Case

A 48-year-old handyman has progressive cystic acne and abnormal liver function.

A 48-year-old man that you are treating for acne vulgaris returns to your clinic for a follow-up appointment. You first saw this patient about 3 weeks ago. At that time, he had multiple acneiform lesions in the malar and periorbital areas. Both cystic and comedonal lesions were present; most ranged between 3 and 6 millimeters (mm) in diameter, and some were edematous. The patient noted that he was surprised about the development of acne at his age; he never suffered from this condition during adolescence. He had used over-the-counter astringents and anti-acne medications, but they had not affected the lesions.

A review of the patient's medical history indicates that he has

• No history of hepatitis,
• No recollection of contact with hepatitis patients,
• No evidence of liver difficulties, and
• No record of blood transfusion.

The patient has no family history of cardiovascular disease or cancer. The patient does not smoke; he drinks two to three bottles of beer each evening and sometimes more on weekends. He is taking no medications other than over-the-counter dermatologic medications.

The patient is married and has three teenaged children. His wife and children are in good health. They live in a high-rise apartment building where the patient has been a handyman and part-time building manager for the past year. He spends a lot of time in the basement area, which includes 

• Heating facilities,
• A laundry,
• A recreation room with pool table, and
• A workshop.

The patient is an avid fisherman who spends most weekends fishing and eating his catch with his two sons.

At the end of the patient's initial visit, you prescribed a topical antibiotic and instructed the patient on its use. After reassuring the patient that stronger prescription medications are available to treat acne, you ordered a serum biochemical and hematologic profile to document baseline values.

During today's physical examination, you note little or no improvement in the patient's acne. The ratio of cystic to comedonal lesions appears to have increased, and many lesions appear to have become more edematous and erythematous. The patient has several new comedones on his chin, and he points out what appears to be developing areas of folliculitis on his chest and forearms.

In addition to this worsening of the patient's acne, your physical examination of the patient reveals mild, non-tender hepatomegaly without jaundice. This finding causes you to review the results of the biochemical panel. You note the following abnormalities:

• Total bilirubin 2.8 milligrams per deciliter (mg/dL) (normal 0–1.5),
• Direct bilirubin 0.4 mg/dL (normal 0–0.4),
• Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) 74 international units per liter (IU/L) (normal 0–50),
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) 88 IU/L (normal 0–50),
• Glutamyl transpeptidase (GGTP or GGT) 190 IU/L (normal 15–85), and
• Lactate dehydrogenase (LDH) 230 IU/L (normal 50–225).

The results of all other tests, including the complete blood count, alkaline phosphatase (ALP), blood urea nitrogen, creatinine, and urinalysis, are within normal limits.

Initial Check Questions

1. What should be included in the patient's problem list?
2. What is a differential diagnosis for the patient's altered liver enzymes?
3. What tests would help you arrive at a diagnosis?

4. You persistently pose detailed questions to the patient regarding his work, hobbies, recreational activities, and possible contact with hepatotoxins.

   The patient reveals that he frequently wipes up a "dark, oily discharge" near a large electrical transformer in the work area in the basement workshop. The discharge has produced a gummy residue on tools and other surfaces. He mentions he sometimes feels dizzy and nauseated after working in the basement all day.

   Is this additional information related to the clinical findings?

5. Is there a need to be concerned about exposure to PCBs when the clinical effects in this patient seem so limited?
6. Are other sources of PCB exposure likely for this patient?
7. What confirming laboratory test can be conducted to establish the diagnosis of PCB exposure?
8. The doctor requests a serum PCB analysis. The laboratory reports a level of 125 parts per billion (ppb), with no normal range indicated. How will you interpret this report?
9. What steps should be recommended to patients when PCB-related health effects are suspected?
10. What additional steps should be taken for the situation described in the case study?

Initial Check Answers

1. The patient's problem list includes acne vulgaris, which is atypical because of the location of the lesions and their late onset with no history of outbreaks during adolescence. The mildly altered liver functions are nonspecific but clinically unexpected.

   More information for this answer can be found in the "Clinical Assessment - Signs and Symptoms" section.

2. The combination of asymptomatic hepatomegaly and mild nonspecific elevations of hepatic enzymes suggests a chronic inflammatory liver process or hepatitis. Hepatitis can be drug-induced, toxic, infectious, genetic, or caused by connective tissue disease.

   The major cause of liver disease in the United States is ethanol ingestion. Less commonly, environmental exposures cause either acute or chronic toxic hepatitis. Some connective tissue diseases such as lupus erythematosus are associated with a specific type of hepatitis. Infectious hepatitis includes those attributed to the viruses such as A, B, C, and other possible agents of non-A, non-B hepatitis. Hepatitis can also occur with Epstein-Barr virus and cytomegalovirus infections. Infiltrative diseases such as sarcoidosis or amyloidosis, and rare genetic diseases such as Wilson disease, primary hemochromatosis, and alpha-1-antitrypsin deficiency should be excluded as causes of hepatitis also.

