Bockenhauer, D

El-Desoky, SM

Kari, JA

Sawan, ZA

Shalaby, MA

UCL Discovery

 Facial Swelling in a child on chronic hemodialysis    1Zinab A. Sawan, 1Sherif M El-Desoky, 1Mohamed A. Shalaby, 2Detlef Bockenhauer, 1Jameela A.Kari,    1Department of Pediatrics, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia and 2Department of Paediatric Nephrology, , Great Ormond Street Hospital for Children NHS Trust, London, WC1N 3JH, UK              Corresponding Author: Name: Zinab A. Sawan  Address: King Abdul-Aziz University, PO Box   80215, Jeddah 21589, Kingdom of Saudi Arabia Phone number: +996 505677904 E-mail address: zenab.a.sawan@gmail.com Answers:  Question 1. CT images show multiple, expansible osteolytic lesions involving the mandible and maxilla, with variability in size. The largest involving the body of the left mandible measuring 3.7 x 37.7 x 31.9 cm with cortical expansion, erosions, and multiple loculations. No peri-osteal reaction and no definite associated soft tissue masses.    Question 2. Brown tumor of the mandible due to secondary hyperparathyroidism (SHPT)   Question 3.  The management of brown tumor depends on the severity of the lesion. Control of hyperparathyroidism is critical as normalization of parathyroid hormone (PTH) levels will typically lead to the regression of tumor size or even its resolution. Surgical resection might be indicated for large, disfiguring tumors which fail to regress by medical treatment.  Parathyroidectomy as well as renal transplantation could resolve the tumor.   Question 4. Cinacalcet is a calcimimetic that targets the calcium sensing receptors on the parathyroid cells, thereby down regulating PTH levels and subsequently serum calcium and phosphate levels in renal failure. It significantly reduces PTH levels in patients with SHPT on dialysis and could help in regression of the tumor.          Discussion:  We present a case of Brown tumor in young child originating from the cranio-facial bones associated with refractory SHPT. Chronic kidney disease (CKD) is associated with a disturbance of mineral and bone homeostasis. This condition is termed CKD-mineral bone disorder (CKD-MBD) and represents an obstacle to optimal bone strength, final adult height, and cardiovascular health (1).  Impaired renal function with progressive glomerular filtration rate (GFR) reduction stimulates a number of compensatory mechanisms, including the increase of bone fibroblast growth factor-23 (FGF-23) FGF23 binds to its receptor FGFR1 and co-receptor Klotho in the kidney, with a key consequence in CKD being reduced 1-hydroxylase activity, resulting in decreased circulating 1,25 (OH)2 D with consequent SHPT) (2). High-turnover renal osteodystrophy and osteitis fibrosa cystica are the consequences of these changes (3).  Chronic hyperparathyroidism increases bone remodeling leading to rapid osteoclastic activity, erosive bony lesions and peritrabecular fibrosis which can result in a local destructive phenomenon called Brown tumor(4). Bone pain and fractures are common complications (5, 6). Brown tumors can be located in any part of the skeleton, but are most frequently encountered in the ribs, clavicles, extremities, and pelvic girdle. Clinically significant lesions in the craniofacial or orbital bones are rare (7,8,9). Costal lesions are more frequent than spinal lesions (6).  It can also be multifocal (6). It has also been reported in children on prolonged hemodialysis (10, 11). A brief review of published pediatric cases is summarized in Table 1.   