Periostitis as Initial Sign of Pediatric Acute Lymphoblastic Leukemia

Abstract

A 5-year-old girl presented with 15 days of insidious-onset pain in the lower legs (left > right) and mild forearm pain with gradual worsening. Examination showed normal limb bulk with tenderness along the lateral forearms and legs. Laboratory evaluation revealed leukocytosis (28,760/mm³), elevated erythrocyte sedimentation rate (29 mm/h), and elevated C-reactive protein (24 mg/L). A radiograph of the left leg was normal. Magnetic resonance imaging of both legs demonstrated diffuse hypointense marrow signal on T1- and T2-weighted images (Figure 1a), bilateral symmetrical short-tau inversion recovery hyperintensity around the fibular shafts with postcontrast enhancement consistent with periostitis (Figure 1b), and multiple irregular peripherally enhancing tibial meta-diaphyseal lesions with nonenhancing fibular shafts, consistent with bone infarcts. Bone marrow biopsy confirmed B-cell acute lymphoblastic leukemia (ALL) with BCR::ABL1 [t (9; 22) (q34.1; q11.2)].

The patient began induction therapy with weekly vincristine and daunorubicin, intrathecal methotrexate, and daily prednisolone for 4–6 weeks. Pegylated asparaginase and daily dasatinib were added from week 2 of treatment. After 1 month, bone marrow examination was normocellular with 3% blast cells, and immunophenotyping showed only 0.18% residual B-cell lymphoblastic leukemia.

Multifocal periostitis as an initial manifestation of ALL is rare. Skeletal involvement occurs in 41%–70% of pediatric ALL and may be associated with better survival, supporting the role of skeletal surveys at diagnosis. In pediatric ALL, leukemic blasts infiltrate the bone marrow, leading to medullary cavity expansion, increased intraosseous pressure, and endosteal disruption. This mechanical stress, along with cytokine-mediated periosteal irritation (e.g., interleukins and tumor necrosis factor-α), stimulates subperiosteal new bone formation, appearing radiologically as periostitis. Thus, periostitis may be the initial radiographic manifestation of ALL, even before hematologic abnormalities.

Differential diagnoses for pediatric periostitis include psoriatic or reactive arthritis, hypervitaminosis A, prostaglandin therapy, hypertrophic pulmonary osteoarthropathy, pachydermoperiostosis, scurvy, infections, malignancy, and fractures, including traumatic and nonaccidental injury (e.g., battered child syndrome).

Persistent or unexplained bone pain in children, even with subtle radiographic findings, carries a risk of misdiagnosis. In such cases, magnetic resonance imaging can detect marrow infiltration earlier than radiography, and hematologic evaluation is essential to exclude acute leukemia. Early recognition prevents diagnostic delay and improves outcomes.

Siddhi Chawla: conceptualization (equal), investigation (equal), methodology (equal), project administration (equal), validation (equal), writing – original draft (equal), writing – review and editing (equal). Gajanand Singh Tanwar: conceptualization (equal), data curation (equal), supervision (equal), validation (equal), writing – original draft (equal), writing – review and editing (equal).

The authors have nothing to report.

The authors have nothing to report.

Written informed consent was obtained from the patient's parents.

The authors declare no conflicts of interest.