Uremic Leontiasis Ossea

Uremic Leontiasis Ossea

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  1 Title Page Uremic LeontiasisOssea A Case Report Sara W. Fakhredine(1) , Jafar Alsaid(2) , Teerath Kumar(1) , Rayees Yousif Sheikh(1). 1 Division of Nephrology and Hypertension, Department of Internal Medicine, Bahrain Specialist Hospital, Bahrain. 2 Ochsner Health Center, New Orleans Louisiana. USA. Queensland University Australia. Corresponding author: Jafar Alsaid, M.B.ChB, MD. FASN. FACP. Assistant Professor University of Queensland- Ochsner Clinical School. Nephrology and Interventional Consultant Ochsner Medical Center. New Orleans, Louisiana, USA Clinic building, fifth floor. Nephrology Department. 1514 Jefferson Hwy, LA 70121 Conflict of Interest: The authors declared no conflicts of interest. Funding: The authors received no financial support.
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  2 Introduction: Lion face syndromeor leontiasis ossea is a rare complication of severe hyperparathyroidism in end-stage renal disease patients (1). It is a severe form of bone remodeling characterized by abnormal bone mineralization with diffuse enlargement of the facial bones, particularly the maxilla and mandible. Bone expansion results in facial disfigurement that appears in some cases like a lion's face (2). Given the widespread use of dialysis, calcimimetics, and phosphate binders, Uremic Leontiasis Ossea (ULO) is rare these days (3). We are presenting a clinical case of this rare complication in an ESRD patient. The clinic presentation, pathophysiology, and management will be discussed according to the latest published data. Clinical history and progress: A 37-year-old female patient was seen in the renal clinic in September 2008. She had a past medical history of recurrent UTIs during childhood, hypertension since the age of 14, hyperuricemia, morbid obesity, hypothyroidism, depression, and CKD. A kidney biopsy showed FSGS with focal collapsing features with moderate arteriosclerosis and severe interstitial fibrosis with approximately 90% tubular atrophy. In October 2010, she progressed to ESRD and was started on Hemodialysis. A few years after the initiation of dialysis, the patient secondary hyperparathyroidism was noticed to be uncontrolled. She was not compliant with dialysis sessions or medications and unfortunately, her condition progressed to tertiary hyperparathyroidism in 2015. The patient's case was refractory to medical treatment because of poor compliance. She refused surgery despite multiple attempts to convince her to get a parathyroidectomy. She continued having progressive facial changes with deformity in the maxillary and mandibular bone as well as severe osteoporosis. She had multiple fractures including left femoral, cervical, lumbar, and Tibia fractures. With time she developed calciphylaxis. Her main complaints were headache, diplopia on lateral gaze with nasal and gums bleeding in addition to bone pain secondary to the fractures. Her mobility was declining, and she was most of the time bound to a wheelchair. On physical exam, the patient had severe maxillary and mandibular bony prominence and enlarged gums with widening of the interdental spaces (Image 1). Her Ca, PO4, and PTH over the years are shown in figures(1 and 2). PTH levels were elevated and reached as high as 1600-5800 pg/mL. Maxillofacial CT showed a pepper pot appearance of the skull with markedly expansile facial and jaw bones (Images 2a, 2b & 3). Ultrasound of the neck showed bilateral hypoechoic nodules posterior-inferior to both thyroid lobes, the largest measuring 29 x 26 mm (Image 4).
