Research Article/Conservative DentistryOpen Access
Dental Manifestations of SSFA2 Homozygous Sickle-Cell Anaemia: Clinical Data From A Cohort of Sixty Patients Monitored in A Referral Centre in Abidjan (Côte D'Ivoire)
1Department UFR of Odonto-Stomatology, Félix Houphouët Boigny University, Cocody (Abidjan, Ivory Coast)
2Faculty of Medicine Pharmacy and Odontology, Department of Odontology, Conservative Dentistry Division Cheikh Anta Diop University, BP 5005 Dakar, Senegal
|Faculty of Medicine Pharmacy and Odontology|
|Department of Odontology|
|Conservative Dentistry Division Cheikh Anta Diop University|
|BP 5005 Dakar, Senegal|
|Tel: +221 77 454 24 55|
Received: February 14, 2018; Published: April 02, 2018
Citation: Gnagne-Koffi Y, Djolé SX and Aidara AW (2018) Dental Manifestations of SSFA2 Homozygous Sickle-Cell Anaemia: Clinical Data From A Cohort of Sixty Patients Monitored in A Referral Centre in Abidjan (Côte D'Ivoire). J Dent Treat Oral Care 2(1): 105
Introduction: Sickle-cell anaemia is a real public health problem in Côte d' Ivoire. The objective of this study is to identify the dental manifestations of patients suffering from homozygous sickle-cell anaemia (SSFA2) in order to propose multidisciplinary management of this condition.
Patients and Methods: The study took place in the Clinical Hematology Department of West Africa located within the Yopougon Hospital and University Center (Abidjan - Côte d'Ivoire). A retrospective analysis of the records of homozygous sickle cell disease patients with SSFA2 followed by oral maintenance and examination were performed.
Results: A total of 60 patients made up our sample. The first dental manifestations in homozygous sickle-cells are represented by pain (75%) during sickle-cell attacks. There is localized pain on apparently healthy teeth. Dental pathologies are predominantly irreversible pulpopathies (43.3%) and the red blood cell deficiency appears to increase susceptibility to tooth decay.
Discussion: Dental caries and ischemia caused by the vaso-occlusive crisis represent the etiologies of dental pain in homozygous sickle cell disease (SSFA2). This painful symptomatology tends to disappear quickly with the recurrence of hemolytic attacks leading to pulp necrosis.
Conclusion: Comprehensive multidisciplinary management involving systematic odontological consultation, such as ophthalmologic consultations, is essential.
Keywords: Homozygous Sickle-Cell Anaemia (Ssfa2); Sickle-Cell Attacks; Dental Manifestations
Sickle-cell anaemia or sickle cell anaemia is due to a genetic mutation that results in the substitution of the 6th Aminated Acid in the? chain of globine (glutamine) with valine . It is the most common hemoglobinopathy, and epidemiological data reveal a higher prevalence (above 10%) between the 15th parallel of north latitude and the 20th parallel of south latitude called "Lehmann's Sicklemic Belt" . SSFA2 homozygous sickle-cell anaemia, a major form of sickle-cell disease, is a chronic hemolytic anaemia interspersed with hemolytic attacks and often complicated vaso-occlusive attacks of severe bacterial infections [3,4]. Pioneering work has shown the impact of the disease on skeletal and mandibular bone alteration, and reported cases have shown that the oral sphere may be the site of various complications [5,6]. The dental organ is made up of a specialized connective tissue called dental pulp and three mineralized hard tissues, enamel (at crown level) and cement (at root level), which cover the dentine, the main mass of the tooth. Dental pulp is made up of a nervous, vascular and lymphatic network, which ensures sensitivity, the supply of nutrients and immune defence . This network allows communication with surrounding support structures (the periodontium) such as the alveolo-dental ligament and alveolar bone . The first studies on the manifestations of sickle-cell anaemia at the dental level showed the presence of sickle-cell anaemia in pulp vessels 24 to 96 hours after the sickle-cell attack and several investigations have shown the presence of necrotic pulp teeth in sickle-cell patients [9,10]. In Côte d' Ivoire, the prevalence of haemoglobin S is high, as in sub-Saharan countries  and makes the disease a real public health problem. To this end, there is one of the largest regional reference centres for the diagnosis, treatment and follow-up of patients. To this end, there is one of the largest regional reference centres for the diagnosis, treatment and follow-up of patients. The objective of this study is to identify the dental manifestations of patients suffering from SSFA2 homozygous sickle-cell anaemia in order to propose multidisciplinary management of this condition.
