Retinoblastoma: autosomal dominant, may affect multiple family members; 500 cases/yr in United States; signs
and symptoms include poor red reflex (white spot in pupil); strabismus as presenting sign; uveitis (late sign);
glaucoma; prognosis depends on stage at presentation; reduction with chemotherapy preferred method of treatment
today, followed by focal laser ablation; enucleation treatment of choice if tumor fills eye
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| Pontine glioma: presents as sixth nerve palsy, with possible fifth and seventh nerve involvement (ask patient to
smile, check ipsilateral facial sensation); prognosis poor, even with early detection; immediate imaging recommended
for any acute-onset sixth nerve palsy
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| Posterior fossa tumors: present with headache, ataxia, nystagmus, and head tilt; most common causes astrocytoma
or medulloblastoma (cause of strabismus may be severe papilledema); do not hesitate to dilate pupil for examination
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| Blinding causes of strabismus: any congenital ocular anomaly may present with strabismus; any childhood strabismus
may cause blindness; amblyopia most common form of blindness secondary to strabismus; causes of
amblyopia—visual deprivation; undetected cataract; unequal refractive error; strabismus; combination of causes;
at birth, visual acuity 20/800 to 20/1000; improves to 20/40 to 20/80 by age 6 mo; anything that interferes with
formation of clear image on retina at this age may produce amblyopia
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| Treatment of amblyopia: correct refraction to eliminate asymmetry between eyes; part-time patch occlusion; atropine
drops in good eye (“penalization”; as effective as patching 6 hr/day)
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| Occlusion amblyopia: amblyopia in weak eye resulting from prolonged patching of good eye; 1 wk of full-time
patching per year of life recommended; part-time occlusion better for development of binocular vision and
depth perception
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| Things to remember: early detection means easier resolution (start screening at age 4-5 yr); compliance determines
outcome; do not obsess over specific number (aim for acuity <20/40); never too late to treat; maintenance
patching 15 to 30 min/day can help maintain improvement; reward patch use with visual activities like
video games
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| Infantile esotropia: differential diagnosis should include bilateral sixth nerve palsy; check by covering one eye, seeing
if baby looks to side, or twirl baby to elicit vestibular evoked nystagmus (no nystagmus suggests sixth nerve
palsy); patients rarely have amblyopia; surgery indicated
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| Accommodative esotropia: most common cause of strabismus; occurs between 2 and 5 yr of age; sometimes hard
to see in one office visit; have patient return for serial examinations; associated hyperopia (farsightedness) and
amblyopia common; treat with glasses (surgery rarely indicated; could result in eyes turning outward later in life
and need for second surgery)
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| Basic esotropia: eyes turn in and child complains of double vision; usually seen in older children; not common;
scan for neurologic disease; surgery usually produces good results
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| Exotropia: easier to detect when child relaxed; observe distance fixation; usually not dangerous; easily corrected
with glasses; surgery usually not necessary, but chances of long-term success good when performed; neonatal
exotropia—in child aged >2 mo, often associated with neurologic disease; refer to pediatric neurologist
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| Head tilt: may suggest fourth nerve palsy; may produce facial misalignment if long-term
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| Infantile nystagmus: consider poor sensory input (bilateral optic nerve hypoplasia) or abnormal output; if child has
no other gross neurologic abnormalities, refer to ophthalmologist first; possible diagnoses include congenital
anomaly, ocular albinism, and congenital motor (benign) nystagmus; reassure parents that baby does not have
oscillopsia
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| Summary: rule out lethal or blinding causes of strabismus; realize that most causes can be corrected with appropriate
diagnosis and treatment
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| WART MANAGEMENT UPDATE —Anna L. Bruckner, MD, Assistant Professor of Dermatology and Pediatrics,
Stanford University School of Medicine, and Director, Pediatric Dermatology, Lucile Packard Children’s Hospital,
Palo Alto
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| Challenges of pediatric dermatologic procedures: heightened fear, anxiety, and pain perception
