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Back to Basics
The American Journal of Medicine (2006) 119, 482-483
DIAGNOSTIC DILEMMA Charles M. Wiener, MD, Section Editor
Back to Basics David Rubin, MD, Barbara McGovern, MD, Richard I. Kopelman, MD Divisions of General Medicine and Geographic Medicine and Infectious Diseases, Department of Medicine Tufts New England Medical Center, Boston, Mass.
PRESENTATION
ASSESSMENT
After several admissions to a local hospital, a 44-year-old male sewer inspector was transferred to our facility for evaluation of recurrent episodes of fever, malaise, headache, and confusion. The patient was in good health until 6 weeks earlier, when he was hospitalized with a gastrointestinal bleed from gastritis. This was felt to be secondary to use of aspirin and nonsteroidal anti-inflammatory medication for chronic back pain. He did well until 1 month later when over the course of 2 days, his wife noticed that he was becoming progressively more lethargic. After becoming confused at work and increasingly ataxic, he returned to the hospital with a temperature of 102°F. The patient was very lethargic but awake. He had mild left-right confusion, difficulty repeating phrases, and diffuse weakness with no other focal findings. A complete blood count, glucose and calcium levels, an electrolyte panel, renal function, and a lumbar puncture were normal, and a toxicology screen was negative. Nonetheless, the neurologist, concerned about encephalitis, initiated acyclovir therapy. However, cultures of blood and cerebrospinal fluid proved negative. Results from computed tomography (CT) of the head, magnetic resonance imaging, and an electroencephalogram were also unremarkable. Acyclovir was stopped. A chest x-ray showed a possible right basilar infiltrate; ceftriaxone was prescribed. The patient’s symptoms improved, and he was discharged with a diagnosis of a probable viral syndrome and underlying depression. He returned 1 week later with similar symptoms. Blood and urine cultures, Lyme titers, a purified protein derivative test, and a Monospot test for mononucleosis were all negative. Thyroid-stimulating hormone levels were normal, and other laboratory studies were unremarkable. Clarithromycin was prescribed after a chest CT suggested right-middle-lobe consolidation. The patient was discharged on the third hospital day, but 2 days later he was back with slurred speech, ataxia, confusion, and urinary incontinence. He was then transferred to our care.
The patient’s medications included paroxetine, 30 mg daily, for depression and pantoprazole, 40 mg daily, for his gastritis. A former cigarette smoker, he had a history of alcohol abuse but had been sober for 6 years. He did not use illicit drugs, had exercised regularly before his illness, and denied recent travel, sick contacts, or pets. Afebrile and in no distress, the patient had an ataxic, unsteady gait. His blood pressure was 100/65 mmHg, and his heart rate was 54 beats per minute with no orthostatic changes. Although oriented, he was slow to respond and could not remember his phone number. Electrolyte, glucose, calcium, magnesium, and creatine kinase levels were all normal, as was liver function. A white blood cell count was 7.4 x 103 cells/mm3 with a normal differential cell count. The hematocrit was 33%, and the sedimentation rate was 53 mm/hr. Hepatitis serologies, an HIV test, and Brucella titers were all negative.
0002-9343/$ -see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2006.04.007
DIAGNOSIS On further questioning, the patient’s wife stated that 2 months previously, the patient began taking kava kava and valerian root along with paroxetine for his depression. With each hospital admission, he stopped the herbals and his symptoms subsided. They rebounded when he started taking them again. The most urgent priority is to rule out conditions with the greatest risks of morbidity and mortality. When this patient first presented with fever, headaches, and confusion, an infection with toxic or metabolic encephalopathy was the foremost concern. After eliminating this possibility, the pattern of similar symptoms on multiple admissions—all of which resolved in the hospital—suggested a home- or workrelated etiology. Environmental triggers come to mind when patients present with symptoms that disappear after changing locations. A careful environmental history usually includes questions about workplace exposures; pets; new medications, cosmetics, and detergents; and common allergens
Rubin et al
Back to Basics
such as pollens. It is not unusual to ask for a list of medications, only to find out later that oral contraceptives, nonprescription products, or other substances not regarded as medications by the patient were excluded. Far less frequently do we inquire about herbal therapies. A 2002 survey of Colorado physicians revealed that 17% never asked about complementary and alternative medicine use, and more than half asked less than 50% of the time.1 Only 8% always asked patients about use of these treatments. Other studies have shown that patients do not regularly tell their physicians about their use of natural products. 