The diagnosis of Brown tumor is established through medical history, clinical examination, laboratory findings and radiological imaging. Borzych et al, reported that at least one in six children on chronic dialysis show radiological and/or clinical signs of bone disease and 44% developed severe secondary HPT with PTH levels five times above the upper limit of normal, with a 10% higher likelihood of developing severe HPT for each year on dialysis (12). This fits with our case who had been on long-term dialysis for 7 years, increasing the risk of complications associated with end stage kidney disease (ESKD), including CKD-MBD and Brown tumor. Our patient had persistent hyperphosphatemia and poor metabolic control despite his regular hemodialysis. Compliance with medications was thought to be inconsistent. Potentially, more frequent and/or prolonged dialysis would have prevented or ameliorated the complications. Cinacalcet was added to his medications at 10-years of age, without significant reponse, again potentially reflecting poor compliance or refractory SHPT. Cincalcet is a calcimimetic that down regulates PTH levels and subsequently serum calcium and phosphate levels in patients with SHPT on dialysis (13). Treatment with cincalcet for nine months showed evidence of revision of high bone turn-over bone disease towards normal in the majority of patients, based on histomorphometry (2), However its use in children is not approved by the Food and Drug Administration (FDA). Pediatric clinical trials are on hold following the death of a 14-year-old patient in February 2013 (14).   Parathyroidectomy (PTX) is another potential treatment option in severe renal HPT refractory to medical treatment. Hypoparathyroidism is a potential complication after extended PTX. Supplementation with calcium and activated vitamin D is needed in these patients to prevent hypocalcaemia with all its clinical manifestations, such as seizures, tetany and arrhythmia. Symptomatic hypocalcaemia is most likely occur in patients with poor compliance with medications. PTX needs to be carefully considered in each individual patient. Timing and extent of parathyroidectomy require an interdisciplinary approach from both nephrologist and endocrine surgeons (15).  One potentially overlooked contributor to CKD-MBD is metabolic acidosis as it results in bone demineralization and release of sodium, potassium and calcium. Furthermore metabolic acidosis stimulates osteoclasts and suppresses osteoblasts activity leading to direct dissolution of bone (16). Graham et al concluded that correction of metabolic acidosis increases the sensitivity of parathyroid gland to the ionized calcium leading to its suppression (17).    Normalizing PTH level with medications, dialysis, parathyroidectomy, or kidney transplantation will often lead to tumor regression or resolution (4). Surgical resection of a Brown tumor should only be considered if the patient needs quick resolution if it is compromising body functions or promoting facial deformation (18).   The management of CKD-MBD remains a challenge in children with ESKD. Our case demonstrates the importance of meticulous attention to markers of CKD-MBD, their correction with medications and/or intensified dialysis and, ideally, early renal transplantation to prevent such serious complications.   First Author Age, years Gender (M/F) HD Duration, years Location PTH (pmol/L) Treatment Responce Youssef 2016 (11) 13 - 4 mandible 602 Complete surgical excision -   Szeverényi_  2011 (19) 9 M Presented late Vertebrae (C1-T2) 188.5 Complete surgical excision PTH level remained high Karabekmez 2008 (20) 11 M 4 Maxilla & mandible 2,528 None Died before surgery Tarrass 2008 (8) 18 M 6 Mandible 1,335 Subtotal parathyroidectomy Significant reduction in the tumor size (Table 1): A brief review of published pediatric Brown Tumor cases             References:   1.  Bacchetta J, Harambat J, Cochat P, Salusky IB, Wesseling-Perry K. The consequences of chronic kidney disease on bone metabolism and growth in children. Nephrol Dial.Transplant. 2012; 27 (8):3063-3071  2.  Drueke TB, Massy ZA. Changing bone patterns with progression of chronic kidney disease. Kidney Int. 2016; 89 (2):289-302  3.  