Molar-Incisor Hypomineralisation and Allergic March.

BACKGROUND: Molar-incisor hypomineralisation is a disturbance in dental development that involves first permanent molars as well as permanent incisors with a prevalence that ranges from 2.5% to 40%. AIM: The objective of this study was to investigate the effect of atopic diseases on the development of molar-incisor hypomineralisation.
MATERIAL AND METHODS: The study was based on the review of the medical records of a group of 102 children whose age was between eight and 12 years and 11 months and who had previously been diagnosed with MIH.
RESULTS: An association (χ2, p≤0.05) has been found between molar-incisor hypomineralisation in children's mouths and the existence of: atopic dermatitis (OR=2.504; 1.54-4.05 CI 95%), food allergies (OR=2.171; 1.03-4.56 CI 95%), allergic rhinitis (OR=0.17; 0.02-1.27 CI 95%), and asthmatic bronchitis/asthma (OR=1.707; 1.05-2.76 CI 95%). When analyzing the pathologies by location, we found that atopic dermatitis, food allergies, allergic rhinitis and asthma were more frequent in children who had (p≤0.05) #12, #11, #21, #22, #36, #31, #41 and #42 affected.
CONCLUSIONS: The association between molar-incisor hypomineralisation and the presence of atopic diseases in the first 36 months of life underlines the convenience of approaching this problem from a multidisciplinary perspective.

Introduction

The meeting of the European Academy of Paediatric Dentistry (EAPD), held in Athens in 2003, accepted the terminology “molar-incisor hypomineralisation” (MIH), suggested by Weerheijm et al. in 2001, (). MIH refers to an alteration of the dental development of unknown etiology that affects permanent first molars while permanent incisors may be affected as well ().

Studies on MIH have been widespread and are currently being studied in almost every country in the world. The prevalence figures that are being considered today vary between 2.4% and 40.2%, (). Also, there is a great consensus on the fact that children with worse health during the first 36 months of their lives are more likely to suffer from severe MIH, ().

Presently, we know more about MIH, but its etiology remains unknown. It is supposed to be of systemic origin and although a wide variety of etiological factors have been proposed as mediators in the onset of MIH, a definitive agreement on its etiology has not yet been reached ().

Among the possible etiological factors of MIH, recent studies on the etiology of MIH point at the presence of immunological immaturity and, at present, it seems increasingly clear that the immune system dysfunction during the first years of the child's life is involved ().

The pathogenesis of atopic dermatitis (AD) – which is the most frequent chronic inflammatory disease of childhood – is not fully understood, but current evidence suggests that AD is characterized by a dysfunction of the skin barrier, (, ). Skin barrier defects allow environmental antigens to enter the body and interact with elements of the immune system, natural and acquired, causing a very intense Th2-type allergic response, ().

AD is often the initial step of the “the atopic march”. The atopic/allergic march is characterized by a typical sequence of immunological responses associated with the production of specific IgE against allergens. It begins with AD and progresses to IgE-mediated food allergy (FA), asthma, and allergic rhinitis (AR), ().

Hernández et al () reported the significant relationship between MIH and the presence of AD and FA, components of the so-called the atopic march, in a study on the etiological factors of MIH. Suspecting that the presence of MIH could be related to allergic march as a whole, the primary rationale for conducting the study was to analyse a sample of children diagnosed with MIH to determine whether or not there was any relationship with the components of allergic march.

Material and Methods

The study was based on the review of the medical records of a group of 102 children whose age was between eight and 12 years and 11 months. All the children – 55 boys and 47 girls who had participated in the previous study on MIH5 without significant differences due to sex had the first four permanent molars and the eight permanent incisors erupted and had been previously diagnosed with MIH. When MIH was diagnosed, all the children had been examined by a calibrated pediatric dentist. The dentist had been graded with an intra-examining Kappa factor of 97.6% ().

The Institutional Review Board (Bioethical Committee, University of Barcelona, Spain) approved the study protocol (IRB00003099) for this study on the etiology of MIH. After informed consent was obtained, the medical records were checked for the presence or absence of AD, asthmatic bronchitis, FA, and allergic rhinitis, all components of the allergic march.

Data were analysed using the 24.0 SPSS statistical software (IBM™) and a Pearson’s χ2 test was used to evaluate associations in MIH etiology. A level of p≤0.05 was considered statistically significant.

No children participants were excluded from the sample since all of them had been diagnosed with having MIH in their teeth in the previous study by the same author.

Results

A statistically significant association (χ2, p≤0.05) was found between atopic dermatitis, food allergies, allergic rhinitis, asthmatic bronchitis/asthma and the presence of MIH in children's mouths (Table 1).

Table 1

Association between atopic dermatitis, food allergies, allergic rhinitis and asthma with MIH.