2,3 Note that the use of herbals rose almost 4-fold from 1990 to 1997, with an expenditure of over $5 billion in 1997 alone.3 Nationally, 12.1% of adults used herbal remedies in 1997; rates of up to 18.3% have been reported.3,4 Most patients appear to use herbals as an adjunct to conventional medicine rather than as an alternative; between 15% and 20% of all patients who take prescription medication use at least 1 additional herbal remedy.3,5,6 The popularity of herbal therapies creates many problems. First, these agents are regulated only by the Dietary Supplement Health and Education Act (DSHEA) of 1994.6 The DSHEA prohibits sale of a product that presents “a significant or unreasonable risk of illness or injury when used as directed on the label.” However, except for new dietary ingredients, companies do not have to submit safety or efficacy data to the Food and Drug Administration. Instead, the manufacturer is entrusted with the task of creating manufacturing practice guidelines that ensure its dietary supplements are safe and contain the ingredients listed on the label.7 Studies have found significant variation between brands, as well as toxic components and unlabeled active compounds in some herbal products.5,6,8 In November 2004, the FDA announced an initiative to improve scientific evaluations of new dietary ingredients and regulatory actions against those deemed to be unsafe or making false claims.9 The strategy for improving safety among products with existing ingredients centers on gradual improvement of the evidence base and increased public awareness through education. Second, herbal remedies can easily be purchased over the counter or via the Internet; no mechanism guarantees that the patient’s medication list is reviewed for potential drug interactions. Fewer than 20% of “e-pharmacies” selling St. John’s wort for the treatment of depression inquired whether the patient was also taking a selective serotonin reuptake inhibitor, a class of antidepressants known to have a significant drug interaction with this popular herbal preparation. Approximately 10% of these retailers advised patients to see a physician before self-medicating.10 Finally, patients may neglect to mention herbal remedies when a medication history is taken.2 In both 1990 and 1997, less than 40% of patients using complementary and alternative therapies disclosed this fact to their physicians.3 Possible explanations include patient perception that over-
483 the-counter remedies need not be reported, fear of stigmatization, or omission of questions about unconventional medicine from the history. Many patients might be using several of these agents. Our patient had been taking both valerian root and kava kava to treat his depression, but both also are used for insomnia. Side effects of valerian root include dizziness, nausea, headache, and somnolence, while kava kava can cause tremor, depression, headache, drowsiness, cognitive impairment, ataxia and sedation.5 Complete knowledge of his medications might have elicited the correct diagnosis during the first hospitalization, reducing morbidity and the duration of illness. While data on side effects associated with individual herbal remedies is accumulating, the possible consequences of using several herbals concurrently are largely unknown. A thorough medication history, including specific questions about the use of alternative and complementary medicine, is critical if an accurate diagnosis is to be reached, particularly when the symptoms and signs don’t fit into the usual medical paradigms.
MANAGEMENT Once we were aware of the patient’s use of herbal medications, all testing and treatment was stopped. Over the next 2 days, his physical and neurological status returned to his baseline. He was discharged with instructions to follow-up with his primary care physician. His symptoms did not recur.
References 1. Winslow LC, Shapiro H. Physicians want education about complementary and alternative medicine to enhance communication with their patients. Arch Intern Med. 2002;162:1176-1181. 2. Busse JW, Heaton G, Wu P, Wilson KR, Mills, EJ. Disclosure of natural product use to primary care physicians: A cross-sectional survey of naturopathic clinic attendees. Mayo Clin Proc. 2005;80:616623. 3. Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA. 1998;280:1569-1575. 4. Rhee SM, Garg VK, Hershey CO. Use of complementary and alternative medicines by ambulatory patients. Arch Intern Med. 2004;164: 1004-1009. 5. DeSmet PA. Health risks of herbal remedies: an update. Clin Pharmacol Ther. 2004;76:1-17. 6. DeSmet PA. Herbal remedies. N Engl J Med. 2002;347:2046-2056. 7. US Food and Drug Administration Center for Food Safety and Applied Nutrition. Overview of dietary supplements. Available at http:// www.cfsan.fda.gov/⬃dms/ds-oview.html. Accessed November 19, 2004. 8. Eisenberg DM. Advising patients who seek alternative medical therapies. Ann Intern Med. 1997;127:61-69. 9. US Food and Drug Administration. FDA announces major initiatives for dietary supplements. Available at http://www.fda.gov/bbs/topics/ news/2004/NEW01130.html. Accessed November 19, 2004. 10. Bessell TL, Anderson JN, Silagy CA, Sansom LN, Hiller JE. Surfing, self-medicating and safety: buying non-prescription and complementary medicines via the Internet. Qual Saf Health Care. 2003;12:88-92.
DIAGNOSTIC DILEMMA Charles M. Wiener, MD, Section Editor
Back to Basics David Rubin, MD, Barbara McGovern, MD, Richard I. Kopelman, MD Divisions of General Medicine and Geographic Medicine and Infectious Diseases, Department of Medicine Tufts New England Medical Center, Boston, Mass.
