Uremic Leontiasis Ossea

Case report

1. 1

Title Page
Uremic Leontiasis Ossea
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.

2. 2


Introduction:
Lion face syndrome or 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).

3. 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.

4. 4

The patient showed a 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).

5. 5

When untreated bone remodeling 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.

6. 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.

7. 7





Image 1: Lion-face features.

8. 8




Figure 1: Ca and 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
201020112012201320142015201620172018201920202021
Calcium
Phosph
orus
Calcium and PhosphateLevels

9. 9

PTH trend over follow up time.






Image (3): coronal sections showing bony growth and bone demineralization.

10. 10




Image (4) Lateral skull CT scan. Maxillofacial protruding and skull changes. pepper pot” appearance.

11. 11




Image (5): Parathyroid nodule

12. 12







Image (6) Right Humerus fracture

13. 13



Image (7) CT scan of the Lumbosacral spine. Collapsed fractures of vertebrae; T12, L1& L2.

14. 14



Image (8) DEXA SCAN

15. 15



Figure 2: Phosphate and calcium homeostasis in normal kidney function. Image created using Servier
Medical Art.