1
Bone and Joint Infections
Janet Wong, M.D.
2
Acute Osteomyelitis - Microbial Etiology
Neonate Infant Older Chid
Group B streptococcus
S. aureus
Candida sp.
Enterobacteriaceae
other streptococci
S. aureus
S. pyogenes
S. pneumoniae
H. influenzae
S. aureus
S. pyogenes
Salmonella (SSA)
There are three different routes of infection in children. The most
common seems to be the hematogenesis route, which gains
entry into the bone from the blood stream. Less commonly is by
direct inoculation and this can be a puncture wound, such as
stepping on a nail or something. This can also occur following
trauma or surgery. Finally, a particular spread, which is really
rare in children and seems to be more common in adults with
various disabilities, especially alterations in blood flow.
3
Unusual Organisms and Osteomyelitis
. Penetrating trauma: soil organisms, yeast, gram negative
. Hemoglobinopathies: salmonella
. Brucella: sacroiliitis
. IV drug abuse: P. aeruginosa
. Chronic Osteomyelitis: Gram negative enteric, Staphylococcus
. Fractures, surgery: chronic osteomyelitis
. Contiguous Infection: anaerobes (bite, ulcer, sinusitis, mastoiditis)
. Fungi: disseminated H. capsulatum, C. immitis
What is thought to happen from the hematogenesis standpoint is
that the during a course of bacteremia, as the organisms enter
into the bone through the nutrient artery towards the growth
plate, there are these loose capillaries that are said to have
sluggish blood flow in them. It is also thought that maybe there is
a fully developed reticulum within this system. There does seem
to be evidence of low oxygen within the metaphysis, and we
always hear about this preceding history of trauma as a possibly
predisposing factor. Perhaps this is simply disruptive blood flow,
but the history of trauma to children is common, and it is hard to
know what really this is contributing to the pathogenesis.
The nutrient artery penetrates into the diaphysis of the bone,
moving up into the metaphysis and making a hairpin turn at the
epiphysis. This is why it is in a long individual, at least for the
tubular long bones, that osteomyelitis is more common at the
ends of the bones because of these here hairpin turns.
More recently there is some evidence in animals, specifically
chickens, who actually can develop osteomyelitis spontaneously.
A chicken strain of Staphylococcus aureus that appears at the
endothelium within the capillaries of bones have gaps, and it
looks as if the organisms can actually access the capillary system
to these particular gaps. If you take a Staph aureus and
inject it into the blood of the chicken, within 12 hours you can see
bacteria in some of these capillaries, and subsequently a day or
two later, evidence of infection at the metaphyseal epiphyseal
junction. So this is sort of an interesting animal experiment,
perhaps showing that these epithelial gaps, at least in chickens,
play some role.
Another factor in the development of osteomyelitis, at least
relating to Staphylococcus aureus, is the organism that produces
this sort of slimy stuff seems to make it more adherent to various
portions of the bones and thus more commonly associated with
osteomyelitis than those other organs.
Microbial etiology of osteomyelitis. In the neonate, the organisms
most commonly associated with osteomyelitis are typically
Group B streptococcus and Staphylococcus aureus. Very small
babies may involve for various gram negative bacteria and certainly
cause osteomyelitis as well as some other bacteria. In the
infant and older child, Staphylococcus aureus is the most common
cause. Streptococcus is the second most common.
Highly encapsulated organisms are unusual causes of
osteomyelitis, but 3 to 5% of patients with acute osteomyelitis
will have pneumococcus as the etiology.
In the older child, the same types of organisms are seen. Salmonella
is an important pathogen in patients with sickle cell anemia.
With penetrating injuries, organisms associated with the soil or
the skin or on clothes can of course lead to infection. Some of
these injuries, such as injuries associated with lawn mower
trauma, can grind the soil-type organism into the skin and ultimately
into the bone.
Now, sacroiliitis is not necessarily specifically an osteo, it is an
osteo-like illness we must keep in mind, especially in dealing
with certain populations, especially those who are likely to ingest
under pasteurized or nonpasteurized dairy products.
IV drug abuse is associated with P. aeruginosa, hopefully not a
major problem in kids, but it certainly is something that is seen in
adults.
Chronic osteomyelitis is associated with gram negative organ
4
Clinical Manifestations of Osteomyelitis
..Fever, limitation of use of involved extremity or area.
. Localized swelling, warmth, erythema and pain (point tenderness)
. Pelvic osteomyelitis: hip and/or abdominal pain, difficulty walking, rectal
mass
. Vertebral osteomyelitis: back pain, tenderness over spinal processes
. Neonates-frequently accompanied by septic arthritis since epiphyseal,
metaphyseal junction within joint capsule; multiple bones Infected,
pseudoparalysis (high risk for sequelae
. Pseudomonas osteochondritis: foot puncture wound followed by local
findings in 48-96h; fever not prominent
isms. With fractures, this may lead to a chronic infection.
Contiguous infections which are not that common in pediatric
patients may be associated with anaerobic organisms. Perhaps
it is a decubitus ulcer, perhaps sinusitis, and after that may lead
to osteomyelitis of facial or scalp or skull bones.
Finally, certain fungi can disseminate and cause infection on the
bone.
The clinical manifestations of osteomyelitis include fever and
limitation of the extremity or the part of the body that is involved.
Localized swelling, warmth, erythema, and point tenderness
especially would be major clinical findings suggesting
osteomyelitis.
Now, outside of the extremities it could sometimes be very
difficult to pinpoint or even think about osteomyelitis. It could be a
subtle finding. For example, patients with pelvic osteomyelitis
may have a slight abdominal pain, perhaps they have some hip
pain or have some trouble walking, but when you examine their
extremities you really cannot pinpoint anything. It is not until you
do some more specific physical examinations, perhaps even a
rectal examination, that they sort of come up on this diagnosis.
Vertebral osteomyelitis typically occurs in older children with
back pain and tenderness when you palpate or stretch over the
spinal processes.
Finally, in neonates, one may see osteomyelitis in association
with septic arthritis because of the way the epiphyseal-
metaphyseal junction is actually positioned inside the joint, so
that the organism is able to rupture through the bone, it will
rupture into the joint space. In older children, typically if there is
a rupture through the periosteum; it will not rupture into the joint
space. Also, in contrast to what might happen in older children
where a single bone is what is most typically seen), in the neonate,
multiple bones are commonly infected.
5
Differential Diagnosis of Osteomyelitis and
Septic Arthritis
. Rheumatic fever
. Cellulitis
. Skeletal Neoplasia (Ewing's sarcoma, leukemia)
. Bone Infarction in hemoglobinopathy
. Hemophilia
. Thrombophlebitis
. Child Abuse/Trauma
. Toxic synovitis
. Appendicitis, UTI, Psoas abscess (Pelvic osteomyelitis)
6
Diagnosis of Osteomyelitis
. Laboratory
ESR or CRP elevated
Blood and bone aspirate cultures
. Radiology
Plain films - typical changes occur in 10-21 days (bone destruction,
periosteal new bone)
Tc99m Bone Scan - abnormal in over 90% (not as useful in neonates or
following fracture or surgery)
CT/MRI - may be helpful in unusual cases (pelvic, vertebral, skull)
Bone biopsy and culture - useful in unusual or chronic cases
Diagnosis of acute osteomyelitis. The erythrocyte sedimentation
rate is generally elevated. Other people like to get the C-reactive
protein and other nonspecific inflammatory laboratory tests. CRP
seems to come down more rapidly than the ESR. If there sed
rate is coming down slower, maybe I can draw out the therapy a
little bit longer.
From a radiographic standpoint, plain films are frequently helpful,
but generally they are useful later in the course because we
know they will not show specific changes for 7, 10 or 14 days.
This is how long it takes for decrease in bone mass to occur,
and that will show on your x-ray. Periosteal new bone formation
may also not be apparent for about 10 or 14 days.
The indications to undergo a technician bone scan. This is
abnormal in the vast majority of patients. It is not helpful in the
neonate, it is not helpful in those patients who have a fracture or
surgery. It is not helpful to patients with hemoglobinopathies
where an infarction and an infection cannot really be distinguished
by a typical bone scan.
In special situations, a CT and MRI could be particularly helpful.
This is especially true in patients that have pelvic osteomyelitis,
perhaps those with vertebral osteomyelitis. Then, many times
when it is not clear what is going on, you really would like to have
an organism, an actual bone biopsy as opposed to aspiration. A
biopsy where one can look at the bone under the microscope as
well as get a good culture can be very helpful.
I think these are most useful in the usual cases. The inflamed
bone is typically of osteomyelitis, for vertebral osteomyelitis they
are very helpful.
CT scans are very helpful. MRIs seems to be getting more
popular, and surgeons particularly like to obtain these types of
radiographic imaging prior to surgical approaches, so I think we
are going to see more MRI evaluations.
7
Antibiotic Management of Osteomyelitis
Organism Agent Duration (minimum)
S aureus Nafcillin/oxacillin
Alternatives:
clindamycin or
cefazolin
3 weeks and ESR <2030
mm/h
Neonate - 4 weeks
Streptococci penicillin as above
P aeruginosa
osteochondritis
Ticarcillin/Piperacillin +
aminoglycoside
7-10 days if adequate
debridement
Salmonella ampicillin if susceptible;
cefotaxime,
ceftriaxone,
TMP-SMX
3-4 weeks
Antibiotic management of acute osteomyelitis. I think that for the
straight forward cases, related especially to Staph aureus, a
typically nafcillin or oxacillin is initially provided and that can be a
good initial therapy. Antibiotics should be continued either IV or
orally for a minimum of three weeks, and shows that treatment
for less than three weeks in acute osteomyelitis will lead to more
relapses. So, greater than three weeks is what is recommended,
and typically four to six weeks is what is provided. I like to see
the sed rate below 30 mL per hour before I discontinue therapy. I
think that whether you should provide therapy intravenously or
orally is somewhat up to each individual and the parents, and
what their home situation is like, what can be done from the
home IV therapy standpoint, and whether the organism has been
isolated.
8
Management of Osteomyelitis
..Indications for Surgery
Drain purulent material from subperiosteal space or other tissue planes
Remove sequestra or infected foreign material
Débride and drain puncture associated infection
In neonate early drainage of bone and joint is critical
Chronic osteomyelitis
. Immobilize extremity
For Group A Streptococcus I think penicillin alone is fine.
Osteochondritis should be treated with a combination of antibiotics,
but an surgical debridement is most important.
For Salmonella, ampicillin is generally the treatment of choice if
the organism is susceptible to this antibiotic.
Serum titers, we are saying that we are taking a specimen of
blood at some point around the dose of an antibody before a
dose which would be the trough level or right after a dose IV,
perhaps an hour and a half after an oral dose would typically
represent the peak in the serum concentration and therefore test
the inhibition of the organism. You simply take the organism
which you hopefully have identified and have isolated in the
micro lab, and inoculate that into serial 2-fold solutions of this
serum.
As I mentioned, typically you like to treat these patients for four to
six weeks; either IV or orally depending on the organism and the
situations. Now, there are some times when you want to perform
surgical drainage; I think that if the surgeon went in to aspirate
the region or he might even see it on an MRI scan or CT scan,
there is an actual subperiosteal abscess that should be drained.
If there is a sequestra or there is swollen material within the
bones, that needs to be drained. In the neonate, these need to
be drained.
9
Etiology of Septic Arthritis and Age
Organism Neonate 2-36 months >36 months
S. aureus +++ +++ +++
S ,pneumoniae + + ++
S. pyogenes + +
Group B streptococcus +++
N. gonorrhoeae + + (adolescent)
Candida sp. ++
H Influenzae
(unimmunized) + ++ +
Salmonella (SSA) ++ ++
Kingella kingae ++
Puncture wounds of the foot frequently are caused by nail injuries
through the tennis shoe or some other shoe penetration and
inoculation of the bones. The majority of the patients have Pseudomonas
aeruginosa isolated either by itself or combination of
Staph aureus or streptococci.
When the surgeons explored the wounds, osteochondritis was
noted in all of the patients. There was also some septic arthritis
and some cutaneous abscesses also noted. So, the course of
exploration clearly is important. I think it is a conclusion that in
this infection, which is a infection of cartilage, that it is important
to perform the optimum surgery which would be to débride and
devitalize the infected soft tissue cartilage and bone. You need to
drain these joints. Then when you do that, one may only have to
treat with antibiotics for perhaps seven to ten days. So, this is in
contrast to what we are typically taught in treating osteomyelitis
for a prolonged period.
Organisms that cause septic arthritis in children. Again, in the
neonate, Staph aureus and Group B streptococcus are going to
be the leading organisms. Candida albicans and gram negative
are also apparent in premature infants. In the child between 2
and 36 months of age, Staph aureus is the most common. The
second most common is going to be pneumococcus. Salmonella
is something to think about in patients with
hemoglobinopathies. In older individuals Staph aureus, Group A
strep, and pneumococcus are the leading causes of septic
arthritis.
