Rheumatic Manifestations of Bartonella Infection in 2 Children MOHAMMAD J

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Case Report Rheumatic Manifestations of Bartonella Infection in 2 Children MOHAMMAD J. AL-MATAR, ROSS E. PETTY, DAVID A. CABRAL, LORI B. TUCKER, BANAFSHI PEYVANDI, JULIE PRENDIVILLE, JACK FORBES, ROBYN CAIRNS, and RALPH ROTHSTEIN

ABSTRACT. We describe 2 patients with very unusual rheumatological presentations presumably caused by Bartonella infection: one had myositis of proximal thigh muscles bilaterally, and the other had arthritis and skin nodules. Both patients had very high levels of antibody to Bartonella that decreased in association with clinical improvement. Bartonella infection should be considered in the differential diag- nosis of unusual myositis or arthritis in children. (J Rheumatol 2002;29:184–6)

Key Indexing Terms: MYOSITIS ARTHRITIS BARTONELLA

Infection with Bartonella species has a wide range of mani- was slightly increased at 9.86 IU/l (normal 4.51–9.16), and IgA was 2.1 IU/l festations in children including cat scratch disease (regional (normal 0.2–1.0). C3 was 0.11 g/l (normal 0.77–1.43) and C4 was 0.28 (normal 0.07–0.40). Antinuclear antibodies were present at a titer of 1:40, the anti- granulomatous lymphadenitis), bacillary angiomatosis, streptolysin O titer was 35 (normal < 200), and the anti-DNAase B titer was encephalitis, Parinaud’s oculoglandular syndrome, Trench 1:85 (normal). Urinalysis showed 50–100 erythrocytes and 5–10 leukocytes fever (Vincent’s angina), osteomyelitis, granulomatous per high power field. Routine cultures of urine, blood, and throat were nega- hepatitis, splenitis, pneumonitis, endocarditis, and fever of tive. Liver enzymes, electrolytes, HIV serology, cerebrospinal fluid analysis, unknown origin1-3. To our knowledge, there have been no radiographs of the legs and back, and a bone scan and bone marrow cytology were all normal. Computerized tomography (CT) of the abdomen and chest reports of myositis caused by Bartonella in immunocompe- revealed a small right pleural effusion. A skin biopsy showed intense histio- tent children, and very few reports of arthritis caused by this cytic inflammation. An excisional biopsy of one subcutaneous nodule showed organism in childhood. We describe 2 children in whom proliferative angiomatosis with features suggestive of intermediate behavior. Bartonella infection presented as rheumatological conditions: A lymph node biopsy showed a reactive appearance and the standard cultures one presented with skin nodules and arthritis and the second for bacteria, fungi, and tuberculosis were negative. Because hematuria and hypocomplementemia suggested acute poststrep- presented with bilateral proximal myositis of the lower limbs. tococcal glomerulonephritis, oral penicillin was given for 10 days. He subse- quently developed many more nodules over his trunk, face, fingers, scalp, and CASE REPORTS arms, but became afebrile. During the next month the nodules became small- Case 1. A 26-month-old healthy Caucasian boy was admitted to British er and he had no further skin desquamation. He developed cold induced Columbia’s Children’s Hospital with a 2 week history of low grade fever, Raynaud-like phenomenon in his fingers with pallor followed by erythema. fatigue, and a fine maculopapular truncal rash. On admission his temperature By the third month of his illness C3 and levels of immunoglobulins returned was 38°C and blood pressure 94/50. He had multiple firm, nontender, mobile to normal, and T and B lymphocyte quantification and their responses to mito- well defined cutaneous nodules over his knees, forearms, shins, elbows, and gens were normal. Serologic testing for Bartonella infection by immunofluo- scalp. They varied in size from 0.5 to 2.5 cm and some were erythematous. rescence assay showed an antibody titer of 1:2048 for both B. henselae and B. He had inguinal and antecubital lymphadenopathy, fine desquamation and quintana [serum for testing was forwarded by the Provincial Laboratory to erythema of his palms and soles, and mild hepatosplenomegaly. There was a the Centers for Disease Control (CDC) in Atlanta, Georgia]. Treatment with history of contact with kittens and rabbits. clarithromycin (20 mg/kg/day) was started. On the third day of treatment, he Initial blood tests showed leukocytosis (21 × 109/l) with a predominance became febrile (38.5°C), possibly representing a Jarish-Herxheimer reaction. of neutrophils. The erythrocyte sedimentation rate (ESR) was 47 mm/h, IgG One month after the initiation of antibiotic therapy, he developed acute arthritis of the right elbow and first, second, and third metatarsophalangeal joints. At this time he was afebrile, ESR was normal, and the urinalysis showed only From the Divisions of Rheumatology, Dermatology, Infectious and 2 WBC and 3 RBC per high power field. Naproxen (15 mg/kg/day) was Immunological Diseases, Departments of Pediatrics and Radiology, given. He continued to take clarithromycin for 3 months. At this time, 4 University of British Columbia at British Columbia’s Children’s Hospital, Vancouver, British Columbia, Canada. months after the initial testing, titers of antibodies to B. henselae and B. quintana fell to 1:512 and 1:128, respectively. The arthritis improved initially, and M. Al-Matar, MBBS, FAAP, Fellow; R. Petty, MD, PhD, FRCPC, Professor; D. Cabral, MBBS, FRCPC, Assistant Professor; L. Tucker naproxen was discontinued; however, it recurred in both elbows. At this time MD, FAAP, Associate Professor; B. Peyvandi, MD, Research Assistant; he was otherwise well except for the persistence of the Raynaud-like phe- J. Prendiville, MB, FRCPC, Associate Professor; J. Forbes, MBChB, nomenon. Radiographs of elbows revealed bilateral effusions and large shal- FRCPC, Associate Professor; R. Cairns, MD, FRCPC, Associate low erosions of the cortical surface of the olecranon (Figure 1). These find- Professor; R. Rothstein, MD, FRCPC, Professor. ings were confirmed on magnetic resonance images (MRI). Joint aspiration Address reprint requests to Dr. D. Cabral, British Columbia’s Children’s and synovial biopsy of the elbow were consistent with a nonspecific inflam- Hospital, 4480 Oak Street, Vancouver, BC V6H 3V4, Canada. matory synovitis, and cultures for Bartonella, tuberculosis, fungi, and bacte- Submitted April 23, 2001; revision accepted July 31, 2001. ria were negative. At this point, naproxen was restarted. There was no clini-

