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 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 ... 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