PROSTHETIC REHABILITATION WITH AMYLOIDOSIS OF THE TONGUE

Managing oral side effects of systemic diseases

Sarah Kay Youny Lee, DDS, MS, FACP

Olivia Muller, DDS, FACP

Chad Rasmussen, DDS

Mayo Clinic

Department of Dental Specialties

200 First Street SW

Rochester, MN 55905

Corresponding author:

Sarah Kay Youny Lee, DDS, MS, FACP

Mayo Clinic

Department of Dental Specialties

200 First Street SW

Rochester, MN 55905

lee.sarah1@mayo.edu

This work has not been previously presented. No financial disclosures are present. No other

conflicts of interest are present.

This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process, which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1111/jopr.13236.

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ABSTRACT

Amyloidosis of the tongue can result in significant and irreversible alterations of tooth

position and function due to prolonged application of imbalanced force on the teeth by the

enlarged tongue. Due to the rarity of this oral form of systemic disease, little has been

elucidated on management of the resulting impaired oral function. While surgery can address

the size of the tongue, it carries significant morbidities, enlargement can recur, and does not

address adverse tooth positioning. Prosthetic rehabilitation can more aptly restore oral

function but it also needs to be tailored based on the patient’s expectations and goals as well

as biologic and mechanical parameters of treatment. This report discusses an effective and

non-invasive application of a tooth-supported, removable prosthesis with an onlay occlusal

design to restore occlusion, speech, and esthetics in a patient with tongue-based amyloidosis.

INTRODUCTION

Macroglossia is an uncommon finding in patients with amyloidosis. The deposition of

amyloid, light chain (AL) type-monoclonal immunoglobulin (Ig) within the tongue correlates

to a systemic disease.1-3 The enlargement of the tongue is irreversible and significantly

impairs oral functions like speech, mastication, and deglutition due to both obstruction by the

tongue but also shifting of tooth form.

Few publications delve into the management of this form of macroglossia and

treatments vary from conservative tooth adjustments to more invasive options like radiation

therapy and surgery.4-7 Surgical intervention is indicated only in cases of severe disability,

like a risk of airway obstruction, as the morbidity is significant and relapse of the tongue

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enlargement often occurs.4-6 At the time that this report was written, no literature on the

prosthodontic management of macroglossia related to amyloidosis has been published.

This clinical report discusses the use of a removable prosthesis to improve both

function and esthetic needs in a patient with macroglossia that irreversibly changed tooth

alignment and occlusion. Creative applications of basic prosthodontic principles enabled a

successful, expedient, and non-invasive oral rehabilitation.

Clinical report

A 64-year old male presented with a history of multiple myeloma, bilateral carpal

tunnel syndrome, and macroglossia secondary to amyloidosis. His symptoms were first noted

in 2011, when the patient complained of a swollen tongue. The tongue enlargement

progressed through the next year, prompting a biopsy that demonstrated Lambda light chain

amyloid deposition. The patient had no other symptoms or signs related to peripheral

neuropathy, congestive heart failure, proteinuria, abnormal renal and hepatic function, or

skeletal lytic lesions. Laboratory studies showed an abnormally large IgG Lambda

gammopathy band with suppressed IgA and IgM levels, though B2 microglobulin, albumin,

and LDH levels were normal. Based on these clinical and laboratory findings, the patient was

diagnosed with stage 1 IgG Lambda myeloma associated with AL systemic amyloidosis.8

Initial treatment consisted of various combinations of chemotherapy drugs including

regimens of bortezomib, cyclophosphamide, and dexamethasone followed by lenalidomide,

bortezomib, and dexamethasone. He also underwent an autologous stem cell transplantation.

Consolidation therapy resulted in a partial response and he continued on maintenance therapy

until April 2015 when the disease was determined to be stable. In 2017, the patient reported

increased tongue enlargement that compromised speech and swallowing, with occasional

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salivary gland obstruction and worsening symptoms with severe chronic lower back pain and

left knee arthritic pain. Disease progression was observed with a marrow biopsy showing an

increase of monoclonal plasma cells, but with a diagnosis of AL amyloidosis as opposed to

myeloma. Chemotherapy was re-initiated using a daratumumab with pomalidomide and

dexamethasone combination for 12 cycles. He was then transitioned to maintenance

monotherapy consisting of daratumumab administered every 6 weeks.

