Orofacial Manifestations of Lyme Disease: A systematic review

Discussion:

The scientific literature was systematically reviewed to synthesize information regarding the orofacial manifestations of Lyme disease that would be most relevant to oral health care providers. Studies that met the inclusion criteria from 1992-2017 were published in journals that do not target the dental professional audience. There is a need for this timely research to appear in dental and dental hygiene journals so that the oral health care community is informed regarding the various ways this growing infectious disease may be manifested within their patient populations. Additionally, none of the included research studies discussed clinical assessments or scales that could be used to quantify the severity of Lyme disease related orofacial manifestations. Such diagnostic tools along with recommendations on how to best manage the orofacial manifestations to ease discomfort, improve function, and track recovery or relapse would be beneficial to oral health care professionals.

Fewer than one half (n=6) of the US endemic states (n=14) were represented in the included studies. More studies are needed in the literature from other endemic and neighboring states, especially since the CDC Morbidity and Mortality Weekly Report concluded that incidence rates are increasing in neighboring states.⁵ Oral health care providers who practice in those geographic areas need to have evidence-based information regarding how to care for affected patient populations. The literature also does not report orofacial manifestations evenly across demographics. Since disease transmission does not discriminate between genders, studies are needed to fully represent both males and females. An underrepresentation of females in the literature may be of concern especially for those residing in low incidence states, since Lyme disease has been found to be more common among females in states with low incidence rates.⁵

A total of eight orofacial manifestations were documented in the included studies. Half of the studies reported higher frequencies of these manifestations than the total number of study participants likely due to participants who experienced multiple oral manifestations. Regarding patients who present with orofacial symptoms of unknown origin, oral health care providers should carefully document their findings following a thorough health history interview and extra/intraoral examination. Questions that may assist dental hygienists and dentists while conducting a health history interview when Lyme disease infection is suspected could include: “Have you noticed a red, circular skin rash?”, “Have you worked or played outdoors within the last month?”, “Do you recall a recent insect bite?”, “Have you recently traveled to states known to be endemic for Lyme disease?”, and “Have you been tested by your medical physician for Lyme disease?”.⁴ Occurrences of these orofacial manifestations should be taken into consideration for any type of differential diagnoses when the typical oral pathologies of trauma or infections cannot be identified. This is particularly important since these presenting signs and symptoms can occur during the localized early stage of Lyme disease when serology testing may fail.

Eight of the included studies reported headache, neck pain/arthralgia, sore throat, facial paralysis, stiff neck, altered taste, and TMJ arthralgia as orofacial manifestations appearing during the early stage of disease,^11-15,17-19 and two studies reported headache, neck pain, and sore throat during the late stage of disease.^12,17 Four included studies did not specify early or late dissemination for disease stage of the sample populations.^8-10,16 While the majority of reported orofacial manifestations appeared during early dissemination among these studies, it is difficult to say this is enough evidence to generalize that all orofacial manifestations primarily occur during early dissemination of the disease. Future research should include specific details about the timeframe of when signs and symptoms appear in the disease process so that a pattern of correlation may be identified over time. Oral health care providers with a keen awareness of the role of these oral manifestations could refer a patient for medical examination when Lyme disease is suspected, increasing the chances of making a timely diagnosis.

A total of 951 patients were confirmed to have Lyme disease across the twelve studies. Headache and facial palsy were reported most frequently while temporomandibular joint arthralgia and altered taste were reported the least. Low frequencies of neck stiffness and temporomandibular joint arthralgia was a surprising finding since the review process revealed several articles and case studies which reported those two symptoms as primary orofacial manifestations.^7,24-34 However, case studies were excluded from this systematic review, due to the high for risk of bias. Considering that neck stiffness and temporomandibular joint arthralgia appeared in several case studies and have been recognized by the CDC as Lyme disease symptoms,² they may merit further study.

Avery et al, devised a statistical model to help predict Lyme meningitis and stated that odds ratios for headaches can serve as an independent predictor of the condition and found that headache duration was an independent predictor of Lyme meningitis in children in an endemic region.⁸ This model allowed practitioners to calculate the probability from .01 to .99 of children having Lyme meningitis.⁸ Each additional day of headache duration increased the odds ratio of having Lyme disease by 0.136.⁸ The Avery prediction model was compared against a “rule of 7’s” prediction model devised by Cohn et al. This prediction model classifies suspicious cases as “low risk” when 3 of the following criteria are met: “<7 days of headache, <70% cerebrospinal fluid mononuclear cells, and absence of seventh or other cranial nerve palsy.”⁹ Cohn et al reported that both the Avery model and the rule of 7’s performed well when applied to a sample population of children. However, the rule of 7’s model had higher sensitivity (96% [95% CI: 90%-99%]) compared to the Avery model (83% [95% CI: 75%-89%]); and fewer misclassifications when assessing patient risk for Lyme disease.⁹

Smouha et al applied a researcher-designed clinical probability scale compared against serology test results to determine if clinical signs and symptoms could accurately assess Lyme disease probability.¹⁶ The researchers defined clinical probabilities of Lyme disease signs and symptoms including orofacial manifestations: “definite” probability (erythema migrans rash), “high” probability (headache and stiff neck), “intermediate” probability (arthralgias), and “possible” (headache alone).¹⁶ However, they concluded that the majority of disease predictors could not be made solely based on clinical data, which contrasts findings from Avery’s prediction model and Cohen’s rule of 7’s model.¹⁶ Risks or odds ratios for orofacial manifestations should be investigated by validated prediction models to determine whether they can assist health care providers who encounter suspicious cases. Since patients presenting with orofacial manifestations are considered medical emergencies, the ability for oral health care providers to apply risk prediction models until serology test results are available, and may help reduce unnecessary antibiotic prescriptions, invasive medical procedures and support timely referrals.

Generalizability of this systematic review is limited because studies of populations outside of the US were not included as Lyme disease variants in other countries may differ from those found in the US. Additionally, the Cochrane Data Collection Form for Randomized Control Trials and Non-randomized Control Trials was modified as there were few randomized control trials identified in the literature that met the inclusion criteria.

Future research focused on the eight orofacial manifestations associated with Lyme disease as presented in oral health care settings is needed. Additionally, there were other less common orofacial manifestations of Lyme disease reported as case studies that were not included in this review. A systematic review of case studies could be helpful to investigate the phenomenon of these less common manifestations. Case-control studies of integrated electronic medical and dental records could be conducted to investigate the frequencies of orofacial manifestations of confirmed Lyme disease cases against healthy cases from endemic states to support evidence-based decision making for all health care providers. Future studies should also investigate the efficacy of integrated electronic medical and dental records to improve the interprofessional collaboration of health care professionals for the management of patients with Lyme disease.