CASE REPORT

https://doi.org/10.5005/jp-journals-10077-3292
Journal of South Asian Association of Pediatric Dentistry
Volume 7 | Issue 1 | Year 2024

Evaluating the Concept of Oral Manifestation of Thalassemia Major and Its Dental Consideration: A Report on Two Cases and a Literature Review

Nidhi Yadav¹, Ajay Parihar², Prashanthi Reddy³ https://orcid.org/0000-0002-0608-4060, Arun D Sharma⁴

^1–4Department of Oral Medicine and Radiology, Government College of Dentistry, Indore, Madhya Pradesh, India

Corresponding Author: Nidhi Yadav, Department of Oral Medicine and Radiology, Government College of Dentistry, Indore, Madhya Pradesh, India, e-mail: yadnidhi19@gmail.com

Received: 13 December 2023; Accepted: 28 January 2024; Published on: 27 April 2024

ABSTRACT

Background: Thalassemia is one of the most prevalent inherited diseases in the world, posing public health and societal challenges in high-risk locations. Thalassemia can be classified into two types—α-thalassemia and β-thalassemia, which are caused by abnormalities in the synthesis of hemoglobin (Hb) α- or β-polypeptide chains. Reduced synthesis of one of the two globin polypeptides leads to diminished Hb production, resulting in hypochromic microcytic anemia with erythrocyte dysplasia and destruction. The case reports presented and evaluated here show distinctive orofacial features, classic radiographic features, and dental considerations in thalassemia major patients.

Conclusion: Thalassemia major causes several orofacial and systemic problems, which worsen with age. Early diagnosis and management result in a better prognosis and decreased morbidity.

Clinical significance: Dental practitioners, particularly those working in multiracial populations, need to comprehend the disease’s complications and therapy.

How to cite this article: Yadav N, Parihar A, Reddy P, et al. Evaluating the Concept of Oral Manifestation of Thalassemia Major and Its Dental Consideration: A Report on Two Cases and a Literature Review. J South Asian Assoc Pediatr Dent 2024;7(1):31–37.

Source of support: Nil

Conflict of interest: None

Patient consent statement: The author(s) have obtained written informed consent from the patients (for case 1,2) and the patient’s parents (for case 3) for publication of the case report details and related images.

Keywords: Case report, Chipmunk facies, Dental consideration, Gingival hypertrophies, Salt and pepper appearance, Thalassemia major

INTRODUCTION

Thalassemia is an autosomal recessive genetic condition that results in defective hemoglobin (Hb) synthesis.¹ Four proteins constitute Hb, including two α- and two β-globin chains arranged in a heterotetrametric pattern. In thalassemia patients, the α and β chains of Hb are faulty, resulting in insufficient Hb production. α-globin chains are genetically encoded on chromosome 16, while β-globin chains are encoded on chromosome 11.²

Thalassemia is categorized as homozygous, heterozygous, or compound heterozygous based on genetic heterogeneity and clinical and hematologic variability. It has several subgroups, each with distinctive clinical characteristics. α-thalassemia results from the deletion of the α-globin gene, whereas β-thalassemia occurs due to a single-point mutation in the β-globin gene.³ Thalassemia major, thalassemia intermedia, and thalassemia minor are the three forms of β-thalassemia.

Orofacial symptoms are frequent due to severe compensatory hyperplasia and its extension into the marrow cavity. Patients exhibit maxillary projection, mandibular atrophy, and skeletal class II malocclusion, as well as an expanded overjet, anterior open bite, malar prominence, a saddle nose, and frontal bossing, which results in a chipmunk or rodent face.⁴ Other oral characteristics include taurodontism, attenuated lamina dura, absence of inferior alveolar canal, short, spiky roots, thin mandibular cortex, and short roots. Due to frequent blood transfusions, iron buildup will result in elevated ferritin levels in the blood, and the gingiva occasionally tends to be dark in color.⁵

CASE DESCRIPTION

Case 1

A 12-year-old child presented to the department with inflamed and bleeding gums for the previous 2–3 months. The patient’s medical history revealed multiple blood transfusions for thalassemia since he was 1 year old, followed by gingival hypertrophy with bleeding gums frequently twice or thrice 1-month postblood transfusion. No history of splenectomy was done, and family history was noncontributing.