10
Clinical Manifestations of Septic Arthritis
..Acute onset fever, refusal to walk or limp
. Large joints (knee, hip, ankle) most common
. Swelling, warmth, erythema of joint with decreased mobility
. Abduction and external rotation is typical with hip
. In neonate systemic symptoms may be minimal
. In neonate multiple joints and contiguous osteomyelitis are common
. Small joints tend to be involved with gonococcal infection
Clinical manifestations of septic arthritis. We have the acute
onset of fever, refusal to walk, a limp would be the classic manifestation
in a baby. Perhaps the parents indicate that when they
change the diaper the baby is crying. Most of the time large joints
are involved. You might see a swelling, warmth, erythema, and
decreasing mobility in the joint. In the hip, the classic presentation
would be abduction and external rotation. In the neonate,
however, the symptoms may be very minimal. You might have
multiple joints involved and many bones infected as well, and it
is more or less hip. When you look at this baby you might see
that there is a slight dyssymmetry, and, in the baby, you may
illicit some pain on movement but it may be very subtle.
11
Differential Diagnosis of Septic Arthritis
..Nonbacterial infection- virus, hepatitis, Tb, fungi, Lyme disease
. Juvenile rheumatoid arthritis, other collagen vascular disease
. Acute rheumatic fever
. Inflammatory bowel disease
. Leukemia
. Toxic synovitis, psoas abscess, pelvic osteomyelitis (when unable to bear
weight)
. Reactive arthritis (Shigella, Yersinia, Salmonella; Endocarditis
. Trauma (hemarthrosis)
. Cellulitis
12
Evaluation- Septic Arthritis
1. Blood cultures positive in approximately 40% of cases
2. Synovial fluid - culture and Gram-stain
WBC count/mm3 %PMN Fluid: blood
glucose
Septic arthritis >50,000 90% 999 (30%)
JRA <15-20,000 60% normal to 9
(75%)
3. Vaginal or urethral culture if appropriate
4. Plane Radiograph: soft tissue swelling, joint space widening, osteomyelitis
5. Bone joint Tc-99m Scan
In the evaluation of septic arthritis, a blood culture is very helpful
and in some studies it has been positive in up to 40% of patients.,
what you want to get is a sample of the synovial fluid, a
blood culture, and a gram stain. Classically, if the white blood
cell count of the synovial fluid is greater than 50,000 with predominance
of polys, then this most likely a bacterial infection. If
the count is between 15,000 to 20,000, maybe less than 10,000,
with a smaller proportion of polys and the glucose limit is normal,
this is more likely to be a juvenile rheumatoid arthritis or
some other collagen vascular disease.
If we are dealing with an adolescent, and GC is a consideration,
then vaginal or urethral cultures should be obtained. Sometimes
the plain radiography can give you some additional clues as to
the foreign body scenario and a bone joint scan can sometimes
be useful as well.
13
Empiric Antibiotics for Septic Arthritis
Age Agents Duration
Neonate Nafcillin/Vancomycin
+
aminoglycoside/
cefotaxime
3 weeks
Infant or child Nafcillin/oxacillin
add cefotaxime/
ceftriaxone
if no Hib vaccine
(cefuroxime)
3 weeks
S. aureus
2 weeks
H. Influenzae
Adolescent with presumed
GC
Ceftriaxone 7 days
Immunocompromised
child
Nafcillin/oxacillin plus
aminoglycoside
or
extended spectrum
cephalosporin
3 weeks
Empiric antibiotics for septic arthritis. Nafcillin is the drug that we
would use in the nursery now. Vancomycin might be started
initially because of what is going on in your nursery with the
aminoglycoside or cefotaxime. In the infant or child this should
read Nafcillin or oxacillin, plus cefotaxime regardless of Hib
immunization, because of the problem with penicillin is just a
pneumococcus. If one should have the organism then, I think you
can tailor the treatment more readily. In the adolescent,
ceftriaxone should be the drug.
14
Septic Arthritis: Indications for Surgery
..Join remains swollen and erythematous after repeat needle aspiration
. Removal of foreign material secondary to penetrating
. Hips should be drained surgically
. In neonate surgical drainage of most joints indicated
. Arthroscopic lavage of knee alternative to arthrotomy
Indications for surgery. If you have repeat aspiration of the joint
and it remains swollen and erythematous, surgery of the joint is
indicated to remove foreign material, certainly all hips should be
drained. Some people might say all shoulder infections as well.
In some situations you can actually do arthroscopy rather than
surgical incision and drainage. It depends on the site and size of
the joint. There are some risk factors for outcome for septic
arthritis that I have also provided for you.
15
Risk Factors for Sequelae of Septic Arthritis
..Young age <6-12 months (especially neonate)
. Prolonged duration of symptoms prior to treatment
. Hip and shoulder infection (especially with S. aureus
. Sequelae
Cartilage damage, stiff joint with poor mobility, abnormal bone growth if
epiphysis involved, unstable joint, chronic dislocation
16
Discitis - Clinical Manifestations
..Low-grade fever
. Infants: Refusal to sit, pain when changing diaper
. Young child: Hip or leg complaints, and refusal to walk or limps; irritable
. Older child with back pain, abdominal pain
. Pain on palpation over vertebral processes
. Paraspinal muscle spasm
. Differential diagnosis: Toxic synovitis, vertebral osteomyelitis, epidural
abscess, pelvic osteomyelitis, sacroiliitis (Brucellosis)
Discitis or disc space infection. This is more common in young
children. The history can be one of nominal pain, a back pain, or
difficulty walking, and a child not wanting to sit. The diagnosis is
typically made on plain film and bone scans. If you do an MRI or
CT on a patient, it can look terrible. Management is with an oral
antistaphylococcal agents and let the child ambulate as tolerated,
usually in their own room with bed rest.
17
Discitis- Diagnostic Evaluation and Management
..Plan radiographs: disc space narrowing
. Bone scan: abnormal uptake in disc space and adjacent vertebral bodies
. MRI or CT are necessary if clinical and initial radiographic findings are not
typical
. Management: Rest and oral antistaphylococcal antibiotic for 34 weeks and
ESR <20 mm/hr
18
References
1. Gutman LT: Acute, subacute, and chronic osteomyelitis and pyogenic arthritis in
children. Curr Prob Pediatr 1985;15(12).
2. Jacobs RF, et al: Pseudomonas osteochondritis complicating puncture wounds of
the foot in children: a 10-year evaluation. J Infect Dis 1989;160:657-61.
3. Edwards MS, et al: Pelvic osteomyelitis in children. Pediatrics 1978;61:62-7.
4. Weinberg ED, et al: Clinical features of neonatal osteomyelitis. Pediatrics
1974;53:505-10.
5. Welkon CJ, et al: Pyogenic arthritis in infants and children: a review of 95 cases.
Pediatric Infect Dis 1986;5:669-76.
6. Cristin L, Sarosi GA: Pyomyositis in North America: case reports and review. Clin
Infect Dis 1992;15:668-77.
7. Correa AG, Edwards MS, Baker C J: Vertebral osteomyelitis in children. Pediatr
Infect Dis J 1993;12:228.
8. Dangman BC, Hoffer JA, Rand FF, O'Rourke E J: Osteomyelitis in children:
gadolinium-enhanced MR imaging. Radiology 1992;182:743.
9. Cushing AH: Diskitis in children. Clin Infect Dis 1993;17: 1-6.
Showing posts with label Allergic illnesses. Show all posts
Showing posts with label Allergic illnesses. Show all posts
Tuesday, August 17, 2010
Antimicrobial Prophylaxis
1
Antimicrobial Prophylaxis Against Acute Rheumatic Fever and Spontaneous
Bacterial Endocarditis
David Kramer, M.D.
2
Rheumatic Fever: Secondary Prophylaxis
. Indicated for patients with previous acute rheumatic fever (ARF) and/or
rheumatic heart disease (RHD)
. Prophylaxis is continuous because subclinical Group A beta-hemolytic
streptococcal pharyngitis can trigger recurrent ARF
. Risk of recurrence is greatest in first 5 years after ARF and in those with
RHD; the risk is 50% per episode of streptococcal pharyngitis
Secondary rheumatic fever prophylaxis. You all should know what
primary rheumatic fever prophylaxis is. That occurs of course to
accurate diagnosis and treatment of acute streptococcal pharyngitis
to prevent a first episode of rheumatic fever. However, secondary
rheumatic fever prophylaxis, that is which is for patients who
have been identified of having had a previous episode of rheumatic
fever and/or have been identified to have the presence of rheumatic
heart disease. So that if you identify someone who appears to have
rheumatic heart disease, but don’t have a clear history of rheumatic
episodes, you still want to institute rheumatic prophylaxis. Rheumatic
fever prophylaxis is continuous and the reason is because
you can not really rely only upon prior treatment of clinically
apparent strep pharyngitis in order to prevent rheumatic fever. One
third of rheumatic fever episodes may follow subclinical, in
clinically apparent streptococcal pharyngitis, and therefore this
should be continued prophylaxis to prevent all those streptococcal
infections. The risk of recurring episodes of rheumatic fever is
greatest in the first five years after a rheumatic fever episode. And
it also greatest in the first five years after a rheumatic fever
episode, and it also greatest in individuals who have had heart
disease. And if you take individuals at risk who have developed a
streptococcal pharyngitis. I gather in time another episode of
rheumatic fever will assume, all odds of sorts with increased heart
disease, or other developments of first-time heart disease. And that
is why this is such an important intervention. A common question
is how long do you get rheumatic fever prophylaxis? The best and
most considerate opinion is that the Committee of the American
Heart Association has recommended, and it’s recommendations
published in 1995, and contained in the Red Book. Patients who
have persistent rheumatic heart disease should receive at least ten
years of prophylaxis and should be at least until they are 40 years
of age, because that gets them through the period of time when
they are most likely to encounter young children who have streptococcal
pharyngitis. And I think really that a patient who has
significant rheumatic heart disease, doesn’t mean he has a life
long list of recurrent episodes of rheumatic fever after streptococcal
pharyngitis infection and lifelong infection ought to be considered
in those individuals.
3
Rheumatic Fever Prophylaxis Duration
. Persistent RHD: Prophylaxis is provided for at least 10 years
and at least until age 40; lifelong prophylaxis
should be considered
. RF with carditis 10 years, or well into adulthood
without residual RHD: (whichever is longer)
. RF without carditis: 5 years, or until age 21
(whichever is longer)
The patient who has an episode of acute rheumatic fever with
cardiac involvement, but then the cardiac involvement has resolved
and echo findings are no longer apparent in those patients. The
recommendation is that ten years of prophylaxis. And the reason
that these are long recommendations is that the consequences are
more obviously severe in the categories of patients considering an
episode of rheumatic fever. In patients who have had an episode of
rheumatic fever without any cardiac involvement, their recommendation
is that they should receive five years of therapy or at least
until the age of 21. The specifically recommended regimens for
rheumatic fever prophylaxis are Penicillin given monthly, the dose
is 600,000 units for children under 60 pounds or 1.2 million units
for individuals over 60 pounds, and then some kind of a regimen
every 3 week or every 4 week should be recommended. In the
United States every 4 week administration is perfectly fine. There
are of course, three acceptable oral agents, the third recommended
is Penicillin G at 250 mg twice daily. But for the individual
who can not tolerate these drugs, erythromycin seems to be the
idea for the standard recommendation.
4
Rheumatic Fever Prophylaxis Regimens
. IM Benzathine Pen G 1.2 M units IM Q3-4 wk
or
. P.O. Penicillin V 250 mg BID
or
. P.O. Sulfadiazine 0.5-1.0 gm QD
or
. P.O. Erythromycin 250 mg BID
Cardiac conditions that the Heart Association has recommended.
I think it would be a good idea to have a clear idea of this group of
patients. Clearly we all know that patients with prosthetic heart
valves are at very high risk. There is also a group of patients who
have other kinds of prosthetic material in their heart. And one of the
reasons that we have seen the highest patients is that they are
probably more likely given this. The consequences in these kinds
of patients are much more serious, and therefore it behooves us to
be as aggressive as we can to try to prevent this. An individual who
has had a previous episode of endocarditis is considered to be a
high risk for future episodes.
5
Infective Endocarditis Prophylaxis
. Goal is to prevent infective endocarditis in susceptible patients (with
underlying structural cardiac disease) when undergoing procedures that are
likely to induce transient bacteremia
. Coverage is provided for the procedure
. No controlled data support efficacy; recommendations are based on in vitro
susceptibility data
Then we have identified the moderate risk group of patients who
have unreformed heart disease, in whom prophylaxis is recommended,
and we will get to some of the new odds between this
group when we are ready. It is a moderate group of patients in that
they have acquired valvular heart disease, such as rheumatic heart
disease where the patients are getting continuous rheumatic fever
prophylaxis that needs in addition while ongoing a procedure for
example. We have ultimately decided that these patients should be
divided into those that have micro-prolapse with regurgitation, and
those that have micro-prolapse that may be associated with thicker
leaflets, this is something that occurs as folks get older, in the 50s
and 60s. So from the pediatric perspective, the findings of micro-
regurgitation is really once you determine whether a MVP patient
is one from whom you should recommend prophylaxis. Now what
we have done this time as a recommendation is to try to spell out
a group of negligible risk patients who have prophylaxis, and these
are patients we have considered to have no measurable risk over
that of the general population in individuals who do not have any
kind of heart disease. So these are kids who are supposed to have
ASD, VSD or PDA presurgical repairs, who do not have any
residual, cardiac disease, six months postoperative. To give it time
for all the patches to become epithelialized, for every 6 months, no
residual shunts.
