Pediatric emergency medicine trisk 1032

FIGURE 125.1 Approach to the evaluation of fever in the transplant patient. EKG,
electrocardiogram; US, ultrasound; CXR, chest radiograph; AXR, abdominal radiograph.

Clinical Considerations
Clinical Recognition
Fever in the posttransplant patient should prompt the emergency clinician to look
for infectious etiologies. The implications of a fever depend on the time since
transplant and the degree of immunosuppression. In children on minimal
immunosuppressive medications without an obvious source of fever and good
caregiver follow-up, no further workup may be indicated. Common etiologies of
fever are discussed below.
Otitis, Sinusitis, and Pharyngitis. As with immunocompetent children, head and
neck infections comprise a major percentage of the pathology seen in the
pediatric transplant population. One retrospective report found a 60% incidence
of such infections, including sinusitis, otitis media, and pharyngitis/tonsillitis.
Proper diagnosis is the cornerstone to successful management, and transplant
recipients should still be tested for routine organisms. Consideration should be
given to atypical or unusual pathogens especially in the face of a recurrent
infection, an infection of long duration or an infection with an unusual


presentation. Furthermore, posttransplant lymphoproliferative disorder (PTLD),
discussed below, can also present with malaise, fevers, lymphadenopathy, and
tonsillar enlargement.
Gastrointestinal Infections. Transplant recipients presenting with simple diarrhea
or vomiting may be managed conservatively with hydration and observation.
They are at risk for renal insufficiency in the face of dehydration with ongoing
CNI therapy. Furthermore, alterations in absorption of immunosuppressant
medications can increase risk for rejection and graft loss. For prolonged
gastrointestinal illnesses, one must consider parasitic infections including
Cryptosporidium parvum or Giardia lamblia , and viral infections, especially

CMV. Transplant recipients having recurrent or prolonged gastroenteritis with
diarrhea should be tested for Clostridium difficile , which may prove to be
indolent and difficult to clear, and may not be related to prior antibiotic use. In
liver transplant patients, fever and ascites should warrant concern for spontaneous
bacterial peritonitis.
Respiratory Infections. Respiratory infections may be more severe in
posttransplant patients. Respiratory viral panels should be used to evaluate for
treatable viral infections such as influenza. It is unclear how effective these types
of drugs are in reducing disease severity in the posttransplant population. Simple
viral infections, such as rhinovirus, may cause lower as well as upper respiratory
disease and require inpatient management. Clearance of these viruses may take
many weeks and may prove challenging to treat. Chest radiographs are helpful if
pneumonia or lower respiratory tract infection is suspected.
Opportunistic Infections. During the early posttransplant period, recipients
typically receive prophylaxis for oral candidiasis, Pneumocystis jirovecii
(formerly Pneumocystis carinii ) pneumonia, as well as CMV and EBV.
Morbidity and mortality from invasive fungal infections are highest in the first 6
months post transplant, especially in patients who have had prior surgery or who
are more debilitated and requiring support. Patients may present after hospital
discharge, so any fevers, lingering illnesses, or concerning findings must be
investigated. In a multicenter registry analysis, invasive fungal infections made
up nearly 7% of the total number of posttransplant infections; 90% of the yeast
infections were due to Candida species and 82% of the mold infections were due
to Aspergillus species.
Herpes zoster can occur in posttransplant pediatric recipients, and may present
with neuralgia as a presenting symptom. This can be progressive and


incapacitating, with internal lesions as well as external. Generally, this disease
requires admission and treatment with intravenous acyclovir until the lesions are

