Oral Amyloidosis - Clinical Features, Diagnosis, and Treatment

Introduction:

Amyloidosis is a rare disease characterized by the pathologic deposition of proteins called amyloid proteins. The systemic form of amyloidosis commonly affects the majority of individuals. However, a localized buildup of amyloid proteins in the oral cavity causes several manifestations that should be diagnosed promptly. Oral amyloidosis can manifest as systemic or abnormal deposition of misfolded and insoluble amyloid fibrils locally within the oral structures.

What Are the Clinical Features of Oral Amyloidosis?

Among the cases of oral amyloidosis reported, the most common sites for localized amyloid deposition are the tongue, non-keratinized buccal mucosa, and gingiva. The clinical presentation of oral amyloidosis is based on the location of amyloid deposition and its severity.

The most common clinical features seen in oral amyloidosis are:

• Macroglossia: There is an unconventional enlargement of the tongue due to amyloid precipitation in the tongue. The formation of insoluble fibrils in oral amyloidosis causes penetration of these fibrils into the connective tissue component or the extracellular matrix. This causes the tongue to swell up and enlarge, secondary to fibril deposition. As the infiltration of the amyloid proteins continues, the structural integrity of the tongue becomes lost. The infiltrative process is progressive, meaning that as more amyloid proteins deposit over time, the degree of enlargement becomes more pronounced. The tongue appears smooth and waxy in oral amyloidosis, which is also a direct consequence of these amyloid deposits altering the normal tissue structure of the tongue.

• Nodular Formation: A solid lesion more than 10 millimeters in diameter can be noticed anywhere in the buccal mucosa, tongue, and gingiva. This lesion can be palpable and appears yellow to whitish. Yellowish nodules with a translucent bluish hue are also noted in some cases. In rare cases, the nodules or papules may also appear on the commissures of the lips.

• Plaque Formation: In regions of severe amyloid deposition, a localized (circumscribed) elevated lesion measuring more than one centimeter can be noted. The plaque will mostly be non-scrapable.

• Ulcer Formation: Persistent and non-healing ulcers are characteristic of amyloidosis in the oral cavity. These can cause severe discomfort and other infections secondary to ulceration.

• Dry Mouth: Amyloid deposition can be noticed in the salivary glands. This reduces the gland's ability to secrete the necessary amount of saliva in the oral cavity. As a result, dry mouth is noted, and secondary to the incidence of dry mouth, affected people may have an increased incidence of dental caries. People with such amyloidosis may find it difficult to form words and speak.

• Gingival Enlargement: Amyloid proteins accumulate within the gingival tissues, manifesting as gingival enlargement or hyperplasia. Localized gingival enlargement can occur when the deposition occurs at a specific gingival site. In most cases, generalized gingival hyperplasia is noted in oral amyloidosis.

• Hemorrhagic Spots: Localized formation of bleeding spots in the tongue and palate are common in localized oral amyloidosis.

Secondary Clinical Features of Oral Amyloidosis:

Such clinical presentations of oral amyloidosis can cause secondary complications, which include:

• Dysphagia.

• Difficulty in phonation.

• Difficulty in opening and closing the mouth.

• Secondary oral infections.

• Dental caries.

• Difficulty in breathing as the tongue enlarges and obstructs the airway.

• Tongue protrusion beyond the alveolar ridge.

• Indentations of the teeth on the smooth, waxy-appearing tongue.

How to Diagnose Oral Amyloidosis?

• History taking can reveal that the patient may be suffering from comorbidities like multiple myeloma that predispose to the incidence of oral amyloidosis. A general intraoral examination can reveal the presence of an enlarged tongue, a generalized occurrence of yellowish nodules and papules, and hemorrhagic spots.

• An excisional biopsy may be performed on smaller nodules, and in cases of large nodules, an incisional biopsy will be performed. The biopsied tissue will be sent for histopathological investigation.

• The specimen may reveal the presence of amyloid deposits within the connective tissue compartment. Congo red staining will be done to the biopsied tissue to confirm the diagnosis of localized oral amyloidosis. When placed under polarized light, Congo red-stained tissues may show apple-green birefringence when amyloid deposits are present in the extracellular matrix.

• Immunohistochemical staining will be indicated to identify the exact type of amyloid deposit (for example, AL or AA).

• Investigations should also focus on the presence of systemic amyloidosis as it can cause oral manifestations as well. The investigations indicated to diagnose systemic amyloidosis include serum marker tests for amyloidosis (serum amyloid P component) and urine test to detect Bence-Jones protein.

• MRI and CT scans can elicit the involvement of the organs and the extent to which amyloid fibrils are deposited in the vital organs.

• If AL amyloidosis is considered to be causing the oral manifestations, then a bone marrow biopsy is certainly needed to detect blood dyscrasias.

• Specialized tests that have the unique ability to identify amyloid deposits are used in recent days. This includes tests like SAP scintigraphy (amyloid detection with Iodine-132) and fat pad aspiration (where adipose tissue will be aspirated to look for amyloids).

How to Manage Oral Amyloidosis?

Managing Oral Manifestations:

• Oral amyloidosis can be managed initially with symptomatic treatments. People with localized oral amyloidosis should be taught the right way to brush and floss, as errors in these methods can cause infectious agents to easily affect the oral tissues (leading to oral infections).

• Saliva substitutes are the best possible ways to combat xerostomia (dry mouth) due to amyloidosis.

• In regions where ulcers cause inflammation and pain, patients will be given topical creams and gels containing NSAIDs.

• For patients with macroglossia affecting routine functions and breathing, a debulking surgery (glossectomy) will be performed. This can help the patients to breathe and speak normally.

• Nodules and papules all over the oral cavity can be excised.

Managing Systemic Manifestations:

• Systemic therapy is necessary in cases where systemic amyloidosis is causing oral manifestations. Chemotherapy for AL amyloidosis will be given with the primary objective of reducing the production of amyloidogenic light chains.

• Recently, immunotherapy targeting the amyloid fibrils has been used for better efficiency.

• Vital organ involvement due to amyloid deposition will be treated accordingly. For example, patients with cardiac amyloidosis will be given diuretics, and patients with renal amyloidosis may even require a renal replacement.

Conclusion:

Oral manifestations due to amyloidosis can cause significant barriers to communication and breathing. But localized oral amyloidosis generally has a better prognosis compared to systemic amyloidosis. So, people with oral amyloidosis may require frequent intraoral assessments for better and prompt management of the condition.