Salmonella Typhi Osteomyelitis
of the Humerus in a normal child:
a case report and review of the literature

L.G. PAPADOPOULOS, D.V. PETRATOS, L.D. ZACHARIADOU, G.S. MATSINOS
Athens Children’s Hospital "Agia Sofia" 2nd Orthopaedic Department.

ABSTRACT
We report a case of Salmonella typhi osteomyelitis of the distal humerus accompanied by septic arthritis of the adjacent elbow joint in a 3½-year-old boy. No underlying medical condition predisposed the child to Salmonella osteomyelitis. The clinical course was prolonged before definitive diagnosis that was performed 6-7 weeks from the onset of symptoms. Salmonella typhi was isolated from the synovial fluid cultures. Operative treatment was followed by a 2 ½-month antibiotic therapy. At 11-year follow-up the child had full function of the elbow and normal radiological appearance of the area except a slight broadening with no signs of recurrence.

INTRODUCTION
Salmonella osteomyelitis is an uncommon condition typically associated with hemoglobinopathies[13,17,29] or other underlying diseases. It has been reported in patients with malignancy[2,8,17], liver disease or alcoholism[8,17], diabetes mellitus[8], previous surgery or trauma[31,36] and also in advanced or very young age[8]. Typically presenting with pain and swelling it has also been reported to resemble a bone tumor[7] as well as a skeletal manifestation of Hodgkin’s disease[2]. Though several recent reports have presented Salmonella osteomyelitis in otherwise healthy patients with no history of underlying disease or immunosupression[4,9,33,34,37], osteomyelitis caused by Salmonella typhi (S. typhi) in nonsickle-cell children is a rare event.
The authors present a case of a 3½-year-old boy with Salmonella osteomyelitis of the distal humerus accompanied by septic arthritis of the adjacent elbow joint.

1.
Figure 1. Plain radiographs of the elbow (34 days from the onset of symptoms) showing mild lytic lesion of the distal humeral metaphysis.

2.
Figure 2. Plain radiographs of the elbow (41 days from the onset of symptoms)
showing clearly the lytic lesion of the distal humeral metaphysis and the periosteal reaction.

3A. 3B.
Figure 3 A,B. Plain radiograph of the elbow, 2½ months postoperatively, showing the
dissapearance of the distal humeral condyle which lasted 1½ year. Ultrasound of the
area reveals the existence of the condyle at the same time.

