Fever - Case 11-1: 18-Month-Old Girl
Fever - Case 11-1: 18-Month-Old Girl: Excerpt from Pediatric Complaints and Diagnostic Dilemmas
I. History of Present Illness
An 18-month-old girl presented with a 1-day history of fever to 38.0°C and cough. While in the examination room, she had tonic flexion of her upper
extremities and eye deviation to the left. This episode lasted 10 minutes and
resolved spontaneously. Mild perioral cyanosis developed just before the end of
the seizure. Afterward, the child was tired and irritable. There was no history
of rash, eye pain, neck pain, or emesis. There were no alterations in gait or
balance. There was no antecedent witnessed trauma. The only pet was a recently
acquired goldfish. Several children at her daycare center had had symptoms of
upper respiratory tract infection. The remainder of the review of systems was
unremarkable.
II. Past Medical History
She was born at term after an uncomplicated pregnancy. She had not previously
required hospitalization. Her immunizations were up to date and included the
pneumococcal conjugate vaccine. She had received supplemental iron starting at
12 months of age for treatment of
“anemia.” The maternal grandmother had type 2 diabetes treated with glyburide, a
sulfonylurea oral hypoglycemic agent. There was no family history of febrile
seizures, but one relative supposedly had a seizure and drowned while swimming.
The family was not able to provide further details.
III. Physical Examination
T, 39.1°C; RR, 26/min; HR, 132 bpm; BP, 97/53 mm Hg; SpO2, 98% in room air
Weight, 25th percentile
The child was crying and seemed mildly disoriented. There were no bruises or
abrasions on her face or scalp. Her tympanic membranes were mildly erythematous
but mobile. There was copious purulent nasal discharge. The neck was difficult
to assess due to the child
's lack of cooperation. While yelling and screaming, she was able to arch her
back and neck without apparent limitation. There was no cervical
lymphadenopathy. The heart and lung sounds were normal. The abdomen was soft
without organomegaly. There were no focal neurologic deficits, but the child
appeared groggy and irritable and was slow to respond to her mother
's voice. Several hyperpigmented macules were noted on her skin as her clothes
were removed for the lumbar puncture (Fig. 11-1).
IV. Diagnostic Studies
A complete blood count revealed the following: 15,500 white blood cells
(WBCs)/mm
3 (61% segmented neutrophils, 22% lymphocytes, 15% monocytes, and 2%
eosinophils); hemoglobin, 12.1 g/dL; and 282,000 platelets/mm
3. Serum electrolytes, calcium, and glucose were normal. Urinalysis revealed no
WBCs or nitrites. Lumbar puncture revealed 2 WBCs and 19 red blood cells per
cubic millimeter. No bacteria were visualized on Gram staining. The
cerebrospinal fluid (CSF) protein and glucose concentrations were normal. Blood
and CSF cultures were subsequently negative.
V. Course of Illness
The skin findings (Fig. 11-1) suggested a diagnosis that was subsequently
confirmed with further evaluation.
Discussion: Case 11-1
I. Differential Diagnosis
This child presented with fever and seizures. Given her age and the difficult
examination, a lumbar puncture was performed to exclude meningitis as a cause
of seizures. The reassuring CSF findings led to other diagnostic
considerations. The maternal grandmother used an oral hypoglycemic agent,
making an ingestion-induced hypoglycemic seizure possible. However, the child
's serum glucose concentration was normal. The history of a cousin drowning
during a reported seizure raised the possibility of a cardiac condition such as
prolonged QT syndrome, Wolff-Parkinson-White syndrome, or hypertrophic
cardiomyopathy as a possible cause of hypoxic seizures. The electrocardiogram,
performed in light of this history, was normal.
In an 18-month-old girl who presents with a brief (less than 10-minute) seizure
in the context of fever, typical febrile seizure is the most likely diagnosis.
However, it is possible that the fever lowered the seizure threshold in a child
with an underlying seizure disorder. Potentially important clues in this case
were the hyperpigmented macules on this child
's skin. Café-au-lait spots are characteristic for neurofibromatosis type 1 (NF1) but may
also be noted in unaffected children and in children with other disorders. The
critical factor in this case was the number of spots seen; fewer than 0.1% of
normal individuals have more than six caf
é-au-lait spots. Inherited disorders associated with café-au-lait spots are summarized in Table 11-2.
II. Diagnosis
Examination of the skin revealed approximately 15 hyperpigmented macules
substantially greater than 5 mm in diameter (Fig. 11-1). Axillary freckling was
also noted on physical examination. An ophthalmology examination revealed
findings suspicious for an optic glioma.