Personal non-commercial use only. The Journal of Rheumatology Copyright © 2002. All rights reserved. 184 The Journal of Rheumatology 2002; 29:1 Downloaded on September 26, 2021 from www.jrheum.org Figure 1. Patient 1: lateral radiograph of the right elbow shows a large joint effusion and extensive irregular erosions of the articular surface of the olecranon (arrowheads).

Figure 2. Patient 2: coronal fast spin echo fat saturation T2 weighted MR of the hips reveals bilateral changes of diffuse increased signal throughout the cal evidence of active arthritis 8 months later, and at last followup (18 months adductor muscles; changes are worse on the right. A small fluid collection after the symptom onset) radiographic findings had improved but not resolved (arrow) is present on the right. completely, and he had diminishing episodes of Raynaud’s phenomenon con- fined to his lower limbs. DISCUSSION Case 2. A previously well 12-year-old girl was hospitalized with a 2 week history of fever, fatigue, and severe left thigh pain worsening with movement. Bartonella henselae infection is most commonly associated There was no history of trauma or viral infection. The medical history and with cat scratch disease, but B. quintana is the other causative family history were noncontributory. She had no history of close contact with organism of bacillary angiomatosis1,3. The former syndrome is cats, but she had an apparently healthy dog at home. A bone scan and hip radi- very commonly associated with a scratch from young cats ograph were normal. The ESR at that time was 90 mm/h. On admission she infected with fleas, but this association is less frequent for was febrile (39°C) and had pain on movement of the left leg, difficulty walk- 1-3 ing, and bilateral weakness of the hip girdle musculature. MRI indicated patients with bacillary angiomatosis . Bacillary angiomato- inflammatory changes involving the adductor muscles bilaterally, more pro- sis occurs primarily in patients with the acquired immune nounced on the right. A small fluid collection (2 cm) was observed in the infe- deficiency syndrome but also in immunocompetent patients1,4. rior right adductor magnus muscle. She was treated for presumed pyomyosi- This syndrome commonly involves the skin, but other organ tis, initially with intravenous cefotaxime and cloxacillin and then oral systems may be involved1,5. cephalexin 500 mg tid for a total of 6 weeks. Naproxen was also given. She had brisk reflexes in the upper and lower extremities; a Gowers’ sign In children, although Bartonella infection is common, was present and her gait was broad based. There was tenderness of the poste- rheumatic manifestations are very rare. Arthritis related to rior thighs bilaterally, worse on the left. Bartonella infection has previously been reported in only 2 Initial laboratory investigations showed a WBC count of 7 × 109/l with a children. Hayem, et al described a girl 2.5 years of age with × normal differential, hemoglobin 106 g/l, platelet count 574 10 g/l, ESR 123 fever, rash, and recurrent brief arthritis of hips, ankles, and mm/h. The following tests gave normal or negative results: HIV antibody, Monospot, bacterial cultures of blood, stool, urine and cerebrospinal fluid knees mimicking systemic onset juvenile rheumatoid arthri- 6 (CSF), CK, urinalysis, CSF analysis, autoantibodies (rheumatoid factor, anti- tis . Carithers described a 17-year-old girl with multiple ery- nuclear antibodies, antineutrophil cytoplasmic antibodies), coagulation stud- thema nodosum lesions and painful ankle swelling that lasted ies including Factor VIII related antigen, immunoglobulin levels, and levels for 3 to 4 days2. It was not clear whether the ankle swelling of hepatic enzymes and angiotensin converting enzyme. Serologic tests represented edema related to the skin lesions or true arthritis. showed no evidence of infection with toxoplasmosis, coxsackie, or enterovirus. In adults, arthritis related to Bartonella may involve more She became afebrile within 14 days but had worsening muscle weakness. than one small or large joint. The arthritis may represent a pri- A second MRI revealed increased signals in both adductors and gracilis mus- mary infectious process, and one report describes arthritis cles, although the fluid collections on the right side had decreased (Figure 2). adjacent to osteomyelitis where granulomata have been iden- Pelvic CT showed no bone abnormality. tified7. It may also be a reactive arthritis, when the synovial Titers of antibody to B. henselae and B. quintana were both 1:512 by immunofluorescence antibody testing at the CDC in Atlanta. Three months histology may show nonspecific chronic inflammatory later titers to both organisms had returned to normal (< 1:64), and all symp- changes, and the arthritis may persist for several months after toms had resolved completely. the primary infection has been appropriately treated6,8,9. For