Cardiac conditions the procedures that individuals are undergoing
where we need to consider whether they should give prophylaxis.
Some general principals are that procedures that are performed
through surgically scrubbed skin, including cardiac catheter,
angiography, are unlikely to be associated with bacteremia and
therefore, are generally not situations where we recommend
prophylaxis. In contrast, procedures that are done across mucosal
surfaces are much more likely to induce bacteremia. Bacteremia
is more common in the presence of poor dental hygiene than it is
in patients who have good dental hygiene, and the intensity of the
bacteremia in terms of the colony forming units, is much greater in
those that have poor dental hygiene. A very good rule of thumb
when it comes to speaking about dental procedures, is that
procedures that induce bleeding, that is that there is significant
trauma to the gingiva, are the ones that are most associated with
bacteremia.
6
Conditions Requiring Infective Endocarditis Prophylaxis
. Cardiac Conditions
Highest-Risk Patients (Recommended)
Prosthetic heart valves
Previous IE
Complex cyanotic congenital lesions
Surgical systemic-pulmonary shunts or conduits
. Moderate-Risk Patients (Recommended)
Acquired valve dysfunction (eg, RHD)
Hypertrophic cardiomyopathy
Most other congenital heart disease not included in categories I or III
Mitral prolapse with MR and/or thickened leaflets
. Negligible-Risk Patients (Not recommended)
Isolated secundum ASD
Surgically repaired ASD, VSD or PDA (without residua >6 months
post-op)
Previous CABG
Mitral prolapse without regurgitation
Functional murmurs; previous Kawasaki disease or rheumatic fever
without valve dysfunction
Pacemakers and defibrillators
So recommended prophylaxis includes extracting, cleaning with
bleeding. Cleaning typically induce bleeding, because then you can
really get down into the gum line and there is scraping and
bleeding. Very important to pediatrics, is the initial placement of
orthodontic bands with associated bleeding, and lots of trauma,
and as in contrast to the adjustment of orthodontic appliances. So
that the general rule is patients who have first time placement of
their orthodontia, they should be prophylaxis. Root canal surgery,
if it extended beyond the apex, is associated with bacteremia.
Periodontal procedures are associated with bacteremia.
Intraligamentary injections. Prophylaxis is not recommended for
shedding of primary teeth. As I said it is the adjustment of the
orthodontia, taking x-rays, fluoride treatments, and oral impressions.
Local anesthesia, placement of a kind of rubber dam and
suture removal interestingly, has not been associated with
bacteremia, and therefore we would not generally recommend
prophylaxis. In addition to dental procedures, there are a number
of nondental procedures involving the oral cavity and upper
respiratory tract, and of course the GI and GU tract.
7
IE Prophylaxis: Procedures
. Procedures (AHA, 1997)
Procedures through surgically scrubbed skin including routine cardiac cath and
angiography are unlikely to induce bacteremia
Trans-mucosal procedures more often induce bacteremia
Bacteremia is more common in the presence of poor dental hygiene
Procedures that induce bleeding are most commonly associated with bacteremia
. Dental Procedures
Prophylaxis Recommended
Extractions
Cleaning (with bleeding)
Initial placement of orthodontic bands
Root canal surgery (only beyond the apex)
Periodontal procedures
Intraligamentary injections
Prophylaxis Not Recommended
Shedding of primary teeth
Adjustment of orthodontic appliances
X-rays, fluoride treatments, oral impressions
Restorative dentistry (filling cavities)
Local anesthetic; placement of dams
Suture removal
..Non-dental Procedures
Prophylaxis Recommended
Respiratory: Tonsillectomy and/or adenoidectomy surgery involving mucosa,
rigid bronchoscopy
GI*: sclerotherapy for varices, esophageal dilatation, endoscopic retrograde
cholangiography with biliary obstruction, biliary tract surgery, surgery involving
GI mucosa
GU: prostatic surgery, cystoscopy, urethral dilatation
*Recommended for high-risk patients, optional for moderate risk
Prophylaxis Not Recommended
Respiratory: endotracheal intubation, flexible scope bronchoscopy (with or
without biopsy*), tympanostomy tube placement
GI: Transesophageal echocardiography*, endoscopy (with or without biopsy)
Genitourinary: Vaginal* or Cesarean delivery, hysterectomy*; in uninfected tissues:
urethral catheterization, dilation and curettage, therapeutic abortion, sterilization
procedures, insertion or removal of intrauterine devices, circumcision
Miscellaneous: cardiac catheterization, balloon angioplasty, placement of pacemakers,
defibrillators, or coronary stents, incision or biopsy of prepped skin
* Prophylaxis optional for high-risk patients
Prophylaxis is clearly recommending for the group of patients at
high risk undergoing these kinds of procedures and will be optional
for the much larger group of individuals who are on that list of
moderateness. So you can see here that the compromise that was
achieved was to make prophylaxis optional for the GI procedures,
accept for the very high-risk patients where we thought the risk
really justified without a doubt, the treatment of prophylaxis. So in
this category then are recommended patients undergoing T&A.
Under the GI procedures, for high-risk patients it is definitely
recommended that optional moderate infection, esophageal
dilatation, endoscopic retroperitoneal endoscopy. Under GU
procedures recommended for patients undergoing prostatic
surgery, got too many kids. So in this book we have simple
endotracheal intubation, flexible bronchoscopy, and that gets an
asterisk. GI procedures: Transesophageal echoes, only optional for
certain patients otherwise they really are not any cases of hepatitis
associated with this procedure, although almost all of your patients
have heart disease. Endoscopy. GU procedures: Vaginal delivery
is actually a higher risk for bacteremia than C-sections, so that gets
an asterisk. Hysterectomy gets an asterisk. If the patients have
nose infection, undergoing GU procedures such as urethral
catheterization of D&C, or circumcision, I strongly suspect that we
would not recommend prophylaxis. Then we have this latest group
of situations where we will not recommend prophylaxis:
angioplasty, placement of a pacemaker, coronary stents.
8
IE Prophylaxis for Dental, Oral, Respiratory
Tract or Esophageal Procedures (AHA, 1997)
Standard PO Amoxicillin 50 mg/kg 1 hour before
(adults=2 gm)
Unable to take orally IM or IV Ampicillin 50 mg/kg 30 min before
(adults=2 gm)
Penicillin-allergic PO Clindamycin 20 mg/kg 1 hour before
(adults=600 gm)
or
PO Cephalexin* or
Cefadroxil* 50 mg/kg 1 hour before
(adults=2 gm)
or
PO Azithromycin or 15 mg/kg 1 hour before
Clarithromycin (adults=500 mg)
Penicillin-allergic and IV Clindamycin 20 mg/kg within 30 min
unable to take orally before (adults=600mg)
or
IV or IM Cefazolin* 25 mg/kg within 30 min
before (adults=1gm)
* Avoid with immediate penicillin hypersensitivity
All Regimens are Single Dose
What are the now recommended prophylactic regimens? For
dental, oral, respiratory or esophageal procedures. Prevents
everything except lower GI and GU procedures, things have been
simplified to the bottom line here, single dose, no second doses.
Standard recommendation is single dose therapy. The standard
here is a single oral amoxicillin dose. For adults it is 2 grams. For
children it is 50 mg per kg. For patients that can not take oral
medication, a single dose of Ampicillin, same dosage, given 30
minutes before food. Now we have had a problem with patients
who are penicillin allergic, and you may remember that
Erythromycin has gotten in the past, standard recommendation. In
the larger group of moderate risk patients undergoing the
nonesophageal, GI plus GU procedures, we can give single dose
oral amoxicillin.
9
Prophylaxis for Genitourinary/gastrointestinal
(Non-esophageal) Procedures (AHA, 1997)
. High-risk Patients IV or IM Ampicillin (50 mg/kg up to 2 gin) plus IV or
IM Gentamicin (1.5 mg/kg up to 120 mg) within 30
min of starting procedure; 6 hours later, ampicillin
(25 mg/kg IV or IM) or amoxicillin (25 mg/kg PO)
. High Risk IV Vancomycin (20 mg/kg up to 1 gm) over 1-2 hr
(Pen-allergic) (1.5 mg/kg up to 120 mg) plus IV or IM Gentamicin
within 30 min of starting procedure
. Moderate Risk PO Amoxicillin or IM or IV Ampicillin (50 mg/kg up
to 2 gm) within 30 min. of starting procedure
. Moderate Risk IV Vancomycin (20 mg/kg up to 1 gm) over 1-2 hrs.,
(Pen-allergic) within 30 min of starting procedure
10
Prophylaxis for Surgical Wounds
. Generally not indicated for clean wounds that do not involve mucosal
surfaces (exceptions: open heart surgery, placement of prosthetic device,
immunocompromise?, neonate?)
. Often utilized for clean-contaminated wounds (across mucosal surface)
. Universally utilized for contaminated or dirty/infected wounds (treatment,
not prophylaxis)
. A single dose shortly before surgery is generally adequate
. Directed against the most likely bacteria (staph for skin; gut flora, etc.)
Other circumstances of antibiotic prophylaxis. One of those is
prophylaxis of surgical wounds. Surgical wounds are divided into
clean, clean contaminated, and infected kinds of wounds. This is
preoperative, not postoperative. Generally surgical prophylaxis is
not indicated for cleaning wounds that do not involve mucosal
surfaces. There are specific exceptions. I think all of us would
agree that I think all of us would agree that patients undergoing
open-heart surgery, placement of a prosthetic device either cardiac
or orthopedic or some other device, is perhaps in compromised
individuals. For clean contaminated surgery across mucosal
surfaces, a surgical incision is going to be across a normal
mucosal surface, it clearly cannot be prepped in the same way that
skin can be, and therefore is going to be contaminated. Most
surgeons would use antibiotics and most time that is the reasonable
thing to do. In individuals who have contaminated or dirty
infected wounds, that incision has to be made, that is a third
compound fracture contaminated with dirt. I think the key is to try to
individualize surgical colleagues that when surgical wound
prophylaxis is given, and is appropriately in judgement of the
surgeon, it really should be a single dose, and should be given
shortly before surgery because it is really critical to have a substantial
level of antibiotics in the patients blood stream at the time of
incision. Antibiotic surgical prophylaxis should be directed against
the most likely bacteria, which would be staphylococci of the skin.
11
Prophylaxis for H Influenzae: Principles
. Observation of exposed household or child care/nursery contacts, with
prompt evaluation if fever develops
. Increased risk of invasive Hib in unvaccinated household contacts <4 years
old (perhaps also in child care contacts)
. Increased risk of Hib colonization among household contacts of all ages
(probably also in child care contacts)
. Risk for secondary cases among child care contacts is less than age-
susceptible household contacts: 2Ecases are rare when all contacts are >2
years old
. Prophylaxis is given as soon as possible because best prevention occurs
in first week after index case
Prophylaxis against H flu. There are some general principals that
is that if a case of invasive AIDS flu and we have exposed individuals,
those exposed are household and childcare and nursery
contact should be observed. There is an increased risk of invasive
HIb in unvaccinated, this really should be incompletely vaccinated,
household contact who are under 40 years of age, and perhaps
there is an increased risk also in childcare contact. Among
household contacts of an invasive case of HIb, there is an increased
risk of HIb colonization among household contacts of all
ages. That is also probably true in daycare and childcare contact
as well. The risk for secondary cases occurring among childcare
contact is definitely less than the risk for aids through susceptible
household contact.
In a household setting, all household members of all ages should
be prophylaxed where there is at least one incompletely vaccinated
contact for those of 48 months of age. For a definition of who is
considered to be completely vaccinated, that is a child who has
received at least one conjugated dose at the age of 15 months or
greater, or has had two doses of vaccine if the child is between 1214
months. In any case, I think the key point is that if you have any
one who is incompletely vaccinated under 4 years of age in a
household, you should really give vaccines to everybody in the
household, because of the concern about carriage. If you have a
child under 12 months of age in the household, all the household
members again of all ages ought to be prophylaxed, and the reason
is because this child may be colonized because of the booster
dose beyond 12 months. If it is in a childcare situation, it really gets
sort of confusing. I have to admit this is not my major field of
interest, but I will relay to you what the Red Book says. It indicates
clearly that the risks in a childcare setting is lower than in households
and secondary cases are less likely to occur in childcare
settings than in households. Secondary cases are rare when all the
people in the childcare center are over 2 years of age. And they
have a definition of what is contact? What is sufficient contact?
