Introduction

The tongue is the only organ of our body which doesn’t have bones. The tongue is a part of our oral cavity which helps in chewing food, swallowing, and phonation (speaking). The tongue also contains taste buds on the surface of it through which one can perceive different tastes.

Let's explore more about macroglossia and amyloidosis. 

Macroglossia: enlarged tongue

What is macroglossia?

Macroglossia is a condition characterized by an abnormal, huge tongue, and is also known as a giant or enlarged tongue. This enlargement of the tongue is painless. The cause of macroglossia is multifactorial and is genetically associated with autosomal dominant traits.^1,2

What are the causes and types of macroglossia?

The condition may be true macroglossia and relative macroglossia. True and relative macroglossia may be further divided into congenital and acquired types.

• True macroglossia – the enlargement of the tongue is due to a disease or condition
• Relative macroglossia - the tongue appears larger than the surrounding structures like teeth
• Congenital macroglossia –  this may include disorders like Beckwith-Wiedemann syndrome (a condition in which excessive growth of other structures is also noted), down syndrome, acromegaly (excessive secretion of growth hormone), Hunter syndrome, and Hurler syndrome ^3,4
• Acquired macroglossia – the enlargement of the tongue is due to chronic infections or inflammatory diseases such as amyloidosis (an accumulation of abnormal proteins), malignancies, hypothyroidism (accumulation of subcutaneous mucopolysaccharides due to the decreased degradation), cretinism, allergic reactions, lymphomas, lymphangiomas, head and neck infection, and trauma or surgery.^5,6

Symptoms of macroglossia

Macroglossia is usually an uncommon condition and is seen more often in children. Severe enlargement of the tongue can cause facial and cosmetic disturbances.⁷

The symptoms are:

• Difficulty in breathing, airway obstruction, and noisy breathing
• Difficulty in eating and swallowing
• Speech difficulties
• Drooling of saliva
• Mouth breathing
• Orthodontic problems like spacing between teeth (diastema)
• Malocclusion, crowding of teeth
• Difficulty in feeding
• Necrosis of the tip of the tongue due to injury from other oral structures
• An enlarged tongue may be prone to infections, drying of the tongue due to prolongation outside the mouth

Diagnosis of macroglossia

Clinical evaluation – the size of the tongue can be evaluated clinically by comparing structures in the oral cavity.

Other tests including detailed ultrasound and foetal echocardiogram are advised for pregnant women to know the condition of the baby. After the delivery of the baby, tests such as a CT Scan and MRI are suggested.

Amyloidosis

Amyloidosis is also known as amyloid disease.⁸ It is the deposition of amyloid in the tissue.

An abnormal proteinaceous substance that is deposited between cells in tissues and organs of the body in a variety of clinical disorders is referred to as an amyloid.⁹

Forms of amyloid

Type A amyloid (secondary) - is a fibrillar protein of unknown origin seen in prolonged inflammatory disease, genetic disease and syndromes such as familial Mediterranean fever.

Type B amyloid (primary) - is immunologic in origin because of its sequence homology with the NH2 terminal end of the immunoglobulin light chain. It is seen in patients with multiple myeloma and macroglobulinemia.

Type C - Includes amyloid of ageing, localized non-specific amyloid and pheochromocytomas.

Types of amyloidosis

• Primary amyloidosis - there is no evidence of preceding or existing disease¹⁰
• Amyloidosis is associated with multiple myeloma
• Secondary amyloidosis - associated with chronic inflammatory diseases
• Localised amyloidosis - it is characterised by small localised deposits of amyloid in the skin, bladder and the respiratory tract
• Familial amyloidosis - it is a rare condition such as familial Mediterranean form or familial amyloidosis with polyneuropathy
• Hormone-related amyloid - is associated with the tumours of endocrine cells which secrete peptide hormones 

What causes amyloidosis?

