PMC5413492_01
(A) Anteroposterior X-ray film revealing metaphyseal osteolytic lesions in femurs (arrowheads). Contrast with panel (B). Radiological improvement after 1 year of antimycobacterial drug treatment, with femoral remodeling. (C) CT scan, sagittal view, showing presacral mass and osteolytic lesions of the S3-S4 vertebral bodies (arrowheads). Contrast with panel (D). Improvement after 1 year of treatment, with vertebral remodeling and decreased antesacral mass.
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F1
X-rays revealed numerous osteolytic lesions over the right femur, left tibia, frontal bone, and right clavicle (Figure 1A). A computed tomography scan from neck to pelvis found bilateral cervical, supraclavicular, and axillar lymphadenopathies, as well as a 5.5 x 4.5 cm presacral mass with lytic features, involving S2 and S3 (Figure 1C). After 1 year of clinical and radiological improvement (Figures 1B,D), the multidrug regime was shifted to maintenance phase, but 6 months later the patient complained of pain in the left arm, again showing radiographic signs of osteomyelitis and abscess on physical examination (Figure 2). ANC 5,800, lymphocytes 700/mm3, platelets 213,000), with serum ferritin 5,540 mug/l, and triglycerides 366 mg/dl. A bone marrow aspirate confirmed hemophagocytosis (Figure 4; Figure S1 in Supplementary Material), and Epstein-Barr virus (EBV) serology identified high viral titers and viral load (691-5,000 copies/ml).
Clinical relapse with upper arm abscess, and new lytic lesions in parietal bone (left panels) and left humerus (right panels). (A) X-ray of skull, lateral view. (B) Posteroanterior view, showing osteolytic lesions (arrows). (C) Swelling of left shoulder over abscess. (D) X-ray of left humerus showing osteolytic lesions (arrow).
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F2
After 1 year of clinical and radiological improvement (Figures 1B,D), the multidrug regime was shifted to maintenance phase, but 6 months later the patient complained of pain in the left arm, again showing radiographic signs of osteomyelitis and abscess on physical examination (Figure 2).
Electropherogram showing a heterozygous four-nucleotide deletion in the patient, as contrasted with a healthy control and the patient's parents.
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F3
Genomic DNA amplification with the polymerase chain reaction and automated Sanger sequencing revealed a monoallelic small deletion in exon 6 of IFNGR1 (818del4) (Figure 3).
Third relapse with CT scans showing left psoas abscess and multiple osteolytic lesions. (A) Fistulized multifocal pneumonia and left psoas abscess. (B) Bone marrow aspirate (Hematoxylin and eosin staining, 40x) showed histiocytes phagocytizing three blood cell lineages. (C,D) CT scan, coronal view, showing lumbar vertebral osteolytic lesions (panel C, arrows) and left psoas abscess (panel D, arrow). (E,F) Gross appearance of chest wall and lung specimen at autopsy, confirming multifocal fistulized pneumonia.
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F4
ANC 5,800, lymphocytes 700/mm3, platelets 213,000), with serum ferritin 5,540 mug/l, and triglycerides 366 mg/dl. A bone marrow aspirate confirmed hemophagocytosis (Figure 4; Figure S1 in Supplementary Material), and Epstein-Barr virus (EBV) serology identified high viral titers and viral load (691-5,000 copies/ml). Image evaluation showed new lumbar and pelvic osteolytic lesions, left psoas abscess, and multifocal pneumonia, with a fistulizing chest wall abscess, despite continued prophylactic treatment (Figure 4).