They define it as 25 hours of the week. In addition, the identification
of a first case, whether or not they give prophylaxis is certainly
enough to take the opportunity to bring everyone to a vaccine center
today. Now if there is a second case of invasive HIb that occurs
within 60 days in one of these centers, and there are many
unvaccinated or incompletely vaccinated children present, the
families should be given and all personnel, a dose as well. Unless,
we have pregnant personnel, and there is a specific exclusion in
the Red Book for pregnant personnel.
Prophylaxis is recommended for household and childcare and
nursery contacts. You do not need a second case. If you have a
case of pneumococcal disease. Whenever there is sharing of oral
secretions, food, drink, kissing, household and childbed nursery
contacts, clearly prophylaxis is indicated. Then, of course, medical
personnel. It should be everyone in the hospital who has passed
within 25 feet of the case, that is really where prophylaxis is
recommend or medical personnel who have been exposed such as
mouth-to-mouth resuscitation.
12
Meningococcal Vaccine
. Indications for Vaccine
Control of outbreak
Travel to epidemic area
Military recruits
Functional or anatomic asplenia, terminal complement deficiency state
. Immunogenicity
Group A >3 months old
Groups C, Y, W-135 >18-24 months old
Protection lasts 3-5 years (or less)
Revaccination is probably indicated for those <4 years if still at risk
Antimicrobial Prophylaxis Against Acute Rheumatic Fever and Spontaneous
Bacterial Endocarditis
David Kramer, M.D.
2
Rheumatic Fever: Secondary Prophylaxis
. Indicated for patients with previous acute rheumatic fever (ARF) and/or
rheumatic heart disease (RHD)
. Prophylaxis is continuous because subclinical Group A beta-hemolytic
streptococcal pharyngitis can trigger recurrent ARF
. Risk of recurrence is greatest in first 5 years after ARF and in those with
RHD; the risk is 50% per episode of streptococcal pharyngitis
Secondary rheumatic fever prophylaxis. You all should know what
primary rheumatic fever prophylaxis is. That occurs of course to
accurate diagnosis and treatment of acute streptococcal pharyngitis
to prevent a first episode of rheumatic fever. However, secondary
rheumatic fever prophylaxis, that is which is for patients who
have been identified of having had a previous episode of rheumatic
fever and/or have been identified to have the presence of rheumatic
heart disease. So that if you identify someone who appears to have
rheumatic heart disease, but don’t have a clear history of rheumatic
episodes, you still want to institute rheumatic prophylaxis. Rheumatic
fever prophylaxis is continuous and the reason is because
you can not really rely only upon prior treatment of clinically
apparent strep pharyngitis in order to prevent rheumatic fever. One
third of rheumatic fever episodes may follow subclinical, in
clinically apparent streptococcal pharyngitis, and therefore this
should be continued prophylaxis to prevent all those streptococcal
infections. The risk of recurring episodes of rheumatic fever is
greatest in the first five years after a rheumatic fever episode. And
it also greatest in the first five years after a rheumatic fever
episode, and it also greatest in individuals who have had heart
disease. And if you take individuals at risk who have developed a
streptococcal pharyngitis. I gather in time another episode of
rheumatic fever will assume, all odds of sorts with increased heart
disease, or other developments of first-time heart disease. And that
is why this is such an important intervention. A common question
is how long do you get rheumatic fever prophylaxis? The best and
most considerate opinion is that the Committee of the American
Heart Association has recommended, and it’s recommendations
published in 1995, and contained in the Red Book. Patients who
have persistent rheumatic heart disease should receive at least ten
years of prophylaxis and should be at least until they are 40 years
of age, because that gets them through the period of time when
they are most likely to encounter young children who have streptococcal
pharyngitis. And I think really that a patient who has
significant rheumatic heart disease, doesn’t mean he has a life
long list of recurrent episodes of rheumatic fever after streptococcal
pharyngitis infection and lifelong infection ought to be considered
in those individuals.
3
Rheumatic Fever Prophylaxis Duration
. Persistent RHD: Prophylaxis is provided for at least 10 years
and at least until age 40; lifelong prophylaxis
should be considered
. RF with carditis 10 years, or well into adulthood
without residual RHD: (whichever is longer)
. RF without carditis: 5 years, or until age 21
(whichever is longer)
The patient who has an episode of acute rheumatic fever with
cardiac involvement, but then the cardiac involvement has resolved
and echo findings are no longer apparent in those patients. The
recommendation is that ten years of prophylaxis. And the reason
that these are long recommendations is that the consequences are
more obviously severe in the categories of patients considering an
episode of rheumatic fever. In patients who have had an episode of
rheumatic fever without any cardiac involvement, their recommendation
is that they should receive five years of therapy or at least
until the age of 21. The specifically recommended regimens for
rheumatic fever prophylaxis are Penicillin given monthly, the dose
is 600,000 units for children under 60 pounds or 1.2 million units
for individuals over 60 pounds, and then some kind of a regimen
every 3 week or every 4 week should be recommended. In the
United States every 4 week administration is perfectly fine. There
are of course, three acceptable oral agents, the third recommended
is Penicillin G at 250 mg twice daily. But for the individual
who can not tolerate these drugs, erythromycin seems to be the
idea for the standard recommendation.
4
Rheumatic Fever Prophylaxis Regimens
. IM Benzathine Pen G 1.2 M units IM Q3-4 wk
or
. P.O. Penicillin V 250 mg BID
or
. P.O. Sulfadiazine 0.5-1.0 gm QD
or
. P.O. Erythromycin 250 mg BID
Cardiac conditions that the Heart Association has recommended.
I think it would be a good idea to have a clear idea of this group of
patients. Clearly we all know that patients with prosthetic heart
valves are at very high risk. There is also a group of patients who
have other kinds of prosthetic material in their heart. And one of the
reasons that we have seen the highest patients is that they are
probably more likely given this. The consequences in these kinds
of patients are much more serious, and therefore it behooves us to
be as aggressive as we can to try to prevent this. An individual who
has had a previous episode of endocarditis is considered to be a
high risk for future episodes.
5
Infective Endocarditis Prophylaxis
. Goal is to prevent infective endocarditis in susceptible patients (with
underlying structural cardiac disease) when undergoing procedures that are
likely to induce transient bacteremia
. Coverage is provided for the procedure
. No controlled data support efficacy; recommendations are based on in vitro
susceptibility data
Then we have identified the moderate risk group of patients who
have unreformed heart disease, in whom prophylaxis is recommended,
and we will get to some of the new odds between this
group when we are ready. It is a moderate group of patients in that
they have acquired valvular heart disease, such as rheumatic heart
disease where the patients are getting continuous rheumatic fever
prophylaxis that needs in addition while ongoing a procedure for
example. We have ultimately decided that these patients should be
divided into those that have micro-prolapse with regurgitation, and
those that have micro-prolapse that may be associated with thicker
leaflets, this is something that occurs as folks get older, in the 50s
and 60s. So from the pediatric perspective, the findings of micro-
regurgitation is really once you determine whether a MVP patient
is one from whom you should recommend prophylaxis. Now what
we have done this time as a recommendation is to try to spell out
a group of negligible risk patients who have prophylaxis, and these
are patients we have considered to have no measurable risk over
that of the general population in individuals who do not have any
kind of heart disease. So these are kids who are supposed to have
ASD, VSD or PDA presurgical repairs, who do not have any
residual, cardiac disease, six months postoperative. To give it time
for all the patches to become epithelialized, for every 6 months, no
residual shunts.
Cardiac conditions the procedures that individuals are undergoing
where we need to consider whether they should give prophylaxis.
Some general principals are that procedures that are performed
through surgically scrubbed skin, including cardiac catheter,
angiography, are unlikely to be associated with bacteremia and
therefore, are generally not situations where we recommend
prophylaxis. In contrast, procedures that are done across mucosal
surfaces are much more likely to induce bacteremia. Bacteremia
is more common in the presence of poor dental hygiene than it is
in patients who have good dental hygiene, and the intensity of the
bacteremia in terms of the colony forming units, is much greater in
those that have poor dental hygiene. A very good rule of thumb
when it comes to speaking about dental procedures, is that
procedures that induce bleeding, that is that there is significant
trauma to the gingiva, are the ones that are most associated with
bacteremia.
6
Conditions Requiring Infective Endocarditis Prophylaxis
. Cardiac Conditions
Highest-Risk Patients (Recommended)
Prosthetic heart valves
Previous IE
Complex cyanotic congenital lesions
Surgical systemic-pulmonary shunts or conduits
. Moderate-Risk Patients (Recommended)
Acquired valve dysfunction (eg, RHD)
Hypertrophic cardiomyopathy
Most other congenital heart disease not included in categories I or III
Mitral prolapse with MR and/or thickened leaflets
. Negligible-Risk Patients (Not recommended)
Isolated secundum ASD
Surgically repaired ASD, VSD or PDA (without residua >6 months
post-op)
Previous CABG
Mitral prolapse without regurgitation
Functional murmurs; previous Kawasaki disease or rheumatic fever
without valve dysfunction
Pacemakers and defibrillators
So recommended prophylaxis includes extracting, cleaning with
bleeding. Cleaning typically induce bleeding, because then you can
really get down into the gum line and there is scraping and
bleeding. Very important to pediatrics, is the initial placement of
orthodontic bands with associated bleeding, and lots of trauma,
and as in contrast to the adjustment of orthodontic appliances. So
that the general rule is patients who have first time placement of
their orthodontia, they should be prophylaxis. Root canal surgery,
if it extended beyond the apex, is associated with bacteremia.
Periodontal procedures are associated with bacteremia.
Intraligamentary injections. Prophylaxis is not recommended for
shedding of primary teeth. As I said it is the adjustment of the
orthodontia, taking x-rays, fluoride treatments, and oral impressions.
Local anesthesia, placement of a kind of rubber dam and
suture removal interestingly, has not been associated with
bacteremia, and therefore we would not generally recommend
prophylaxis. In addition to dental procedures, there are a number
of nondental procedures involving the oral cavity and upper
respiratory tract, and of course the GI and GU tract.
7
IE Prophylaxis: Procedures
. Procedures (AHA, 1997)
Procedures through surgically scrubbed skin including routine cardiac cath and
angiography are unlikely to induce bacteremia
Trans-mucosal procedures more often induce bacteremia
Bacteremia is more common in the presence of poor dental hygiene
Procedures that induce bleeding are most commonly associated with bacteremia
. Dental Procedures
Prophylaxis Recommended
Extractions
Cleaning (with bleeding)
Initial placement of orthodontic bands
Root canal surgery (only beyond the apex)
Periodontal procedures
Intraligamentary injections
Prophylaxis Not Recommended
Shedding of primary teeth
Adjustment of orthodontic appliances
X-rays, fluoride treatments, oral impressions
Restorative dentistry (filling cavities)
Local anesthetic; placement of dams
Suture removal
..Non-dental Procedures
Prophylaxis Recommended
Respiratory: Tonsillectomy and/or adenoidectomy surgery involving mucosa,
rigid bronchoscopy
GI*: sclerotherapy for varices, esophageal dilatation, endoscopic retrograde
cholangiography with biliary obstruction, biliary tract surgery, surgery involving
GI mucosa
GU: prostatic surgery, cystoscopy, urethral dilatation
*Recommended for high-risk patients, optional for moderate risk
Prophylaxis Not Recommended
Respiratory: endotracheal intubation, flexible scope bronchoscopy (with or
without biopsy*), tympanostomy tube placement
GI: Transesophageal echocardiography*, endoscopy (with or without biopsy)
Genitourinary: Vaginal* or Cesarean delivery, hysterectomy*; in uninfected tissues:
urethral catheterization, dilation and curettage, therapeutic abortion, sterilization
procedures, insertion or removal of intrauterine devices, circumcision
Miscellaneous: cardiac catheterization, balloon angioplasty, placement of pacemakers,
defibrillators, or coronary stents, incision or biopsy of prepped skin
* Prophylaxis optional for high-risk patients
Prophylaxis is clearly recommending for the group of patients at
high risk undergoing these kinds of procedures and will be optional
for the much larger group of individuals who are on that list of
moderateness. So you can see here that the compromise that was
achieved was to make prophylaxis optional for the GI procedures,
accept for the very high-risk patients where we thought the risk
really justified without a doubt, the treatment of prophylaxis. So in
this category then are recommended patients undergoing T&A.
Under the GI procedures, for high-risk patients it is definitely
recommended that optional moderate infection, esophageal
dilatation, endoscopic retroperitoneal endoscopy. Under GU
procedures recommended for patients undergoing prostatic
surgery, got too many kids. So in this book we have simple
endotracheal intubation, flexible bronchoscopy, and that gets an
asterisk. GI procedures: Transesophageal echoes, only optional for
certain patients otherwise they really are not any cases of hepatitis
associated with this procedure, although almost all of your patients
have heart disease. Endoscopy. GU procedures: Vaginal delivery
is actually a higher risk for bacteremia than C-sections, so that gets
an asterisk. Hysterectomy gets an asterisk. If the patients have
nose infection, undergoing GU procedures such as urethral
catheterization of D&C, or circumcision, I strongly suspect that we
would not recommend prophylaxis. Then we have this latest group
of situations where we will not recommend prophylaxis:
angioplasty, placement of a pacemaker, coronary stents.
