Keywords
Bartonella henselae - cat scratch disease - osteomyelitis
Introduction
Bartonella henselae, the causative agent of cat scratch disease (CSD), is one of the most common
causes of regional lymphadenitis in children, usually resulting in mild, self-limited
infection. However, cat scratch disease has a broad spectrum of presentations in healthy
children, including fever of unknown origin (with multiple hepatosplenic abscesses),
neuroretinitis, osteomyelitis, and encephalitis.[1 ],[2 ] Serologic testing usually confirms the diagnosis of Bartonella infections, but both false positive and false negative results have been reported.
New diagnostics, including nucleic acid amplification tests such as polymerase chain
reaction (PCR), have allowed confirmation of B. henselae infection in patients with
atypical manifestations.[3 ] In this report, we describe a 3-year-old female with a recent history of typical
CSD lymphadenitis who subsequently developed osteomyelitis of the skull, a very rarely
recognized complication of this infection.
Case Report
A 3-year-old Caucasian female who was recently diagnosed and treated for CSD presented
to the emergency department for a 2-week history of worsening scalp lump with redness.
The lesion was in the left frontal region. She did not have a fever or any other systemic
symptoms. Two weeks earlier, she finished a 5-day course of azithromycin for suspected
CSD lymphadenitis. At that time, she had presented with right side inguinal and preauricular
lumps, measuring 2 cm and 1 cm, respectively. Both lumps were tender and erythematous.
The patient had no significant medical history. Her growth and development were appropriate
for her age. Her immunizations were complete for her age. She lived with her parents
in Flint and had never traveled outside Michigan. The family had one dog and two kittens
at home. Her mother reported that the kittens scratched the patient frequently.
On admission, the patient was alert, interactive, and in no distress. She was afebrile,
and her vital signs were normal. Her examination was significant for a 4 cm × 4 cm
lump located in the left frontal area. There was mild erythema overlying the lesion,
but it was not tender. There was a small area of fluctuance at the center. A 1 cm
× 1 cm preauricular lymph node was palpable on the right. A 2 cm area of induration
and hyperpigmentation was noted in the right groin with no drainage. Skin examinations
showed no other lesions. Her abdominal examination revealed no organomegaly and the
remainder of the physical examination was normal.
The patient's white blood cell count was 5600/mm3, with 48% neutrophils, 44% lymphocytes,
5% monocytes, and 3% eosinophils. The hemoglobin was 9.6 g/dL, and the platelet count
was 389,000/mm3. Aspartate aminotransferase and alanine aminotransferase were 12 and
24 units/L, respectively. The C reactive protein was 3.5 mg/dl and the erythrocyte
sedimentation rate was 44 mm/h. Rapid plasma reagin and human immunodeficiency virus
antibody by enzyme-linked immunosorbent assay were negative. A tuberculin skin test
had 0 mm of induration. B. henselae immunoglobulin M and immunoglobulin G titers,
by indirect florescent antibodies, were elevated at 1:32 and 1:512, respectively.
Skull radiography revealed that a focal irregular lucency involving the left frontal
bone [Figure 1 ] and computed tomography of the head showed a focal soft-tissue lesion and a destructive
process affecting the adjacent bone in the left frontal region. Magnetic resonance
imaging of the head revealed septated scalp swelling with a destructive process involving
adjacent calvaria with intracranial extension [Figure 2 ]. Pediatric neurosurgery performed a left frontal craniotomy and described purulent
material on opening the skin, along with the erosion of the left frontal bone. Tissue
microscopic examination showed chronic granulomatous tissue. The examination of the
aspirate with a Warthin–Starry stain showed multiple clusters of organisms [Figure 3 ]. Aerobic, anaerobic, fungal, and mycobacterial culture were performed; a few colonies
of Staphylococcus epidermidis grew in aerobic culture (considered a contaminant),
and other cultures were negative. Finally, PCR from the skull abscess aspirate was
positive for Bartonella species. No further speciation was performed, and culture for Bartonella culture was not attempted. The patient received 6-week treatment course with azithromycin
and rifampin therapy with complete healing at the site of the infection.
Figure 1: Skull X-ray showing lytic lesion in the left frontal bone (original)
Figure 2: Septated scalp swelling measuring 5.5 cm × 2.4 cm × 1.7 cm within the left
frontal region with a destructive process involving adjacent calvarium (original)
Figure 3: Warthin stain showing clumps of rod-shaped organisms (original)
Discussion
Although rare, osteomyelitis is a known complication of CSD, with the vertebral column
and pelvic girdle being the most commonly reported sites.[4 ] Skull osteomyelitis has been reported previously as a complication of Bartonella infection, but is exceedingly rare. A literature review by Hajjaji et al . before 2007 found 47 reported cases of osteomyelitis due to B. henselae, with 4
of those involving the skull.[4 ] In this review, patients with Bartonella osteomyelitis usually had a subacute presentation with mild constitutional symptoms.
Fever was present in 78% as part of their initial presentation, and most cases involved
the axial skeleton.[4 ],[5 ] Since 2007, skull involvement was noted in just 1 of the 14 cases reported by Puri
et al .[5 ] The frontal bone, parietal bone, and mastoid bone have all been reported to be involved.[4 ],[5 ],[6 ] In addition, one other child presenting with lytic skull lesion involving the forehead
after having cervical nodal disease has been reported.[7 ] Overall, the clinical presentation of skull Bartonella osteomyelitis resembled that of Bartonella infection involving other bones. The skull infection had subacute or chronic course,
associated lymph node disease, and need for debridement.[7 ] Nevertheless, the reported long-term prognosis has been excellent, with complete
recovery.[4 ],[7 ] Similarly, our patient had complete healing and recovery, consistent with the good
outcome reported in other patients with Bartonella osteomyelitis.
The pathogenesis of Bartonella osteomyelitis is poorly understood, but both direct extension from infected lymph
nodes (contiguous infection) and distant infection (presumably from hematogenous or
lymphohematogenous spread) have been reported.[4 ],[5 ],[7 ] Eight of the 14 cases reported by Puri et al . tested positive for Bartonella by PCR at the site of the infection.[5 ] The hematogenous spread seems likely in our patient, who presented with inguinal
and R-sided preauricular adenopathy and later developed osteomyelitis of the left
frontal bone.
Spontaneous clinical improvement is expected in most cases of classical CSD. Thus,
it is not surprising that the review by Hajjaji et al . concluded that some cases of Bartonella osteomyelitis have resolved despite treatment with antibiotics lacking activity against
this organism.[4 ] On the other hand, the poor response to antibiotic treatment and the progression
despite treatment in other reported cases suggests that therapy must be individualized.[7 ] The role of antibiotic therapy of usually self-limited CSD in normal hosts is not
well defined, while the evidence for benefit in immunocompromised patients with Bartonella infection is much stronger. Antibiotics that are considered effective against CSD
include azithromycin, rifampin, ciprofloxacin, trimethoprim-sulfamethoxazole, and
parenteral gentamicin. In patients with a hepatosplenic CSD with prolonged fever,
rifampin therapy reportedly has been effective.[8 ] Gentamicin in combination with doxycycline is recommended as a treatment regimen
for endocarditis. For musculoskeletal disease, most cases are managed with a combination
of multiple courses of antibiotics and surgery. The optimal approach is yet to be
determined.[4 ],[7 ]
Conclusion
Our case highlights the importance of considering CSD in the differential of lytic
skull lesions. Although rare, CSD may cause lytic skull lesions, which poses a diagnostic
challenge, as immunologic, neoplastic, and other infectious etiologies must be ruled
out.