CASE REPORT
A 3½-year-old boy presented to our hospital with a 20-day history of swelling of his right elbow. No history of trauma of the affected area was reported.
Forty days before admission the child had fever up to 40.5[0]C. After 5-day treating with antipyretic agents given by his parents he was examined by a pediatrician who diagnosed tonsillitis and supplied oral ampicillin for two days followed by oral penicillin which was stopped because of a fungal infection of the mouth three days later.
Fourteen days after the onset of symptoms the child continued to have fever and was evaluated at a private clinic. Laboratory examination revealed a white blood cell (WBC) count of 8600/mm3, an erythrocyte sedimentation rate (ESR) of 14/h and a raised C-reactive protein (CRP). Serology for Brucella was negative whilst Widal agglutination test was positive for S. typhi (TO: 1/640, TH: 1/640, BO: 1/160, BH: - ). With the diagnosis of typhoid fever the child was given chloramphenicol and became afebrile two days later. The 21st day from the start of history while the boy was being given chloramphenicol complained for painful swelling of his right elbow that was at first attributed to the previous venepuncture and four days later the WBC count was 9000/mm3, the ESR was 80/h and Widal test was getting negative (TO: 1/40, TH: 1/80). The 8-day oral chloramphenicol changed to oral co-trimoxazole. Besides the antibiotic therapy the edema of the right elbow was getting worse. Therefore the 12th day of co-trimoxazole treatment he was evaluated by pediatrician at another hospital where radiographs of the affected area showed mild lytic lesions of the distal humeral metaphysis resembling osteomyelitis (figure 1). The child was admitted to that hospital and was given cloxacillin and cephamycin intravenously (I.V.). Seven days after the start of I.V. treatment swelling of the elbow decreased to half but new radiographs revealed lytic defects of the medial aspect of the distal humeral metaphysis and periosteal reaction of the area (figure 2). Because of the new radiographic findings the child was transferred to the "Aghia Sophia" Children’s hospital.
Admission temperature was normal. Physical examination revealed a painful right elbow edema without erythema or increased local temperature. Severe irritability was seen with passive motion of the elbow. Palpation revealed an almond shaped mass of the posteromedial aspect of the distal humerus and also lymph nodes in the axilla. The WBC count was 9600/mm3 and the ESR was 62/h. CRP measured 79mg/L and Widal agglutination test was positive again (TO: 1/320, TH: 1/640, BO: 1/320, BH : -). On the second hospital day the child was taken to the operating room where arthrocentesis and surgical exposure of the medial aspect of the distal humeral metaphysis were performed under general anesthesia. The aspiration of the joint demonstrated serohemmoragic fluid. The subcutaneous palpable mass was removed and sent for histological examination which revealed an inflamed lymph node. Examination showed a corrosion of the distal humeral metaphysis but bone aspiration didn’t yield any pus. Gram stain of the synovial fluid revealed 25-30 leucocytes per field and no microorganisms. On the contrary its cultures were positive for S. typhi isolated not from the culture solid media but from the culture of the incubated broths four days later. This S. typhi was sensitive to ampicillin, netilmicin, amikacin, cephalothin, cefoxitin, cefotaxem, cefuroxime, ceftriaxone, ceftazidime, co-trimoxazole, tetracycline, chloramphenicol, aztreonam and amoxicillin – clavulanic acid. Further laboratory studies were performed once the diagnosis of S. typhi osteomyelitis was confirmed. Hemoglobin electrophoresis was normal and solubility test for hemoglobin-S suckling was negative. After the culture results – the 6th postoperative day – the antibiotic treatment initially consisted of I.V. lincomycin and amoxicillin - clavulanic acid was changed to 11-day I.V. aztreonam and chloramphenicol followed by seven days of I.V. aztreonam. During hospitalization the child remained afebrile. The patient was discharged home on Hospital day 28 with administration of oral amoxicillin – clavulanic acid. He received one-week of oral amoxicillin – clavulanic acid followed by thirty-two days of oral co-trimoxazole, fourteen days of oral ampicillin and finally fifteen days of oral co-trimoxazole.
2½ months after surgery, radiographs of the affected area showed "radiological dissapearance" of the lateral humeral condyle (figure 3a) which lasted 1½ years. During that period of time the lateral humeral condyle was not visible on the plain radiographs but the ultrasound did reveal the existence of the "decalcified’’ condyle (figure 3b).
Four months after surgery the WBC count was normal and the ESR was 3/h. At the same time Widal test, stool cultures and urine cultures for S.typhi were negative. X-rays revealed healing of the lytic lesions seven months after surgery (figure 4). Eleven months after the operation the child had full range of motion of the elbow and four years later new X-rays showed full reconstruction of the lateral humeral condyle (figure 5).
At 11-year follow-up the patient was pain free with full function of the right elbow and the radiographs of the area were normal except a slight broadening of the distal humerus (figure 6).

4.
Figure 4. Plain radiographs of the elbow, 7 months postoperatively, showing healing of the
lytic lesions of the distal humerus – doesn’t reveal the humeral condyle.

5.
Figure 5. Plain radiograph of the right elbow, 4 years later, which reveals full reconstruction
of the lateral humeral condyle and early closure of the proximal physeal disc of the radius
(comparing to the left) because of the inflammation.

6.
Figure 6. At 11-year follow-up the radiographs of the right elbow are absolutely normal except a slight broadening of the distal humerus(comparing to the left elbow).