8
IE Prophylaxis for Dental, Oral, Respiratory
Tract or Esophageal Procedures (AHA, 1997)
Standard PO Amoxicillin 50 mg/kg 1 hour before
(adults=2 gm)
Unable to take orally IM or IV Ampicillin 50 mg/kg 30 min before
(adults=2 gm)
Penicillin-allergic PO Clindamycin 20 mg/kg 1 hour before
(adults=600 gm)
or
PO Cephalexin* or
Cefadroxil* 50 mg/kg 1 hour before
(adults=2 gm)
or
PO Azithromycin or 15 mg/kg 1 hour before
Clarithromycin (adults=500 mg)
Penicillin-allergic and IV Clindamycin 20 mg/kg within 30 min
unable to take orally before (adults=600mg)
or
IV or IM Cefazolin* 25 mg/kg within 30 min
before (adults=1gm)
* Avoid with immediate penicillin hypersensitivity
All Regimens are Single Dose
What are the now recommended prophylactic regimens? For
dental, oral, respiratory or esophageal procedures. Prevents
everything except lower GI and GU procedures, things have been
simplified to the bottom line here, single dose, no second doses.
Standard recommendation is single dose therapy. The standard
here is a single oral amoxicillin dose. For adults it is 2 grams. For
children it is 50 mg per kg. For patients that can not take oral
medication, a single dose of Ampicillin, same dosage, given 30
minutes before food. Now we have had a problem with patients
who are penicillin allergic, and you may remember that
Erythromycin has gotten in the past, standard recommendation. In
the larger group of moderate risk patients undergoing the
nonesophageal, GI plus GU procedures, we can give single dose
oral amoxicillin.
9
Prophylaxis for Genitourinary/gastrointestinal
(Non-esophageal) Procedures (AHA, 1997)
. High-risk Patients IV or IM Ampicillin (50 mg/kg up to 2 gin) plus IV or
IM Gentamicin (1.5 mg/kg up to 120 mg) within 30
min of starting procedure; 6 hours later, ampicillin
(25 mg/kg IV or IM) or amoxicillin (25 mg/kg PO)
. High Risk IV Vancomycin (20 mg/kg up to 1 gm) over 1-2 hr
(Pen-allergic) (1.5 mg/kg up to 120 mg) plus IV or IM Gentamicin
within 30 min of starting procedure
. Moderate Risk PO Amoxicillin or IM or IV Ampicillin (50 mg/kg up
to 2 gm) within 30 min. of starting procedure
. Moderate Risk IV Vancomycin (20 mg/kg up to 1 gm) over 1-2 hrs.,
(Pen-allergic) within 30 min of starting procedure
10
Prophylaxis for Surgical Wounds
. Generally not indicated for clean wounds that do not involve mucosal
surfaces (exceptions: open heart surgery, placement of prosthetic device,
immunocompromise?, neonate?)
. Often utilized for clean-contaminated wounds (across mucosal surface)
. Universally utilized for contaminated or dirty/infected wounds (treatment,
not prophylaxis)
. A single dose shortly before surgery is generally adequate
. Directed against the most likely bacteria (staph for skin; gut flora, etc.)
Other circumstances of antibiotic prophylaxis. One of those is
prophylaxis of surgical wounds. Surgical wounds are divided into
clean, clean contaminated, and infected kinds of wounds. This is
preoperative, not postoperative. Generally surgical prophylaxis is
not indicated for cleaning wounds that do not involve mucosal
surfaces. There are specific exceptions. I think all of us would
agree that I think all of us would agree that patients undergoing
open-heart surgery, placement of a prosthetic device either cardiac
or orthopedic or some other device, is perhaps in compromised
individuals. For clean contaminated surgery across mucosal
surfaces, a surgical incision is going to be across a normal
mucosal surface, it clearly cannot be prepped in the same way that
skin can be, and therefore is going to be contaminated. Most
surgeons would use antibiotics and most time that is the reasonable
thing to do. In individuals who have contaminated or dirty
infected wounds, that incision has to be made, that is a third
compound fracture contaminated with dirt. I think the key is to try to
individualize surgical colleagues that when surgical wound
prophylaxis is given, and is appropriately in judgement of the
surgeon, it really should be a single dose, and should be given
shortly before surgery because it is really critical to have a substantial
level of antibiotics in the patients blood stream at the time of
incision. Antibiotic surgical prophylaxis should be directed against
the most likely bacteria, which would be staphylococci of the skin.
11
Prophylaxis for H Influenzae: Principles
. Observation of exposed household or child care/nursery contacts, with
prompt evaluation if fever develops
. Increased risk of invasive Hib in unvaccinated household contacts <4 years
old (perhaps also in child care contacts)
. Increased risk of Hib colonization among household contacts of all ages
(probably also in child care contacts)
. Risk for secondary cases among child care contacts is less than age-
susceptible household contacts: 2Ecases are rare when all contacts are >2
years old
. Prophylaxis is given as soon as possible because best prevention occurs
in first week after index case
Prophylaxis against H flu. There are some general principals that
is that if a case of invasive AIDS flu and we have exposed individuals,
those exposed are household and childcare and nursery
contact should be observed. There is an increased risk of invasive
HIb in unvaccinated, this really should be incompletely vaccinated,
household contact who are under 40 years of age, and perhaps
there is an increased risk also in childcare contact. Among
household contacts of an invasive case of HIb, there is an increased
risk of HIb colonization among household contacts of all
ages. That is also probably true in daycare and childcare contact
as well. The risk for secondary cases occurring among childcare
contact is definitely less than the risk for aids through susceptible
household contact.
In a household setting, all household members of all ages should
be prophylaxed where there is at least one incompletely vaccinated
contact for those of 48 months of age. For a definition of who is
considered to be completely vaccinated, that is a child who has
received at least one conjugated dose at the age of 15 months or
greater, or has had two doses of vaccine if the child is between 1214
months. In any case, I think the key point is that if you have any
one who is incompletely vaccinated under 4 years of age in a
household, you should really give vaccines to everybody in the
household, because of the concern about carriage. If you have a
child under 12 months of age in the household, all the household
members again of all ages ought to be prophylaxed, and the reason
is because this child may be colonized because of the booster
dose beyond 12 months. If it is in a childcare situation, it really gets
sort of confusing. I have to admit this is not my major field of
interest, but I will relay to you what the Red Book says. It indicates
clearly that the risks in a childcare setting is lower than in households
and secondary cases are less likely to occur in childcare
settings than in households. Secondary cases are rare when all the
people in the childcare center are over 2 years of age. And they
have a definition of what is contact? What is sufficient contact?
They define it as 25 hours of the week. In addition, the identification
of a first case, whether or not they give prophylaxis is certainly
enough to take the opportunity to bring everyone to a vaccine center
today. Now if there is a second case of invasive HIb that occurs
within 60 days in one of these centers, and there are many
unvaccinated or incompletely vaccinated children present, the
families should be given and all personnel, a dose as well. Unless,
we have pregnant personnel, and there is a specific exclusion in
the Red Book for pregnant personnel.
Prophylaxis is recommended for household and childcare and
nursery contacts. You do not need a second case. If you have a
case of pneumococcal disease. Whenever there is sharing of oral
secretions, food, drink, kissing, household and childbed nursery
contacts, clearly prophylaxis is indicated. Then, of course, medical
personnel. It should be everyone in the hospital who has passed
within 25 feet of the case, that is really where prophylaxis is
recommend or medical personnel who have been exposed such as
mouth-to-mouth resuscitation.
12
Meningococcal Vaccine
. Indications for Vaccine
Control of outbreak
Travel to epidemic area
Military recruits
Functional or anatomic asplenia, terminal complement deficiency state
. Immunogenicity
Group A >3 months old
Groups C, Y, W-135 >18-24 months old
Protection lasts 3-5 years (or less)
Revaccination is probably indicated for those <4 years if still at risk
Thursday, August 12, 2010
Allergic Disorders
Allergic Disorders
Allergic illnesses have a significant impact that allergic diseases have on children's health and quality of life. Allergic diseases, including
asthma, are among the major causes of chronic illnesses in the United States, affecting approximately 50 million patients or as many as
one in five children. The economic impact is enormous; asthma alone is estimated to cost more than 6.2 billion dollars of health care
expenditures annually. Of all the chronic illnesses, allergic respiratory problems, including allergic asthma, is the most common cause of
school absenteeism. Even though allergic disease usually is not fatal, death can result as a consequence of allergic anaphylaxis related to
medication, food, or insect venom allergy or from a complication of asthma. Therefore, the pediatrician must be capable of diagnosing
allergic disease so as to institute appropriate management. This review will emphasize those clinical diagnostic features ascertained by
history and physical examination as well as the appropriate laboratory studies useful in the diagnosis of respiratory (inhalant) and
gastrointestinal (food) allergy.
General Features of Allergic Diseases
Allergic diseases are immunoglobulin E (IgE)-mediated immunologic illnesses that can affect any of the body's major organ systems
either individually or collectively. Typically, children are not born having allergies because maternal IgE normally does not cross the placenta.
In rare instances, neonates and young infants who apparently were sensitized in utero have been born with specific IgE to foods and had
allergic reactions to those foods. Development of an allergy requires a familial predisposition and repeat exposure to an allergen (antigen)
that provokes specific IgE antibody.
Epidemiologic surveys indicate that the familial trait for allergy is inherited as autosomal recessive. Whereas the frequency of
positive allergy skin tests is similar in boys and girls, asthma is twice as common in males as in females prior to adolescence, but it appears
equal in prevalence thereafter. A specific immune response gene has been identified for IgE antibody synthesis in rodents, but it has not yet
been demonstrated conclusively in humans. With the recent advances in molecular genetics, it is anticipated that the genetic basis of allergy
will be understood better in the near future.
Allergens sensitize by several potential routes and are categorized as inhalants, ingestants, injectants, and contactants (Table 1).
It is important for the physician to define the route by which any specific allergen provokes clinical allergy in individual patients.
Of the inhalant IgE-mediated allergies, allergic rhinitis is by far the most common, affecting approximately 15% of all children.
Asthma, of which 80% has an allergic inhalant basis, occurs in more than 5% of children. Gastrointestinal (ingestant) allergy typically is
associated with food allergy; however, ingestants also may provoke urticaria and atopic dermatitis and less often may trigger respiratory
symptoms. Anaphylaxis is a systemic generalized allergic response consisting of hypotension, urticaria, and angioedema as well as upper
and lower airway obstruction; it can be caused by severe allergic reactions to foods (ingestant), insect venom stings (injectant), or
medications (ingestant, injectant, or contactant).
Although incriminated anecdotally as the cause for hyperactivity, poor school performance, learning disabilities, or abnormal child
behavior, there are no definitive, appropriately controlled studies that document an IgE allergic etiology for these predominantly psychosocial
or educational problems. The possibility that overgrowth of a yeast such as Candida is important in the pathogenesis of allergy never has
been substantiated. The concept of such a candidal syndrome in the context of abnormal child behavior has no validity, and antifungal
therapy in the absence of overt clinical candidal infection should be discouraged.
Inhalant Allergy
Microscopic inhaled airborne allergens are responsible for most respiratory allergy (Table 2). In temperate climates, seasonal allergic
rhinitis is induced by tree pollens in the early spring, grass pollens in the late spring and early summer, and ragweed in the late summer and
early fall. Because of geographic differences in the US, clinicians must become familiar with the pollination patterns in their individual regions.
Hay fever is an inappropriate term for allergic rhinitis because these patients neither are allergic to hay nor have fever. Flowering vegetation,
such as roses and fruit blossoms, rarely cause allergy because these pollens are too heavy to become airborne; their germination is
facilitated by bees and other insects. Fungi (mold) spores may be important outdoor aeroallergens in humid climates throughout the year,
but their numbers decrease once there is significant frost in temperate climates. Fungi can be important indoor perennial allergens in damp
environments. In perennial allergic rhinitis, house dust, animals, and molds all may be significant indoor inhalant allergens. The principal
allergens in house dust are the cuticles and feces of the microscopic house dust mite Dermatophagoides. Animal allergens, such as
epidermal danders, salivary proteins, urinary proteins, feces, and feathers, especially from pets such as cats, dogs, and birds are important
because about 50% of households in the US have indoor animal pets. Food allergens are of lesser importance in the etiology of allergic
rhinitis but cannot be ignored, especially in young children. Patients can be sensitive to one or multiple allergens. Certain individuals react
to miniscule amounts of inhaled allergens, while others tolerate a large allergen dose before developing symptoms.