Upon general examination, he had a small stature, was moderately built, and was well nourished. His skin, eyes, and nails were all pale. Examination of the head and neck revealed a depressed cranial vault, frontal bossing, and saddle nose, which collectively reflect the typical “chipmunk facies.” There was no sign of extraoral swelling or lymphadenopathy (Fig. 1 and case 1).

Figs 1A to D: Exraoral features (A and B) Case 1—pale skin, saddle nose, frontal bossing showing classic chipmunk face. (A and C) Case 2—conjunctiva, skin, and nails were pale with depressed nasal bridge, frontal bossing, and maxillary hypertrophy, depicting the classic “chipmunk face” appearance (B and D)

Intraoral examination showed many hemorrhagic gingival hypertrophies associated with bleeding. On palpation, the gingiva was soft to firm in consistency, nontender, and bled profusely. Hyperpigmentation seen in palate and tongue region. When compared to analogous case studies in the literature, this patient did not have maxillary protrusion, expansion, or any other relevant malocclusion (Fig. 2 and case 1).

Figs 2A to E: Intraoral features Case 1—Hyper-pigmentation of palate with multiple pinpoint pigmentation on tongue. (A and B) Multiple hemorrhagic gingival hypertrophies; (C and D) Case 2—multiple caries (55, 74, 74, 84, and 85) yellowish brown staining, hypoplastic enamel, generalized hyperpigmented gingiva, proclined maxillary anterior, and generalized spacing (a, b)

On hematological examination, the Hb level was 5.7 gm/dL, the total leukocyte count/differential leukocyte count (TLC/DLC) level was 2300/μL, the platelet count was 1.01 lac, the white blood cell count was 5000/μL, the prothrombin time (PT) time was 18.1 seconds, the international normalized ratio (INR) was 1.4, and the activated partial thromboplastin time (APTT) time was 30 seconds.

An orthopantomogram (OPG) revealed mixed dentition with thinned cortical boundaries, short spiky roots, and a changed trabecular pattern. The lateral skull view depicted a typical “hair on end” appearance, widening of the diploic space, salt-and-pepper appearance, and enlarged marrow spaces with wider trabeculae of the skull (Fig. 3 and case 1).

Figs 3A and B: Radiographic features cases 1 and 2: (A) Lateral skull view depicted typical “hair on end” appearance and widening of the diploic spaces; (B) Orthopantomogram (OPG) shows mixed dentition with thinned cortical boundaries, short spiky roots, and a changed trabecular pattern

Case 2

A 10-year-old girl came to the department with a complaint of pain in the lower left tooth back region for the last 15 days. When her medical history was reviewed, it was obvious that she had thalassemia major, for which she had been receiving blood transfusions since the age of 1. No Family history was present, and no history of splenectomy.

On examination, she had a small stature and adequate body mass index. Conjunctiva, skin, and nails were pale. An examination of the head and neck revealed typical “chipmunk face” characteristics, including a shallow nasal bridge, frontal bossing, and maxillary hypertrophy (Fig. 1 and case 2).

Intraorally, multiple caries (55, 74, 74, 84, and 85), yellowish brown staining, hypoplastic enamel, generalized hyperpigmented gingiva, proclined maxillary anterior, and generalized spacing were seen (Fig. 2 and case 2).

Initially, the Hb level was 4.1 gm/dL. After three consecutive blood transfusions, the current Hb level is 9.4 gm/dL, TLC/DLC level was 2500/μL, and the current value is 4400/μL, platelet count reduced from 1.17 to 94,000 lac, PT time was 19.2 seconds, INR was 1.6, APTT time was 34 seconds, serum bilirubin, serum glutamic oxaloacetic transaminase, and serum glutamate pyruvate transaminase levels were high.

Orthopantomogram (OPG) and lateral skull radiographs revealed short spiky roots, changed trabecular pattern, typical “hair on end” appearance and widening of the diploic space (Fig. 3 and case 2), which were similar to the radiographic features described and compared with case 1 (Table 1).