	OR	LOWER	UPPER	χ2	p
ATOPIC DERMATITIS	2,5046	1,5468	4,0555	14,5698	p≤0,01
FOOD ALLERGIES	2,1710	1,0316	4,5689	4,3493	p≤0,05
ALLERGIC RHINITIS	0,1706	0,0229	1,2719	3,8126	p≤0,05
ASTHMA	1,7070	1,0536	2,7655	4,7918	p≤0,05

†OR (Odds Ratio), ‡ χ (Pearson´s Chi-square test)

When analyzing the pathologies by location, we realized that AD is more frequent in children who have #31 (OR=2.23; 1.06-4.69 CI 95%), #41 (OR=2.22; 1.04-4.68 CI 95%), and #42 (OR=1.65; 0.86-3.16 CI 95%) affected. Regarding FA, we could see that they were more frequent in children with involvement of #12 (OR=1.94; 1.48-2.54 CI 95%), #11 (OR=3.02; 1.30-7.03 CI 95%), #21 (OR=2.05; 1.53-2.76 CI 95%), #22 (OR=2.06; 1.09-3.90 CI 95%), #31 (OR=2.22; 1.10-4.50 CI 95%), #41 (OR=3.68; 1.19-11.37 CI 95%) and #42 (OR=2.94; 1.04-8.36 CI 95%). Likewise, in our study, allergic rhinitis is related to the presence of MIH in #11 (OR=2.63; 1.85-3.73 CI 95%), #21 (OR=3.47; 1.34-8.99 CI 95%), #31 (OR=1.91; 1.07-3.39 CI 95%), #41 (OR=1.14; 0.73-1.76 CI 95%), and #42 (OR=1.17; 0.82-1.68 CI 95%), while asthmatic processes manifested more frequently in children who had affected #36 (OR=7.48; 2.53-22.24 CI 95%), #41 (OR=3.07; 1.79-5.27 CI 95%), and #42 (OR=2.14; 1.76-2.75 CI 95%).

Discussion

Although it was recommended that children be observed at age eight when it comes to MIH studies, our sample ranged from age eigh to the day before their thirteenth birthday (). In this study, this age range was used because it was considered that, once the tooth had erupted, the age at which it had erupted was not so important as whether it was affected by MIH.

Little is known about the etiological factors of MIH (, -). It has been suggested that there is a greater risk in children who during the first three years of their life have had, among others, adenoid infections, tonsillitis, respiratory diseases, diseases accompanied by high fevers and certain environmental pollutants (, -).

Several authors have reported the significant associations between postnatal diseases of atopic origin (AD, asthma, bronchitis or allergic rhinitis) and MIH. The research suggested that respiratory diseases and asthma may be causative factors of MIH (, , , , -).

However, other studies have found the associations not to be statistically significant (-, , ). Analyzing potentially associated factors, Souza et al () found no significant statistical association between allergies, and MIH. Sönmez et al () found no association between asthma, pneumonia, bronchitis and MIH. Dantas-Neta et al () indicate that asthma, bronchitis, sinusitis, and rhinitis, which were more prevalent in the MIH group, but not associated with MIH, were among the variables analysed in the children’s medical history during the postnatal period of life. Rhinitis, bronchitis and high fever were more prevalent but not significantly represented in the group of Brazilian children with MIH (). In their recent paper Salem et al () have found “dermatitis of allergic origin” to be a statistically significant predictor for MIH, although not many details about how the study was performed are given.

It has been suggested that hypoxia may play a major role as a causal factor in the development of enamel deformations upon acting on the ameloblasts during the active phase (). Experimental studies reveal that the conditions affecting the pH of the enamel matrix in various respiratory diseases inhibit the action of the proteolytic enzymes and the precursors of enamel affecting ameloblastic activity and altering development of hydroxyapatite crystals resulting in enamel’s hypomineralisation ().

Atopic dermatitis is a childhood disease with immunological and skin barrier malfunction showing a high degree of comorbidity. The term atopy represents IgE-mediated hypersensitivity reactions ().

Our environment and lifestyle are changing very rapidly and the appearance of new pollutants that may affect the period of amelogenesis could be an etiological factor to consider in future studies ().

Endocrine Disrupting Chemicals (EDCs) are exogenous substances that alter functions of the endocrine system and consequently cause adverse health effects in an intact organism ().

Many of the proposed causal factors for MIH, including EDCs, involve the large family of the steroid receptors. Most of them are expressed in ameloblasts and their levels of expression are dependent on their stage of differentiation (). Steroid receptors thus appear as the common elements able to modulate the expression of enamel key genes controlling enamel synthesis or leading to enamel hypomineralisation in case of disruption ().

Exposure to EDCs alters innate and adaptive immune mechanisms interfering with cellular and humoral activities that affect cell maturation and lifespan ().

Atopic comorbidities (AD, AR, and asthma) are common and often appear together (). They usually begin early in life with their co-occurrence greater than expected by chance alone, regardless of IgE sensitization (). A dysfunctional skin barrier is a gateway for the entry of environmental and bacterial antigens facilitating the allergic sensitization and promoting a systemic lymphocytic immune response of type Th2, ().

Currently, the prevailing theory defines AD as a starting point of the allergic march and signals the skin as being mainly responsible for early allergic sensitization that occurs in patients with AD suggesting a cutaneous and systemic immune activation ().

Our study found a significant relationship (p≤0,05) between having MIH and having or having had atopic dermatitis, food allergies, allergic rhinitis, and asthma.

Today, there is a research path that follows the idea that genetic variations and agents that act negatively on the skin barrier and its development may be at the root of amelogenesis alterations since the enamel formation process is genetically controlled ().

Jeremias et al () were the first to evaluate the possibility that the genetic mutations somehow interact with the environmental factors and are associated with the amelogenesis process and the presence of MIH.

Discrepancies between the studies regarding the possible etiological factors of MIH highlight the importance of conducting more research on this pathology.

Conclusion

The statistically significant and widely demonstrated association between MIH and the presence of atopic diseases in the first years of a child’s life underlines the convenience of approaching this problem from a multifocal perspective.

Pediatric dentists must take into account in their protocols that children with AD and atopic comorbidities are more likely to suffer MIH and that they should advise parents of children with the atopic march about the need for increased oral health care for their children.