Personal non-commercial use only. The Journal of Rheumatology Copyright © 2002. All rights reserved. Al-Matar, et al: Bartonella infection 185 Downloaded on September 26, 2021 from www.jrheum.org our Patient 1, the clinical course, involvement of more than weeks depending on clinical response; however, longer cours- one joint, and synovial histology would be more typical of es or retreatment may be required if relapses occur1. Patient 1 reactive arthritis. Shallow erosions of the olecranon were pre- received antibiotics specifically directed at Bartonella, and sent in Patient 1, and such changes have been described pre- Patient 2 received broad spectrum antibiotic coverage at the viously8. Our patient and other reported cases were responsive time of the acute febrile presentation. It is not known what to treatment with nonsteroidal antiinflammatory drugs8,9. In role these antibiotics played in their recoveries. addition to arthritis, Patient 1 had bacillary angiomatosis (manifesting with skin nodules and possibly accounting for REFERENCES the Raynaud’s phenomenon) and features consistent with a 1. Adal KA, Cockerell CJ, Petri WA Jr. Cat scratch disease, bacillary postinfectious nephritis. angiomatosis, and other infections due to Rochalimaea. N Engl J Med 1994;330:1509-15. To our knowledge, myositis related to Bartonella infection 2. Carithers HA. Cat-scratch disease. An overview based on a study of has not previously been reported in an immunocompetent 1,200 patients. Am J Dis Child 1985;139:1124-33. patient. Fox and Gurtler10 reported a 12-year-old boy with a 3. American Academy of Pediatrics. 2000 Red Book: Report of the mass in the epitrochlear area mimicking a rhabdomyosarcoma Committee of Infectious Disease. 25th ed. 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J Rheumatol 1996;23:1263-5. include erythema nodosum2, leukocytoclastic vasculitis13, 7. Goddard NJ, Golding DN. Cat-scratch disease presenting with fever of unknown origin with myalgia14, and arthralgia13. arthropathy of the ankles. J Roy Soc Med 1989;82:499-500. Bartonella infection is increasingly and reliably diagnosed 8. Jendro MC, Weber G, Brabant T, Zeidler H, Wollenhaupt J. [Reactive arthritis after cat bite: a rare manifestation of cat scratch serologically by indirect fluorescence antibody tests in a ref- disease — case report and overview]. Z Rheumatol 1998; 3 erence laboratory such as the CDC . Enzyme immunoassays 57:159-63. that are more specific15 and highly sensitive polymerase chain 9. Arnold MM, McKenna F. Reactive arthritis in a patient with cat- reaction assays are not widely available3. When infected tis- scratch disease [letter]. Postgrad Med J 1994;70:147. sue is examined, Warthin-Starry silver impregnation stain may 10. Fox BC, Gurtler RA. 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In immunocompetent patients antibiotic therapy may be required for 2–4