Wesseling-Perry K, Salusky IB. Chronic kidney disease: mineral and bone disorder in children. Semin.Nephrol 2013; 33 (2):169-179  4.  Triantafillidou K, Zouloumis L, Karakinaris G, Kalimeras E, Iordanidis F. Brown tumors of the jaws associated with primary or secondary hyperparathyroidism. A clinical study and review of the literature. Am.J.Otolaryngol. 2006; 27 (4):281-286  5.  Fatma LB, Barbouch S, Fethi BH, Imen BA, Karima K, Imed H, Fethi eY, Fatma BM, Rim G, Taieb BA, Maiz HB, Adel K. Brown tumors in patients with chronic renal failure and secondary hyperparathyroidism: report of 12 cases. Saudi.J.Kidney Dis.Transpl. 2010; 21 (4):772-777  6.  Gorsane I, Zammouri A, El MJ, Younsi F, Bartkiz A, Abdelmoula J, Barbouch S, Ben AT. [Brown tumors in chronic hemodialysis patients]. Nephrol.Ther. 2016; 12 (2):86-93  7.  Tarrass F, Benjelloun M, Bensaha T. Severe jaw enlargement associated with uremic hyperparathyroidism. Hemodial.Int. 2008; 12 (3):316-318  8.  Gonzalez-Martinez E, Santamarta-Gomez D, Varela-Rois P, Garcia-Cosamalon J. Brown tumor of the orbital roof as an initial and isolated manifestation of secondary hyperparathyroidism. Orbit. 2010; 29 (5):278-280  9.  Can O, Boynuegri B, Gokce AM, Ozdemir E, Ferhatoglu F, Canbakan M, Sahin GM, Titiz MI, Apaydin S. Brown Tumors: A Case Report and Review of the Literature. Case.Rep.Nephrol.Dial. 2016; 6 (1):46-52  10.  Youssef DM, Mohammed FF, Adham T. Mandibular mass in a child on hemodialysis. Saudi.J.Kidney Dis.Transpl. 2016; 27 (1):144-146  11.  Krause I, Eisenstein B, Davidovits M, Cleper R, Tobar A, Calderon S. Maxillomandibular brown tumor--a rare complication of chronic renal failure. Pediatr.Nephrol. 2000; 14 (6):499-501  12.  Borzych D, Rees L, Ha IS, Chua A, Valles PG, Lipka M, Zambrano P, Ahlenstiel T, Bakkaloglu SA, Spizzirri AP, Lopez L, Ozaltin F, Printza N, Hari P, Klaus G, Bak M, Vogel A, Ariceta G, Yap HK, Warady BA, Schaefer F. The bone and mineral disorder of children undergoing chronic peritoneal dialysis. Kidney Int. 2010; 78 (12):1295-1304  13.  Ballinger AE, Palmer SC, Nistor I, Craig JC, Strippoli GF. Calcimimetics for secondary hyperparathyroidism in chronic kidney disease patients. Cochrane.Database.Syst.Rev. 2014;  (12):CD006254  14.  FDA. FDA Drug Safety Communication: Pediatric clinical studies of Sensipar (cinacalcet hydrochloride) suspended after report of death. FDA . 2014. (GENERIC) Ref Type: Electronic Citation 15. Lorenz K, Bartsch D, Sancho J, Guigards S, Triponez F, Surgical management of secondary hyperparathyroidism in chronic kidney disease- a consensus report of the European society of endocrine surgeons. Langenbecks Arch Surg(2015) 400:907-927  16.  Bailey JL. Metabolic acidosis: an unrecognized cause of morbidity in the patient with chronic kidney disease. Kidney Int.Suppl 2005;  (96):S15-S23  17.  Graham KA, Hoenich NA, Tarbit M, Ward MK, Goodship TH. Correction of acidosis in hemodialysis patients increases the sensitivity of the parathyroid glands to calcium. J.Am.Soc.Nephrol. 1997; 8 (4):627-631  18.  Leal CT, Lacativa PG, Gomes EM, Nunes RC, Costa FL, Gandelmann IH, Cavalcante MA, Farias ML. Surgical approach and clinical outcome of a deforming brown tumor at the maxilla in a patient with secondary hyperparathyroidism due to chronic renal failure. Arq Bras.Endocrinol.Metabol. 2006; 50 (5):963-967 19. Szeverenyi C, Dezso B, Demenyi T, Csernatony Z, Vertebral brown tumor in childhood (case report), Surgical science,  2011, 2,244-347 20. Karabekmez FE, Duymaz A, Keskin M, Tosun Z: Huge deforming brown tumour of the maxilla and mandible in a patient with secondary hyperparathyroidism. J Plast Reconstr Aesthet Surg 2008;61:1404–1405.    

Facial swelling in a child on chronic hemodialysis: Answers

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Facial swelling in a child on chronic hemodialysis: Answers

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