**Table 1:** Orofacaial and radiographic features of cases 1 and 2
Features in head and neck region	Case 1	Case 2
Orofacial features	Depressed cranial vault, frontal bossing, and saddle nose Paleness Hemorrhagic gingival hypertrophies associated with bleeding Hyperpigmentation seen in palate and tongue region	Depressed nasal bridge, frontal bossing, and maxillary hypertrophy Evident icterus Multiple caries Yellowish brown staining Hypoplastic enamel Generalized hyperpigmented gingiva Proclined maxillary anterior and generalized spacing
Radiographic features	Mixed dentition with thinned cortical boundaries, short spiky roots, and a changed trabecular pattern “Hair on end” appearance, a diploic spacing enlargement, salt-and-pepper resemble, and enlarged marrow spaces with wider trabeculae of the skull	Short spiky roots and a changed trabecular pattern “Hair on End” impression Diploic spacing enlargement

Symptomatic management of case 1 involves the use of a 0.5% chlorhexidine antiseptic mouthwash. The prescribed dosage is 10 mL twice daily. Patients are instructed to pour 10 mL into a measuring cup, rinse it around the mouth for approximately 1 minute, and then spit it out without swallowing. It is advised to wait at least 30–60 minutes before consuming food or beverages. Additionally, a safe analgesic, paracetamol, is recommended at a dose of 15 mg/kg per 6–8 hours for 1 week. Several months afterward, the patient presented without hemorrhagic gingival enlargement. Only a mild pigmentation on the tongue was observed, attributed to consistent and consecutive blood transfusions (Fig. 4).

Figs 4A and B: Follow-up case 1 with no hemorrhagic gingival enlargement and reduced pigmentation on the tongue

In case 2, the patient presented with tooth pain caused by caries and received treatment involving conservative restoration for the affected teeth.

DISCUSSION

Thalassemia is a hereditary, autosomal recessive, monogenic or multigenic blood disorder characterized by a decrease or absence of Hb. A heterotetrametric protein made up of two α and two β chains is Hb. Red blood cells with decreased or total Hb are produced by faulty α- or β-chains in thalassemia.⁵ Cooley’s anemia, the most severe form of thalassemia, occurs in individuals who have been found homozygous for more severe chain mutations (B/B0, B0/B0) or compound heterozygous B/B) (Galanello and Origa and Tari et al.).⁶^,⁷ The Mediterranean region, bordering Africa’s northern coast, has the highest prevalence of β-thalassemia (Weatherall).⁸

Typically, the occurrence occurs between 6 months and 2 years, resulting in defective Hb that can be managed with blood or blood product transfusions. However, continuous blood transfusion can lead to iron overload in various organs and complications such as diabetes, hypopituitarism, hypoparathyroidism, hypothyroidism, liver cirrhosis, skin pigmentation and arrhythmia.

Cooley facies, brought on by inefficient erythropoiesis and the emergence of bone-expanding erythroid masses, are the cause of the orofacial features of thalassemia. Significant open bites, abnormal saddle nose spacing, and large malar bones are examples of facial and dental anomalies. Upper lip retraction caused by the skeletal alterations gives the child “chipmunk facies.”⁹ Patients with α-thalassemia do not have symptoms; hence, mucosal pallor indicates mild anemia in the oral cavity. Other oral concerns include an increased risk of tooth decay, pale gums, glossopyrosis, sialadenosis, xerostomia, and reduced salivary defence due to decreased immunoglobulin A (IgA).⁸

Radiographic features are widened marrow spaces, usually not visible until a child is 1 year old. Ineffective erythropoiesis leads to damage of the red blood cell (RBC) membrane, which proceeds to severe anemia, to compensate this body responds by increasing the production of RBC, which leads to the expansion of marrow up to 15–30 times than the average amount.¹⁰ The “hair on end appearance” and hyperplasia of the maxillary alveolar processes that result in a reduction of the average volume of the sinuses are evident on the skull radiograph as a result of the arrangement of trabeculae in vertical rows and expansion of diploid space. The results include a thin cortex, short root with a spiky form, thin lamina dura and inferior alveolar canals. Incidence of fractures occurs in thalassemia due to the coarse trabecular pattern and cystic formation.¹¹ Some peculiar orofacial and radiographic manifestations in thalassemia are reviewed in Table 2.

