Migratory Arthralgia in a 3-year-old Girl

A previously healthy 3-year-old girl presents to the pediatric rheumatology clinic for evaluation of 5 to 6 weeks of arthralgia of the left wrist and right elbow. Initial atraumatic right elbow pain prompted her pediatrician to refer her to orthopedic surgery. The orthopedic surgeon’s physical examination revealed decreased right elbow range of motion (ROM), and initial laboratory evaluation was notable for an erythrocyte sedimentation rate of 33 mm/hr (reference range, 0–20 mm/hr), a C-reactive protein level of 1.30 mg/dL (13 mg/L) (reference range, 0–1.0 mg/dL [0–10 mg/L]), and a normal complete blood cell (CBC) count: white blood cell (WBC) count, 9,000/µL (9.0 × 109/L) (reference range, 5,000–17,000/µL [5.0–17.0 × 109/L]); hemoglobin level, 12.3 g/dL (123 g/L) (reference range, 11.5–14.0 g/dL [115–140 g/L]); and platelet count, 442 × 103/µL (442 × 109/L) (reference range, 160–370 × 103/µL [160–370 × 109/L]). Her symptoms improved after 3 days of immobilization, but recurrence of right elbow pain another 2.5 weeks later prompted her orthopedic surgeon to refer her to rheumatology with consideration for an inflammatory arthritis process.On initial rheumatology evaluation the patient’s history is notable for arthralgia; in addition to recurrence of right elbow pain, she also developed left wrist pain. There are no other reported symptoms, and review of systems is notable for an absence of rash or constitutional symptoms: no fever, sweats, fatigue, appetite suppression, weight loss, or changes in activity level. Examination reveals subtle edema, tenderness to palpation with stiffening/guarding, and pain with left wrist ROM. There is no swelling or frank reduction in ROM in the right elbow, but she demonstrates guarding with hyperextension. She is otherwise well-appearing, with no other noted physical abnormalities. Repeated laboratory evaluation demonstrates improvement in inflammatory markers (erythrocyte sedimentation rate, 16 mm/hr; C-reactive protein level, 0.9 mg/dL [9 mg/L]); left wrist radiography is notable for sclerosis at the distal radius suspected to be the result of a healing occult fracture. A trial of twice-daily naproxen use is initiated for symptom management.Rheumatology follow-up approximately 5 weeks later (>10 weeks after initial presentation to orthopedic surgery) was conducted via telemedicine amid the early coronavirus disease 2019 (COVID-19) pandemic. Despite nonsteroidal anti-inflammatory drug therapy, the patient experienced progression in arthralgia, with 2 days of new right ankle pain at the time of follow-up but still no systemic symptoms. A presumed diagnosis of polyarticular juvenile idiopathic arthritis (JIA) was suspected by her rheumatologist. Methotrexate therapy was planned, and, in the meantime, a trial of systemic corticosteroids (prednisolone, 0.5 mg/kg per day) was initiated in an attempt to provide timely pain relief. However, a repeated CBC count revealed interval development of isolated normocytic anemia (hemoglobin level, 7.9 g/dL [79 g/L]), prompting discontinuation of prednisolone therapy after 3 days. Another CBC count 3 days later revealed interval development of mild neutropenia (absolute neutrophil count, 1.4 × 103/µL [1.4 × 109/L]; reference range, 1.5–8.0 × 103/µL [1.5–8.0 × 109/L]); the platelet count remained normal at 307 × 103/µL (307 × 109/L). The patient’s symptoms rapidly progressed during the next 3 to 5 days to include fatigue, shortness of breath, pallor, refusal to bear weight, and worsening pain now also involving her back, hips, and lower extremities.The clinical evaluation of migratory arthritis in pediatric patients involves a detailed history and physical examination. JIA was the initially suspected diagnosis in this case, but the inconsistent clinical course soon raised concern for alternate etiologies. A broad differential diagnosis is depicted in Table 1; distinguishing clinical features can often help differentiate among these possibilities.JIA typically presents with subacute onset of swelling and reduced ROM in 1 or more joints. In young children with the oligoarticular JIA subtype, pain is usually absent. The clinical diagnosis is based on the presence of persistent joint inflammation (characterized by swelling, limitation in ROM, warmth, and/or occasionally pain with palpation or ROM) of at least 6 weeks’ duration. Characteristic laboratory findings (elevated inflammatory markers, antinuclear antibody positivity) and imaging can support the diagnosis but are frequently absent. Symptoms are generally responsive to nonsteroidal anti-inflammatory drug therapy, corticosteroids, or disease-modifying antirheumatic medications such as methotrexate. In patients with inconsistent features, such as pain out of proportion to examination, severe nocturnal pain, significant cytopenias, or failure to respond to typical therapies, further laboratory evaluation, imaging, and specialist consultation are indicated to evaluate for alternate etiologies. Radiographic imaging in JIA is typically unremarkable but can display soft tissue swelling or periarticular osteopenia; the sclerotic lesions noted on this patient’s initial wrist radiograph are atypical of JIA.In the setting of concurrent cytopenia(s) or an otherwise unclear clinical picture, unexplained arthralgia and/or bone pain in a child should prompt consideration for a bone marrow infiltrative process. Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, most often presenting in children aged 2 to 5 years (5) with symptoms related to the sequelae of disordered hematopoiesis. Diffuse bone pain is a common presenting symptom of acute leukemia resulting from predominance of leukemic blasts in the bone marrow regardless of circulating WBC count. Fevers and refusal to walk—a result of nonlocalizing, diffuse bone pain—are typical clinical features at leukemia presentation. Associated anemia often results in pallor and fatigue and, when severe, can present with evidence of congestive heart failure; thrombocytopenia precipitates bruising, petechiae, and/or mucosal bleeding.The insidious onset of the patient’s cytopenias and the need for remote follow-up in the setting of the COVID-19 pandemic resulted in a prolonged clinical course before definitive diagnosis. Details are depicted in Fig 1. Rapid symptom progression ultimately prompted an expedited pediatric hematology/oncology evaluation. A follow-up CBC count revealed a rapid exacerbation in anemia (hemoglobin level, 5.4 g/dL [54 g/L]) and neutropenia (absolute neutrophil count, 0.4 × 103/µL [0.4 × 109/L]) with 1% blasts noted on the differential count. Peripheral smear revealed few small- to intermediate-sized blasts with a high nuclear-cytoplasmic ratio, fine nuclear chromatin, and conspicuous nucleoli. An expedited bone marrow aspirate/biopsy revealed 77% lymphoblasts with immunophenotype (CD34+, CD19+, CD10+, CD79a+, HLA-DR+) consistent with the diagnosis of B-cell ALL.The prognosis of childhood ALL has dramatically improved in recent decades, with overall event-free survival greater than 90% among affected children and adolescents. (6) At presentation, children with ALL undergo preliminary risk stratification based on numerous clinical and cytogenetic variables. Assignment of National Cancer Institute risk group—standard risk (SR) versus high risk (HR)—at diagnosis is determined by the patient’s age (1–9.99 years is SR and ≥10 years is HR) and presenting WBC count (<50,000/μL [<50 × 10/L] is SR and ≥50,000/μL [≥50 × 109/L] is HR). (7) Additional stratification into subcategories of treatment intensity (eg, SR-favorable, SR-average, SR-high) involves the detection of favorable versus unfavorable cytogenetic features; the extent of leukemia involvement of sanctuary sites, namely, the central nervous system and testes; and, most critically, leukemia responsiveness to early-phase chemotherapy as measured by minimal residual disease evaluation at the end of the induction phase. (8)Corticosteroids are an integral element of the multitherapy standard of care for ALL. In fact, historical data demonstrated that single-agent corticosteroid treatment alone induced leukemia remission in more than half of patients. (9) However, patients treated with corticosteroid monotherapy consistently demonstrated leukemia recurrence (10); multiagent combination therapy is thus critical for sustained cure. Prolonged or intensive corticosteroid exposure before definitive leukemia diagnosis has been suspected to promote corticosteroid resistance and partially treat and mask other critically risk-stratifying features, such as presenting WBC count or central nervous system involvement, thereby resulting in inadequate risk stratification and wrongly assigned treatment intensity. (11) To achieve meaningful and actionable clinical trial outcomes in the setting of such confounders, the Children’s Oncology Group enforces rigorous enrollment criteria in all their clinical trials, with strict guidelines surrounding the acceptability of patients having undergone corticosteroid pretreatment. Our patient’s risk stratification was altered by the brief course of prednisolone administered in the week before diagnosis: pretreatment prednisolone exposure precluded her from stratification to the lowest risk treatment arm of the SR group.One day after bone marrow evaluation our patient was formally enrolled in the current Children’s Oncology Group SR B-cell ALL clinical trial. She began therapy with 3-drug induction chemotherapy (dexamethasone, vincristine, and polyethylene glycol–conjugated asparaginase). She tolerated induction therapy well, with resolution in migratory arthralgia and complete return to baseline activity level by day 4 of treatment. The cytogenetics of her leukemia were favorable (trisomy 4 and 10). Her end-of-induction bone marrow evaluation revealed no detectable disease by morphology or cytogenetics, but minimal residual disease assessment by multiparameter flow cytometry was positive at a level of 0.037%. Taken together with her disease’s favorable cytogenetics, her final risk stratification remains SR-average. Her excellent prognosis is estimated at approximately 95% long-term survival after completion of an approximately 2.3-year treatment course.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.