Could Periodontitis Aggravate Psoriasis: Comparison
Please note this is a comparison between Version 1 by JUANJO MENEU ESTELLES and Version 2 by Dean Liu.

Psoriasis is a chronic and inflammatory systemic disease that has been associated with periodontal pathologies, specifically periodontitis.

  • psoriasis
  • periodontitis
  • inflammatory disease

1. Introduction

Psoriasis is a chronic, immune-mediated inflammatory skin disease, characterized by red and scaly plaques occurring more frequently on the elbows, knees, scalp, and lower back [1]. Worldwide, in 2017, an estimated 29.5 million adults had psoriasis, corresponding to a physician-diagnosed lifetime prevalence of 0.59% of the adult population [1]. Plaque psoriasis is the most frequent type, representing more than 80% of psoriasis cases [2]. The pathogenesis of plaque psoriasis consists of a feed-forward mechanism of inflammation involving primarily the T-helper cell type 17 (TH17) pathway [2]. In the past, psoriasis was considered a disease that was limited to the skin and was treated with topical agents or phototherapy. 
Psoriasis is a visible skin disease, and therefore relationships with other people can be disturbed. Many patients encounter prejudice and rejection and feel that their attractiveness is diminished. Therapy and skin care are time-consuming, so psoriasis patients may be limited in their work, leisure time, and freedom of movement due to physical symptoms [1][3][1,4]. Apart from comorbidities [4][5], people with psoriasis not only have to cope with physical limitations but also with severe psychological burdens such as depression, anxiety, and suicidal thoughts [1][3][1,4].
Guideline-indicated therapeutic options involve topical treatments, phototherapy, and systemic therapies which encompass both oral treatments and injectable biologics. Eighty per cent of patients with psoriasis have mild-to-moderate forms of psoriasis and can be treated exclusively with topical agents such as corticosteroids and vitamin D analogs. Phototherapy and systemic agents are recommended for patients with moderate-to-severe psoriasis, where the extent of the disease makes topical therapy of all lesions impractical [5][6].
Psoriasis has been related to other chronic inflammatory conditions, such as periodontitis. Accumulated epidemiologic, genetic, and pathogenetic evidence indicates that psoriasis is associated with this condition [6][7]. The American Academy of Periodontics defines periodontal disease as an inflammation of the supporting tissues of the tooth [7][8]. It is a progressive destruction process that leads to the loss of the supporting bone of the tooth and its periodontal ligament [8][9]. The prevalence of periodontitis is reported to vary from 20% to 50% around the world. Additionally, periodontitis is one of the major causes of tooth loss, which can undermine function, aesthetics, self-confidence, and quality of life [9][10].
Periodontitis is a chronic inflammatory condition provoked by a bacterial infection that activates the host immune response [9][10][11][12][13][14][15][10,11,12,13,14,15,16]. Psoriasis could cause periodontal lesions and sometimes white plaque and erythema lesions on the oral mucosa and palate [10][15][11,16]. This disease is an inflammatory condition considered a result of the complex interaction between the oral microbial community and the host response, modified by genetics and environmental factors. There has been increasing evidence supporting a strong relationship between periodontitis and systemic conditions. These conditions include cardiovascular diseases, metabolic syndrome, obesity, rheumatoid arthritis, polycystic ovary syndrome, and adverse outcomes during pregnancy [10][11][12][11,12,13].
Since psoriasis and periodontitis have similar pathogenic mechanisms and associated conditions in common, there has been a renewed interest in research into possible links between these diseases. The current hypothesis of common etiopathogenic processes between the conditions comprises several possible mechanisms, such as amplified inflammatory response and T-cell activation and a lower concentration of salivary IgA and lysozymes [10][11]. Some studies have already indicated that patients with psoriasis have a significantly elevated risk of periodontitis compared with controls without psoriasis [13][14][15][16][17][18][19][14,15,16,17,18,19,20]. This was especially observed in patients with severe psoriasis [20][21]. In addition, a meta-analysis reported that patients with periodontitis have a significantly increased risk of psoriasis [21][22].