**Table 2:** Review of peculiar orofacial and radiographic manifestations in thalassemia reported
Peculiar oral manifestations in thalassemia major	Causes	Author
Orofacial features
The parotid glands in thalassemia major patients have pain and swelling	Serous cells with iron overload		Goldfarb et al.¹⁹
Median rhomboid glossitis, palatal petechiae, and contact lesions on the palate	Although Candida albicans is an opportunistic organism, the chronic anemia condition’s decreased human resistance may present a chance for the growth of virulence and resistance to therapy		Langlais et al.²⁰
Tongue reduction of the papillae, glossopyrosis, and glossodynia	Due to a deficiency of iron and folic acid		Van Dis et al.²¹
A slightly mongoloid facial deformity is characterized by prominent frontal and parietal bones, a collapsed nasal bridge, depression of the zygomaticus, upward-slanted eyes, broader cheekbones, a rodent or “squirrel-like” face, a depressed nasal bridge, and a protruding maxilla	A lack of erythropoiesis and the growth of erythroid masses that extend into the bone		Bassimitci et al.²²
Teeth discoloration	Increased iron concentration		Greenberg and Glick⁹
Cranial nerve palsies	There is pressure on the nerves as a result of the increased medullary hemopoiesis		Greenberg and Glick⁹
Multiple dental cavities increase the risk of root infections (or abscesses)	Median salivary concentrations of IgA and phosphorus		Madhok et al.⁵
Incompetent lips, incompetent lower lip, a severe convex facial profile, and a skeletal class II relationship	Increased overjet, maxillary tooth spacing, and other degrees of malocclusion are typically the results of excessive maxilla development		Einy et al.²³
Gingival hypertrophies, bleeding gums, and intraoral pigmentation on the hard palate and buccal mucosa	The function of saliva itself in preserving the balance of the oral flora, including the bacteria that cause gingivitis, will automatically be impacted by changes in the components of saliva. The development of periodontal disease is significantly influenced by the increased virulence of Porphyromonas gingivalis, one of the major bacteria in the subgingival region		Muhammad et al.²⁴
Radiographic features
“Chicken-wire” appearance in tooth-bearing region and “salt-and-pepper” effect in the skull	Because of larger marrow spaces and a changed trabecular pattern, which is characterized by the apparent coarsening of certain trabeculae	Hattab²⁵
Hair-on-end appearance Roots-short and spike-shaped, taurodontism	A radial pattern of long, thin vertical striations appears due to an alternation of opaque trabeculae and diploic (spongy) radiolucent marrow that is aligned perpendicular to the inner and outer tables of the skull	Aldallal et al.²⁶
Osteoporosis and osteopenia	This is caused by the incorporation of iron into calcium hydroxyapatite crystals, which in turn inhibits the development of hydroxyapatite crystals and lowers the tensile strength of the basic multicellular unit	Gaudio et al.²⁷

Iron Overload in Tissues and its Mechanism of Action

Hemochromatosis, a condition in which there is an excessive accumulation of iron, is one of the most common adverse effects of thalassemia. If this inherited metabolic condition is not identified and treated, it can cause organ damage and even death. Due to a deficiency of hepcidin, usually, thalassemia patients develop iron accumulation in parenchymal tissue after a year of routine blood transfusions.¹²^,¹³ The role of hepcidin in iron accumulation is discussed in the below flow chart (Fig. 5).