The study took place in the Clinical Hematology Department of West Africa located within the Yopougon Hospital and University Center (Abidjan - Côte d' Ivoire). It was carried out over two months in two main phases, including a retrospective analysis of patient files, which consisted of a review of patient files followed by a prospective investigation combining interviews and oral examinations.
Regarding acute apical abscess, criteria differ only by the presence of pain at apical palpation or the presence of a submucosal or subperiosteal swelling . These criteria have been proposed and accepted in the literature but few have been validated by clinical studies [7,8]. So the criterion pain at apical palpation which would be the only one to distinguish acute apical periodontitis from acute apical abscess in case of absence of swelling has never been evaluated or validated. This clinical study was to evaluate the relationship between a positive response to the apical palpation test and the presence of purulent collection in acute apical abscess in his endodontic evacuation expression.
The medical records of sickle cell patients with hemoglobin phenotype have been consulted. Information relating to the discovery of the pathology, hematological analyses, periodicity and type of seizure (hemolytic or vaso-occlusive) was recorded.
Each patient was asked about the annual frequency of onset of sickle-cell attacks and the association of dental pain with the occurrence of these attacks. The intensity of the pain was assessed according to the Analog Visual Scale (AVS) with "0" for no pain,[1-4] for mild pain,[5-7] for moderate pain,[8-9] for severe pain and "10" for very severe and insomniac pain. Subsequently, the oral examination was carried out in search of decayed teeth in order to make the associated diagnoses.
The data collected was processed by the EPI Info version 6.01 software. Statistical analyses were performed using the Chi2 test and the Kruskall-Wallis non-parametric test was used to compare the means between qualitative and quantitative variables. The significance threshold is set at 5% for observed differences.
Sixty patients aged 12 to 40 years old, 56.7% of whom were women and 43.3% of whom were male, were selected for complete records and consent to participate in the study. A large majority of patients (85%) had been diagnosed with SSFA2 homozygous sickle-cell anaemia before the age of 12 years (Table I). Blood counts of patients are characterized mainly (85%) by erythrocyte deficiency with white blood cell (65%) and platelet (62%) levels higher than normal (Table II). With respect to the frequency of seizures, records data were superimposed on patient claims. During these attacks, 75% of the latter confirmed that they had experienced dental pain and at the request of the localization, 26.7% of them indicated apparently healthy teeth, free of carious lesions, traumas, periodontal injuries and previous dental care (Table III). The majority of patients (55.6%) had fewer than three seizures per year, and 44.4% of patients had pain on decayed teeth and 11.2% had pain on apparently healthy teeth (Table IV). Vaso-occlusive seizures are the largest in the sample (46.7%) and dental pain during these seizures involve 37.8% of decayed teeth and 8.9% of apparently healthy teeth (Table V). Oral examination revealed that 65% of the patients in the sample had carious lesions, but this proportion was mainly due to patients with erythrocyte deficiency, i. e. 60% (Table VI). The majority of dental manifestations are characterized by carious lesions of dentin (18.3%), pulsed inflammations with painful symptomatology of decay-free teeth (20%) and peripheral lesions at the top of the dental roots (periapical lesions) of decay-free teeth (15%) (Table VII).
