Langerhans Cell Histiocytosis Mimicking Osteomyelitis

To the Editors: The literature has reported many cases of Langerhans cell histiocytosis (LCH) mimicking osteomyelitis on imaging studies and in observable clinical symptoms (Table 1).1,2,3,4,5 One such case was seen recently at our institution. Thus, we would like to discuss the importance of considering LCH as an alternative diagnosis in patients presenting with bone pain and factors that should prompt clinicians to consider bone biopsy as a diagnostic tool—to avoid missing a diagnosis of LCH—in the context of our case and the present literature. TABLE 1. - Comparison of Case Reports of Osteomyelitis Mimicking LCH1,2,3,4 Case Age Gender Symptoms Lesion Location WBC (103/μL) ESR (mm/h) CRP (mg/dL) Our case 16 m/o F Decreased active ROM, pain with passive ROM Radial diaphysis with extension to proximal and distal radial metaphysis 12.4 38 <0.5 M Yusof and Johari 1 4 y/o F Swelling, limping Upper third of tibia 18.52 86 16.35 Erdem et al 2 9 m/o M Pain, mobile palpable mass Upper metaphysis of femur NR 69 NR Pavlik et al 3 (case 1) 3 y/o M Pain, inability to bear weight Proximal femoral physis to the proximal diaphysis with sparing of the epiphysis Within normal limits (specific value not reported) 47 NR Pavlik et al 3 (case 2) 6 y/o M Pain, difficulty with ambulation Femoral mid-diaphysis NR NR NR Ando et al 4 (case 1) 6 y/o M Pain, limping, painful ROM Acetabulum 7800 21 NR Ando et al 4 (case 2) 4 y/o M Pain, limping, tenderness to palpation Acetabulum 8250 35 NR Ando et al 4 (case 3) 2 y/o M Limping Ilium 11,460 30 NR CRP indicates C-reactive protein; ESR, erythrocyte sedimentation rate; F, female; M, male; m/o, months old; NR, not reported; ROM, range of motion; WBC, white blood cells; y/o, years old. Osteomyelitis is an infection of bone that affects 1–13 per 100,000 children per year, occurs mostly in children 2.5–4.5 years old with a mean age of 6.6 years old, chiefly affects the metaphysis, and occurs most commonly in the tibia and femur.6 LCH is characterized by hyperproliferation of cells of the monocyte, macrophage and dendritic lineage that affects 4–5 per million children each year and is most common in children less than 1 year old with a median age of 3.5 years old.7 Although the skull is the most common site of skeletal involvement, when long bones are involved, LCH involves the metaphysis and diaphysis equally with rare epiphyseal involvement.8 In the case seen at our institution, a 16-month-old female presented with decreased use of her left forearm and associated swelling and tenderness of the area for 5 days were significant for elevated erythrocyte sedimentation rate (38 mm/h), normal C-reactive protein (<0.5 mg/dL), an age-appropriate white blood cells (12.4 × 103/μL) and negative blood cultures. Radiograph of the left radius showed an aggressive diaphyseal lesion, while magnetic resonance imaging findings were consistent with acute diaphyseal osteomyelitis. Following discharge, bone biopsy results returned with a diagnosis of LCH. The key similarities between our case and other cases of LCH mimicking osteomyelitis in the literature include lack of fevers, normal white blood cells and only slightly elevated erythrocyte sedimentation rate (Table 1).1,2,3,4,5 Another key factor in our case that prompted us to pursue a bone biopsy was the diaphyseal lesion location—atypical for osteomyelitis and relatively common with LCH. Because LCH can mimic osteomyelitis on imaging studies and in observable clinical symptoms, it is an important to keep this alternative diagnosis in mind in young children presenting with bone pain. Although osteomyelitis is much more common than LCH, misdiagnosis can lead to a prolonged, unnecessary course of antibiotics and delay of appropriate treatment. Therefore, in atypical presentations of osteomyelitis—such as our case—where patients are afebrile, have normal or only slightly elevated inflammatory markers, negative blood cultures and imaging with lesions consistent with osteomyelitis but in atypical locations, clinicians should strongly consider bone biopsy of the lesion to ensure that a diagnosis of LCH is not missed.