Sickle cell disease (SCD) is the most commonly inherited hematological disorder, affecting millions of patients worldwide ^[1]. This condition produces abnormal hemoglobin, which leads to the “sickling” of red blood cells leading to vaso-occlusion. Because this commonly happens in the bones, patients with SCD are at an increased risk for orthopedic manifestations such as osteomyelitis, septic joint, or osteonecrosis. The increased propensity for osteomyelitis in SCD has been also attributed to functional asplenia and the presence of infarcted or necrotic bone [2, 3]. The most common infecting organisms are the capsulated bacteria such as Salmonella species, Staphylococcus aureus, Streptococcus pneumoniae, and Bacteroides species have also been described. However, Klebsiella has been reported as a new emerging organism ^[4]. Klebsiella sp. is a common pathogen responsible for infections such as urinary tract infections, community-acquired pneumonia, solid organ abscesses, as well as invasive infectious due to bacterial dissemination [4, 5]. Rarer complications include necrotizing fasciitis, osteomyelitis, and meningitis. Sturm et al. ^[5] described bilateral osteomyelitis and liver abscess caused by hypervirulent Klebsiella. Bilateral pyogenic osteomyelitis as a clinical entity is exceedingly rare as is long bone osteomyelitis attributable to infection with hypervirulent Klebsiella. We describe our experience of treating bilateral symmetrical ulna and fibula osteomyelitis.

A 25-year-old female health-care worker from central India, known SCD on folic acid and hydroxyurea, was admitted to our hospital 1 year back with complaints of fever and pain in the abdomen. She was diagnosed as a case of dengue, for which she was admitted under a physician. During the hospital course, her blood parameters revealed thrombocytopenia and blood culture showed growth of Klebsiella (all sickle cell patients are susceptible to capsulated organisms such as pneumococcus, Klebsiella, hemophilus due to functional asplenia, the patient did not receive any steroids during her hospitalization for dengue). She was then managed with a transfusion of platelets and blood products and was started on IV antibiotics injection Ceftriaxone + Tazobactam 8 hourly for 3 days, following which she showed improvement and was shifted to, oral doses of Cefixime 200 mg + Dicloxacillin 500 mg that were given for a week and was discharged.

Following an asymptomatic period of 2 weeks, the patient presented with pain over the bilateral forearm and legs. On examination, there was local warmth and bony tenderness at the right forearm, no local discharging sinus, and no clinical evidence of a subcutaneous collection. On evaluation, the plain radiological features (Fig. 1) were suggestive of periosteal changes and lytic lesions-osteomyelitis, although, the uniqueness of presentation of her symptoms was “Multifocal Bilaterally symmetrical involvement.” Laboratory evaluations were remarkable for leukocytosis with a white blood cell count of 18.4  ×  10³ (6.0–17.5) and C‐reactive protein of 35 mg/dL.

Differential diagnosis of the presenting condition was:

1. Chronic multifocal recurrent osteomyelitis (CMRO)
2. Multifocal pyogenic osteomyelitis
3. Vaso-occlusive crisis leading to multiple bone infarcts.

Further to confirm our diagnosis, the incisional bone biopsy by corticotomy and debridement of the lesion from the most symptomatic right forearm region (right ulna) (Fig. 2) was performed.

The culture of biopsy from right ulna showed the growth of Klebsiella sp. and was only sensitive to Co-trimoxazole. The patient was started on co-trimoxazole, and she tolerated well and had a significant clinical improvement in the form of subsidence of pain, normalization of the blood counts along with the acute phase reactants. The antibiotic treatment was continued for 6 weeks, the patient was observed closely post-hospitalization, continued to recover well, and completed her antibiotic course without any issues. She has not had any more recurrences of osteomyelitis or other serious infections till 1-year follow-up (Fig. 3 and 4).

Patients with SCD present with osteomyelitis in both acute and chronic stages. The natural history of SCD is characterized by chronic anemia that is accompanied by simple or complicated vaso-occlusive crises (VOCs) that can compromise prognosis and cause chronic, life-threatening complications. The high susceptibility of SCD to bacterial infections is known to be due to functional asplenia resulting and its associated genetic, immunological, and sometimes environmental factors ^[6]. Although, conventionally, Salmonella has been suggested as the most common organism associated with SCD patients, the emerging causative organisms are Klebsiella, Clostridium ^[7], S. aureus among others. In our patient, SCD would be the predisposing host factor for the hypervirulence of Klebsiella. Osteomyelitis is an extremely challenging diagnosis to make in patients with SCD due to overlapping clinical and laboratory manifestations with the more common VOC of the bone or bone infarction. A high level of technology is required to differentiate between bone infarction and osteomyelitis in people with SCD. Routine investigations involving radiographs are usually within normal limits or may show vague signs such as soft-tissue edema, periostitis, or osteopenia. The lytic changes suggestive of osteomyelitis usually lag at least 2 weeks behind the process of the infection on radiographs which may delay diagnosis and aggravate the clinical scenario. Alternatively, ultrasonography was an upcoming promising screening tool as it has the ability to show acute findings of extraosseous pathology and/or periosteal elevation in osteomyelitis at an earlier stage ^[8]. MRI is the imaging modality of choice for the diagnosis of osteomyelitis and shows marrow edema typically presents as a localized marrow abnormality of decreased signal on T1-weighted images and increased signal on T2-weighted images ^[9]. The most acute finding of osteomyelitis on MRI is bone marrow edema or indirect findings of osteomyelitis such as soft-tissue collections, cellulitis, and cortical bone sinus tracts. PET‐CT helps in identifying additional foci of osteomyelitis. The bone scan is useful in multifocal diseases in particular, because easy to scan the whole body. However, the gold standard tool remains tissue biopsy and culture [9, 10]. The possibility of multifocal osteomyelitis was initially raised in this case based on the clinical history of preceding constitutional symptoms and the imaging findings. Other potential differential diagnoses include vaso-occlusive crises resulting in multiple bone infarcts, which can be distinguished through biopsy ^[10], and CMRO, a rare non-infective inflammatory disorder that mimics the pain associated with osteomyelitis ^[11]. We have reported this case owing to the rarity of its “Multifocal Bilaterally symmetrical” presentation due to bacterial seedings of bones at multiple sites that may have been traumatized in the course of SCD. Early diagnosis with biopsy and culture and prompt treatment with appropriated culture-sensitivity antibiotics helped in the faster recovery of our patient.

In an increasingly globalized world, our case highlights the importance of clinician awareness of the manifestations and management of Klebsiella sp. hypervirulent strains. The possibility of multifocal involvement should be kept in mind, based on the clinical history and preceding constitutional symptoms. These strains pose a substantial threat to human health because they have the potential to cause invasive and severe diseases, are highly transmissible, and are difficult to treat.

This case report presents multifocal osteomyelitis with bilateral symmetrical involvement due to post-viral illness bacteremia. Our case presents unusual manifestations of Klebsiella sp. and a rarity of bilateral symmetrical involvement. In patients with SCD, we must be more cognizant of the possibility of multifocal osteomyelitis. This clinical description narrates the same.