In addition to allergens, viral infections, aerosolized cosmetics, cigarette smoke, industrial fumes, and changes in temperature,
humidity, and barometric pressure contribute to exacerbation of both upper and lower respiratory tract symptoms in the allergic child.
Psychologic and social stresses also can enhance symptoms. The importance of these additional contributory factors varies greatly from
patient to patient but should not be ignored when evaluating any individual.
Symptoms of nasal allergy consist of frequent sneezing, nasal pruritus, watery rhinorrhea, and often, nasal obstruction. Patients
also may complain of red, itchy eyes as well as itchy throat and ears. If there is nasal obstruction, the patient will be a mouth breather and
snoring can be a bedtime symptom; smell and taste also may be lost. Increased symptoms frequently are noted with increased exposure
to the responsible allergen, such as after cutting grass or sleeping on a feather pillow.
When an allergic reaction develops, clear nasal secretions will be evident, and the nasal mucous membranes will become
edematous without much erythema. The mucosa appear boggy and blue-gray. With continued exposure to the allergen, the turbinates will
appear swollen and can obstruct the nasal airway. Conjunctival edema, itch, tearing, and hyperemia are frequent findings in patients who
have associated allergic conjunctivitis. Patients who have allergic rhinitis, particularly children who have significant nasal obstruction and
venous congestion, also may demonstrate edema and darkening of the tissues beneath the eyes. These so-called "shiners" are not
pathognomonic for allergic rhinitis because they also can be seen in patients who have chronic rhinitis and/or sinusitis. Thick, purulent
secretions indicate the presence of infection, including the possibility of sinusitis.
DIAGNOSTIC TESTS
Nonspecific Allergy Tests
Many pediatricians believe in the need for a screening test for allergy. Blood eosinophilia and total serum IgE levels have been
proposed as screening tests, but they have relatively low sensitivity and should be used selectively (Table 3). The nasal secretions or sputum
of patients who have a respiratory allergy contain increased numbers of eosinophils, which forms the basis of a useful nonspecific test,
although not one that will identify any specific allergen etiology. Eosinophilia may not be present in patients who have not been exposed to
allergens recently or who have a superimposed upper respiratory tract infection. Both systemic and inhaled steroids can reduce eosinophilia
in secretions significantly; antihistamines have no direct effect on eosinophils.
The usefulness of nasal eosinophilia as a diagnostic test depends in large part on the technique used to obtain the specimens to
prepare the slides for examination. Patients should expel nasal secretions onto wax paper or parafilm; secretions then are spread on a
microscope slide, stained, and eosinophils counted under a microscope. It is difficult to quantify nasal eosinophilia accurately, although a
finding of more than 3% eosinophils on stained smear of expelled nasal or bronchial secretions is considered increased. Because cotton or
nylon nasal swabs trap secretions, they are not recommended for collecting secretions, except in the young child who will not or cannot expel
secretions by blowing the nose. Peripheral blood eosinophilia is observed in allergic asthma but less commonly in allergic rhinitis. Blood
eosinophilia is more frequent in atopic dermatitis and other conditions, such as parasite infection.
Total serum IgE is elevated in about 60% of patients who have allergic asthma but only in 30% of those who have allergic rhinitis.
Unfortunately, commercial laboratories have promoted tests of total serum IgE excessively, but its usefulness in screening for allergy is
limited to positive tests only because more than 60% of patients who have nasal allergy will have normal levels of total serum IgE.
Specific Inhalant Allergy Tests
Laboratory confirmation of the presence of IgE antibodies to specific allergens such as dust mites, pollens, or animals is very helpful
in establishing a specific allergic diagnosis, especially if the history of exposure to a specific allergen is not clear-cut. It may be necessary
to test for specific allergens to convince the family and patient of an allergic diagnosis and to reinforce the importance of environmental
control.
Although skin testing might be performed in any child at any age, children less than 1 year of age may not mount a positive reaction.
Often, the child who has seasonal respiratory allergy will not manifest a positive test until after two seasons of exposure. Clinicians should
use allergens for skin testing selectively and employ only common allergens of potential clinical importance. The most useful allergens for
which to test in the child who has perennial inhalant allergy are house dust mites (Dermatophygoides), animal danders, and fungi (molds)
(Table 2). Allergens important in the diagnosis of seasonal allergic rhinitis are weeds, grasses, and tree pollens. These allergens vary not
only by season of year but by geographic distribution. Therefore, allergens used for skin testing must be individualized and should be selected
on the basis of prevalence in the local area and the home and school environment.
IgE antibody can be tested via two methods: in vivo skin testing and in vitro serum testing (Table 3). Their advantages and
disadvantages are outlined in Table 4. For most patients, skin tests that are performed properly offer the best available method for detecting
the presence of allergen-specific IgE. The prick, also called the puncture or epicutaneous skin test, is preferred; scratch testing has been
abandoned as too traumatic. If prick tests are negative and allergy is highly suspect, then intradermal testing, which is more sensitive, may
be employed. Skin tests are both 10% to 20% more sensitive and less expensive on a per test basis than are in vitro serum tests.
The in vitro serum tests employ specific antisera, and the allergen antibody reactions are amplified as a radioimmunoassay (RAST),
fluorescent immunoassay (FAST), or an enzyme-linked immunosorbent assay (ELISA). Each of these techniques is comparable when
performed properly. In vitro tests are acceptable substitutes for skin tests in the following circumstances: 1) The patient has abnormal skin,
such as dermatographism or extensive dermatitis, 2) The patient cannot or did not discontinue antihistamines or other interfering
medications, 3) The patient is very allergic by history, and anaphylaxis is a possible risk, and 4) The patient is noncompliant regarding skin
testing. The results of either skin tests or in vitro assays depend very much on the quality of the allergen and the competence with which the
test is performed.
Although the quality of allergens is improving, there is need for more and better standardization. Both skin testing and in vitro assays
have been criticized for lack of good quality control. Skin testing should not be an occasional test for the inexperienced and obviously never
should be delegated to an inadequately trained or unsupervised assistant. Board certified allergy and immunology specialists are best
qualified to correlate patient histories with tests results. Quality control also has been a major problem for in vitro serum IgE antibody tests.
Compulsory participation in quality control programs, such as that offered by the College of American Pathologists and mandated by the
Clinical Laboratory Improvement Act, eventually will lead to better quality and standardization of in vitro serum IgE tests.
Positive tests for allergen-specific IgE do not diagnose allergy; they only indicate the presence of IgE molecules that have a
particular immunologic specificity. Whether the specific IgE antibodies are responsible for clinically apparent disease must be determined
by a well-trained physician. The ultimate standard for the diagnosis of allergic disease remains the combination of: a positive history, the
presence of specific IgE antibodies, and demonstration that the symptoms are the result of IgE-mediated inflammation.
To avoid false-negative skin tests, short-acting antihistamines should be withheld for 36 to 48 hours and long-acting antihistamines
(ie, astemizole) for 4 to 6 weeks before skin tests are performed because antihistamines suppress skin testing results. The specifics of skin
testing are outlined in standard allergy textbooks. Skin tests with the appropriate allergens are mandatory in all patients prior to initiation of
immunotherapy with allergy extracts, and the intensity of the local wheal and flare skin reactions is a guide for determining the initial dose
of allergen.
Skin testing by the multiple serial dilution (end-point titration method) is not recommended by this author because multiple skin tests
increase the cost of evaluating the patient and the postulated more quantitative results have not been validated. Sublingual challenge with
allergen is not a useful diagnostic test for inhalant allergy, and so-called neutralization of allergy via sublingual drops of allergen has not been
substantiated. In vitro cytotoxic leukocyte test has not been documented as a useful laboratory test in controlled studies and is not
recommended.
Ingestant (Food) Allergy
The evaluation of the child who is suspected of having a food allergy can be fraught with unnecessary confusion because of misuse
of terms. It is important to define the clinical syndrome to enhance understanding of the medical problem. An adverse food reaction is a
generic term used to describe any untoward reaction following the ingestion of a food or food additive. Adverse food reactions can be
categorized into food allergy (food hypersensitivity) or food intolerance. A food allergy is an abnormal immunologic response. A food
intolerance is due to a nonimmunologic mechanism, such as toxins contained in the food, metabolic disorders (eg, disaccharidase
deficiencies), or idiosyncratic reactions. Lactose intolerance due to lactase deficiency, a common cause of cow milk intolerance, often is
mislabeled as milk allergy. In addition, patients may experience a nonimmune adverse reaction to a constituent in food, such as monosodium
gluconate added to food during processing, spices such as peppers (capsacian) added as flavoring during cooking, or preservatives. Although
food additives, such as coloring or preservatives, may induce urticaria and, rarely, systemic allergy, the hypothesis that they contribute to
behavior problems such as hyperactivity or other entities such as learning disabilities has never been substantiated in well-designed and
controlled studies.
Symptoms other than those of the gastrointestinal system can result from allergic reactions to food. Anaphylactic reactions, fatal
and near-fatal, have been reported both in children and adults. Anaphylactic shock associated with exercise following ingestion of certain
foods has been reported in individuals, even though neither food nor exercise alone induced anaphylaxis. Ingestion or contact with food is
a common cause of acute urticaria or angioedema. Chronic (>6 weeks' duration) urticaria secondary to food allergy is much less common.
Atopic dermatitis in infants and children commonly is associated with food allergy, especially from eggs, milk, wheat, peanuts, and fish.
Within 10 to 60 minutes after ingestion of a food allergen, some children may develop a pruritic, erythematous morbilliform rash. It has been
postulated that repeated ingestion of the offending allergen leads to continuation of the IgE inflammatory response, which provokes the
pruritus, scratching, and development of eczematous lesions of atopic dermatitis. Although not common, both upper and lower respiratory
tract symptoms also have been described secondary to food allergy; however, respiratory symptoms associated with food allergy in the
absence of gastrointestinal or skin symptoms is unusual.
Several gastrointestinal immune-mediated disorders have been described. Food-induced enterocolitis, generally associated with
ingestion of cow milk or soy-based formula, has its onset between 1 week and 3 months of age, with vomiting and diarrhea severe enough
to produce dehydration. Stools contain gross or occult blood and often are watery and positive for carbohydrate (reducing substances). When
diarrhea contains gross or occult blood only and pathology is limited to the distal bowel, the condition is defined as food-induced colitis. Both
syndromes improve within 72 hours of eliminating the allergen. Malabsorption syndromes have been described secondary to ingestion of
cow milk, soy-based products, egg, and wheat. These patients have patchy intestinal villous atrophy when biopsied. The more extensive
malabsorption enteropathy with total villous atrophy (often called celiac syndrome) is associated with sensitivity to gliadin, a component of
gluten. Allergic eosinophilic gastroenteropathy syndrome can affect children and presents with postprandial nausea, vomiting, abdominal
pain, diarrhea, and steatorrhea. Affected patients may have elevated serum IgE levels, positive skin tests, peripheral eosinophilia, iron
deficiency anemia, hypoalbuminemia, and a specific food allergy.
The natural history of food allergy in children varies from patient to patient, and food allergies are not always life-long. Studies have
shown loss of gastrointestinal food allergy in 1 to 3 years among one third of children, even though results of skin tests and RASTs may not
change. The likelihood of losing a food allergy depends on the food that provokes the symptoms and the degree to which the patient
maintains the allergen elimination diet. Allergy to peanuts, tree nuts, and fish and seafood appear to be more long-lasting than allergy to milk,
soy, and egg.
DIAGNOSTIC TESTS FOR FOOD HYPERSENSITIVITY
The evaluation for adverse food reactions begins by attempting to define whether the patient is suffering from a nonimmunologic
intolerance or from an immune reaction, which can be IgE- or nonIgE-mediated. The following must be established if possible: 1) the identity
and quantity of the food allergen suspected of provoking the reaction, 2) the time elapsed between the ingestion of the suspected food and
the onset of symptoms, 3) a complete description of the symptoms elicited and the duration of the reactions, 4) whether similar symptoms
have occurred in the past when the food was eaten and the therapeutic measures taken, and 5) whether other factors (eg, exercise) appear
necessary for symptoms to develop. Diet diaries sometimes are useful for the infant as an adjunct to the history; however, with the frequent
use of processed foods and prepackaged meals, this may be difficult in the older child and adolescent. Parents are asked to keep a
chronologic record of symptoms and foods ingested, generally for no longer than a week. The diary then is reviewed to correlate ingestion
of specific food with the development of symptoms.
An elimination diet can be used as a diagnostic and therapeutic test when the history suggests that certain foods may be provoking
the specific symptoms. Foods and all "hidden" sources of those foods suspected of inducing symptoms are eliminated from the patient's diet
for 1 to 2 weeks. In chronic disorders (such as atopic dermatitis or chronic diarrhea), additional factors may be contributing to symptoms.
Therefore, failure to resolve symptoms during the elimination period does not completely rule out a food hypersensitivity.
