and Mhamed Harif2
(1)
South African Medical Research Council, Cape Town, South Africa
(2)
Université Mohammed VI des Sciences de la Santé Cheikh Khalifa Hospital, Casablanca, Morocco
Keywords
NeutropeniaInfective markersC-reactive protein (CRP)Procalcitonin (PCT)Blood cultureTemperatureLumbar punctureAntibioticsIsolationAntifungal therapyCase Presentation
A 2-year-old boy known with acute lymphoblastic leukemia (ALL) , presented with a 1-day history of fever, 7 days after completing the induction phase of chemotherapy. His mother also reported lesions in his mouth and refusal to eat.
Findings on Examination
The patient appeared irritable and acutely ill.
Weight: 14 kg; Height: 85 cm.
Observations: temperature 38.7 °C, pulse rate 125/min, respiratory rate 33/min, oxygen saturation 98 % in room air.
Pallor was present and ulcers were seen on his tongue and buccal mucosa.
There was no lymphadenopathy, but petechiae were noted on his trunk and limbs; no active bleeding was present. He was mildly dehydrated.
Respiratory examination: except for mild tachypnea, no other abnormalities were noted.
Abdominal and neurological examinations were normal, except for the irritability.
What Is Your Initial Diagnosis Based on the Available Information?
A 2-year-old boy, post-ALL induction (expected to be neutropenic at this stage), with fever, mucositis, anemia, and most likely thrombocytopenia.
What Other Information (History, Clinical, or Other) Is Important to Obtain to Make a Complete Assessment ?
Does this patient have a central venous catheter (CVC) in situ?
Has he had exposure to someone with an infection and if so, which type of infection?
Any recent infection and antibiotic use, while receiving induction chemotherapy?
When was he discharged from hospital, i.e. could this be a hospital-acquired infection?
What medication is he currently taking?
What is his cardiovascular status: blood pressure , adequate peripheral circulation (capillary refill time, warm peripheries, pulse volume, etc.)?
Ask his mother for a recall of oral intake and urine output over the last 24 h.
Is he indeed neutropenic or not?
His full blood count showed the following:
WCC | Neutro | Lymph | Hb | Plt | Na | K | Urea | Creat | CRP |
|---|---|---|---|---|---|---|---|---|---|
1.9 | 0.43 | 1.0 | 7 | 19 | 138 | 3.8 | 9 | 55 | 255 |
What Is the Most Likely Diagnosis Now?
ALL post-induction phase
Febrile neutropenia
Pancytopenia
Mucositis
Mild dehydration with pre-renal failure picture on biochemistry
Which Special Investigations Should Be Performed in Cases of Febrile Neutropenia?
Full blood and differential count
Infective markers —C-reactive protein (CRP) or procalcitonin (PCT)
Blood cultures —peripheral and from central venous catheter
Urine dipstix—urine culture if clinically indicated or if dipstix abnormal
Urea, creatinine, and electrolytes
Blood cross-match (patient is pale, has a tachycardia and fever; so a transfusion may be indicated)
The following should be performed only if indicated by history or clinical examination :
Stool culture (MCS, viruses, and parasites)—if diarrhea or dysentery present
Chest X-ray—if signs of a lower respiratory tract infection
Lumbar puncture —if signs and/or symptoms of meningitis/encephalitis
Echocardiogram—if signs of infective endocarditis
How Is Neutropenia Classified and What Is the Definition of Febrile Neutropenia in Children?
For the diagnosis of febrile neutropenia, severe neutropenia needs to be present (Table 24.1).
Table 24.1
Classification of neutropenia
Mild
1–1.49 × 109/L
Moderate
0.5–0.99 × 109/L
Severe
<0.5 × 109/L
Fever :
There are several definitions of fever. The most common definitions used in febrile neutropenia are:
- 1.
A sustained temperature of ≥38 °C for at least 1 h duration more than once in 24 h, or a single oral temperature of >38.3 °C
- 2.
Two consecutive temperatures of ≥38 °C for 2 h or an oral temperature of ≥38.5 °C
What are the risk factors and pathophysiology of febrile neutropenia in children?
A functional immune system is made up of the innate and the humoral (or adaptive) immune systems. The innate system includes physical barriers (skin and mucosa), phagocytic cells, and cytokine responses, while the humoral (adaptive) component refers to the T-lymphocyte-mediated immune system, where specific pathogens are targeted. Both these systems are affected by the malignancy itself and/or the treatment.
Humoral (Adaptive) System
Besides causing reduced erythropoiesis and megakaryopoiesis, hematological malignancies and bone marrow infiltration caused by solid tumors, also result in reduced production of functional white blood cells (phagocytic cells and lymphocytes). Chemotherapeutic agents and radiotherapy cause further bone marrow suppression of all cell lines, aggravating the immune deficiency.
The resultant neutropenia leads to abnormal (inadequate) phagocytosis and the lymphopenia causes an abnormal pathogen-specific response (generated by T-lymphocytes) with an increased risk for viral and bacterial infections.
Innate System
Because chemotherapeutic agents act on all rapidly dividing cells, it results in impaired mucosal function and mucosal lesions, therefore, causing a breach in the mucosal barrier and increasing the risk of bacterial invasion. Overgrowth of intestinal flora further increases the risk of acquiring an infection.
The use of indwelling central venous catheters disrupts the skin and is a foreign body, therefore increasing the susceptibility to bacterial infections in particular.
Most children with cancer in developing countries are malnourished, which further reduces the immune function (both innate and humoral (adaptive) systems). Children with HIV infection are of course, also immune suppressed because of the presence of the virus.
The patient’s cardiovascular examination reveals good peripheral circulation with warm peripheries, a good capillary refill time of 2 s and a blood pressure of 110/65 mmHg.
Should he be admitted to hospital? (Motivate your answer).
Yes, all children with febrile neutropenia in developing countries should be admitted to hospital. Febrile neutropenia is a medical emergency with a high mortality rate if not managed appropriately.
This patient most likely has severe neutropenia after the ALL induction; he also has mucositis, thus the risk for infection is very high and empiric intravenous antibiotics should be initiated for febrile neutropenia. Since he has mild dehydration and his oral intake is reduced, he will also require intravenous fluids and/or nasogastric feeding .
In developed countries, some low-risk cases of febrile neutropenia are treated on an outpatient basis. This can only be done if appropriate monitoring can take place at home, if appropriate oral antibiotics are available, and the caregivers have transport to return to hospital should the child worsen.
Which Other Systemic Areas/Sites Should Specifically Be Examined and Why?
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