Alcoholism and its implications for the dental team, an update and review of the literature

The American Medical Association de ines alcoholism as an illness characterised by signi icant impairment (a type of drug dependence) that is directly associated with persistent and excessive use of alcohol [1]. Alcoholism is a broad term that envelopes a variety of Alcohol Use Disorders (AUD). The World Health Organization (WHO) estimates that approximately 3.3 million deaths globally are a result of harmful drinking and lists alcohol consumption as the third largest risk factor for disease and disability [2].


Introduction
The American Medical Association de ines alcoholism as an illness characterised by signi icant impairment (a type of drug dependence) that is directly associated with persistent and excessive use of alcohol [1]. Alcoholism is a broad term that envelopes a variety of Alcohol Use Disorders (AUD). The World Health Organization (WHO) estimates that approximately 3.3 million deaths globally are a result of harmful drinking and lists alcohol consumption as the third largest risk factor for disease and disability [2].
Alcoholism raises several distinct dif iculties for dental patients. Alcoholics may exhibit greater levels of caries, periodontal disease and Pathological Tooth Wear (PTW) [3][4][5]. Management of these conditions is more dif icult due to a lower level of compliance observed in alcoholics [6]. The alcoholic dental patient has an increased risk of developing oral cancer [7]. In alcoholic liver disease, there is an increased risk of prolonged bleeding after invasive dental procedures, because of a reduction in production of clotting factors by the liver [8]. Dif iculties exist when prescribing medications for these patients, as alcohol interacts with most of the frequently prescribed pharmaceuticals in dentistry. In addition, chronic alcoholism can alter the pharmacodynamics of some of these medications [9]. During episodes of acute intoxication, abusers may participate in antisocial and sometimes violent behaviour, which can be challenging for the dentist to manage, all the while obstructing the fruition of a positive and healthy relationship between dentist and patient [9].
The focus of this article has been to primarily identify and critically appraise the associations between alcoholism and the various dif iculties that have been described above.

Alcoholism and saliva/salivary glands
Sialadenosis (asymptomatic enlargement of the salivary glands) is observed frequently in alcoholics [10][11][12]. Depending on the study incidence varied from 30%-80% [13][14][15][16][17]. The precise mechanism is unknown but it is thought to be due to adipose in iltration (abnormal fat metabolism due to altered liver function) and acinar hypertrophy [18][19][20][21][22]. The morphological and histological change found could account for the reduction in Salivary Flow Rate (SFR) observed in alcoholic patients [18]. The reduction in SFR appears to be more prevalent in cirrhotic alcoholics but a reduction is also seen in non-cirrhotic alcoholics [23]. There is also an altered mineral, electrolyte and enzyme composition of saliva observed in these patients and such differences in composition may be in part contributory to the increased incidence of dental diseases in alcoholic patients [24][25][26][27].

Alcoholism and caries
Globally, reliable epidemiological data on dental caries and alcohol abusers are scarce, however a link between regular consumption of alcohol and caries has been established [3,[28][29][30].
A common treatment for liver cirrhosis is diuretic drugs which can cause reduced SFR, also patients may suffer from Sjögrens syndrome as a result of primary biliary cirrhosis which may contribute to the development of caries [31,32]. An in vivo study on rats ingesting only an alcoholic diet showed a higher count of Streptococcus mutans. The precise mechanism is unknown but may be related to an increased rate of production of acetaldehyde [33].
Interestingly, a considerable number of studies found lower or comparable caries experience when compared to control groups, national averages and other substance abusers [34][35][36][37][38][39][40]. Summaries of the main indings of these studies are included in table 1. Possible explanations for the decreased caries rate observed are explored in igure 1. Enberg, et al. [28]. Radiological Observational 85 Using panoramic radiographs to assess for caries authors found a higher rate of caries when compared to non-alcoholic controls, but panoramic radiographs are not the gold standard for the diagnosis of caries. [129] Rooban, et al. [30]. Retrospective 268 Lower DMFT score in alcoholics when compared with alcoholics who smoke.
Harris, et al. [37]. Observational Cross-Sectional 107 DMFT scores were comparable with the national levels in the UK.
Hornecker, et al. [38]. Pilot Study 100 The number of teeth with carious lesions was relatively low and high DMFT is a result of missing teeth which may be due to periodontal disease.
Niquille, et al. [29]. Descriptive Cross-Sectional 624 Compared hospitalised alcoholics to non-alcoholics and found strongest differences between young alcoholics and non-alcoholics suggesting an important role of non-alcohol related factors, such as a traumatic childhood.
Dasanayake, et al. [39]. Observational Cross Sectional 363 Alcohol only abusers had a lower caries experience (DMFT) when compared to Alcohol and Drug abusers.
Kaplan and Shapiro [34]. Comparative 57 No differences in DMFT between institutionalized alcoholics and the non-institutionalized population.
DMFT: Decayed, Missing, Filled Teeth; DF: Decayed and Filled Teeth [42,43]. A fundamental law in many of the studies cited in table 1 is that Information on participants alcohol consumption was based on self-reporting which cannot be validated independently (However, a detailed study comparing selfreporting to dietary analysis interview found very little difference in the rates of consumption [41]). Clinical indings were also subjective in nature and no appropriate radiographs were used in the diagnosis of caries. Cross-sectional studies also fundamentally do not allow temporal relationships to be formed between two variables.