|Sample characteristics||n (%)||N (%)|
|Age bracket||[10-20] years||34 (57)||60 (100%)|
|[21-30] years||21 (35)|
|[31-40] years||5 (8)|
|Diagnostic period for sickle cell disease||Before 12 years||51 (85)||60 (100%)|
|After 12 years||9 (15)|
Table I: Demographic characteristics of the sample
|Hematogram||n (%)||N (%)|
|Erythrocytes||Normal||9 (15)||60 (100%)|
|Abnormal (lower)||51 (85)|
|Leukocytes||Normal||21 (35)||60 (100%)|
|Abnormal (upper)||39 (65)|
|Platelets||Normal||23 (38)||60 (100%)|
|Abnormal ((upper)||37 (62)|
ormal values: Erythrocytes [Female 4-4.5.106/mm3; Male 4.5-6.10 6/mm3] Leukocytes[4-10.103 / mm3] Platelets[150000- 400000 / mm3]
Table II: Distribution of Patient Hematologic Parameters
|Painful manifestations||n (%)||N (%)|
|Dental pain during seizures||yes||45 (75)||60 (100)|
|Status of tooth with painful symptomatology||Decayed tooth||34 (75.4)||45 (100)|
|Apparently healthy tooth||11 (24.6)|
Table III: Patient distribution by occurrence of dental pain during sickle-cell attacks and their location
|Frequency of seizures||Pain localization||Total N (%)|
|Decayed tooth N (%)||Apparently sound tooth N (%)|
|< 3||20 (44.4)||5 (11.2)||25 (55.6)|
|[3 – 5]||6 (13.3)||5 (11.1)||11 (24.4)|
|> 5||8 (17.7)||1 (2.3)||9 (20)|
|Total||34 (0)||11 (0)||45 (100)|
Chi-square = 3.76 ddl = 1 p = 0.001 (significant test)
Table IV: Patient distribution between frequency of seizures and teeth with painful symptoms
|Type of seizure||Pain localization||Total N (%)|
|Decayed tooth N (%)||Apparently healthy tooth N (%)|
|Hemolytic||6 (13.4)||4 (8.8)||10 (22.2)|
|Vaso-occlusive||17 (37.8)||4 (8.9)||21 (46.7)|
|Mixed||11 (24.4)||3 (6.7)||14 (31.1)|
|Total||34 (75.6)||11 (24.4)||45 (100)|
Chi-square = 1.71 ddl = 2 p = 0.4252 (not meaningful test)
Table V: Patient distribution between type of seizure and teeth with painful symptomatology
|Number of red blood cells /mm3||Patients||Total N (%)|
|Without cavity N (%)||With cavity N (%)|
|[0-3.106]||15 (25)||36 (60)||51 (85)|
|[4 -6.106] VN*||6 (10)||3 (5)||9 (15)|
|Total||21 (35)||39 (65)||60 (100)|
*Normal value Khi 2 = 3.17 ddl = 1 p = 0.0074 (significant test)
Table VI: Distribution of patients between erythrocyte counts and the presence of decayed teeth
|Dental manifestations||Associated diagnoses||n (%)||N (%)|
|Dentinal Manifestations||Dentine carious lesion||11 (18.3)||14 (23.3)|
|Pulp pulses||Irreversible pulpopathy with pain without carious lesion||12 (20)||26 (43.3)|
|Irreversible pulpopathy with pain with carious lesion||03 (5)|
|Chronic irreversible pulpopathy with carious lesion||05 (8.3)|
|Irreversible pulpopathy with pulp necrosis and carious lesion||06 (10)|
|Periapical Manifestations||Acute acute carious apical periodontitis||01 (1.7)||10 (16.7)|
|Chronic apical periodontitis of carious origin||09 (15)|
|Patients free of dental pathology (carie, trauma, periodontal disease)||10 (16.7)||10 (16.7)|
|Total||60 (100)||60 (100)|
Acute apical periodontitis: ligament and bone damage confined to the tip of the root with pain; Chronic apical periodontitis: ligament and bone damage confined to the tip of the root without pain
Table VII: Types of manifestation by dental tissue
Overall, 16.7% of patients are free from all dental manifestations, with the latter represented 43.3% of the patients being free from all dental manifestations.