   More information for this answer can be found in the "Clinical Assessment - Laboratory Tests" section.

3. Repeat ALT, AST, GGT, and bilirubin testing; test ALP and prothrombin time; and test for hepatitis viral serologies, heterophil antibody (anti-EBV capsid IgM), anti-nuclear antibody, anti-smooth muscle antibody, and anti-mitochondrial antibody. Consider hemachromatosis (serum ferritin, iron, and iron binding capacity), Wilson disease (serum copper and ceruloplasmin), and parasitic hepatitis as possible causes of chronic hepatitis.

   Assays for suspected hepatotoxins and biopsy of adipose tissue might also be of value. Further evaluation might include ultrasound and percutaneous liver biopsy if other tests do not provide sufficient information.

   More information for this answer can be found in the "Clinical Assessment - Laboratory Tests" section.

4. Older electrical transformers and capacitors can contain PCBs as a dielectric and heat-transfer fluid. Leaks in this equipment could allow PCBs to volatilize under conditions of increased temperature. A person with chronic exposure to the vapors or residue could eventually receive a significant PCB dose through both dermal and inhalation routes.

   More information for this answer can be found in the "How Are People Exposed to PCBs?" section.

5. Notably, potential carcinogenicity is the main reason PCB production was banned in the United States. EPA has determined that PCBs are probable human carcinogens and has assigned them the cancer weight-of-evidence classification B2. DHHS concluded that PCBs are reasonably anticipated to be carcinogenic in humans, based on sufficient evidence of carcinogenicity in animals. In February 2013, 26 experts from 12 countries met at the International Agency for Research on Cancer (IARC), Lyon, France, to reassess the carcinogenicity of polychlorinated biphenyls (PCBs). On the basis of sufficient evidence of carcinogenicity in humans and experimental animals, the IARC classified PCBs as carcinogenic to humans (Group 1). The classification is based on consistent association between PCB exposure and increased risk of melanoma in humans.

   More information for this answer can be found in the "What Are the Physiologic Effects of PCBs?" section.

6. In addition to possible dermal and inhalation exposure, the patient might be exposed by consuming contaminated fish, a potential source of PCBs.

   More information for this answer can be found in the "How Are People Exposed to PCBs?" section.

7. Select laboratories have the capability to perform PCB analyses on human tissue. The lipophilic nature of PCBs causes them to accumulate in fat; consequently, analysis of adipose tissue obtained by biopsy has been advocated as a measure of long-term exposure. Serum PCB analysis, which is less invasive than fat biopsy, is readily available. Health risks are not consistent necessarily with PCB levels, but a serum measurement is useful for gauging the patient's exposure.

   More information for this answer can be found in the "Clinical Assessment - Laboratory Tests" section.

8. A correlation between increasing levels of serum PCBs and dermatologic findings, including chloracne, has not been found consistently in human epidemiologic studies. However, statistically significant associations between dermatologic effects and plasma levels of higher chlorinated PCB congeners have been reported.

   PCB compounds generally can be found at the parts per trillion (ppt) levels in the lipid stores of humans, especially persons living in an industrialized society. The general population is exposed to PCB compounds primarily through the ingestion of high-fat foods such as dairy products, eggs, animal fats, and some fish and wildlife [CDC 2009b; Hopf et al. 2009; Patterson et al. 2008]. By comparison, the case study patient's PCB serum level of 125 ppb is consistent with PCB exposure as a cause for his unusual acne, and PCB exposure might be contributing to the hepatic effects noted.

   More information for this answer can be found in the "Clinical Assessment - Laboratory Tests" section.

9. The first objective should be to stop the exposure. In this case, the patient should stay away from the basement until the transformer is repaired and the basement area is cleaned by a professional familiar with PCB removal. He should also check with his state advisory on PCB-fish contamination and not eat fish from contaminated areas until his PCB level normalizes and the fish are declared uncontaminated. Many states issue advisories on fish consumption based on where the fish are caught. Fish advisories also provide guidance on how to choose fish that are safer to eat and on safer ways to prepare and cook fish. Avoiding exposure is especially important because no specific treatment exists for PCB accumulation. The need to avoid other hepatotoxic substances, including ethanol, should be stressed. Confirmation of exposure with a serum PCB level should be obtained.

   More information for this answer can be found in the "How Should Patients Exposed to PCBs Be Treated and Managed?" section.

10. Because stopping exposure is of prime importance, the physician can be most helpful by advising the patient that proper abatement by professionals is necessary. In this case, the owner of the building should be notified of the potential health hazard and should contact the local public health agency. This might require the assistance of local, state, or federal agencies such as the department of public health and EPA. These agencies can cooperate with entities involved to ensure remediation of the harmful exposure. It is important to prevent other persons from using the basement areas until cleanup is complete. In addition, the patient should be informed of the availability of fishing and game advisories particular to his state, and he should be encouraged to observe the recommendations of these advisories.

    More information for this answer can be found in the "How Should Patients Exposed to PCBs Be Treated and Managed?" section.