DISCUSSION
Salmonella is a non-spore-forming Gram (-) bacillus belonging in the family of the Enterobacteraciae which can be easily cultured on a simple media. More than 1800 serotypes have been isolated subdivided into 6 groups (A,B,C1,C2,D,E). Numerous hosts exist including poultry, pigs, cows, pets (turtles, cats, dogs, mice) and humans. Transmission occurs through ingestion of contaminated food or water or by direct inoculation[18,26]. 98.1% of Salmonella infections belong to the above somatic groups with the most common serotypes being S. enteritidis, S. typhimurium, S. newport and S. heidelberg[32]. Salmonella infections assume five clinical manifestations in humans. These are gastroenteritis (the most common clinical presentation – 70%), typhoid fever, bacteremia-septicemia, chronic carrier state and focal infection (7.4%).
In 1876 Paget was the first to report Salmonella osteomyelitis as a complication of typhoid fever. Saphra and Winter in 1957 reported 59 (0.76%) cases of osteomyelitis in 7779 patients who had Salmonellosis[32]. The association between Salmonella osteomyelitis and sickle-cell disease (SCD) has been a well described condition[3,20,22,23] since its original report in 1925 by Carington and Davidson5. Although the increased incidence of osteomyelitis in SCD is now universally accepted controversy exists concerning the incidence, common etiology, diagnosis and treatment. St. aureus has been reported to be the most common causative organism of osteomyelitis in SCD[14] but most studies support the attitude that Salmonella is the most common causative organism[6,13,25,30,35[. The reason and the exact mechanism for the increased incidence of S. osteomyelitis in patients with SCD remain elusive. Some of the unproven theories are the following: I) bowel wall is susceptible to passage of the Salmonella organism because of the multiple gastrointestinal infarcts II) phagocytosis by the reticuloendothelial system of large quantities of erythrocytes interfere with the ability of this system to control bacteria[21] III) bone infarction, a common sequale of SCD combined with sluggish microcirculation and impaired opsonization causes Salmonella bacteremia to "almost invariably localize to bone"[38].
Salmonella osteomyelitis in normal children is a rare type of infection. A review of the literature demonstrates a total of seventeen cases of Salmonella osteomyelitis in children who didn’t have SCD or the sickle cell trait[1,10,12,16,19,27-29,34]; all of them caused by non-typhi forms. Of the seventeen reported cases nine were aged 1½-year or younger, three were between 1½-year and 10-year-old while the rest five were older than 10-year-old. Four patients had multiple-site involvement. The commonest location of the infection was the metaphysis. Of the thirteen patients with single-bone involvement the humerus was affected in five, the lumbar spine in four while the tibia and the pelvis were affected in two either. Seven cases were infected by Salmonella group B, two with group D, one with group C1, one group V and one with S. enterica serovar Newport. The organisms were not grouped in the remaining five patients. In ten cases the treatment was conservative (I.V. and oral antibiotics); in three cases the treatment was irrigation with debridement followed by antibiotics while the rest four patients were managed by pus aspiration-instillation of streptomycin into the abscess cavity and consequently by antibiotics[12]. All the patients had complete recovery except a girl with multifocal infection whose her right tibia osteomyelitis was treated surgically[16].
With the decrease in enteric fever and the recognition of many new salmonella serotypes in the past 40 years it is evident that serotypes other than typhi and paratyphi A are now prevalent among salmonella species in bone infection[19]. S. typhimurium, S. paratyphi B and S. enteritidis are the three most common strains of Salmonella causing osteomyelitis in westernized nations because animals are carriers of these bacteria[8,17]. Osteomyelitis caused by S. typhi (is exclusively transmitted from human to human[24]) has greatly diminished in west countries but it does exist in East Europe and Arabic countries following usually a previous episode of gastroenteritis[11].
The bones of the limbs are usually affected in very young children whilst the axial skeleton (vertebrae-pelvis) is affected in older children. The humerus has been affected more than the other bones with the metaphysis being the most common location of the infectious microorganism although the diaphysis has been referred to be the commonest site of S. osteomyelitis[4,16]. Painful swelling of the affected area and high temperature (up to 400) are the usual clinical signs. Laboratory exams reveal mild to moderate increase of the WBC count and ESR, while conventional radiographs show lytic lesions and periosteal elevation usually 3-4 weeks after the onset of symptoms.
Conservative treatment with at least 6-week (I.V.-oral) antibiotics leads to complete recovery with decreased danger of recurrence[15].

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