Alcoholism and periodontal disease
Early associations between alcoholism and periodontal disease have been made but most of these studies attributed the higher incidence of periodontal disease due to poor oral hygiene (OH) practices [31,46]. More recent research may indicate that alcoholism is an independent risk factor for periodontal disease.
Alcoholics are more likely to have poor OH, this may be related to impaired motor activity as a result of alcoholism, use of a hard toothbrush, the alcoholic lifestyle or limited knowledge and access to dental care. Alcoholics may use a hard toothbrush to mask the alcoholic odor after consumption [6].
A systematic review including twelve studies on alcohol consumption and four studies on alcohol dependence concluded that there is insuf icient evidence to support that there is a relationship between alcoholism and periodontal disease, however suf icient evidence exists to suggest alcohol consumption is a risk indicator for periodontitis. Metaanalysis could not be performed as each of the studies used different measures to clinically assess alcohol consumption/ dependence and periodontal disease [47]. However, a recent meta-analysis concluded that there was a linear dose-response relationship between alcohol consumption and risk of periodontal disease ( Figure 2). Eleven of the Eighteen studies showed a statistically signi icant correlation between alcohol consumption and periodontitis. This risk, when strati ied was doubled in females compared to a 25% increase in men. The analysis was based on a large number of studies (18) and the studies were adjusted for confounding variables which did not seem to have a major effect on the results. However, differences between the studies contributed to a large amount of heterogeneity, this high level of heterogeneity may have not been completely explained by meta-regression of the sub-group analysis. The combination of data from both crosssectional and cohort studies could mean an overestimation of Relative Risk (RR), as the cohort studies showed lower risk. There was little information included on type of beverage and associated risk. A number of the studies did not adjust for OH [4,48].
Few studies have found that no relationship exists between the two variables [49,50]. Kongstad, et al. [51], suggested a possible antimicrobial effect of ethanol similar to that of alcohol containing mouthrinses and the possible bene icial effect of wine as men consuming wine and spirits had lower odds-ratios for bleeding on probing [51]. Chronic alcoholism as indicated by Gamma-Glutamyl Transpeptidase (GGTP) levels was positively associated with increased plaque levels in one study, suggesting that for alcohol to exert its antibacterial effect it requires more time than the mere act of swallowing and drinking. This study used GGTP as a biological marker for alcohol abuse in order to alleviate the biases involved with self-reporting [52].
Tezal, et al. [53], found that alcoholics harbored high levels of Bacteroides forsythus and Porphyromonas gingivalis. In an attempt to quantify periodontal pathogens and cytokines in alcoholics a study found that alcohol dependents with periodontal disease had a higher frequency of some periodontal pathogens namely Prevotella intermedia, Eikenella corrodens and Fusobacterium nucleatum [54]. An increased production of cytokines has been observed in these patients suggesting that cytokines may be regulated as a result of alcohol induced damage to the periodontium [52,54,55]. When smokers were excluded from this group the microbiological and immunological results were similar suggesting an independent effect of alcohol. Novacek, et al., highlighted that dental aggregates of bacteria could be a potential source of liver transplantation failure in patients with advanced cirrhosis [31].
Shimazaki, et al. [56], postulated that alcoholism increases the risk of periodontitis when drinking causes a buildup of acetaldehyde, the precise mechanism was not explored.