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| Factors that affect child’s pain tolerance: age, psychologic preparedness, and family environment; child usually
passes through 3 psychologic stages; stage 1—indifference to lesion; stage 2—awareness of lesion and possible
desire to see it gone, but no clear understanding of treatment; stage 3—acceptance of discomfort involved with
treatment; biggest challenges arise when treating children in stages 1 or 2; in general, severity of treatment
should match severity of problem
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| Canthardin: topical agent compounded by pharmacist; active ingredient blistering agent produced by Coleoptera
family of beetles; used as 0.7% concentration in collodion applied as sticky film; used only in physician’s office;
blistering occurs within 24 to 48 hr of application, then heals within 4 to 7 days; intensity of reaction can
be tempered by washing off canthardin 2 to 6 hr after application; pediatric indications—molluscum contagiosum
(treatment of choice); common and flat warts; apply small drop to each lesion, using wooden end of cotton-tipped
applicator; allow to dry completely; have parents wash it off 4 to 6 hr later; treat 5 to 6 lesions first,
and tailor future therapy to patient’s reaction; can treat ≤20 lesions on subsequent visits at 3- to 4-wk intervals;
in study of 300 patients, 90% of lesions cleared and 8% improved within 2 visits; patient and parent satisfaction
high; in 2006 comparison of curettage, canthardin, topical salicylic plus lactic acid, and topical imiquimod,
canthardin proved highly effective, easier than curettage, and less irritating than salicyclic acid
preparation; in general, bloodless and painless (unlike curettage)
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| Pitfalls and precautions—redness and irritation (warn parents); itching or burning; hyper- or hypopigmentation
in dark-skinned patients (skin color eventually returns to normal); small risk for scarring (may occur with any
treatment for molluscum); do not use on face or occluded areas, eg, armpit, diaper area; doughnut warts—if
wart large, blister may lift it up and out
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| Cryotherapy: application of cold liquid, eg, liquid nitrogen at -196°C to induce controlled frostbite; cell death occurs
during thaw; freezing leads to blister, inflammation, and crust or scab; lesion dries up and falls off or
shrinks; pediatric indications—warts (verruca vulgaris, plana, or plantaris); good choice for child with few lesions
who is mature enough to tolerate procedure; application—use spray canister or cotton-tipped applicator
(spray promotes faster freezing); spray until entire lesion plus 1- to 2-mm margin around it turns white (painful);
allow lesion to thaw, and repeat freezing if necessary; repeat at 3- to 4-wk intervals
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| Pitfalls and precautions: >1 treatment often needed; throbbing may last up to 20 min (administer ibuprofen or acetaminophen
first); complications include temporary dyspigmentation; damage to nail matrix if included in
treated area; nerve injury or permanent scarring if freezing too aggressive; depth of freeze correlates with diameter
(avoid freezing lesions >6 mm in diameter, near joints, or on plantar surface of feet); limit number of
lesions treated in 1 session to minimize pain; doughnut warts potential complication
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Suggested Reading
Asplin D: Telling the parents: newborn blood spot screening for cystic fibrosis. J R Soc Med 101 Suppl 1:28, 2008; Brown J
et al: Childhood molluscum contagiosum. Int J Dermatol 45:93, 2006; Chintagumpala M et al: Retinoblastoma: review of
current management. Oncologist 12:1237, 2007; Farrell PM et al: Guidelines for diagnosis of cystic fibrosis in newborns
through older adults: Cystic Fibrosis Foundation consensus report. J Pediatr 153:S4, 2008; Hanna D et al: A prospective randomized
trial comparing the efficacy and adverse effects of four recognized treatments of molluscum contagiosum in children. Pediatr
Dermatol 23:574, 2006; Kirk VG et al: Preverbal photoscreening for amblyogenic factors and outcomes in amblyopia
treatment: early objective screening and visual acuities. Arch Ophthalmol 126:489, 2008; Mishra A et al: Diagnosis of cystic
fibrosis by sweat testing: age-specific reference intervals. J Pediatr June 25, 2008 [Epub ahead of print]; Pitts J et al: Improving
nutrition in the cystic fibrosis patient. J Pediatr Health Care 22:137, 2008; Quast TMet al: Diagnostic evaluation of bronchiectasis.
Dis Mon 54:527, 2008; Rutstein RP: Update on accommodative esotropia. Optometry 79:422, 2008; Silverberg
NG et al: Childhood molluscum contagiosum: experience with canthardin therapy in 300 patients. J Am Acad Dermatol 43:503,
2000; Titomanlio L et al: Pediatric strabismus. N Engl J Med 356:2750, 2007.
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