Sickle cell disease is described primarily in black subjects . Up to the 5th - 6th month postpartum, the pathology remains asymptomatic as red blood cells contain high levels of fetal haemoglobin, blocking the falcification process. It is then very severe, marked by a critical phase called the vaso-occlusive crisis. It is the most common syndrome and is essentially represented by pain. This pain sits on the hands and feet "hand foot syndrome" and is accompanied by fever in infants. In children and adolescents, the pain is abdominal, caused by visceral infarction (mesenteric, spleen, liver) and is accompanied by fever [4,11]. These symptoms are at the origin of the consultations, resulting in a higher proportion of patients identified as suffering from the pathology as early as childhood in this study.
The etiology of dental pain in sickle cell disease is explained by ischemia caused by the vaso-occlusive crisis. In fact, it is due to the loss of elasticity of deformed red blood cells, which results in obstruction of vascular light by sickle cell anaemia creating ischemia . This explains the low or moderate pain, contrary to the intense pain encountered during pulp aggression. Indeed, in this type of process, it is the synergistic intervention of inflammation mediators that will cause vasodilation, and the increase in pulp pressure associated with the inextensibility of hard tooth tissue will trigger severe pain. The results of this study show that patients report that they experience mild pain when having seizures on apparently healthy teeth. The duration of the seizures of the increasingly regular frequency leads to drainage of inflammatory exudate, resulting in the disappearance of pain and a progression towards pulp necrosis. As a result, dental pain is less and less noticeable for patients with more than three attacks a year.
Various experiments have shown hypomineralizations of enamel and dentin and periapical bone lyses [12,13]. This hypomineralization of hard tooth tissue is a weakness criterion that favours a rapid evolution towards pulpopathy in the event of bacterial attack. In another sense, sickle cell disease is characterized by hemoglobinopathy, which results in a deficiency of red blood cells, the vectors of an element such as blood iron. The correlation between iron deficiency anaemia and high susceptibility to developing carious disease is admitted [14,15]. This investigation is consistent with the data from the literature, showing that of the 65% of patients affected by carious disease, 60% have a deficiency of red blood cells. The presence of sickle cell anaemia in the dental pulp during seizures and pulp calcifications appears to be the cause of significant pulp manifestations compared to dentinal and periapical damage [9,12,13]. The impact of the disease on periapical lesions is still unclear but pulp necrosis is a bacterial source capable of initiating apical periodontitis. The results show that all periapical manifestations are associated with decayed teeth .
There is no current evidence that dental pain outside of the vaso-occlusive crisis is a potential prodrome of dental pain. It seems that, on the other hand, sickle-cell anaemia promotes the onset of dental pain, the weakening of hard tissues and ultimately tooth pathologies. From presumption to certainty, a correlation has been established to date between sickle cell anaemia and pulp necrosis . The management plan for treatment in the Ivorian context consists of:
(1) identifying and removing the triggering factors for seizures
(2) relieving pain with non-steroidal anti-inflammatory drugs (NSAIDs)
(3) assessing the need for blood transfusion (systematic when the hemoglobin level is less than 6 g/dl)
(4) restoring the rheological properties of red blood cells with vasodilators.
The contribution of an odontological examination from the early stages of management (Phase 1 and Phase 2) could make it possible to treat initial lesions and instruct patients in oral hygiene advice in order to prevent complications of these initial lesions. Systematic integration of an oral examination into the hematological control check-up is one of the key features of this framework. Systematic integration of an oral examination into the hematological check-up is one of the ways.
