Bartonella Osteomyelitis of the Acetabulum: Case Report and Review of the Literature

Introduction

Bartonella henselae is the causative agent of cat scratch disease, usually presenting with regional lymphadenopathy, fever, and mild constitutional symptoms (Al-Rahawan et al. 2012). Osteomyelitis is an unusual manifestation of Bartonella, but should be considered when typical pathogens are not identified or the patient does not respond to standard therapies (Al-Rahawan et al. 2012). Most diagnoses of B. henselae infection are based upon serologic testing, but newer methods for Bartonella detection, such as PCR, are becoming more widely available (Johnson et al. 2003). Here, we describe a case of pediatric B. henselae osteomyelitis of the acetabulum with indeterminate serologic and positive PCR results. We also review the literature regarding pediatric osteomyelitis due to B. henselae.

Case

A previously healthy 3-year-old girl presented to the emergency department (ED) with a 2-week history of fever and loose stools, and a 5-day history of pain in her right leg and refusal to bear weight. She did not have any associated rash, and there was no history of trauma.

On initial presentation, her vital signs were temperature of 37.9°C, heart rate 105 beats/min, blood pressure 123/76 mmHg, and respiratory rate 20 breaths/min. On general physical exam, she appeared well but uncomfortable. She had no significant lymphadenopathy. She had full range of motion at the ankle, hip, and knee joints, and no localized joint swelling or tenderness. The initial workup was significant for a total white blood cell (WBC) count of 12.6×10³/mm³ (normal 4×10³/mm³ to 12×10³/mm³), hemoglobin of 12.6 grams/dL (normal 11.5–14.5 gm/dL), platelets of 619×10³/mm³ (normal 200×10³/mm³ to 400×10³/mm³), and erythrocyte sedimentation rate (ESR) of 90 mm/h (1–8 mm/h). Blood, urine, and stool cultures were obtained. X-rays of the ankle and the tibia/fibula were normal. The patient was discharged home from the ED after consultation with the Orthopedics Department. Her differential diagnosis included viral syndrome, transient synovitis, and early osteoarthritis. The patient was instructed to return if symptoms did not resolve.

The patient presented again in the ED 2 days later with progressive worsening of pain and refusal to bear weight, although fever had resolved. She had asthenia and significant pain with knee flexion and hip flexion. The remainder of her exam remained normal. All previous cultures were negative, and repeat investigations revealed WBC 9.0×10³/mm³, platelets 599×10³/mm³, ESR 71 mm/h, C-reactive protein 5.9 mg/dL (normal 0.068–8.2 mg/dL), and creatine phosphokinase 137 units/L (normal 20–128 units/L). Hip ultrasound revealed a small hip effusion; aspiration yielded serosanguineous fluid with no organisms on microscopy. She was admitted for suspicion of septic arthritis of the hip joint and started on medical therapy with broad-spectrum antibiotics (vancomycin and ceftriaxone), because surgical access to site of infection was relatively difficult. The patient continued to spike moderate- to high-grade fevers, refused to move her right leg, and had persistent elevation of inflammatory markers. She underwent magnetic resonance imaging (MRI) of the hip, which revealed an osteolytic lesion suggestive of focal osteomyelitis within the right acetabulum, as well as a 4-mm abscess within the bone. After irrigation and debridement, pathological examination of the surgical biopsy revealed granulomas. Purified protein derivative (PPD) for tuberculosis, B. henselae serum immunoglobulion M (IgM) and IgG (positive if ≥1:16 and 1:256, respectively), human immunodeficiency virus (HIV) testing, and Histoplasma urine and serum tests were performed, all of which were negative, as were all microbiologic cultures.

Further history revealed that the family had received a young kitten as a present about 3 weeks prior to onset of symptoms. The family had removed the kitten from the home after 3 weeks of contact because it was “always scratching” the patient. The biopsy specimen was sent to Associated Regional and University Pathologists (ARUP) Laboratories, a national reference laboratory, for qualitative Bartonella PCR. The PCR was positive for DNA specific to B. hensaelae. Additionally, Steiner staining of the tissue section demonstrated small numbers of short, plump bacilli, consistent with Bartonella spp.