Alcoholism and oral cancer
Ethanol is a well-established carcinogen [65-69] and table 2 identi ies the plausible biological mechanisms involved.
A recent meta-analysis reviewing 43 case-control and two cohort studies (17000 cases) provided more de inite quanti ication of Oral and Pharyngeal Cancer (OPC) risk for heavy alcohol drinkers (≥ to 4 drinks/day), the overall Relative Risk (RR) for heavy drinking was 5.24 (95% Con idence Interval, 4.36-6.30) [90]. Figure 3 demonstrates the dose-response relationship observed. Further analysis was performed using the same set of studies in an attempt to ind particular subsites more at risk, the authors concluding that the RR was greater for pharyngeal cancer when compared to oral cancer [91]. Bagnardi, et al. [92], used previous analyses to create site speci ic dose-response relationships for all types of cancer, inding that OPC had the highest relative risk when compared to cancer of other parts of the body. An additional 5 publications were included in a more recent meta-analysis attempted to quantify risk by sex, smoking status and other potential confounders. RR was similar between men and women, risk was present in the absence of tobacco smoking (however the association was weaker in non-smokers than in smokers, particularly in those who consumed heavy doses of alcohol, suggesting smoking increases risk in a multiplicative fashion) [7]. Many of the studies included in the analysis demonstrate that the interaction between the two risk factors could be more than multiplicative [93][94][95][96]. Recent evidence from the International Head and Neck Cancer Epidemiology Consortium supports this inding [97]. There was little variation in geographic pattern of risk and type of alcoholic beverage consumed suggesting that ethanol and its metabolites are the primary carcinogens conveying this increased risk. The most frequently consumed alcoholic beverages tend to be associated with the highest risk of OPC [65,98].
The above analyses suffer from many drawbacks, those studies included relating to heavy drinking were prone to heterogeneity and the use of random-effect models may account for only part of this heterogeneity, meaning the dose response analysis could be inaccurate. There may have also been signi icant residual confounding by other risk factors for OPC. Only one study accounted for Human-Papilloma Virus (HPV) [99] which is now a recognized risk factor for OPC [100], there may also be interaction between HPV and alcohol that further affects the risk pro ile [101].
Whether or not alcohol cessation has an effect on OPC risk requires further investigation as it is dif icult to assess without the in luence of potential confounders such as smoking, studies with larger sample sizes are required [109]. Larger studies are also required to investigate the impact of alcohol consumption on OPC survival. A systematic review is currently ongoing to investigate the effect of alcohol cessation on oral dysplasia and head and neck cancer [110].

Alcoholism and pathological tooth wear (PTW):
Alcoholism has also been implicated as a risk factor for PTW. Evidence and possible mechanisms are summarized in igure 4.

Pharmacological management of the alcoholic dental patient
There are several recognized adverse interactions

Mucosal Permeability
Ethanol may increase the permeability of the oral mucosa which increases the penetration of carcinogens [70][71][72].
Damage by acetaldehyde Acetaldehyde (the primary and most putative carcinogenic agent in ethanol metabolism) [76][77][78] can cause damage to epithelial cells [79] and is found in the saliva of alcoholics [80,81]. Poor dental status may be associated with increased acetaldehyde production [82]. Acetaldehyde has been shown to cause altered DNA production in human cells [71,83].
Alcohol and salivary fl ow Discussed above. Inadequate rinsing may increase the exposure of carcinogens to the oral mucosa [71,88].

Systemic Effects
Altered hepatic metabolism of carcinogens Alcoholic liver disease may affect the metabolism of potential carcinogens and toxic substances in the liver [70,89] Immunosuppression Immunosuppression as a result of alcohol consumption results in increased susceptibility to specifi c neoplasms. Natural Killer cells are involved in tumour surveillance and alcohol has been shown to cause suppression of NK cell [83].

Malnutrition
Alcoholics are frequently nutrient defi cient and impaired absorption and storage of nutrients has been shown to increase cancer risk [70,83].   Table 3: Adverse Interactions between Alcohol/Chronic alcoholism and medications used in dentistry. Adapted from Friedlander, et al. [9].