• Collagen disease like rheumatoid arthritis.
• Chronic infections like tuberculosis, osteomyelitis, regional enteritis, and ulcerative colitis.
• Malignant diseases like multiple myeloma, Hodgkin’s lymphoma and renal cell carcinoma.

Clinical manifestation of amyloidosis¹¹

• It commonly affects the kidneys, liver, heart, GI tract, respiratory tract, skin, eyes, adrenals, nerves and spleen
• Symptoms like fatigue, weakness, ankle oedema, dyspnea, paresthesia, orthostatic hypotension and weight loss
• Purpuric spots are caused by haemorrhage resulting in the formation of amyloid deposits in the blood vessels
• Superficial waxy lesions occur on the eyelids, nasolabial folds, neck, axilla or perineum; the lesions may bleed when pressure is applied
• Amyloid deposits in the myocardium result in congestive cardiac failure
• Amyloid deposition in the GI tract causes hepatomegaly, malabsorption or colitis

Diagnosis of amyloidosis

• Clinically it can be seen on the patients' faces in case of macroglossia
• Scintiscanning is done to localise soft tissue deposits
• Congo red is used to diagnose amyloid which shows birefringence and dichroism

Macroglossia and amyloidosis

Oral manifestations of amyloidosis 

• Amyloid deposits in the tongue result in macroglossia
• The tongue is abnormally enlarged and studded with small garnet-coloured enlargements along with nodes of cheeks and lips
• Movement of the tongue is restricted
• Yellow nodules are present along the lateral border of the tongue
• Other problems like difficulty in chewing, swallowing, and talking 

Further symptoms of amyloidosis

Other than macroglossia, there are a few more symptoms associated with amyloidosis.

• Amyloid deposition in the upper third of the larynx results in paresis of the vocal cord and causes speech difficulties
• Gingiva is infiltrated and may be bluish, spongy and hypertrophied due to amyloid deposits
• Xerostomia with the dysfunction of the salivary gland

Pathogenesis of amyloidosis in causing macroglossia

Fibrous glycoproteins are deposited in the submucosa as well as in deeper muscular layers of the tongue. Amyloid deposition of the tongue is found resulting in macroglossia of the tongue. It is seen in both primary and secondary forms.

Treatment of macroglossia

Treatment and management include a cross-functional team that includes dentists, orthodontists, periodontists, surgeons, speech-language pathologists and psychologists for the mental care of the patient and caretakers.

• Surgery of the enlarged tongue to reduce the size of the tongue ¹²
• Treatment of  malocclusion with brackets and orthodontic appliances
• Treatment of underlying causes like amyloidosis, hypothyroidism
• Gingival health – once the tongue size is reduced and the underlying cause is treated, the decayed tooth should be restored, gingivitis is treated with antibiotics, and proper tooth brushing techniques and flossing are suggested to maintain healthy gingival tissue
• Speech disorder is treated with speech-language therapy for children and adults ¹³
• Oral hygiene is maintained by advising mouthwashes and floss

Treatment of amyloidosis¹⁴  

• Amyloidosis is treated by alkylating agents like melphalan¹
• Combination therapy using melphalan, prednisone and fluoxymesterone; significant improvement is seen in this therapy¹⁶
• Renal transplantation- arrests the progression of bone lesions

Summary

1. Macroglossia is a rare condition seen most commonly in children and a few cases in adults. The condition is characterised by abnormal enlargement of the tongue compared to the normal size of the tongue
2. The cause is multifactorial; it may be due to any underlying disease such as hypothyroidism, or amyloidosis or it may be due to genetic conditions like Beckwith-Wiedemann syndrome, acromegaly, Turner’s syndrome
3. Amyloidosis is a condition characterised by abnormal protein deposition
4. The deposition is seen most commonly in the heart, kidney, liver, spleen, and GI tract
5. Amyloidosis has an association with macroglossia
6. Amyloid deposits in the tongue result in macroglossia