The patient's antibiotic regimen was changed to rifampin and azithromycin. She responded well clinically and was discharged home on oral antibiotics to complete a 4-week course. Subsequent repeat Bartonella serologies remained indeterminate at 8 weeks after initial testing.

Discussion

B. henselae is a Gram-negative bacillus usually acquired from exposure to infected cats or kittens. Human infection most commonly manifests in immunocompetent hosts as regional lymphadenopathy, referred to as “cat scratch disease.” Although any organ system can be involved after bacteremia, osteomyelitis due to B. henselae is a rare presentation (American Academy of Pediatrics Committee on Infectious Diseases 2012). Most reports of Bartonella osteomyelitis involve vertebral sites, with only one previously reported pediatric case of osteomyelitis of the acetabulum (Solder et al. 1995).

A Medline search using the terms “Bartonella” and “osteomyelitis,” limited to human studies, English language, and pediatric patients, yielded 31 articles. In 2007, Hajjaji et al. (2007) reported 36 pediatric cases, and since then, an additional 13 cases of osteomyelitis due to B. henselae have been described, including ours. One case of Bartonella osteomyelitis of the acetabulum was reported by Krause et al. in 2000 in a 29-year-old adult male (Krause et al. 2000).

Table 1 lists the clinical features, diagnostic methodologies, and treatments used for the 13 B. henselae pediatric osteomyelitis cases since Hajjaji's 2007 review. On the basis of the aggregate data compiling Hajaji's article and Table 1, patients generally had a subacute presentation with mild constitutional symptoms. Seventy-eight percent had fever as part of their initial presentation, and 74% of cases involved the axial skeleton. Thirty-one percent were found to have an abscess contiguous with the site of bone involvement. Concomitant superficial lymphadenopathy was reported in only 59% of patients. For diagnosis, 95% of patients who had serologic studies performed had positive results. Multiple antimicrobials were employed for treatment, and no definitive regimen evolved as the most efficacious.

For our patient, initial empiric therapy was directed toward the most common etiologies of osteomyelitis in her age group. The diagnosis of B. henselae usually hinges upon serology by commercially available indirect fluorescence assay (IFA)-based testing, which is highly sensitive and specific (Zangwill et al. 1993, Dalton et al. 1995). ARUP Laboratories used IFA-based serologic testing for our patient. Positive IgM titers strongly indicate acute disease, but the production of IgM is usually very short-lived. This may explain the IgM response in our patient, because she was tested about 3 weeks after last contact. Furthermore, positive IgG titers represent active or recent Bartonella infection, but the sensitivity of the IgG assays is suboptimal, and the prevalence of positive serology in 4–6% of the population increases the false positivity rate.

For our patient, convalescent serologic studies did not show a significant rise in the titer, even 2 months after the initial presentation. There are a few case reports of less common species of Bartonella that cause cat scratch disease that do not lead to serologic cross reactivity with B. henselae antigen (Kordick et al. 1997, Margileth and Baehren 1998). There is a possibility that the primers/probes to amplify B. henselae DNA could also amplify other genetically closely related Bartonella spp. Another possibility is that our patient had a weak, but technically four-fold, increase in titers that was undetected by the assay available in the ARUP Laboratory at the time. Bartonella is a very fastidious organism to culture. Further typical histopathology findings of granulomas or plump bacilli on Warthin–Starry or similar silver staining (e.g., Steiner) may not be present during the initial inflammatory phase. Additional tests, including PCR-based assays, are now commercially available through multiple laboratories and can be even more sensitive than serologic studies (Matar et al. 1999, Sander et al. 1999, Murakami et al. 2002, Metzkor-Cotter et al. 2003). PCR of tissue is specific, but sensitivity again is variable, ranging from 40% to 70%. Timing of sample collection affects yield, with greater chance of negative PCR results in the first 6 weeks after exposure. Our patient's diagnosis was confirmed by PCR testing of the bone specimen.

Conclusions

In summary, B. henselae is a rare cause of pediatric osteomyelitis that should be considered in patients who have had cat exposure or who do not respond as expected to typical therapies for osteomyelitis. The diagnosis has historically rested upon serologic evidence of infection, but newer testing modalities such as PCR-based techniques may be more sensitive in cases with indeterminate or negative serology but strong clinical suspicion.