As the patient was undergoing care, he observed shifting of his mandibular dentition

that accompanied tongue enlargement. By May 2019, the patient reported having limited

tooth contacts only between the maxillary and mandibular incisors. He was subsequently

referred for management of malocclusion. Clinical examination at the time of initial

presentation revealed no significant extra-oral asymmetries, lymphadenopathies, trismus,

TMJ abnormalities, nor lip incompetence. The patient had a reverse smile line frontally and

his facial profile was concave, indicative of a skeletal class III relationship (Fig 1).

Intraorally, the patient had bilateral posterior crossbite with end-to-end anterior relationship

(Fig 2). A bilateral posterior open bite ranging 4-7mm of interocclusal space and tooth

contacts limited to the maxillary and mandibular incisors were observed. A reverse curve of

Wilson was present due to significant facial tipping of the mandibular posterior dentition.

The tongue demonstrated diffuse enlargement with bilateral tongue biting. No significant

mobility of dentition was observed, though severe generalized clinical attachment loss was

present. Non-carious cervical lesions were associated with teeth #11, 12, 20, 21, 22.

Moderate to severe attrition was observed on the incisal-lingual surfaces of the maxillary

incisors and occlusal-facial surfaces of the mandibular incisors, canines, and premolars.

Existing dental restorations were intact without signs of secondary disease or new carious

lesions. Panoramic and lateral cephalometric radiographs were obtained. The panoramic

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radiograph revealed no significant periapical pathology (Fig 3). Bilateral sinus

pneumatization was observed and moderate generalized horizontal bone loss was present in

the posterior mandibular segments. Root apices associated with teeth #18, 19, 30 appeared

radiographically foreshortened due to significant tooth angulation. A Class III skeletal

relationship characterized by a hypoplastic maxilla and optimally positioned mandible in the

anterior-posterior dimension was observed (Fig 4). Maxillary and mandibular incisors

demonstrated no significant facial or lingual inclinations. Vertical dimensions were

appropriate.

In discussing treatment goals, the patient expressed his desire to improve mastication

and esthetics with non-surgical intervention. A removable prosthesis was proposed as a

conservative treatment modality to improve occlusion, mastication, and esthetics. The

rehabilitation was staged in interim and definitive phases to allow for adequate assessment of

feasibility and optimization of prosthetic design.

Intraoral scanning of the maxilla and mandible was completed (Itero Element,

OrthoCAD 5.7.0.301 software, Cadent LTD, Align Technology Inc., San Jose, CA, USA)

and diagnostic casts were 3D printed. Silicone molds (Wirosil, Bego, Pawtucket, RI) of the

printed casts were fabricated for duplication and poured in type IV stone (Silky- Rock; Whip

Mix Corp, Louisville, KY). A wax occlusal rim was fabricated with indexing against the

mandibular incisal and occlusal surfaces. The rim was used to test an opened occlusal vertical

dimension (OVD) that would provide interocclusal space between the anterior dentition of at

least 2 mm to accommodate for an acrylic resin onlay. At the increased OVD, lip

competence, phonetics, swallowing of fluid, and patient comfort were evaluated and found

satisfactory. Aluwax (Aluwax Dental Products, Allendale, MI) was applied to the

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mandibular wax rim and a centric relation (CR) record was made by bimanual manipulation

of the mandible.9

The record was then transferred to articulate the printed casts. Duplicate stone casts

were also cross-mounted to the articulated printed casts. A provisional prosthesis was

designed with ball clasps engaging tooth embrasures between mandibular canines, premolars,

and 1st molars. Baseplate wax was used to design the overlay portion of the prosthesis,

covering the lingual and occlusal surfaces of the mandibular dentition. Bilateral posterior

occlusal contacts were established with light contact in the anterior segment. The provisional

prosthesis was then heat processed in clear acrylic resin (Orthodontic Resin, DENTSPLY

Caulk, Milford, DE).