2. Periodontal Parameters

The periodontal parameters used in most of the investigations were probing depth (PD) [17][18][22][23][24][18,19,24,25,26], clinical attachment loss (CAL) [17][18][22][23][24][18,19,24,25,26], and the community periodontal index of treatment need (CPITN) (15,16). All of these indices are indicative of the stage of periodontitis according to the new classification of 2017 [25][27]. PD had higher values in one study [17][18], but in the others that analyzed it there were no differences between cases and controls [18][22][23][24][19,24,25,26]. CAL had higher values in some of the studies reviewed [17][18][18,19] but not in others [22][23][24][24,25,26]. There were significant differences in CPITN in the two studies involving it [14][15][15,16]. In addition, plaque index (PI) was used to assess the oral hygiene of some patients [17][18][22][23][24][18,19,24,25,26], with most studies finding no differences in this measure between cases and controls. On the other hand, other authors have used some less frequent indexes, such as bleeding on probing (BOP) [15][17][18][22][23][24][16,18,19,24,25,26]; the decayed, missing, and filled teeth index (DMFTI) [15][18][26][16,19,28]; the papilla bleeding index (PBI) [26][28]; and the gingival index (GI) [26][28].

3. Epidemiological Parameters

Likewise, it is especially important to mention the epidemiological factors identified in this review. Some of the studies used prevalence indicators [13][17][18][14,18,19] while other publications used incidence rates [19][20]. Thus, the prevalence of periodontitis was 23.9–46.1% in psoriasis patients compared with 7.7–33.1% in healthy controls [13][17][14,18]. An OR of between 1.72 (95% CI 1.28–2.32; p < 0.001) [17][18] and 3.76 (95% CI 1.60–10.27; p = 0.001) [13][14] was found for the risk of psoriasis patients suffering periodontitis. Regarding the incidence of periodontitis in the cohort study [19][20], the authors found significant differences between cases and controls. The incidence rate ratio (IRR) in mild psoriasis was 1.66 (95% CI 1.43–1.94; p < 0.001), 2.24 (95% CI 1.46–3.44; p < 0.001) in psoriatic arthritis, and 3.48 (95% CI 2.46–4.92; p < 0.001) in severe psoriasis. Finally, Macklis [16][17] used a validated WHO survey to establish the state of gums in adult patients with psoriasis compared with healthy controls, and it was observed that psoriasis patients who considered their gum health to be poor or very poor had significantly more severe psoriasis symptoms.