Fig. 5: The role of hepcidin in iron accumulation

Dental Consideration of Thalassaemia

Before beginning an extensive dental procedure, a baseline health assessment is necessary to obtain. The assessment should include:

The current Hb level.
Iron chelators and other medications, including antibiotics, were taken.
History of splenectomy.
The general prognosis and life expectancy of the patient.⁵

Thalassaemic patients have been advised to have dental procedures done under the guidance of a hematologist. Before the start of therapy, the adverse effects of the drugs recommended for thalassemia patients should be considered. Performing dental oral procedures on patients with low Hb levels is typically not advised.¹⁴

Dental Caries and Periodontal Health

Dental caries in individuals with thalassemia have been widely documented in numerous populations. Low salivary flow compromises salivary defence, resulting in greater amounts of salivary Streptococcus mutans. Other factors that increase the risk of caries include poor eating habits, a lack of dental awareness, and neglected dental treatment.¹⁵ Ja’afar and Al-Aswad reported in a recent study that salivary aspartate and alanine aminotransferase enzyme levels were significantly greater in Transverse myelitis (TM) patients than in the control group. These enzymes may serve as markers for compromised periodontal cases.¹⁶ Precautions such as Prophylaxis, fluoridation, and the use of fissure sealant are all recommended precautions to reduce challenging dental practices.

Orthodontic Management

To improve esthetics orthodontic management in terms of reduction of overjet, gingival inflammation, and predisposition to injury for improving mental health. To prevent and intercept the consequences, it’s recommended to initiate the orthodontic procedures sooner. Before orthodontic therapy, one should consider altered dental arch and tooth morphology proportions.

Iron Overload and Deposition in Tissue

Within 1 year of blood transfusion, iron deposition is observed over the parenchymal tissues of thalassemia patients.

Continued blood transfusions will be required to maintain Hb levels; however, side effects, such as excessive iron accumulation inside the tissues, produce hemosiderosis with clinical manifestations of grayish pigmentation in the oral mucous. Decreased Hb levels, increasing bilirubin levels, and repeated blood transfusions will eventually have an alternation in the color of the oral mucous into grayish yellow, which is a combination of pale, icterus/yellow, and grayish pigmentation of the hemosiderosis process.¹⁷

Cardiac Anomaly

Excessive accumulation of iron provokes cardiomyopathy in patients with thalassemia. Dental professionals should decide carefully whether to use anesthetic when treating patients with cardiac issues. Adrenaline content in anesthesia may result in cardiac problems in patients with cardiac issues, which involve high blood pressure, angina (chest pain), heart attack and arrhythmias.¹⁸

Psychological Modification

Mental health problems are common in cases of thalassemia, such as despair and anxiety, which can reduce the motivation and willingness of patients to undergo dental treatments. On the day of treatment, psychological assistance for the purpose of improving mental health should be individualized to the patient’s age and level of comfort with the intended procedure.

Any invasive operation performed on thalassemia patients must be under antimicrobial protection immediately following a transfusion. Before performing dental procedures, liver function and coagulation testing should be performed. In less severe cases of thalassemia, surgery can be utilized to manage orofacial abnormalities and malocclusions, followed by orthodontic therapy to align the teeth.⁵

Routine blood transfusion, along with iron chelation, prevents orofacial anomalies.⁹ Instead of non-steroidal anti-inflammatory drugs and aspirin, paracetamol is a safe alternative. Avoid using tetracycline, metronidazole, and erythromycin estolate. Patients with thalassemia requiring dental care may benefit from sedation or anesthesia for greater autonomy and cooperation.⁵ Dental experts should be cautious before performing any procedures because of immune-compromised status, impaired liver function, splenectomy, and cardiovascular problems. Implementing a multidisciplinary strategy, including an orthodontist, hematologist, and dental surgeon, is recommended.

Unique and peculiar oral manifestations of thalassemia with radiographic features were reported in previous studies conducted by various authors, as shown in Table 2.

CONCLUSION

Individuals who undergo insufficient blood transfusions during childhood face a heightened risk of experiencing skeletal changes during adolescence. This phenomenon is attributed to heightened bone marrow activity as a response to chronic anemia. Timely identification and regular blood transfusions play a pivotal role in diminishing the occurrence of orofacial disorders and mitigating psychological stress. Dentists should possess a comprehensive understanding of addressing oral manifestations in thalassemic patients. Proactive dental care is imperative, and treatment approaches must be tailored to the unique needs of each patient to minimize complications and enhance treatment efficacy.

ORCID

Prashanthi Reddy https://orcid.org/0000-0002-0608-4060

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