2748
SOUSA ET AL
15. Conde-Jaldon M, Montes-Cano MA, Garcia-Lozano JR, OrtizFernandez L, Ortego-Centeno N, Gonzalez-Leon R, et al. Epistatic interaction of ERAP1 and HLA-B in Behc ¸et disease: a replication study in the Spanish population. PLoS One 2014;9: e102100. 16. Xavier JM, Davatchi F, Abade O, Shahram F, Francisco V, Abdollahi BS, et al. Characterization of the major histocompatibility complex locus association with Behc¸et’s disease in Iran. Arthritis Res Ther 2015;17:81. 17. Meguro A, Inoko H, Ota M, Katsuyama Y, Oka A, Okada E, et al. Genetics of Behc¸et disease inside and outside the MHC. Ann Rheum Dis 2010;69:747–54.
18. Kappen JH, Medina-Gomez C, Hagen PM, Stolk L, Estrada K, Rivadeneira F, et al. Genome-wide association study in an admixed case series reveals IL12A as a new candidate in Behc ¸et disease. PLoS One 2015;10:e0119085. 19. Kastelein RA, Hunter CA, Cua DJ. Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Annu Rev Immunol 2007;25:221–42. 20. Saunders EJ, Dadaev T, Leongamornlert DA, Jugurnauth-Little S, Tymrakiewicz M, Wiklund F, et al. Fine-mapping the HOXB region detects common variants tagging a rare coding allele: evidence for synthetic association in prostate cancer. PLoS Genet 2014;10:e1004129.
DOI: 10.1002/art.39241
Clinical Images: Multifocal noninfectious osteitis as a presentation of pediatric granulomatosis with polyangiitis (Wegener’s)
The patient, a 12-year-old girl born to nonconsanguineous parents and with no family history of autoimmunity/autoinflammation, presented with a 2-month history of worsening facial, nose, and right ear pain, bony tenderness of the anterior right sixth rib, pain and restriction of motion at the left hip, otorrhea, and epistaxis with nasal polyps. Laboratory studies revealed increased levels of inflammatory markers (erythrocyte sedimentation rate 157 mm/hour [normal #10], C-reactive protein .270 mg/liter [normal ,20]) and positive proteinase 3 (PR3)–specific antineutrophil cytoplasmic antibody (ANCA) (50 IU/ml [normal #1.99]) with normal renal function and absence of proteinuria. Bone biochemistry analysis showed the following (all within normal range): calcium 2.51 mmoles/liter, phosphate 1.33 mmoles/liter, and alkaline phosphatase 157 units/liter. Chest radiography revealed a nodule in the right upper zone, with cavitation and bony expansion of the anterior sixth rib (A) (arrows). Whole-body single-photon–emission computed tomography revealed multiple sites of highly increased tracer uptake (B), with a vascular, highly metabolically active process within the left acetabulum (C) that exhibited marked hyperemia on blood pool images (not shown). Biopsy of the rib lesion (D) demonstrated extensive fibrosis with a heavy, patchy, mixed inflammatory infiltrate with no necrosis but prominent plasma cells and macrophages. Immunostaining revealed CD68-positive histiocytes; CD1a and langerin were absent. Immunoglobulin 4 staining was negative, and there was no evidence of malignancy. Granulomatosis with polyangiitis (Wegener’s) (GPA) was diagnosed. Treatment with high-dose corticosteroids combined with rituximab resulted in rapid induction of remission (within 2 months), after which a regimen of low-dose corticosteroids and azathioprine was instituted to maintain remission. PR3-ANCA became negative after 6 months, and 12 months after presentation the patient remains well with this maintenance treatment, with repeat chest radiography revealing near-complete resolution and remodeling of the rib lesion. While craniofacial involvement is well recognized in GPA, extracranial skeletal involvement is exceptionally rare, has been previously described only in adults, and presents with unifocal skeletal lesions (1,2). Bone biopsy is essential to exclude malignancy, infection, and rare histiocytic syndromes such as Erdheim-Chester disease, the latter typically demonstrating symmetric osteosclerosis of the long bones (3). To the best of our knowledge, this is the first description of multifocal noninfectious osteitis in GPA. 1. Kim SD, Kim GW, Kim TE, Nam EJ, Han SW. Granulomatosis with polyangiitis (Wegener granulomatosis) as a differential diagnosis of sternal osteomyelitis: the challenges in diagnosis. J Clin Rheumatol 2013;19:446–8. 2. Hemington MH, Detterbeck FC, Kahai J, Szwerc MF, Jennette JC, Egan TM, et al. Wegener’s granulomatosis mimicking a sternal abscess. South Med J 1996;89:438–41. 3. Antunes C, Graca B, Donato P. Thoracic, abdominal and musculoskeletal involvement in Erdheim-Chester disease: CT, MR and PET imaging findings. Insights Imaging 2014;5:473–82.