These findings confirmed the diagnosis of neurofibromatosis type 1. As is common in children with NF1, this child's seizures were not related to a structural lesion in the brain. This child's febrile seizures were likely related to her NF1, but the relationship among
seizure type, presence or absence of brain lesions, and evolution of epilepsy
in children with NF1 is not clear.
III. Epidemiology and Incidence
NF1 and NF2 are genetic disorders in which affected patients develop both benign
and malignant tumors at increased frequency. NF1 is associated with cutaneous
lesions, vision loss, and skeletal problems; cataract formation and hearing
loss are more typically associated with NF2. NF1, also known as von
Recklinghausen
's neurofibromatosis or peripheral neurofibromatosis, is an autosomal dominant
condition. Half of the cases occur in patients with a family history of NF1,
and the other half occur as spontaneous mutations. The incidence is
approximately 1 in 3,000. The clinical manifestations of NF1 result from
alterations of the NF1 gene located on chromosome 17. The gene product, termed
neurofibromin, is thought to function as a tumor suppressor, but research is
still ongoing.
IV. Clinical Presentation
Despite advances in our understanding of the molecular basis for NF1, the
diagnosis remains one that is largely based on clinical criteria. Clinical
diagnosis of NF1 requires the presence of at least two of the seven consensus
criteria stipulated by the National Institutes of Health (NIH) (Table 11-3).
Children with sporadic rather than inherited cases may not meet the NIH
diagnostic criteria until later in life. At 1 year of age, approximately 50% of
individuals with sporadic disease lack two or more of the cardinal clinical
features permitting diagnosis, but by age 8 years, 95% meet NIH criteria.
The most visible features of NF1 are flat, evenly pigmented macules known as café-au-lait spots. These macules, often present at birth, increase in both number
and size over the first few years of life. One or two caf
é-au-lait macules are present in up to 25% of the normal population, but the
presence of six or more macules should raise suspicion for NF1. These macules
are easier to visualize with the use of a Wood
's lamp. Skinfold freckling, another pigmentary change associated with NF1,
usually occurs in the axillae, groin, nape of the neck, or under the chin. By 6
years of age, approximately 80% of children with NF1 demonstrate axillary or
inguinal freckling.
Lisch nodules are benign pigmented hamartomas of the iris that occur in patients
with NF1. These nodules do not interfere with vision. Lisch nodules may not be
apparent in young children, but they are present in more than 95% of adolescent
and adult patients. Detection of Lisch nodules on bedside examination is
challenging, and diagnosis frequently requires a slit-lamp examination by an
experienced ophthalmologist. In contrast to Lisch nodules, optic nerve tumors,
such as optic nerve gliomas, occur primarily in younger children. They are
often associated with asymmetric, noncorrectable vision loss, diminished
peripheral vision and color discrimination, and proptosis.
Subcutaneous or cutaneous (dermal) neurofibromas are rarely seen in young
children but appear during or just before adolescence. Neurofibromas are
present in 48% of 10-year-old patients and 84% of 20-year-old patients.
Cutaneous lesions frequently begin as small papules on the face, scalp, trunk,
and extremities. Deep lesions may be detected only through palpation. These
lesions represent a major cosmetic problem but do not transform into malignant
tumors. In contrast, plexiform neurofibromas surround soft tissue and bone,
causing aberrant growth. Plexiform neurofibromas, present in 30% of patients,
are locally invasive and may undergo malignant transformation. They may be
accompanied by overlying hyperpigmentation or hypertrichosis. Other tumors that
occur with higher frequency in patients with NF1 include pheochromocytomas,
juvenile chronic myeloid leukemia, and rhabdomyosarcomas.
Seizures occur in approximately 4% to 5% of patients with NF1. Seizures may be
generalized or partial. In a study by Korf et al., 22 of 359 NF1 patients
developed seizures. The seizures were most often characterized as
complex-partial (9 patients), febrile (6 patients), or generalized epilepsy (3
patients). Other manifestations of NF1 include learning disabilities, pain,
scoliosis, headaches, stroke, and bowel or bladder complications (secondary to
pelvic plexiform neurofibromas).
V. Diagnostic Approach
NF1 is diagnosed by the presence of the clinical features mentioned previously.
Evaluation should focus on symptoms associated with NF1, such as neurocognitive
deficits, visual complaints, progressive neurologic deficits, altered bowel or
bladder function, weakness, seizures, and headaches. Other medical
complications associated with NF1 include hypertension, short stature, and
precocious puberty. Once the diagnosis is made, the following strategies may be
used.
Orthopedic referral. Tibial dysplasia appears at birth with anterolateral bowing of the lower leg.