Medication Adverse interaction with alcohol Chronic Alcoholism Dentists Actions Evidence
Paracetamol Hepatotoxicity may occur because of toxic acetaminophen metabolites and glutathione depletion [9].
Increased risk of hepatotoxicity in alcoholic liver disease [9].
Limit acetaminophen dosage to 2 grams per day. Counsel patient about the risk of long term alcohol use and acetaminophen toxicity [9].
A systematic review [130] and meta-analysis [131] conclude that therapeutic dosing of paracetamol is not associated with liver damage in alcohol users. This conclusion is supported by several other studies [132,133]. However there have been cases of acute liver toxicity even at therapeutic doses [134] and been reports of acute interstitial nephritis in acetaminophen overdose in patients with acute/ chronic alcohol toxicity [135,136].
Nonsteroidal Antiinfl ammatory drugs (NSAIDs) Excessive bleeding may occur because of aspirin induced prolongation of bleeding time.
Increased risk of Mucosal ulceration. Renal toxicity with binge drinking with ibuprofen [9].
Possible increased risk of Gastrointestinal Bleeding (GIB).
Counsel patient to discontinue alcohol use during analgesic therapy [9].
It is unclear from the literature whether chronic alcohol consumption affects risk estimation of GIB [137][138][139]. Many studies have found increased risk and incidence of GIB with greater amounts of alcohol consumption [140][141][142] this is further supported by the fact that alcohol has been shown to cause damage to the gastric epithelium [143,144] and alcohol induced gastric damage is enhanced by the presence of NSAIDs in dogs [145].
Cephalosporins (some) Cephalosporin and alcohol may interact to produce a cephalosporin induced disulfi ram reaction(CIDLR) presenting as facial fl ushing, nausea or vomiting and in severe reactions angioedema, hypotension, shock, or death [9].
Not explored in the literature. Avoid use of cefoperazone and cefotetan [9].
Erythromycin Decreased absorption of erythromycin, with consequent decrease in effectiveness possibly due to an increase in gastric emptying [9].
Not explored in the literature. Counsel patient to discontinue alcohol use during erythromycin therapy [9].
Metronidazole A disulfi ram effect may occur, permitting the accumulation of acetaldehyde, leading to facial fl ushing, headache, palpitation and nausea [9].
Not explored in the literature. Counsel patient to discontinue alcohol use during metronidazole therapy [9].
Tetracycline Increased absorption and increased plasma concentration in healthy subjects after acute ingestion of ethanol [9].
Diminished effectiveness in long term alcoholics because of induction of metabolizing enzymes. Preexisting liver disease such as alcoholic liver disease has been associated with increased risk of developing tetracycline induced hepatotoxicity [159].
Counsel patient to discontinue alcohol use during tetracycline therapy [9].
Evidence based from case reports and analytic studies [159,160].
Ketoconazole A disulfi ram effect may occur, permitting the accumulation of acetaldehyde, leading to facial fl ushing, headache, palpitation and nausea [9].
May increase risk of liver damage [9].
Counsel patient to discontinue alcohol use during ketoconazole therapy [9].
Only 1 case report found in the literature [161].

Benzodiazepines
Fatal poisoning can occur with concomitant use of benzodiazepines and alcohol as well as increased sedative effects [162].
Diminished effectiveness in longterm alcoholics because of cellular tolerance to CNS depression [9], increased induction of CYP2E1 enzyme [165], or both.
Initially decrease the usual dosage of medication and observe patient for CNS depression. Counsel patient to discontinue alcohol during treatment.
Not explored in the literature.
Initially decrease the usual dosage of medication and observe patient for CNS depression. Counsel patient to discontinue alcohol during treatment [9].
Not explored in the literature Initially decrease the usual dosage of medication and observe patient for CNS depression. Counsel patient to discontinue alcohol during treatment [9].

Warfarin
There is only one case report evaluating possible interaction between warfarin and ethanol suggesting alcohol consumption daily may decrease the effectiveness of warfarin reducing the International Normalised Ratio (INR) [178]. A recent study suggests that alcoholism is risk factor for major bleeding in patients on warfarin therapy [179].
Other Beta lactams There does not appear to be a clinical signifi cant interaction between alcohol and other B-lactams but the rate of absorption appears to be increased [180].
between alcohol and medications used in dentistry. In addition, chronic alcohol abuse alters the pharmacodynamics of certain pharmaceuticals [9]. These interactions and speci ic recommendations are summarized in table 3.
Many of the pharmacotherapies used for alcohol dependence have oral side effects for example Naltrexone treatment has been associated with xerostomia, cold sores, headaches and sinusitis raising additional dif iculties for these patients [181]. Patients using disul iram should not use alcohol containing mouth rinses because of potentially adverse reactions [9].

