A. Signs & Symptoms
Patients with a history of AUD can present in various clinical settings such as outpatient, the emergency room, or the general hospital (Table 17–2). Clinical presentation varies widely; problems may sometimes be vague/nonspecific or even seemingly unrelated to alcohol. Initial screening can be accomplished using brief screening measures, followed by more in-depth history. A detailed history and examination are vital in making a diagnosis of AUD.
Table 17–2 Clinical Features of Alcohol Use Disorders
| History | Clinical Signs and Symptoms |
|---|---|
Presentation | Intoxication, withdrawal symptoms, intense cravings, physical and psychosocial consequences of chronic alcohol consumption. |
Chemical dependence history | Coexisting drug use. History of nicotine dependence. |
Psychiatry history | Primary psychiatric disorder or a substance-induced psychiatric disorder (anxiety, mood disorder, psychosis), personality disorders, insomnia |
Trauma history | History of domestic violence, sexual or physical abuse, posttraumatic stress disorder |
Medical history | Multisystemic Cardiovascular—hypertension, cardiomyopathy, elevated triglycerides Gastrointestinal—gastritis, stomach and duodenal ulcers, liver cirrhosis/physical stigmata of chronic liver disease, pancreatitis Endocrine—feminizing syndromes in males (due to reduced testosterone), menstrual irregularities in females Hematology—anemia, macrocytosis, thrombocytopenia Oncology—stomach, esophageal, liver, and breast cancer Neurology—paresthesia, neuropathy, cognitive impairment, Wernicke-Korsakoff syndrome, tremor, ataxia Musculoskeletal evidence of body injury (multiple causes, such as fall risk, vehicular accidents) Sexual—erectile dysfunction in males |
Family history | History of family member with drug and alcohol use disorder as well as mental illness |
Social | Low academic achievement, legal issues, marital discord/divorce |
B. Alcohol Screening Questions
AUD is a major public health concern, associated with high rates of morbidity and mortality as well as a global health and economic burden. As a result, the U.S. Preventive Services Task Force recommends that clinicians screen adults for hazardous use with one of two brief validated screens (AUDIT-C or NIAAA SASQ) and provide brief behavioral interventions to those who screen positive. There are several validated screening tools available in clinical practice, with varying degrees of efficacy.
1. The NIAAA single alcohol screening question (SASQ)
The SASQ has similar sensitivity and specificity to other longer screening tools, with the advantage of requiring only a single question: “How many times in the past year have you had (4 for women, or 5 for men) or more drinks in a day?” Any response greater than zero requires further assessment. The SASQ can be woven easily into a clinical interview, as there is no scoring (unlike other screens).
2. The AUD identification test (AUDIT)
The AUDIT is also recommended by the USPSTF as an initial screening tool (in the abbreviated version) for identifying current at-risk drinking and can detect hazardous and harmful drinking as well as AUD. The full AUDIT is a 10-question screening tool with ratings from 0 to 4. A value of 8 or higher is indicative of hazardous alcohol use. A revised and more concise three-item version, AUDIT-C, is used more frequently in clinical practice. The three questions asked and scoring guidelines are presented in Table 17–3. The AUDIT-C is a reliable tool, with 57–97% sensitivity and 78–96% specificity for identifying at-risk drinking within different ethnicities and genders. A limitation of the AUDIT is its lack of efficacy in detecting AUD in the older population (Reinert & Allen 2007).
Table 17–3 AUDIT-C Questions, Response Options, and Scoring Values
| Question | Response Options (Response Score) | ||||
|---|---|---|---|---|---|
How often do you have a drink containing alcohol? | Never (0) | Monthly or less (1) | 2–4 times a month (2) | 2–3 times a week (3) | ≥4 times a week (4) |
How many drinks containing alcohol do you have on a typical day when drinking? | 1 or 2 (0) | 3 or 4 (1) | 5 or 6 (2) | 7 to 9 (3) | ≥10 (4) |
How often do you have six or more drinks on one occasion? | Never (0) | Less than monthly (0) | Monthly (2) | 2–3 times per week (3) | ≥4 times a week (4) |
Total score ranges from 0 to 12. A score of ≥4 identifies 86% of alcohol use disorders criteria in men, whereas a score ≥2 identifies 84% of alcohol use disorder criteria in women.
3. CAGE
The four-item CAGE questionnaire asks respondents: (1) Have you ever felt you need to Cut down on your drinking? (2) Have people Annoyed you by criticizing your drinking? (3) Have you ever felt bad or Guilty about your drinking? (4) Have you ever had a drink first thing in the morning to steady your nerves or to get rid of a hangover (Eye-opener)? The CAGE questionnaire has the advantage of being very brief (less than a minute to administer) and easy to memorize. It is scored from 0 to 4 with a score of 1 for every positive answer. A cutoff of ≥2 is suggestive of an AUD. The CAGE questionnaire is reliable, with a sensitivity of 77–94% and a specificity of 79–97%. A limitation of the CAGE questionnaire is its inability to distinguish between current and past drinking disorders (Fiellin et al. 2000).
C. Laboratory Investigations
The diagnostic value of laboratory tests to help detect AUD is limited by the short half-life of alcohol as well as the low specificity of the available biomarkers. Despite these limitations, laboratory test results help raise a level of suspicion or supplement findings seen in clinical/mental state examination. They are of value in giving patients objective feedback, which can motivate patients to seek assistance with their drinking or make conscious positive changes such as reduction in drinking. Laboratory tests are also useful for monitoring treatment response (Conigrave et al. 2003).