Occlusal adjustments were made to ensure appropriate occlusal contact at the

premolar to molar dentition with light occlusal contact against the anterior dentition (Fig 5).

Laterotrusive and mediotrusive movements were guided by the canines and first premolars

and protrusive movement was guided by incisors and canines. The patient used the interim

prosthesis for 4 months since he was unable to return for a 6-8 week follow-up. He tolerated

the prosthesis well at the increased OVD and reported significant improvement in his ability

to masticate without interferences to speech and deglutition. The prosthesis remained

retentive and stable throughout the interim phase.

With the provisional prosthesis in place, a new CR record was made with poly(vinyl

siloxane) bite registration material (Blu-Mousse, Parkell, Edgewood, NY, USA) and a

clinical remount was completed. The provisional prosthesis was seated on the mandibular

cast, and then re-articulated to the mounted maxillary mounted with the new CR record.

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 The definitive removable prosthesis was designed based on the interim prosthesis.

The framework was fabricated in cobalt chromium alloy (Vitallium 2000 Plus, Dentsply

International, York, PA, USA), with a lingual plate design on all the mandibular dentition and

posterior occlusal contacts on metal. The patient’s existing casts were surveyed to evaluate

retentive areas; wear facets on the canines and premolars provided the most favorable

undercuts for retention.

The cast metal framework was seated on the 3D-printed, articulated cast and a

diagnostic wax-up of the incisal onlay was completed (Fig 6). After a silicone matrix of the

wax-up was made, the wax was removed and composite resin (Radica, Dentsply

International, York, PA, USA) was used in conjunction with the silicone matrix to fabricate

the incisal onlay, integrated within the framework. Composite resin material was added

directly to the posterior aspects of the framework to create the buccal surfaces of the posterior

dentition (Fig 7). Upon achieving complete seating, retention, and stability of the prosthesis,

adjustments were made intraorally to ensure appropriate posterior occlusal contacts and

minimal anterior contacts, absence of mediotrusive occlusal contacts, and tooth guidance

primarily by first premolars and canines in laterotrusion and by the incisors during protrusion.

The patient was satisfied with the oral function and esthetics achieved with the

definitive prosthesis. He required no significant adjustments to the prosthesis after 24 hours

and one-week post-insertion visits. He wears the definitive prosthesis at all times with

exception of nocturnal sleep – at which time he uses the interim prosthesis as an occlusal

guard. He continues to report satisfactory utilization of the prosthesis.

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Discussion

AL amyloidosis can occur as a complication of multiple myeloma due to monoclonal

plasma cell expansion, IgH translocations, and dysproteinemia.10, 11 The course of therapy

and prognoses differ depending on disease involvement to various organs and structures.1, 10,
12
The systemic form of the amyloidosis carries a poor long-term prognosis and highest rate

of mortality since the heart, kidneys, nerves, gastrointestinal tract, and muscles are often

affected. This patient’s form of the disease was particularly rare, as the amyloidosis was

localized within the head and neck region.

The position of teeth within the alveolus is dependent on the balance of forces

delivered by the tongue on the lingual and the lips and cheeks on the facial and buccal.13 The

patient’s acquired macroglossia resulted in a disequilibrium of forces delivered by the tongue

on the lingual, and resulted in severe buccal inclination displacement of the posterior

dentition. Intrusive forces placed on these same teeth are likely the result of the tongue

encroachment on the interocclusal space, evidenced by the presence of continuous biting of

the tongue.

In reviewing options for prosthetically managing the displacement of teeth and

malocclusion that resulted from the macroglossia, the following prosthodontic routes could

be explored: an implant-supported prosthetic rehabilitation, tooth-supported fixed dental

prosthesis (FDP), and removable dental prosthesis (RDP).

An implant-based rehabilitation has the benefit of restoring tooth form and function.

Biologically, osseointegration has not been shown to be necessarily impaired in patients with

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significant medical co-morbidities.14 But, implant restorations require adequate alveolar bone

quantity and quality for implants to be appropriately placed so that the implant long axes are

parallel to and directly supporting forces from occlusal loading of the prosthesis.15

Additionally, pre-prosthetic procedures, including extractions and bone augmentation, not

only require more surgeries, but also prolong the time to actual prosthetic insertion. Although

this treatment option could be considered, significant time investment and increased surgeries

can be not ideal or unrealistic.