crusted over. Varicella naïve patients may present to the ED after exposure and
varicella immune globulin should be given if the time interval is favorable.
Triage Considerations
Transplant recipients presenting with infectious symptoms and fever should be
seen and evaluated quickly as prompt diagnosis and treatment can mitigate
disease progression and obviate a potentially lethal situation. Vital signs and
perfusion should be checked to monitor for signs of compensated and
decompensated shock. Assessment of hydration status and treatment of
hypovolemia is crucial. Antipyresis with acetaminophen and topical cooling will
aid in patient comfort. Notably, NSAIDs should not be used as they limit renal
perfusion. In combination with CNIs, and especially in the face of hypovolemia,
they can cause acute renal failure. Direct and early communication with the
transplant team is essential in obtaining necessary historical input and direction
regarding potential sources and therapies.
Clinical Assessment
Given the many potential causes for fever in the posttransplant patient, a
comprehensive history and physical examination must be performed. History
should focus on sick contacts as well as obtaining a detailed posttransplant history
including time since transplant, type and dose of immunosuppression, and any
prior infectious exposures such as CMV and EBV. Conditions that impair the
patient’s ability to take or absorb medications such as vomiting or diarrhea should
be noted.
A comprehensive examination for source of fever is required on every patient
regardless of chief complaint. Detailed ENT, pulmonary, cardiovascular, and
abdominal examinations should all be performed. Abdominal examinations
should include an assessment for hepatosplenomegaly and other signs of liver
involvement such as jaundice or ascites.
Management
Screening labs should include complete blood count (CBC), electrolytes, liver
function tests (LFTs), blood culture, urinalysis, and urine culture. Knowledge of a

patient’s baseline laboratory values is useful for comparison. Neutropenia should
prompt assessment for other infectious etiologies such as fungal or viral
infections. Depending on recipient exposure and risk factors, EBV and CMV


titers should also be obtained. For patients on CNIs, a trough level should be
obtained as these medication levels may fluctuate during an infection. Other
diagnostic testing to consider will be guided by the clinical presentation and may
include inflammatory markers, viral panels, or stool cultures. In the child with
fever and ascites, spontaneous bacterial peritonitis should be considered, and
workup may require a diagnostic paracentesis with ascites fluid sent for culture,
Gram stain, cell count, LDH, glucose, and protein.
If the patient is obviously septic or meningitic, blood cultures should be drawn
and broad-spectrum antibiotics administered expeditiously. Headache, seizures, or
neurologic changes in the setting of a fever are indications for a lumbar puncture
with cerebrospinal fluid cell count, as well as comprehensive stains and culture
for bacteria, viruses, fungi, and acid-fast organisms, to be performed as part of the
primary evaluation.
For liver transplant patients, in addition to laboratory assessment, an ultrasound
examination with Doppler flow should be obtained to view arterial and venous
blood flow to the graft and to assess the biliary tree for evidence of dilation,
which suggests obstruction. If obstruction is suspected from the ultrasound
evaluation, percutaneous transhepatic cholangiography (PTC) is usually
necessary to image the biliary tree and biliary-enteric anastomosis. Prior to the
PTC, the patient is given broad-spectrum antibiotic coverage for the common
biliary pathogens (e.g., gram-negative enteric organisms). Ampicillin (200
mg/kg/day) and ceftazidime (100 mg/kg/day) are usually adequate. If the
ultrasound evaluation is abnormal (i.e., demonstrating a fluid collection), the
situation could require surgical revision of the biliary anastomosis or biliary stent
placement either by an interventional radiologist or by open procedure by a

transplant surgeon. If the ultrasound evaluation is normal and no source for the
fever or increased LFTs are found, the patient may require admission for
monitoring and possibly a liver biopsy to rule out rejection or viral infection.
For intestinal transplant patients, infectious complications are the leading cause
of posttransplant mortality. Intra-abdominal infections or sepsis from gut
translocation must be considered in these patients in the setting of fever.
For the majority of uncomplicated infections, the typical course of standard
antibiotics should be sufficient. However, many antibiotics interfere with
metabolism or excretion of CNIs. A list of common interactions is shown in
Table 125.1 . Initiating an antibiotic should be cleared first with the treating
transplant team, as they will likely want to manage follow-up and drug levels
while on the additional medication.