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  3 Pathophysiology: During human growth,bone modeling will shape the skeleton. After maturity, bone remodeling takes place, and the old bone gets replaced by new bone through resorption and bone formation. In normal adults, bone resorption and formation are balanced, and any abnormality can result in an alteration of the bone mass. The major balance in this process is kept by the calcium-regulating hormones; parathyroid hormone (PTH) and calcitriol. With intact kidney, phosphate, and calcium concentrations are regulated through interaction between PTH, 1,25(OH)2D (calcitriol), Fibroblast growth factor-23 (FGF-23), and their principal targets: bone, kidney, the GI tract, and parathyroid glands (figure 2) (1). CKD-MBD is defined by KDIGO as a systemic disorder of mineral and bone metabolism due to CKD, manifested by a combination of factors including (i) changes in calcium, phosphorus, PTH, and vitamin D metabolism. (ii) variation in bone turnover, mineralization, volume, linear growth, or strength. (iii) vascular or other soft tissue calcification. (11) CKD-MBD is invariably present beyond CKD stage III. The treatment represents a significant clinical challenge. (1) Renal osteodystrophy is an alteration of bone morphology in patients with CKD leading ultimately to diminished bone strength. (11) When CKD develops, the loss of renal function will result in phosphate accumulation, and FGF-23 will increase causing decreased 1,25(OH) Vitamin D which will decrease serum calcium. This will increase PTH synthesis and release, resulting in secondary hyperparathyroidism. Prolonged stimulation of parathyroid tissue will cause clonal proliferation of Parathyroid cells with areas of nodular hyperplasia. Failure of the hyperplasic, overactive glands to be suppressed adequately in response to optimal medical therapy will result in tertiary/autonomous Hyperparathyroidism. The persistently elevated PTH will cause skeletal as well as non-skeletal complications such as LVH, cardiac fibrosis, extraskeletal calcifications, and peripheral neuropathy (1). Discussion: Secondary HPT is a frequent endocrinal disease in the CKD population. If untreated properly, this condition can evolve into severe skeletal disorders (renal osteodystrophy), in addition to high cardiovascular morbidity and mortality due to vascular calcifications (4). This was clear in our case, because of the poor compliance which led to the disease progression. Renal osteodystrophy can lead to numerous craniofacial changes, including demineralization or osteomalacia that can predispose to fractures, mixed osteolysis, and sclerosis that produce a salt- and-pepper appearance, brown tumors, and Uremic Leontiasis Ossea (ULO) (5). All these features are clearly illustrated in our patient's x-rays, skull CT scan, and DEXA scan.
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  4 The patient showeda pathognomonic facial deformity due to long-standing renal failure along with poorly controlled and progressive hyperparathyroidism. All the facial deformities and bony changes known as Uremic Leontiasis Ossea (ULO) are reported to be preventable if the Parathyroid disease is properly treated. The disease was first described in 1940 when the term ULO (lion head) was first used by Kienböck (3). It is a very rare manifestation of renal osteodystrophy and only a few cases have been published (5,6). It is characterized by the massive craniofacial bones thickening (5). Patients present typically with progressive painless jaw enlargement, widening of the nares, flattening of the nasal bridge, and increased interdental spacing. In addition, to the cosmetic impact, patients often suffer functional impairment, including dysphagia, speech impairment, respiratory distress, and cranial nerve paralysis that can lead to blindness. (7,3). ULO affects mainly young people, often with a long dialysis history. The major reported risk factors are attributed to insufficient access to healthcare with poor management of CKD-MBD control(8). ESRD patients who are non-adherent to hemodialysis regimens and medications are susceptible more to the disease (9). Both factors led to the form of severe Mineral bone deformity. The poor compliance and refusal to undergo Parathyroidectomy early in the disease course led to the continuous progression and development of multiple fractures. We do not have evidence of the bone healing process in such cases. We noticed that the pain was the main problem in our case and because she was immobile most of the time the functional impairment in her daily lifestyle was not appreciated. The physiopathology of ULO is unclear, however, there is a significant bone remodeling mainly in the facial bones compared to the rest of the skeleton. (8) Why this happens mainly in the face is not known. The diagnosis can be ascertained based on the combination of clinical picture, laboratory, and diagnostic imaging (7). The treatment for ULO usually includes (1) reduction of phosphate levels, (2) treatment for hyperparathyroidism, and (3) surgical contouring of the enlarged facial bones if needed (3). The standard management of secondary and tertiary hyperparathyroidism with consideration of parathyroidectomy (7). Percutaneous fine needle ethanol injection of the parathyroid gland and percutaneous injection using Calcitriol and vitamin D Analogue were other reported treatment options for non-surgical candidates. (10).
