Oral warning signs of elastic pseudoxanthoma

Abstract

The pseudoxanthoma elasticum is a multisystemic heritable disease that primarily affects the connective tissue. It has been characterized by fragmentation and calcification of elastic fibers that can lead to complications of skin and cardiovascular system and changes in retina. Involvement of the oral mucosa has been described like white patches striated especially in the mucosa of both upper and lower lips. These oral signs are potentially useful to diagnose the disease, since it is an often undiagnosed disease due to the variability in phenotypic expressions. This study reports a case of pseudoxanthoma elasticum affecting a woman who developed lesions in the oral mucosa during the disease progression. Intraoral clinical assessment revealed the presence of changes mainly in lower labial mucosa and also slightly changes in the mouth floor and the upper labial mucosa. Therefore, the acknowledgment of oral pseudoxanthoma elasticum lesions helps dental practitioners to establish an early and appropriate diagnosis of this disease. This is very important because pseudoxanthoma elasticum is a multisystem disease with morbidity and mortality, and its early diagnosis and also the establishment of a follow-up protocol for these patients could prevent systemic and oral complications.

Background

Pseudoxanthoma elasticum (PXE) is a metabolic disorder caused by genetic factors associated with extensive fragmentation and calcification of elastic tissue. It was first described by Jean Darier (1856–1938); however, only in 1929, the ophthalmologist and dermatologist Grönbland and Esther James Strandberg both scored the association of skin lesions with ocular and established the syndrome. ¹

This syndrome was related to the locus located on chromosome 16p PXE 13:01 arm in ABCC6 gene ² and the mutations in a gene encoding an ABC transporter cause PXE. ³ Mutations within ABCC6 cause reduced or absent transmembranous transport that leads to accumulation of extracellular material. Presumably, this mechanism causes calcification of elastic fibers.^2,4 However, other studies suggest the increased levels of oxidative stress, as observed in fibroblasts of PXE patients, could be an alternative pathological mechanism of disease. ⁴

PXE is a rare disease, with estimated prevalence between 1:25,000 and 100,000 inhabitants. ⁵ This prevalence seems to be highest in South America and it is twice more common among women. ⁶

The first manifestation of this disease is in the skin, with the formation of papules and yellowish streaks conglomerate forming little wrinkled appearance and prominence plates. ⁷ Around the plates can be isolated punctate papules, telangiectasia, and calcium deposits. The most characteristic symptom in the eyes is the presence angioid streaks due to rupture of the Brunch’s membrane. It can lead to cicatrix and hemorrhages in the retina. There may be loss of vision over time that begins with a minor trauma to the eye and sclerosis, posterior to the retina, leading to almost complete blindness and macular degeneration. The main morbidity is decreased visual acuity secondary ocular hemorrhage. ⁷ Other organs can be affected resulting in internal bleeding, such as gastrointestinal, uterine, epistaxis, and hematuria. ⁷ Furthermore, one-third of patients have hypertension associated with intermittent decrease or absence of peripheral pulses. ⁸ The cardiovascular involvement in these patients includes degeneration of elastic fibers in the middle layer, propensity to bleed, and hypertension in adults over 30 years.^9,10

There is a lack of studies about the impact of PXE on periodontal tissue. The frequency of periodontal involvement in a preliminary study without control subjects did not appear to be higher than that seen in the general population. Clinical examination showed the additional presence of active periodontal disease in four cases, despite the radiological examination revealed periodontal lysis in nine subjects. The prevalence and distribution of oral mucosa and periodontal lesions in elastic pseudoxanthoma patients are still not fully known. ¹¹

Although there are few studies reporting oral manifestations of PXE,^10,11 it is important to describe these oral signs since they can lead to early diagnosis of the disease. Thus, the aim of this article is to report an oral signal of patient with PXE.

Case description

A 50-year-old woman was admitted at the School of Dentistry, Federal University of Juiz de Fora, with discomfort in the posterior maxillary region due to a fractured tooth. The Institution does not require ethics approval for reporting individual cases. The medical history revealed that she was diagnosed with PXE 21 years ago, and the reticular manifestations were observed 15 years ago. During the anamnesis, the patient related that she presented a disease with “fur farms” and that she would have done two plastic surgeries to remove this abnormal production of skin on the neck (Figure 1), groin, and the armpit area. As a complication of PXE, the patient reported to have partial loss of vision. Currently, she uses acetylsalicylic acid.

Figure 1.

Abnormal production of skin on the neck.

Intraoral clinical assessment revealed the presence of alterations mainly in lower labial mucosa (Figure 2) and also slight alterations in the mouth floor (Figure 3) and the upper labial mucosa. These changes were a yellowish-white macula with a reticular pattern of growth without changing the smoothness of the mucosa and constitute oral signs of PXE.

Figure 2.

Alterations in lower labial mucosa.

Figure 3.

Slight alterations in the mouth floor.

Discussion

It is rare to find studies describing oral signs of PXE in the literature. However, it seems that the oral mucosa involvement is not so rare. Nozzi et al., ¹¹ 2008, evaluated 18 PXE patients through clinical evaluation and dental panoramic X-ray and they have showed that oral mucosa was involved in 15 (83%) patients.

The oral lesions usually occur inside the lower lip^{4,10 –12} as reported in this case. These oral lesions can appear still when the skin lesions are atypical or absent, so identifying these alterations is very important since it could provide early diagnosis of PXE.^10,11

The oral yellowish macula with a reticular pattern of growth observed in the patient was predominantly in lower labial mucosa, mouth floor, and upper labial mucosa. Similarly, these kinds of lesions were described previously in other studies, showing fragmented, granular, and calcified elastic fibers surrounded by ordinary connective tissue.^{10 –13}

Besides the oral lesions, our patient showed injuries in the neck, armpits and the skin of the arm, groin, and around the navel, compatible to alterations in tissues and organs associated to PXE. Although the pathogenesis of these lesions is still unknown, possibly they occur due to increase in mineralized and fragmented elastic fibers in the skin, vascular walls, Bruch’s membrane in the eye, and progressively lead to sagging skin, arterial insufficiency, and retinal hemorrhages. ⁴ Also, it has been suggested that an increase in proteoglycan in the PXE lesions may occur, and the clinical problems associated with the presence of PXE include elastic fiber ruptures as a result of calcification or even during tissue manipulation.^8,14

Previous studies have suggested that the severity of skin lesions and mucous membranes, as well as a higher distribution score and the presence of oral mucosa lesions can be correlated with the level of cardiovascular involvement in PXE patients.^10,11,13 Accordingly, our patient was using acetylsalicylic acid (AAS) to prevent a possible ischemia. This fact alerts the health professionals, including dental professionals, about additional care during management of patients with PXE, and the establishment of an appropriate diagnosis is necessary to provide adequate information and attention to the patient.

Conclusion

PXE is a metabolic disorder caused by genetic factors associated with extensive fragmentation and calcification of elastic tissue with significant degree of morbidity. Therefore, early diagnosis is imperative. Cardiovascular, ocular, and gastrointestinal complications could be prevented if a follow-up protocol was established for PXE patients. Thus, these patients must be referred for oral evaluation, since oral lesions may be present before other lesions.