1. Blood or breath alcohol level
A high blood alcohol level (BAL) or breath alcohol concentration at the time of presentation can be informative. For example, a BAL greater than 35 mmol/dL in an alert patient likely reflects high tolerance to alcohol as seen in individuals with an AUD. The clinical use of a BAL test, however, is limited by the very short period alcohol is detectable in the blood (<10–12 hours) and even shorter in breath. Newer devices that allow for multiple random breath alcohol level testing throughout the day or for breath alcohol testing prior to operating a motor vehicle may be used by diversion courts or professional monitoring programs, including physician health programs, for enhanced detection of relapsed alcohol use in high-risk populations.
2. Serum gamma-glutamyltransferase (GGT)
This is a liver enzyme involved in amino acid metabolism. An elevated serum GGT (levels > 35 U/L) can be indicative of heavy drinking. GGT is limited by its low sensitivity and multiple false positives from other causes (such as pregnancy, smoking, diabetes, medications, and obesity).
3. Alanine and aspartate aminotransferase ratio
These liver enzymes are both elevated in AUD but may also be elevated because of hepatocellular injury from various causes, so they are not specific markers. An aspartate aminotransferase to alanine aminotransferase ratio greater than 2 is more indicative of liver damage secondary to heavy alcohol use.
4. Carbohydrate-deficient transferrin test (CDT)
CDT measures structural changes in transferrin, which can occur following heavy alcohol consumption. The plasma half-life of CDT is about 14 days, and so levels remain elevated for 2–3 weeks following abstinence from alcohol. Like GGT, CDT has a relatively low sensitivity, with false positives seen in cases of transferrin deficiency and hepatocellular carcinoma. However, CDT has a higher specificity than serum GGT.
5. Mean corpuscular volume (MCV)
The red blood cell MCV is often enlarged in patients with history of AUD. An MCV greater than 100 fL is suggestive of heavy drinking. It has a low sensitivity and specificity compared to CDT and GGT and is elevated in several conditions, such as vitamin B12 and folic acid deficiency; in those taking medications such as methotrexate, anticonvulsants, or chemotherapeutic drugs; and in those with endocrinopathies such as hypothyroidism. Because of the long half-life of erythrocytes, values may remain abnormal for up to 3 months after abstinence. MCV is more useful in conjunction with other tests or in monitoring treatment response.
6. Ethyl glucuronide (EtG) and ethyl sulfate (EtS)
EtG is a water-soluble direct metabolite of alcohol and can be detected in several body fluids, tissues, and hair. It is detectable in the human body shortly after the consumption of alcohol and for longer periods than can be measured with blood or breath alcohol. A single drink on the previous evening should be detectable the next morning. The duration of positivity depends on the amount of alcohol consumed and the assay cutoff used. A cutoff of 100 ng/mL is more sensitive but could potentially be influenced by extraneous sources of alcohol (e.g., extreme use of hand sanitizers); a cutoff of 200 ng/mL reduces this risk with little loss of sensitivity. This cutoff can detect moderate alcohol consumption that occurred 24 hours earlier. Heavier drinking may be detected up to 48 hours later in some people. A commercially available immunoassay uses a cutoff of 500 ng/mL; although less sensitive, this test has the advantage of real-time feedback. EtG is a direct metabolite of ethanol metabolism and hence is more specific than other biochemical markers of alcohol consumption, which mainly measure end-organ damage. Because of this unique quality of EtG, it has been used in forensic psychiatry for cases of driving under the influence, as well as in judging driving ability (Wurst et al. 2003), and its use in clinical practice has been recommended (Jatlow & O’Malley 2010).
EtS is also a direct metabolite of ethanol, which has been used and studied to a lesser extent than EtG.
7. Phosphatidylethanol (PEth)
PEth is detected in the blood after consumption of about 1000 g of alcohol over about a 2-week period. Some advantages of the PEth test are its high sensitivity and specificity compared to many other biomarkers, its long window for assessment (2 weeks), and its use in patients with liver disease (values are less affected by liver disease). This test is increasingly used in early abstinence monitoring (Schrock et al. 2017).
D. Neuroimaging
Neurodegenerative alcohol-related brain changes are seen on radiology studies, showing volume loss and shrinkage of brain tissue. These changes have a predilection for the white matter. Alcohol-related brain changes seen on computed tomography (CT) and magnetic resonance imaging (MRI) scans include shrinking of the frontal lobe (due to neurodegeneration of the superior and inferior frontal cortex), ventricular enlargement with widening of cortical sulci, and shrinkage of the thalamus, inferior colliculus, and mammillary bodies (which are seen more specifically in Wernicke-Korsakoff syndrome). The cerebellum is also affected, with volume deficits and shrinkage, which is more profound in the anterior superior vermis. Functional MRI studies show frontocerebellar circuitry disruption as the principal mechanism underlying symptoms such as ataxia, cognitive impairment, and visuospatial impairment in individuals with chronic AUD (Sullivan & Pfefferbaum 2005).
There is also a difference in imaging findings based on gender, with women showing more brain-related radiological changes (Pfefferbaum et al. 2001; Sullivan & Pfefferbaum 2005). With abstinence, there is improvement in neuroimaging scans, but some changes may not reverse entirely (Mann et al. 1995).