Alcoholism and bleeding
Thrombocytopenia as a result of alcohol consumption is usually transient and platelet counts generally return to reference ranges within 4-8 weeks [182].
There is reduced synthesis of coagulation proteins in alcoholic liver disease. As a result, Prothrombin-time (PT) and Activated-Partial-Thromboplastin time (APTT) may be prolonged [183,184]. Hematological investigations are not required in alcoholics without a positive bleeding history. A Full Blood Count (FBC) and coagulation screening may be indicated in patients where there is a positive bleeding history prior to invasive dental/oral surgical procedures. If prolonged bleeding occurs it can be successfully managed using local measures, an emphasis should be placed on gathering an accurate bleeding history from the alcoholic patient. These guidelines are based on an audit completed in the UK, evidence-based guidelines may be required on the hematological management of the alcoholic dental patient [8,185,186].

Alcoholism and facial fractures/oral surgery
Alcohol intoxication has been associated with facial fractures [187][188][189][190]. These fractures tend to occur in young men as a result of Interpersonal-Violence (IPV) [191,192]. Alcohol related injuries are more likely to occur in binge drinkers rather than chronic alcohol dependents [193][194][195][196]. A review on the temporal distribution of these facial fractures is awaiting publication [197]. Research suggests that interventions in practice may have a role in preventing alcohol related facial injuries. Closed reduction of these fractures should be avoided in alcoholics due to the risk of vomiting and aspiration [198].
Poorer wound healing is seen in alcoholics because ethanol has been shown to decrease the mobility of and phagocytic capabilities of white blood cells, [199][200][201] poorer wound healing would confer a theoretical increased risk of infection and osteomyelitis following dental extractions [9]. More thorough research is most de initely warranted in this area.
Alcohol has been shown to cause a decrease in bone formation [202][203][204] and alcoholism is considered a risk factor for osteoporosis [205][206][207]. Patients prescribed bisphosphonates for the treatment of osteoporosis are at risk of developing Medication-Related-Osteonecrosis of the Jaw (MRONJ) after dental extractions [208], another possible dif iculty that may be encountered in the alcoholic dental patient.

Alcoholism and access to dental care
Few studies have evaluated access to dental care in alcoholics, however a low level of access would be expected because of depression and psychiatric disorders coexisting in these patients. Interestingly, two studies found access to dental care which was comparable to national levels, this high level of access may be because participants from both studies were selected from alcohol treatment centres [6,40].
Dentists have a professional duty to enquire about alcohol intake. It is unlikely that an alcoholic will disclose their alcohol consumption because of the stigma associated with alcoholism. To overcome this, there have been various questionnaires that can be used by dental and medical professionals in practice that identify alcohol dependence and dentists should refer patients with suspected alcohol dependence to their general medical practitioner [209][210][211]. An Example of one of these questionnaires (AUDIT (Alcohol Use Disorder Identi ication Test)) that may be used in primary care can be seen in igure 5 [214,215]. In addition, it has been shown that brief interventions and motivational interviewing are effective in reducing alcohol consumption in primary care settings, [212,213] whether such interventions are feasible and practical in dental practice remains to be seen.

Conclusion
There are many considerations to take into account when treating the alcoholic dental patient. These patients are at a greater risk of developing oral/dental diseases, namely PTW, periodontal disease and OPC. Poor compliance and limited access to dental care confounds issues, allowing conditions to deteriorate further and making management more challenging. Medical management of these patients is more dif icult, as alterations in coagulation, drug metabolism, liver function and bone remodeling may be encountered as well as gastrointestinal and central nervous system disturbances. Dentists are professionally obligated to enquire about alcohol consumption and are well positioned to offer appropriate referrals to primary care physicians.
Larger scale epidemiological and interventional studies are needed to explore the effect of alcoholism on caries and sleep bruxism, as well as supportive experimental studies to explore the mechanisms involved.
To conclude, alcoholism among patients raises signi icant dif iculties among dental patients, however, dentists who are familiar with the manifestations of the illness, as well as the challenges raised in dental practice can con idently offer these patients a full range of dental treatment.