K. S. Brogan, BSc D. Eleftheriou, PhD University College London Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust L. Biassoni, MSc, FRCP N. Sebire, FRCPath Great Ormond Street Hospital NHS Foundation Trust P. A. Brogan, FRCPCH, PhD University College London Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust London, UK
SOUSA ET AL
15. Conde-Jaldon M, Montes-Cano MA, Garcia-Lozano JR, OrtizFernandez L, Ortego-Centeno N, Gonzalez-Leon R, et al. Epistatic interaction of ERAP1 and HLA-B in Behc ¸et disease: a replication study in the Spanish population. PLoS One 2014;9: e102100. 16. Xavier JM, Davatchi F, Abade O, Shahram F, Francisco V, Abdollahi BS, et al. Characterization of the major histocompatibility complex locus association with Behc¸et’s disease in Iran. Arthritis Res Ther 2015;17:81. 17. Meguro A, Inoko H, Ota M, Katsuyama Y, Oka A, Okada E, et al. Genetics of Behc¸et disease inside and outside the MHC. Ann Rheum Dis 2010;69:747–54.
18. Kappen JH, Medina-Gomez C, Hagen PM, Stolk L, Estrada K, Rivadeneira F, et al. Genome-wide association study in an admixed case series reveals IL12A as a new candidate in Behc ¸et disease. PLoS One 2015;10:e0119085. 19. Kastelein RA, Hunter CA, Cua DJ. Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Annu Rev Immunol 2007;25:221–42. 20. Saunders EJ, Dadaev T, Leongamornlert DA, Jugurnauth-Little S, Tymrakiewicz M, Wiklund F, et al. Fine-mapping the HOXB region detects common variants tagging a rare coding allele: evidence for synthetic association in prostate cancer. PLoS Genet 2014;10:e1004129.
DOI: 10.1002/art.39241
Clinical Images: Multifocal noninfectious osteitis as a presentation of pediatric granulomatosis with polyangiitis (Wegener’s)
The patient, a 12-year-old girl born to nonconsanguineous parents and with no family history of autoimmunity/autoinflammation, presented with a 2-month history of worsening facial, nose, and right ear pain, bony tenderness of the anterior right sixth rib, pain and restriction of motion at the left hip, otorrhea, and epistaxis with nasal polyps. Laboratory studies revealed increased levels of inflammatory markers (erythrocyte sedimentation rate 157 mm/hour [normal #10], C-reactive protein .270 mg/liter [normal ,20]) and positive proteinase 3 (PR3)–specific antineutrophil cytoplasmic antibody (ANCA) (50 IU/ml [normal #1.99]) with normal renal function and absence of proteinuria. Bone biochemistry analysis showed the following (all within normal range): calcium 2.51 mmoles/liter, phosphate 1.33 mmoles/liter, and alkaline phosphatase 157 units/liter. Chest radiography revealed a nodule in the right upper zone, with cavitation and bony expansion of the anterior sixth rib (A) (arrows). Whole-body single-photon–emission computed tomography revealed multiple sites of highly increased tracer uptake (B), with a vascular, highly metabolically active process within the left acetabulum (C) that exhibited marked hyperemia on blood pool images (not shown). Biopsy of the rib lesion (D) demonstrated extensive fibrosis with a heavy, patchy, mixed inflammatory infiltrate with no necrosis but prominent plasma cells and macrophages. Immunostaining revealed CD68-positive histiocytes; CD1a and langerin were absent. Immunoglobulin 4 staining was negative, and there was no evidence of malignancy. Granulomatosis with polyangiitis (Wegener’s) (GPA) was diagnosed. Treatment with high-dose corticosteroids combined with rituximab resulted in rapid induction of remission (within 2 months), after which a regimen of low-dose corticosteroids and azathioprine was instituted to maintain remission. PR3-ANCA became negative after 6 months, and 12 months after presentation the patient remains well with this maintenance treatment, with repeat chest radiography revealing near-complete resolution and remodeling of the rib lesion. While craniofacial involvement is well recognized in GPA, extracranial skeletal involvement is exceptionally rare, has been previously described only in adults, and presents with unifocal skeletal lesions (1,2). Bone biopsy is essential to exclude malignancy, infection, and rare histiocytic syndromes such as Erdheim-Chester disease, the latter typically demonstrating symmetric osteosclerosis of the long bones (3). To the best of our knowledge, this is the first description of multifocal noninfectious osteitis in GPA. 1. Kim SD, Kim GW, Kim TE, Nam EJ, Han SW. Granulomatosis with polyangiitis (Wegener granulomatosis) as a differential diagnosis of sternal osteomyelitis: the challenges in diagnosis. J Clin Rheumatol 2013;19:446–8. 2. Hemington MH, Detterbeck FC, Kahai J, Szwerc MF, Jennette JC, Egan TM, et al. Wegener’s granulomatosis mimicking a sternal abscess. South Med J 1996;89:438–41. 3. Antunes C, Graca B, Donato P. Thoracic, abdominal and musculoskeletal involvement in Erdheim-Chester disease: CT, MR and PET imaging findings. Insights Imaging 2014;5:473–82.
K. S. Brogan, BSc D. Eleftheriou, PhD University College London Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust L. Biassoni, MSc, FRCP N. Sebire, FRCPath Great Ormond Street Hospital NHS Foundation Trust P. A. Brogan, FRCPCH, PhD University College London Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust London, UK