4. Relationship Between Periodontitis and Psoriasis

In two previous similar studies it was determined that psoriasis patients had higher chances of suffering from periodontitis. Qiao et al. [20][21] carried out a meta-analysis of eight articles, finding significant differences in BOP, PD, CAL, and remaining and missing teeth, as well as in the level of alveolar bone loss. There were no differences in PI and GI. The authors elucidated that psoriasis patients suffer from worse periodontal health compared with non-psoriasis subjects, and, despite a more detailed investigation being needed, it was concluded that the confounding factors should be taken into much more consideration. Moreover, it was stated that there were not enough studies to establish solid conclusions for some indexes and that more papers should undertake adequate quality meta-analysis. Zhang et al. [10][11] performed a systematic review, concluding that psoriasis and periodontitis were bidirectionally related, but the authors mention that there was high heterogeneity among the papers and a higher number of articles was needed. Zang et al. [10][11] also report that the role of confounding factors such as age, gender, or systemic conditions should be highlighted. Additionally, establishing precise and common criteria for the diagnosis of periodontitis was deemed critical. Regarding the present paper, there were three studies that did not find any differences between the psoriasis patients and the control groups [23][24][26][25,26,28]. Ligia et al. (24) also show no statistical significance between groups, although periodontitis was more frequent in psoriasis patients. The remaining seven articles [12][13][14][15][16][17][18][13,14,15,16,17,18,19] gathered significant evidence that patients with psoriasis were more susceptible to suffering periodontal disease. These articles [13][14][15][16][17][18][19][14,15,16,17,18,19,20] used epidemiological indexes (prevalence [13][17][18][14,18,19] and incidence [19][20]), periodontal indexes [14][15][17][18][15,16,18,19], and questionnaires [16][17]. In several studies [12][16][17][13,17,18], it was found that there was a higher prevalence of periodontitis in psoriasis patients with an OR (95% CI) of between 1.72 (1.28–2.32, p ˂ 0.001) [17][18] and 3.76 (1.60–10.27, p = 0.001) [13][14]. Eberg et al.’s cohort study [19][20] has to be highlighted as the initial sample was all individuals aged 18 or over from Denmark, with a final sample was composed of 5,470,428 individuals. Their results show through the IRR that there is an increased risk of periodontitis in mild psoriasis (IRR: 1.66; 95% CI 1.43–1.94; p < 0.001), severe psoriasis (IRR: 2.24; 95% CI 1.46–3.44; p < 0.001), and psoriatic arthritis (IRR: 3.48; 95% CI 2.46–4.92; p < 0.001). However, the results are not as clear for the PD measure with four out of five articles not finding any differences [18][22][23][24][19,24,25,26]. For the CAL measure, three out of five papers found no differences between cases and controls [22][23][24][24,25,26]. Furthermore, all of the studies that analyzed PI did not find any differences [17][18][22][23][24][18,19,24,25,26]. Regarding prevalence, three out of three studies showed significant differences [13][17][18][14,18,19]. All of this may indicate that psoriasis can be a risk factor for developing periodontal disease. Nevertheless, the diagnosis of periodontitis in these three publications was different. While Painsi et al. [13][14] used registers to identify periodontal disease patients, Mendes et al. [17][18] employed interproximal CAL and/or PD and Barros et al. [18][19] only used the CAL measure in interproximal sites. The different diagnosis methods in the studies increases the heterogeneity of the results and the subsequent conclusions. For further studies, there should be criteria for always establishing the same method of diagnosis since without this, it is difficult to compare and generalize results, especially in relation to registers. Although it is a good method for large studies, it reduces their precision. Thus, a goal for this line of research would be having a common diagnosis for both periodontitis and psoriasis. In addition, there is the question of confounding factors, with age, gender, or systemic conditions having been mentioned already. However, there may be other factors that have the capacity to modify the results. Socioeconomic status is likely to alter periodontitis outcomes, so patients with less access to healthcare or healthy conditions are more likely to have worse outcomes. Another confounding factor is the presence of plaque, as there will not be the same outcomes for people with poor hygiene vs. people with good oral care. There have been articles involved in some systematic reviews with very high PI values, and these values are going to change the results because the periodontium is not going to react in the same way to good hygiene as it does to poor hygiene. Both diseases have been shown to cause inflammatory changes in the form of increased cytokine values [13][14][15][18][19][22][23][24][14,15,16,19,20,24,25,26]. Since they are essential in the pathogenesis and progression of periodontitis and psoriasis, it can be speculated that increased cytokine values may favor the development of periodontitis [13][14][15][17][24][14,15,16,18,26]. This altered state would render the individual susceptible to developing inflammatory diseases. Therefore, it has been shown that if periodontal disease is treated, the psoriasis condition improves [27][28][29,30]. In addition, systemic psoriasis therapy could lead to better periodontal parameters [27][28][29][29,30,31]. An association between psoriasis and periodontitis has been shown, and increased concentrations of proinflammatory cytokines such as TNF-α and IL-1β have been found in saliva from patients with psoriasis [28][29][30][31][3,30,31,32]. Activated TH17 cells producing IL-17 are key pathogenic players in psoriasis, and bacterial infection, including infection with P. gingivalis, may also activate TH17 cells. This bacterial infection can activate inflammatory pathways, promoting secretion of interleukins and increasing the clinical manifestations of psoriasis by contributing to systemic inflammation. Moreover, activated TH17 cells have been found in periodontal lesions and in mild psoriasis, and increased IL-17 levels have been demonstrated in crevicular fluid from patients with mild psoriasis [2][28][29][30][31][2,3,30,31,32]. These findings show that TH17 hyperactivation could be a pathway that connects both pathologies, sharing pathophysiological mechanisms present in psoriasis and periodontitis [2][6][16][17][18][29][30][31][32][2,3,7,17,18,19,31,32,33].