Restoration with FDPs would entail placement of onlays and new full coverage

crowns that would replace the existing crowns. These tooth-supported, indirect restorations

have had good long-term success and survival, but are still prone to complications that can be

exacerbated by the initial compromised state of the foundational tooth form.16 Re-establishing

occlusion on teeth that have significant tipping carries risks. Increases in the level and

frequency of loading in a non-axial direction can occur and place teeth under the risk of

fatigue fracture.17, 18 If treated with individual tooth restorations, no rigid splinting would be

present to prevent further tooth movements. Even if the crowns were splinted together, it

would not be sufficient to resist bodily movement when excess soft tissue forces are applied

by the tongue over time. Splinted restorations are also more challenging to maintain

hygienically and thus, increase risks of development of complications like secondary caries

and periodontal diseases. This treatment would be less invasive than implant surgery, but it

still requires irreversible changes to a majority of the existing natural dentition and impact a

tooth’s health and vitality.

Tooth-supported RDPs with an overlay component have been used to re-establish the

occlusal plane and support an opened occlusal vertical dimension.19-23 This prosthetic option

requires minimal changes to existing dentition and can be produced and utilized in a quicker

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timespan. In spite of its conservative nature, techniques in planning, designing, and inserting

a RDP are complex. Design choices are dictated (and limited) by factors like oral health

status that would be conducive to support a removable, tooth-retained prosthesis, obtaining or

creating an appropriate path of draw for prosthesis insertion and removal, and identifying

undercuts and contours on abutment teeth to provide sufficient retention.24-26 Even with an

accurate impression, conventional casting of the framework is also technique sensitive and

the fit can be inaccurate due to errors inherent with this process.27 Compounded errors can

ultimately compromise the stability and quality of the prosthesis. Misfits and the frequency of

adjustments to accommodate for compromised stability can decrease the RPD’s utility,

functionality, and acceptability by the patient.28 The RDP clasping and overlay also

compromise esthetics as these components do not replicate natural tooth form. The technique

sensitivity of treatment and esthetic limitations of an RDP should be considered in this

option.

This patient did not desire any surgery and, given the reversibility and conservative

nature of removable prosthesis, elected to pursue this mode of treatment. Although the

procedures required planning, additional laboratory steps, and patient compliance for wear

and maintenance of the prosthesis, the patient’s care goals were achieved. Future

considerations to this treatment would include continual and routine monitoring to assess for

further tooth movements or size changes to the tongue. Although the RDP’s major connector

plates against the lingual aspects of the natural dentition and the onlay component indexes to

the occlusal surfaces, the splinting capability is not known. Immobilization of these teeth in a

splinted manner may help to limit further displacement if the tongue enlarges, but we did not

find any study that has explored the long-term outcomes of prosthetic-based intervention in

patients with macroglossia. The longevity of this prosthesis is unknown; but, its conservative

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nature makes this treatment both viable and beneficial for this patient in the immediate future.

Given the stability of his multiple myeloma, if the tongue size remains consistent, then we

can anticipate that the prosthesis will function for the long-term. Even as an interim

application, this rehabilitation would appropriately address functional needs while other

definitive options are being evaluated. This treatment could also be better translated into a

digital platform to decrease laboratory procedures and sources of error inherent with analog

methods of impression or fabrication of the prosthesis.

Summary

A tooth-supported overlay prosthesis can be considered as a timely and effective

solution for rehabilitation of a migrated tooth position secondary to macroglossia.

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FIGURES LEGEND

Figure 1. Pre-treatment frontal and lateral extraoral views

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Figure 2. Pre-treatment frontal and lateral intraoral views of teeth in maximal intercuspation.

Figure 3. Pre-treatment panoramic radiograph

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Figure 4. Pre-treatment lateral cephalometric radiograph

Figure 5. Frontal and lateral intraoral view of the inserted provisional prosthesis

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Figure 6. Frontal view of the framework and diagnostic wax-up of the onlay anterior

mandibular dentition

Figure 7. Frontal intraoral view of the inserted definitive prosthesis

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