This study shows that sickle cell patients have dental manifestations with type of dental pain during vaso-occlusive and hemolytic seizures. Dental pain without carious lesions is characterized by symptomatic irreversible pulpopathy that tends to disappear with the recurrence of sickle cell attacks and progress to pulp necrosis. Subjects with low levels of red blood cells appear to be more likely to develop carious disease. The interest of this investigation is to propose a multidisciplinary treatment of patients suffering from SSFA2 homozygous sickle-cell anaemia by integrating a systematic oral examination, from the diagnosis of the disease to the different phases of surveillance.
We would like to thank Professor SAWADOGO Douni from HOSPITAL UNIVERSITY of YOPOUGON and Dr YAO Guillaume Frank for their support in the process of this study.
- 1. Terezhalmy GT, Moore WS, Bsoul SA, Flint DJ (2003) Sickle cell disease. Quintessence International. 2003;34 (1): 76-77.
- 2. Allison AC (1964). Polymorphism and natural selection in human populations. Cold Spring Harbor Cool. As for Biol 24 :137-149.
- 3. Ranque B, Menet A, Diop IB, Thiam MM and Diallo D., et al. (2014) Early renal damage in patients with sickle cell disease in sub-Saharan Africa: a multinational, prospective, cross-sectional study. Lancet Haematol. 1(2):e64-73.
- 4. Page C, Gardner K, Height S, Rees DC, Hampton T., et al. (2014) Nontraumatic extradural hematoma in sickle cell anemia: a rare neurological complication not to be missed. Am J Hematol. 89(2):225-7.
- 5. Kelleher M, Bishop K, Briggs P (1996) Oral complications associated with sickle cell anemia: a review and case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 82(2):225-8.
- 6. Javed F, Correa FO, Nooh N, Almas K, Romanos GE, Al-Hezaimi K (2013) Orofacial manifestations in patients with sickle cell disease. Am J Med Med Sci. 345(3): 234-7.
- 7. Solé-Magdalena A, Martínez-Alonso M, Coronado CA, Junquera LM, Cobo J., et al. (2018) Molecular basis of dental sensitivity: The odontoblasts are multisensory cells and express multifunctional ion channels. Ann Anat. 2018 Jan;215:20-29.
- 8. Husain MA (2018) Dental Anatomy and Nomenclature for the Radiologist.Radiol Clin North Am. 56(1):1-11.
- 9. Soni NN (1966) Microradiographic study of dental tissues in sickle-cell anaemia.Arch Oral Biol. 11(6):561-4.
- 10. Basati MS (2014) Sickle cell disease and pulpal necrosis: a review of the literature for the primary care dentist. Prim Dent J. 3(1):76-9.
- 11. Miller ST (2011) How I treat acute chest syndrome in children with sickle cell disease. Blood. 117(20):5297-305.
- 12. Cox GM, Soni NN (1984) Pathological effects of sickle cell anemia on the pulp. ASDC J Dent Child. 51(2): 128-32.
- 13. Andrews CH, England MC Jr, Kemp WB (1983) Sickle cell anemia: an etiological factor in pulpal necrosis. J Endod. 9(6):249-52.
- 14. Venkatesh Babu NS, Bhanushali PV (2017) Evaluation and association of serum iron and ferritin levels in children with dental caries. J Indian Soc Pedod Prev Dent. 2017 Apr-Jun;35(2):106-109.
- 15. Souza SFC, Thomaz EBAF, Costa CPS (2017) Healthy Dental Pulp Oxygen Saturation Rates in Subjects with Homozygous Sickle Cell Anemia: A Cross-Sectional Study Nested in a Cohort. J Endod. 2017 Dec;43(12):1997-2000.
- 16. Tolo-Diebkilé A, Koffi KG, Nanho DC, Sawadogo D, Kouakou B (2010) [Homozygous sickle cell disease in Ivory Coast adults]. Sante. 2010 Apr-Jun;20(2):63-7.