In cases in which food hypersensitivity or intolerance is suspected but no specific foods can be incriminated, a brief trial (ie, 2 to
4 weeks) of an oligoantigenic or elemental diet may be helpful. If symptoms persist unabated during that period, it is very unlikely that food
is a contributing factor. If symptoms appear to improve, further characterization of the sensitivity may be pursued by allergy skin tests or
serum IgE antibody tests. These should be performed prior to initiating the elimination diet because the presence or absence of food
allergen-specific IgE antibodies is useful for counseling patients. When compared with the double-blind, placebo-controlled oral food
challenge (described below), prick skin tests have been found to have excellent negative predictive accuracies for IgE-mediated food allergy
but poor positive predictive accuracies.
The major problem with skin testing for foods as well as with many serum IgE antibody tests for foods has been the lack of potent,
stable, and pure standardized allergen solutions. At times, a few food allergens produce false-positive reactions secondary to an irritating
effect on the skin. The results of food skin tests must be interpreted carefully because there may be a discrepancy between the production
of clinical symptoms and positive skin tests to foods.
In the practice setting, an open or single-blind oral food challenge may be used to screen for allergic reactions to food. However,
in cases in which multiple food allergies are diagnosed, positive responses should be confirmed by double-blind, placebo-controlled food
challenges (DBPCFCs). DBPCFCs are the gold standard for diagnosing food allergies and have been used successfully in both children and
adults for examining a variety of food-related complaints. The choice of foods used in DBPCFCs is based on history, skin test (or serum IgE
antibody) results, or foods suspected on the basis of elimination diets. DBPCFC testing should be performed by a specialist or an experienced
clinician; it is not a procedure suited for most primary care practices. (For details see Bock 1988 in Suggested Readings.)
Diagnosis of nonIgE-mediated food hypersensitivity such as malabsorption syndromes and eosinophilic gastroenteritis is facilitated
by endoscopy and intestinal biopsy prior to and after the child is placed on an elimination diet. In the malabsorption syndromes, villous
atrophy may be partial or complete and often is patchy. Consequently, multiple biopsies may be required to exclude this diagnosis, especially
in young children. IgA antigliadin and IgA antiendomysial antibodies can be measured to screen for celiac disease. However, this diagnosis
depends on demonstrating biopsy evidence of villous atrophy and inflammatory infiltrate while the patient is ingesting gluten, resolution of
biopsy findings after 6 to 12 weeks of gluten elimination, and recurrence of biopsy changes following reinstitution of gluten.
Food-induced enterocolitis and colitis syndromes may require an oral food challenge in the office or hospital. A positive challenge
will provoke occult or grossly apparent blood in the stools, an increase in stool neutrophils and eosinophils over baseline, and an increase
in the total peripheral blood neutrophil count of 3500 cells/mm³ over baseline at 6 to 8 hours after the challenge.
The diagnosis of food allergy requires a careful history, physical examination, selective skin or serum IgE antibody tests in cases
of suspected IgE-mediated disorders, appropriate exclusion diets, and sometimes blinded provocation challenges. At present, there is no
evidence of the diagnostic utility for the following assays: quantitation of food-specific serum IgG or IgG4 antibodies, serum food
antigen-antibody complex assays, cytotoxic food testing, tests of lymphocyte activation (proliferation, interleukin-2, or leukocyte inhibitory
factor studies), or sublingual or intracutaneous neutralization or provocation.
Once food allergy or hypersensitivity has been diagnosed definitively, the only proven form of therapy is strict elimination of the
offending food. This requires considerable time (and ideally a dietitian) to educate the patient on spotting all forms of "hidden foods" and
assuring a nutritionally sound diet. Teaching patients to read food labels is necessary to ensure good compliance with an elimination diet.
Patients who have IgE-mediated food allergies also must be prepared to treat accidental ingestions; this includes using injectable epinephrine
and oral liquid antihistamines. In addition, patients must be prepared to go to the nearest emergency facility for further treatment when
indicated.
The role of breastfeeding and food allergen avoidance in the prevention of atopy and food allergy remains controversial. However,
it appears that breastfeeding (especially when the mother avoids major allergens--milk, egg, peanut, fish--during lactation) and/or the use
of hydrolyzed infant formulas can prevent some atopic dermatitis and food allergy in high-risk infants, but whether it actually prevents
respiratory allergy is not yet clear.
Allergic illnesses have a significant impact that allergic diseases have on children's health and quality of life. Allergic diseases, including
asthma, are among the major causes of chronic illnesses in the United States, affecting approximately 50 million patients or as many as
one in five children. The economic impact is enormous; asthma alone is estimated to cost more than 6.2 billion dollars of health care
expenditures annually. Of all the chronic illnesses, allergic respiratory problems, including allergic asthma, is the most common cause of
school absenteeism. Even though allergic disease usually is not fatal, death can result as a consequence of allergic anaphylaxis related to
medication, food, or insect venom allergy or from a complication of asthma. Therefore, the pediatrician must be capable of diagnosing
allergic disease so as to institute appropriate management. This review will emphasize those clinical diagnostic features ascertained by
history and physical examination as well as the appropriate laboratory studies useful in the diagnosis of respiratory (inhalant) and
gastrointestinal (food) allergy.
General Features of Allergic Diseases
Allergic diseases are immunoglobulin E (IgE)-mediated immunologic illnesses that can affect any of the body's major organ systems
either individually or collectively. Typically, children are not born having allergies because maternal IgE normally does not cross the placenta.
In rare instances, neonates and young infants who apparently were sensitized in utero have been born with specific IgE to foods and had
allergic reactions to those foods. Development of an allergy requires a familial predisposition and repeat exposure to an allergen (antigen)
that provokes specific IgE antibody.
Epidemiologic surveys indicate that the familial trait for allergy is inherited as autosomal recessive. Whereas the frequency of
positive allergy skin tests is similar in boys and girls, asthma is twice as common in males as in females prior to adolescence, but it appears
equal in prevalence thereafter. A specific immune response gene has been identified for IgE antibody synthesis in rodents, but it has not yet
been demonstrated conclusively in humans. With the recent advances in molecular genetics, it is anticipated that the genetic basis of allergy
will be understood better in the near future.
Allergens sensitize by several potential routes and are categorized as inhalants, ingestants, injectants, and contactants (Table 1).
It is important for the physician to define the route by which any specific allergen provokes clinical allergy in individual patients.
Of the inhalant IgE-mediated allergies, allergic rhinitis is by far the most common, affecting approximately 15% of all children.
Asthma, of which 80% has an allergic inhalant basis, occurs in more than 5% of children. Gastrointestinal (ingestant) allergy typically is
associated with food allergy; however, ingestants also may provoke urticaria and atopic dermatitis and less often may trigger respiratory
symptoms. Anaphylaxis is a systemic generalized allergic response consisting of hypotension, urticaria, and angioedema as well as upper
and lower airway obstruction; it can be caused by severe allergic reactions to foods (ingestant), insect venom stings (injectant), or
medications (ingestant, injectant, or contactant).
Although incriminated anecdotally as the cause for hyperactivity, poor school performance, learning disabilities, or abnormal child
behavior, there are no definitive, appropriately controlled studies that document an IgE allergic etiology for these predominantly psychosocial
or educational problems. The possibility that overgrowth of a yeast such as Candida is important in the pathogenesis of allergy never has
been substantiated. The concept of such a candidal syndrome in the context of abnormal child behavior has no validity, and antifungal
therapy in the absence of overt clinical candidal infection should be discouraged.
Inhalant Allergy
Microscopic inhaled airborne allergens are responsible for most respiratory allergy (Table 2). In temperate climates, seasonal allergic
rhinitis is induced by tree pollens in the early spring, grass pollens in the late spring and early summer, and ragweed in the late summer and
early fall. Because of geographic differences in the US, clinicians must become familiar with the pollination patterns in their individual regions.
Hay fever is an inappropriate term for allergic rhinitis because these patients neither are allergic to hay nor have fever. Flowering vegetation,
such as roses and fruit blossoms, rarely cause allergy because these pollens are too heavy to become airborne; their germination is
facilitated by bees and other insects. Fungi (mold) spores may be important outdoor aeroallergens in humid climates throughout the year,
but their numbers decrease once there is significant frost in temperate climates. Fungi can be important indoor perennial allergens in damp
environments. In perennial allergic rhinitis, house dust, animals, and molds all may be significant indoor inhalant allergens. The principal
allergens in house dust are the cuticles and feces of the microscopic house dust mite Dermatophagoides. Animal allergens, such as
epidermal danders, salivary proteins, urinary proteins, feces, and feathers, especially from pets such as cats, dogs, and birds are important
because about 50% of households in the US have indoor animal pets. Food allergens are of lesser importance in the etiology of allergic
rhinitis but cannot be ignored, especially in young children. Patients can be sensitive to one or multiple allergens. Certain individuals react
to miniscule amounts of inhaled allergens, while others tolerate a large allergen dose before developing symptoms.
In addition to allergens, viral infections, aerosolized cosmetics, cigarette smoke, industrial fumes, and changes in temperature,
humidity, and barometric pressure contribute to exacerbation of both upper and lower respiratory tract symptoms in the allergic child.
Psychologic and social stresses also can enhance symptoms. The importance of these additional contributory factors varies greatly from
patient to patient but should not be ignored when evaluating any individual.
Symptoms of nasal allergy consist of frequent sneezing, nasal pruritus, watery rhinorrhea, and often, nasal obstruction. Patients
also may complain of red, itchy eyes as well as itchy throat and ears. If there is nasal obstruction, the patient will be a mouth breather and
snoring can be a bedtime symptom; smell and taste also may be lost. Increased symptoms frequently are noted with increased exposure
to the responsible allergen, such as after cutting grass or sleeping on a feather pillow.
When an allergic reaction develops, clear nasal secretions will be evident, and the nasal mucous membranes will become
edematous without much erythema. The mucosa appear boggy and blue-gray. With continued exposure to the allergen, the turbinates will
appear swollen and can obstruct the nasal airway. Conjunctival edema, itch, tearing, and hyperemia are frequent findings in patients who
have associated allergic conjunctivitis. Patients who have allergic rhinitis, particularly children who have significant nasal obstruction and
venous congestion, also may demonstrate edema and darkening of the tissues beneath the eyes. These so-called "shiners" are not
pathognomonic for allergic rhinitis because they also can be seen in patients who have chronic rhinitis and/or sinusitis. Thick, purulent
secretions indicate the presence of infection, including the possibility of sinusitis.
DIAGNOSTIC TESTS
Nonspecific Allergy Tests
Many pediatricians believe in the need for a screening test for allergy. Blood eosinophilia and total serum IgE levels have been
proposed as screening tests, but they have relatively low sensitivity and should be used selectively (Table 3). The nasal secretions or sputum
of patients who have a respiratory allergy contain increased numbers of eosinophils, which forms the basis of a useful nonspecific test,
although not one that will identify any specific allergen etiology. Eosinophilia may not be present in patients who have not been exposed to
allergens recently or who have a superimposed upper respiratory tract infection. Both systemic and inhaled steroids can reduce eosinophilia
in secretions significantly; antihistamines have no direct effect on eosinophils.
The usefulness of nasal eosinophilia as a diagnostic test depends in large part on the technique used to obtain the specimens to
prepare the slides for examination. Patients should expel nasal secretions onto wax paper or parafilm; secretions then are spread on a
microscope slide, stained, and eosinophils counted under a microscope. It is difficult to quantify nasal eosinophilia accurately, although a
finding of more than 3% eosinophils on stained smear of expelled nasal or bronchial secretions is considered increased. Because cotton or
nylon nasal swabs trap secretions, they are not recommended for collecting secretions, except in the young child who will not or cannot expel
secretions by blowing the nose. Peripheral blood eosinophilia is observed in allergic asthma but less commonly in allergic rhinitis. Blood
eosinophilia is more frequent in atopic dermatitis and other conditions, such as parasite infection.
Total serum IgE is elevated in about 60% of patients who have allergic asthma but only in 30% of those who have allergic rhinitis.
Unfortunately, commercial laboratories have promoted tests of total serum IgE excessively, but its usefulness in screening for allergy is
limited to positive tests only because more than 60% of patients who have nasal allergy will have normal levels of total serum IgE.
Specific Inhalant Allergy Tests
Laboratory confirmation of the presence of IgE antibodies to specific allergens such as dust mites, pollens, or animals is very helpful
in establishing a specific allergic diagnosis, especially if the history of exposure to a specific allergen is not clear-cut. It may be necessary
to test for specific allergens to convince the family and patient of an allergic diagnosis and to reinforce the importance of environmental
control.
Although skin testing might be performed in any child at any age, children less than 1 year of age may not mount a positive reaction.
Often, the child who has seasonal respiratory allergy will not manifest a positive test until after two seasons of exposure. Clinicians should
use allergens for skin testing selectively and employ only common allergens of potential clinical importance. The most useful allergens for
which to test in the child who has perennial inhalant allergy are house dust mites (Dermatophygoides), animal danders, and fungi (molds)
(Table 2). Allergens important in the diagnosis of seasonal allergic rhinitis are weeds, grasses, and tree pollens. These allergens vary not
only by season of year but by geographic distribution. Therefore, allergens used for skin testing must be individualized and should be selected
on the basis of prevalence in the local area and the home and school environment.
