Patient context to the project:
A middle aged man with chronic intermittent dental pain
The above X-rays are that of a middle aged man with chronic intermittent toothache that first began when he touched 30 when he underwent a series of dental interventions that successfully removed his wisdom teeth sometime around 2000.
Following that in 2004 he developed bleeding gums for which he received periodontal cleaning interventions on one or two occasions.
In 2016 he had an episode of prolonged toothache nagging so much so that he got his first alveolar X-ray. That showed remarkable bone loss in his alveoli for the first time along with severe periodontal inflammation in the area for which a deeper cleaning with "flap reflection to gain visual access to the root surfaces and alveolar bone" was suggested.
The pathophysiologic rationale for the intervention is to quote,
" to facilitate debridement of root surfaces...for the removal of excessive soft periodontal tissue onfacilitate debridement of root surfaces through access. Resective surgery is indicated for the removal of excessive soft periodontal tissue to correct true periodontal pockets (with loss of attachment) in periodontitis when both the pocket epithelial lining and the inflamed connective tissue are removed to promote reattachment of connective tissue fibers to the root surface the gingival margin."
The surgery was done in autumn 2019 captured slightly in the image below :
The patient felt much better and the teeth that were troubling him quietened down to a large extent.
The most recent X-ray shared above in the beginning was done as there was fresh pain in the left lower jaw that hadn't been earlier tackled by the flap surgery.
The current problem statement for the project is :
Chronic endothelial dysfunction due to inflammation and microvascular dysfunction is a very common cause of organ dysfunction in humans that needs urgent better understanding in terms of pathophysiology.
This project aims to study patients of periodontal microvascular inflammation with or without indicators to microvascular dysfunction elsewhere in retina, heart, kidneys, cerebrum etc but with definite evidence of visceral fat and a body phenotype that is being increasingly recognized as key in the pathophysiology of microvascular dysfunction.
Recently the tooth getting impinged on by the left lower wisdom tooth had severe pain for a week and finally had to be extracted the image of which is attached below and biopsy of the microvasculature is awaited :
Some review of literature :
The most significant limitation is that there is no single gold standard definition of a threshold for a diagnosis of ‘periodontitis’. Most studies use varying thresholds which has a significant impact on prevalence rates and means studies need to be compared with caution "
"Periodontitis and other comorbidities such as cardiovascular diseases and diabetes, share many common risk factors, including obesity and smoking [34, 35] which both have an effect on the systemic inflammatory profile [36]. This might account for a spurious association between periodontitis and systemic inflammation."
Meanwhile the index case suffered a fresh problem in that the last upper right molars were pressing on the lower gingiva and causing ulcerations and so the last upper right molar had to be removed as in the images below :
There is some macroscopic inflammation apparent in the periodontal ligament (as noticed by the extractor) and this triggered past similar analogies drawn between periodontal ligamental inflammation as well as a more common autoimmune disease phenotype of sacroiliac ligament inflammation aka spondyloarthropathy and below is some review of literature around it :
"HLA A9 and B15, both associated with susceptibility to AS, may also be a susceptibility factor in aggressive periodontitis [82]. In particular, T lymphocyte-driven inflammation certainly plays a role in periodontitis [83] as well as in AS [84]. Interleukin (IL)-2, IL-6 and TNF-Ξ± are all raised in AS [85] as well as being implicated in periodontitis"
The index case has started to develop an ulcer in the left cheek that appears to be a result of the upper molars and the last left lower jaw wisdom tooth biting into the biting plane aka Linea alba as visualized here in the patient's oral examination below π
So out came the last left lower wisdom tooth π
and was submitted along with some perialveolar tissue for a biopsy to study the microvasculature. A long meeting with the oral pathologists followed and it was decided to also obtain immunohistochemistry to guide our search for the nature and patterns of endothelial injury that led to this person's periodontal inflammation and to see if one can also join the dots between convincing evidence of microvascular inflammation (if elucidated) and dysbiosis.
Some review of literature again around the last point shared below :
An introduction to dysbiosis and periodontal inflammation and dysbiosis and I quote, π
"Known since antiquity, periodontitis became prevalent after the domestication of plants and animals in Neolithic societies (≈10,000 years ago) when the oral microbiota underwent a distinct compositional shift — with increased frequency of Porphyromonas gingivalis and other periodontitis-associated species — compared with earlier hunter-gatherer societies. In its severe form, which afflicts 8.5% of U.S. adults, periodontitis may not only cause tooth loss, but can also affect systemic health by increasing the patients’ risk for atherosclerosis, adverse pregnancy outcomes, rheumatoid arthritis, aspiration pneumonia and cancer"
However contrary to the initial hypothesis of our project, the current popular hypothesis attributes a bacterial pathogenesis with bacteria as the central aggressor and villain in this entire drama and I quote again from the above article π
"P. gingivalis prevents TLR4 signalling while activating TLR2 (...and this possibly) leads to atherogenic inflammation at sites distant from initial infection."
So as soon as the bacteria is identified as the central villain and protagonist, the rest of the story in this article assumes a "James Bond" style of narrative with Trojan horses and lipid rafts and I quote further (just for kicks) π
"Although periodontal bacteria have been identified in atheromas25-27,92-94, the mode of their relocation is uncertain and could involve mechanisms alternative or additional to the bacteraemic route. In principle, bacteria might exploit recirculating leukocytes — such as macrophages and/or dendritic cells (DCs) — as ‘Trojan horses’ for dissemination to systemic tissues."
"To persist intracellularly in macrophages, P. gingivalis needs to enter the macrophage via complement receptor-3 in cholesterol-rich lipid rafts102,103, which is consistent with observations that pathogens which invade through lipid rafts are not readily directed to late endosomes and lysosomes where they would be killed"
And then eventually the narrative progresses to enable a James Bond style takeover over of all organs in internal medicine by the chief protagonist of periodontology aka P Gingivalis!
Sir nice initiative the periodontal disease is recognised as major culprit as oral foci of infection to aggravate systemic conditions
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