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  5 When untreated boneremodeling may cause progressive disfigurement, visual impairment, deafness, dysphagia, airway obstruction, and even compressive myelopathy (8). However, there are conflicting reports of partial improvement, stabilization, or worsening of facial deformity after parathyroidectomy. Alternatively, some patients may benefit from corrective reconstructive surgery (7). Keywords: Uremic leontiasis ossea, secondary hyperparathyroidism, lion face, ULO, CKD. References: 1)Simon Steddon, Neil Ashman, Alistair Chesser, John Cunningham. CKD-MBD Chapter 3 Chronic Kidney Diseases. Oxford handbook of nephrology and hypertension second edition. Oxford, Oxford University Press, 2014. 2) Heard B, Raj K, Yu FF, Agarwal A. Uremic Leontiasis Ossea. J Clin Imaging Sci. 2021 Apr 29;11:27. doi: 10.25259/JCIS_18_2021. PMID: 33948342; PMCID: PMC8088473. 3) Wang J, Zhao X, Shi H, Zhu L, Tao X. Radiological diagnostic features of uremic leontiasis ossea: a case report. Dentomaxillofac Radiol 2019; 48: 20190253. 4) Luchi, W.M., Vianna, J.G.P., Roberto, L.E.V. et al. Uremic leontiasis ossea. Endocrine 65, 707– 709 (2019). https://doi.org/10.1007/s12020-019-01976-z 5) Donoso-Hofer F, Gunther-Wood M, Romero-Romano P, Pezoa-Opazo N, Fernández-Toro MA, Ortega-Pinto AV. Uremic leontiasis ossea, is a rare presentation of severe renal osteodystrophy secondary to hyperparathyroidism. J Stomatol Oral Maxillofac Surg. 2018 Feb;119(1):56-60. doi: 10.1016/j.jormas.2017.10.006. Epub 2017 Oct 14. PMID: 29037869. 6) Gameiro J, Duarte I, Outerelo C, Lopes JA. Uremic lion face syndrome. J Bras Nefrol. 2019;41(2):304-305. doi:10.1590/2175-8239-JBN-2018-0198 7) Haroyan H, Bos A, Ginat DT. Uremic leontiasis ossea. Am J Otolaryngol. 2015 Jan-Feb;36(1):74- 6. doi: 10.1016/j.amjoto.2014.08.007. Epub 2014 Aug 20. PMID: 25224511.
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  6 8) Tassin C,Moscatelli L, Di Ascia L, Vacher-Coponat H, Gosset C. Reversible bone deformities in a severe case of uremic Leontiasis Ossea. J Nephrol. 2021 Jan 28. doi: 10.1007/s40620-021-00968- 5. Epub ahead of print. PMID: 33507522. 9) Nasra K, Dervishi M, Li S, et al. (October 20, 2020) Uremic Leontiasis Ossea in a Patient With End-Stage Renal Disease in Hemodialysis. Cureus 12(10): e11060. doi:10.7759/cureus.11060 10) Chandran M, Wong J. Secondary and Tertiary Hyperparathyroidism in Chronic Kidney Disease: An Endocrine and Renal Perspective. Indian J Endocrinol Metab. 2019;23(4):391-399. doi:10.4103/ijem.IJEM_292_19 11) KDIGO, Kidney Disease: Improving Global Outcomes. KDIGO clinical practice guidelines for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD) (2009). Kidney Int, 76 (Suppl 113), 1–132.
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  7 Image 1: Lion-facefeatures.
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  8 Figure 1: Caand PO4 trends 8.85 9.2 9.18 12.31 11.46 10.57 8.01 8.68 9.36 8.57 9.22 9.01 7.4 5.54 5.26 6.79 6 4.63 3.97 3.49 4.3 4.13 4.04 4.18 0 2 4 6 8 10 12 14 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 Calcium Phosph orus Calcium and Phosphate Levels
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  9 PTH trend overfollow up time. Image (3): coronal sections showing bony growth and bone demineralization.
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  10 Image (4) Lateralskull CT scan. Maxillofacial protruding and skull changes. pepper pot” appearance.
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  11 Image (5): Parathyroidnodule
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  12 Image (6) RightHumerus fracture
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  13 Image (7) CTscan of the Lumbosacral spine. Collapsed fractures of vertebrae; T12, L1& L2.
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  14 Image (8) DEXASCAN
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  15 Figure 2: Phosphateand calcium homeostasis in normal kidney function. Image created using Servier Medical Art.