IgE antibody can be tested via two methods: in vivo skin testing and in vitro serum testing (Table 3). Their advantages and
disadvantages are outlined in Table 4. For most patients, skin tests that are performed properly offer the best available method for detecting
the presence of allergen-specific IgE. The prick, also called the puncture or epicutaneous skin test, is preferred; scratch testing has been
abandoned as too traumatic. If prick tests are negative and allergy is highly suspect, then intradermal testing, which is more sensitive, may
be employed. Skin tests are both 10% to 20% more sensitive and less expensive on a per test basis than are in vitro serum tests.
The in vitro serum tests employ specific antisera, and the allergen antibody reactions are amplified as a radioimmunoassay (RAST),
fluorescent immunoassay (FAST), or an enzyme-linked immunosorbent assay (ELISA). Each of these techniques is comparable when
performed properly. In vitro tests are acceptable substitutes for skin tests in the following circumstances: 1) The patient has abnormal skin,
such as dermatographism or extensive dermatitis, 2) The patient cannot or did not discontinue antihistamines or other interfering
medications, 3) The patient is very allergic by history, and anaphylaxis is a possible risk, and 4) The patient is noncompliant regarding skin
testing. The results of either skin tests or in vitro assays depend very much on the quality of the allergen and the competence with which the
test is performed.
Although the quality of allergens is improving, there is need for more and better standardization. Both skin testing and in vitro assays
have been criticized for lack of good quality control. Skin testing should not be an occasional test for the inexperienced and obviously never
should be delegated to an inadequately trained or unsupervised assistant. Board certified allergy and immunology specialists are best
qualified to correlate patient histories with tests results. Quality control also has been a major problem for in vitro serum IgE antibody tests.
Compulsory participation in quality control programs, such as that offered by the College of American Pathologists and mandated by the
Clinical Laboratory Improvement Act, eventually will lead to better quality and standardization of in vitro serum IgE tests.
Positive tests for allergen-specific IgE do not diagnose allergy; they only indicate the presence of IgE molecules that have a
particular immunologic specificity. Whether the specific IgE antibodies are responsible for clinically apparent disease must be determined
by a well-trained physician. The ultimate standard for the diagnosis of allergic disease remains the combination of: a positive history, the
presence of specific IgE antibodies, and demonstration that the symptoms are the result of IgE-mediated inflammation.
To avoid false-negative skin tests, short-acting antihistamines should be withheld for 36 to 48 hours and long-acting antihistamines
(ie, astemizole) for 4 to 6 weeks before skin tests are performed because antihistamines suppress skin testing results. The specifics of skin
testing are outlined in standard allergy textbooks. Skin tests with the appropriate allergens are mandatory in all patients prior to initiation of
immunotherapy with allergy extracts, and the intensity of the local wheal and flare skin reactions is a guide for determining the initial dose
of allergen.
Skin testing by the multiple serial dilution (end-point titration method) is not recommended by this author because multiple skin tests
increase the cost of evaluating the patient and the postulated more quantitative results have not been validated. Sublingual challenge with
allergen is not a useful diagnostic test for inhalant allergy, and so-called neutralization of allergy via sublingual drops of allergen has not been
substantiated. In vitro cytotoxic leukocyte test has not been documented as a useful laboratory test in controlled studies and is not
recommended.
Ingestant (Food) Allergy
The evaluation of the child who is suspected of having a food allergy can be fraught with unnecessary confusion because of misuse
of terms. It is important to define the clinical syndrome to enhance understanding of the medical problem. An adverse food reaction is a
generic term used to describe any untoward reaction following the ingestion of a food or food additive. Adverse food reactions can be
categorized into food allergy (food hypersensitivity) or food intolerance. A food allergy is an abnormal immunologic response. A food
intolerance is due to a nonimmunologic mechanism, such as toxins contained in the food, metabolic disorders (eg, disaccharidase
deficiencies), or idiosyncratic reactions. Lactose intolerance due to lactase deficiency, a common cause of cow milk intolerance, often is
mislabeled as milk allergy. In addition, patients may experience a nonimmune adverse reaction to a constituent in food, such as monosodium
gluconate added to food during processing, spices such as peppers (capsacian) added as flavoring during cooking, or preservatives. Although
food additives, such as coloring or preservatives, may induce urticaria and, rarely, systemic allergy, the hypothesis that they contribute to
behavior problems such as hyperactivity or other entities such as learning disabilities has never been substantiated in well-designed and
controlled studies.
Symptoms other than those of the gastrointestinal system can result from allergic reactions to food. Anaphylactic reactions, fatal
and near-fatal, have been reported both in children and adults. Anaphylactic shock associated with exercise following ingestion of certain
foods has been reported in individuals, even though neither food nor exercise alone induced anaphylaxis. Ingestion or contact with food is
a common cause of acute urticaria or angioedema. Chronic (>6 weeks' duration) urticaria secondary to food allergy is much less common.
Atopic dermatitis in infants and children commonly is associated with food allergy, especially from eggs, milk, wheat, peanuts, and fish.
Within 10 to 60 minutes after ingestion of a food allergen, some children may develop a pruritic, erythematous morbilliform rash. It has been
postulated that repeated ingestion of the offending allergen leads to continuation of the IgE inflammatory response, which provokes the
pruritus, scratching, and development of eczematous lesions of atopic dermatitis. Although not common, both upper and lower respiratory
tract symptoms also have been described secondary to food allergy; however, respiratory symptoms associated with food allergy in the
absence of gastrointestinal or skin symptoms is unusual.
Several gastrointestinal immune-mediated disorders have been described. Food-induced enterocolitis, generally associated with
ingestion of cow milk or soy-based formula, has its onset between 1 week and 3 months of age, with vomiting and diarrhea severe enough
to produce dehydration. Stools contain gross or occult blood and often are watery and positive for carbohydrate (reducing substances). When
diarrhea contains gross or occult blood only and pathology is limited to the distal bowel, the condition is defined as food-induced colitis. Both
syndromes improve within 72 hours of eliminating the allergen. Malabsorption syndromes have been described secondary to ingestion of
cow milk, soy-based products, egg, and wheat. These patients have patchy intestinal villous atrophy when biopsied. The more extensive
malabsorption enteropathy with total villous atrophy (often called celiac syndrome) is associated with sensitivity to gliadin, a component of
gluten. Allergic eosinophilic gastroenteropathy syndrome can affect children and presents with postprandial nausea, vomiting, abdominal
pain, diarrhea, and steatorrhea. Affected patients may have elevated serum IgE levels, positive skin tests, peripheral eosinophilia, iron
deficiency anemia, hypoalbuminemia, and a specific food allergy.
The natural history of food allergy in children varies from patient to patient, and food allergies are not always life-long. Studies have
shown loss of gastrointestinal food allergy in 1 to 3 years among one third of children, even though results of skin tests and RASTs may not
change. The likelihood of losing a food allergy depends on the food that provokes the symptoms and the degree to which the patient
maintains the allergen elimination diet. Allergy to peanuts, tree nuts, and fish and seafood appear to be more long-lasting than allergy to milk,
soy, and egg.
DIAGNOSTIC TESTS FOR FOOD HYPERSENSITIVITY
The evaluation for adverse food reactions begins by attempting to define whether the patient is suffering from a nonimmunologic
intolerance or from an immune reaction, which can be IgE- or nonIgE-mediated. The following must be established if possible: 1) the identity
and quantity of the food allergen suspected of provoking the reaction, 2) the time elapsed between the ingestion of the suspected food and
the onset of symptoms, 3) a complete description of the symptoms elicited and the duration of the reactions, 4) whether similar symptoms
have occurred in the past when the food was eaten and the therapeutic measures taken, and 5) whether other factors (eg, exercise) appear
necessary for symptoms to develop. Diet diaries sometimes are useful for the infant as an adjunct to the history; however, with the frequent
use of processed foods and prepackaged meals, this may be difficult in the older child and adolescent. Parents are asked to keep a
chronologic record of symptoms and foods ingested, generally for no longer than a week. The diary then is reviewed to correlate ingestion
of specific food with the development of symptoms.
An elimination diet can be used as a diagnostic and therapeutic test when the history suggests that certain foods may be provoking
the specific symptoms. Foods and all "hidden" sources of those foods suspected of inducing symptoms are eliminated from the patient's diet
for 1 to 2 weeks. In chronic disorders (such as atopic dermatitis or chronic diarrhea), additional factors may be contributing to symptoms.
Therefore, failure to resolve symptoms during the elimination period does not completely rule out a food hypersensitivity.
In cases in which food hypersensitivity or intolerance is suspected but no specific foods can be incriminated, a brief trial (ie, 2 to
4 weeks) of an oligoantigenic or elemental diet may be helpful. If symptoms persist unabated during that period, it is very unlikely that food
is a contributing factor. If symptoms appear to improve, further characterization of the sensitivity may be pursued by allergy skin tests or
serum IgE antibody tests. These should be performed prior to initiating the elimination diet because the presence or absence of food
allergen-specific IgE antibodies is useful for counseling patients. When compared with the double-blind, placebo-controlled oral food
challenge (described below), prick skin tests have been found to have excellent negative predictive accuracies for IgE-mediated food allergy
but poor positive predictive accuracies.
The major problem with skin testing for foods as well as with many serum IgE antibody tests for foods has been the lack of potent,
stable, and pure standardized allergen solutions. At times, a few food allergens produce false-positive reactions secondary to an irritating
effect on the skin. The results of food skin tests must be interpreted carefully because there may be a discrepancy between the production
of clinical symptoms and positive skin tests to foods.
In the practice setting, an open or single-blind oral food challenge may be used to screen for allergic reactions to food. However,
in cases in which multiple food allergies are diagnosed, positive responses should be confirmed by double-blind, placebo-controlled food
challenges (DBPCFCs). DBPCFCs are the gold standard for diagnosing food allergies and have been used successfully in both children and
adults for examining a variety of food-related complaints. The choice of foods used in DBPCFCs is based on history, skin test (or serum IgE
antibody) results, or foods suspected on the basis of elimination diets. DBPCFC testing should be performed by a specialist or an experienced
clinician; it is not a procedure suited for most primary care practices. (For details see Bock 1988 in Suggested Readings.)
Diagnosis of nonIgE-mediated food hypersensitivity such as malabsorption syndromes and eosinophilic gastroenteritis is facilitated
by endoscopy and intestinal biopsy prior to and after the child is placed on an elimination diet. In the malabsorption syndromes, villous
atrophy may be partial or complete and often is patchy. Consequently, multiple biopsies may be required to exclude this diagnosis, especially
in young children. IgA antigliadin and IgA antiendomysial antibodies can be measured to screen for celiac disease. However, this diagnosis
depends on demonstrating biopsy evidence of villous atrophy and inflammatory infiltrate while the patient is ingesting gluten, resolution of
biopsy findings after 6 to 12 weeks of gluten elimination, and recurrence of biopsy changes following reinstitution of gluten.
Food-induced enterocolitis and colitis syndromes may require an oral food challenge in the office or hospital. A positive challenge
will provoke occult or grossly apparent blood in the stools, an increase in stool neutrophils and eosinophils over baseline, and an increase
in the total peripheral blood neutrophil count of 3500 cells/mm³ over baseline at 6 to 8 hours after the challenge.
The diagnosis of food allergy requires a careful history, physical examination, selective skin or serum IgE antibody tests in cases
of suspected IgE-mediated disorders, appropriate exclusion diets, and sometimes blinded provocation challenges. At present, there is no
evidence of the diagnostic utility for the following assays: quantitation of food-specific serum IgG or IgG4 antibodies, serum food
antigen-antibody complex assays, cytotoxic food testing, tests of lymphocyte activation (proliferation, interleukin-2, or leukocyte inhibitory
factor studies), or sublingual or intracutaneous neutralization or provocation.
Once food allergy or hypersensitivity has been diagnosed definitively, the only proven form of therapy is strict elimination of the
offending food. This requires considerable time (and ideally a dietitian) to educate the patient on spotting all forms of "hidden foods" and
assuring a nutritionally sound diet. Teaching patients to read food labels is necessary to ensure good compliance with an elimination diet.
Patients who have IgE-mediated food allergies also must be prepared to treat accidental ingestions; this includes using injectable epinephrine
and oral liquid antihistamines. In addition, patients must be prepared to go to the nearest emergency facility for further treatment when
indicated.
The role of breastfeeding and food allergen avoidance in the prevention of atopy and food allergy remains controversial. However,
it appears that breastfeeding (especially when the mother avoids major allergens--milk, egg, peanut, fish--during lactation) and/or the use
of hydrolyzed infant formulas can prevent some atopic dermatitis and food allergy in high-risk infants, but whether it actually prevents
respiratory allergy is not yet clear.
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