Sickle beta-thalassemia (S/β-thalassemia) is a genetic disorder resulting from the inheritance of both a sickle cell gene and a at beta-thalassemia gene. The clinical presentation varies depending on whether the beta-thalassemia gene is β⁺ or β^+o. Early diagnosis is essential for starting supportive treatment and forecasting the clinical course, especially in patients with homozygous sickle cell disease (SS disease) [1].

S/β-thalassemia occurs when one parent passes down an abnormal hemoglobin S gene and the other an abnormal beta-thalassemia gene. Both genes are located on chromosome 11, with one gene for each condition present on each chromosome [2]. The inheritance patterns are summarized in Table 1.

Chronic osteomyelitis is a major cause of prolonged illness in patients with hemoglobinopathies, especially in developing nations. A study in Nigeria by Onuminya and Onabowale [3] involving 60 chronic osteomyelitis patients found that 20 had hemoglobinopathies, with sickle cell trait (HbAS) and sickle cell anemia (HbSS) being the most prevalent as shown in Table 2. The femur was the most commonly affected bone, and treatment generally involved culture-specific antibiotics along with surgical procedures like saucerization and sequestrectomy.

Emphysematous osteomyelitis (EO) is a severe, life-threatening condition with a reported mortality rate of up to 32% [4]. Since the first case was reported in 1981, only 29 cases have been documented worldwide [5], EO is characterized by the formation of gas within the bone, often caused by anaerobic bacteria or members of the Enterobacteriaceae family, while Salmonella osteomyelitis is well known in sickle cell anemia, EO caused by E. coli is extremely rate, with just one previous case reported in a beta-thalassemia trait patient [6],[7].

This report describes a rare case of multifocal emphysematous osteomyelitis caused by E. coli in a 32-year-old male with sickle β⁺ thalassemia major, a combination not previously reported in the literature.

A 32-year-old Asian male was admitted to a tertiary care hospital in Northern India on July 29, 2023, with a 15-day history of high fever, chills, lower abdominal pain, and back pain. He had previously been hospitalized 10 days earlier at another facility for subacute appendicitis and E. coli septicemia, but his condition worsened despite treatment. At the referring hospital, the patient was managed conservatively with intravenous antibiotics for subacute appendicitis. No rupture or surgical intervention was reported. E. coli was isolated from blood cultures during that admission, suggesting a gastrointestinal source of bacteremia.

Upon admission, his vitals were: pulse rate 122/min, blood pressure 140/90 mmHg, oxygen saturation 94% on room air, respiratory rate 18/min, and temperature 103 °F. Physical examination revealed course crepitations in both scapular regions and tenderness in the gluteal area.

Initial lab results showed microcytic anemia, thrombocytopenia, indirect hyperbilirubinemia, and nutritional deficiencies (iron, vitamin B12, and vitamin D) Hemoglobin levels were decreasing (7.7 g/dL), while white blood cell count was elevated (13,000/µL). C-reactive protein (CRP) was significantly high at 386.2 mg/L. Imaging studies included an unremarkable chest X-ray, an abdominal ultrasound showing hepatosplenomegaly, and a high-resolution CT (HRCT) of the chest indicating diffuse ground-glass opacities. Contrast-enhanced CT (HRCT) of the abdomen suggested subacute appendicitis, blood cultures grew E. coli (ESBL producer).

Despite treatment with meropenem and ciprofloxacin, the patient’s fever and back pain persisted. Further investigation with MRI and PET-CT revealed multifocal emphysematous osteomyelitis affecting the clavicles, sacrum, and left shoulder joint, along with adjacent soft tissue inflammation and abscess formation as shown in Figure 1. Deep bone biopsy and tissue cultures confirmed E. coli as the causative agent.

Sickle β⁺ thalassemia major was diagnosed based on high-performance liquid chromatography (HPLC) results (HbA 41.3%, HbA2 4.8%, HbF 8.0%, HbS 41.4%) and parental screening, which identified the mother the mother as a carrier of the beta-thalassemia trait.

Treatment involved intravenous antibiotics (imipenem, teicoplanin, and polymyxin B), empirical antifungal therapy, and hydroxyurea to prevent sickling. A partial red blood cell exchange transfusion was performed to reduce HbS levels to below 30%. The patient gradually improved clinically, with fever resolution and normalization of lab parameters. He was discharged with a plan for six weeks of intravenous ceftriaxone based on sensitivity profile of the E. coli isolate.

Emphysematous osteomyelitis is a rare and potentially life-threatening condition, with E. coli being an unusual pathogen in sickle cell disease [8], while the link between sickle cell disease and osteomyelitis is well documented, Salmonella is typically the most common cause. This case emphasizes the need to consider fewer common pathogens like E. coli in patients with hemoglobinopathies.

The patient's treatment involved a team-based approach. The patient was managed by a multidisciplinary team involving internal medicine, infectious diseases, hematology, and surgery. Surgical consultation was essential for diagnostic evaluation and exclusion of residual intra-abdominal focus. Other modalities that included targeted antibiotics, surgery, and exchange transfusion to minimize sickling were also administered. Positron emission tomography-computed tomography and MRI were crucial in diagnosing multifocal emphysematous osteomyelitis, and tissue cultures confirmed E. coli as the causative organism. Given the patient’s recent history of subacute appendicitis and E. coli septicemia, this organism was suspected early. Although Salmonella is more typical in sickle cell disease, the recent gastrointestinal (GI) infection pointed to E. coli.

This case highlights the uncommon occurrence of E. coli-induced emphysematous osteomyelitis in sickle β⁺ thalassemia major and emphasizes the critical need for prompt diagnosis and aggressive treatment. A combination of exchange transfusion to lower Hbs levels and culture-targeted antimicrobial therapy is crucial for effectively managing these complex cases.