The presence of tibial bowing should prompt referral to an orthopedic surgeon
who is familiar with the management of orthopedic problems in children with
NF1.
Ophthalmologic referral. Symptomatic optic gliomas are diagnosed during the first year of life in 1% of
NF1 patients, although they typically develop between 4 and 6 years of age.
They are ultimately present in 15% of patients with NF1 and cause symptoms in
2% to 5% of cases. An annual vision evaluation by an experienced
ophthalmologist is part of the routine follow-up for children with NF1.
Head magnetic resonance imaging (MRI). Routine presymptomatic screening for central nervous system tumors is not necessary. However, any evidence of optic nerve dysfunction, seizures, or
neurologic abnormalities warrants neuroimaging with special attention to the
orbits.
Other radiology studies. Plain radiographs may detect a variety of bony abnormalities. They should be
ordered if the clinical findings suggest bony erosion secondary to an adjacent
plexiform neurofibroma, scoliosis, or bone pain.
Genetic evaluation. Families who have a child with NF1 may benefit from genetic counseling. A
protein truncation assay is available in some settings to genetically confirm
the diagnosis. However, this test detects the abnormality in at most 65% of
patients with a clear clinical diagnosis of NF1, making it less useful
diagnostically. Linkage analysis may be used to track the NF1 gene through
generations of affected family members, allowing prenatal diagnosis in some
situations.
Other studies. Children with NF1 should be monitored for blood pressure elevations associated
with renal artery stenosis or pheochromocytomas. Approximately 6% of patients
with NF1 develop hypertension, and a secondary cause (e.g., renal artery
stenosis) is identified in one third of cases. Learning disabilities are seen
in 40% to 60% of children with NF1. Children should undergo evaluation for
cognitive and motor function, with prompt referral or intervention as required.
Plexiform neurofibromas grow in early childhood, are difficult to remove, and
tend to regrow. A multidisciplinary team that includes the primary pediatrician
as well as surgeons, radiologists, and oncologists should manage these
neurofibromas.
VI. Treatment
No specific therapy is currently available. In the future, targeted therapies
for NF1-associated tumors may be designed to inhibit growth-promoting pathways
activated in the absence of neurofibromin. Other potential therapies focus on
blockade of angiogenic factors that could potentially decrease tumor growth.
Routine office visits should focus on detection and management of complications,
as discussed previously. Annual ophthalmologic examinations are important to
detect optic nerve lesions. Interval history should focus on subtle sensory or
motor symptoms such as paresthesia or muscle atrophy. Pediatricians should also
inquire about incontinence, given the risk of spinal cord neurofibromas.
Consultation with specific surgical specialists is warranted based on the
location of neurofibromas. Laser treatment has not yet proved successful in
permanently removing caf
é-au-lait spots.
VII. References
1. Gutmann DH, Aylsworth A, Carey J, et al. The diagnostic evaluation and
multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2.
JAMA 1997;278:51–57.
2. DeBella K, Szudek J, Friedman JM. Use of the National Institutes of Health
criteria for diagnosis of neurofibromatosis 1 in children.
Pediatrics 2000;105:608–614.
3. Jones KL. Smith's recognizable patterns of human malformation, 5th ed. Philadelphia: WB Saunders, 1997.
4. Korf BR, Carrazana E, Holmes GL. Patterns of seizures observed in
association with neurofibromatosis 1.
Epilepsia 1993:34;616–620.
5. Listernick R, Darling C, Greenwald M, et al. Optic pathway tumors in
children: the effect of neurofibromatosis 1 on clinical manifestations and
natural history.
J Pediatr 1995;127:718–722.
6. Lynch TM, Gutmann DH. Neurofibromatosis 1. Neurol Clin 2002;20:841–865.
7. Reynolds RM, Browning GGP, Nawroz I, et al. Von Recklinghausen's neurofibromatosis: neurofibromatosis type 1. Lancet 2003;361:1552–1554.
8. Riccardi VM, Eichner JE. Neurofibromatosis: past, present, and future. N Engl J Med 1991;324:1283–1285.
9. Tekin M, Bodurtha JN, Riccardi VM. Café au lait spots: the pediatrician's perspective. Pediatr Rev 2001;22:82–90.
Pictures
Book Source Details
- Book Title: Pediatric Complaints and Diagnostic Dilemmas
- Author(s): Samir S Shah MD; Stephen Ludwig MD
- Year of Publication: 2003
- Copyright Details: Pediatric Complaints and Diagnostic Dilemmas, Copyright © 2003 Lippincott Williams & Wilkins.
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