PRESENTATION
ASSESSMENT
After several admissions to a local hospital, a 44-year-old male sewer inspector was transferred to our facility for evaluation of recurrent episodes of fever, malaise, headache, and confusion. The patient was in good health until 6 weeks earlier, when he was hospitalized with a gastrointestinal bleed from gastritis. This was felt to be secondary to use of aspirin and nonsteroidal anti-inflammatory medication for chronic back pain. He did well until 1 month later when over the course of 2 days, his wife noticed that he was becoming progressively more lethargic. After becoming confused at work and increasingly ataxic, he returned to the hospital with a temperature of 102°F. The patient was very lethargic but awake. He had mild left-right confusion, difficulty repeating phrases, and diffuse weakness with no other focal findings. A complete blood count, glucose and calcium levels, an electrolyte panel, renal function, and a lumbar puncture were normal, and a toxicology screen was negative. Nonetheless, the neurologist, concerned about encephalitis, initiated acyclovir therapy. However, cultures of blood and cerebrospinal fluid proved negative. Results from computed tomography (CT) of the head, magnetic resonance imaging, and an electroencephalogram were also unremarkable. Acyclovir was stopped. A chest x-ray showed a possible right basilar infiltrate; ceftriaxone was prescribed. The patient’s symptoms improved, and he was discharged with a diagnosis of a probable viral syndrome and underlying depression. He returned 1 week later with similar symptoms. Blood and urine cultures, Lyme titers, a purified protein derivative test, and a Monospot test for mononucleosis were all negative. Thyroid-stimulating hormone levels were normal, and other laboratory studies were unremarkable. Clarithromycin was prescribed after a chest CT suggested right-middle-lobe consolidation. The patient was discharged on the third hospital day, but 2 days later he was back with slurred speech, ataxia, confusion, and urinary incontinence. He was then transferred to our care.
The patient’s medications included paroxetine, 30 mg daily, for depression and pantoprazole, 40 mg daily, for his gastritis. A former cigarette smoker, he had a history of alcohol abuse but had been sober for 6 years. He did not use illicit drugs, had exercised regularly before his illness, and denied recent travel, sick contacts, or pets. Afebrile and in no distress, the patient had an ataxic, unsteady gait. His blood pressure was 100/65 mmHg, and his heart rate was 54 beats per minute with no orthostatic changes. Although oriented, he was slow to respond and could not remember his phone number. Electrolyte, glucose, calcium, magnesium, and creatine kinase levels were all normal, as was liver function. A white blood cell count was 7.4 x 103 cells/mm3 with a normal differential cell count. The hematocrit was 33%, and the sedimentation rate was 53 mm/hr. Hepatitis serologies, an HIV test, and Brucella titers were all negative.
0002-9343/$ -see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2006.04.007
DIAGNOSIS On further questioning, the patient’s wife stated that 2 months previously, the patient began taking kava kava and valerian root along with paroxetine for his depression. With each hospital admission, he stopped the herbals and his symptoms subsided. They rebounded when he started taking them again. The most urgent priority is to rule out conditions with the greatest risks of morbidity and mortality. When this patient first presented with fever, headaches, and confusion, an infection with toxic or metabolic encephalopathy was the foremost concern. After eliminating this possibility, the pattern of similar symptoms on multiple admissions—all of which resolved in the hospital—suggested a home- or workrelated etiology. Environmental triggers come to mind when patients present with symptoms that disappear after changing locations. A careful environmental history usually includes questions about workplace exposures; pets; new medications, cosmetics, and detergents; and common allergens
Rubin et al
Back to Basics
such as pollens. It is not unusual to ask for a list of medications, only to find out later that oral contraceptives, nonprescription products, or other substances not regarded as medications by the patient were excluded. Far less frequently do we inquire about herbal therapies. A 2002 survey of Colorado physicians revealed that 17% never asked about complementary and alternative medicine use, and more than half asked less than 50% of the time.1 Only 8% always asked patients about use of these treatments. Other studies have shown that patients do not regularly tell their physicians about their use of natural products. 2,3 Note that the use of herbals rose almost 4-fold from 1990 to 1997, with an expenditure of over $5 billion in 1997 alone.3 Nationally, 12.1% of adults used herbal remedies in 1997; rates of up to 18.3% have been reported.3,4 Most patients appear to use herbals as an adjunct to conventional medicine rather than as an alternative; between 15% and 20% of all patients who take prescription medication use at least 1 additional herbal remedy.3,5,6 The popularity of herbal therapies creates many problems. First, these agents are regulated only by the Dietary Supplement Health and Education Act (DSHEA) of 1994.6 The DSHEA prohibits sale of a product that presents “a significant or unreasonable risk of illness or injury when used as directed on the label.” However, except for new dietary ingredients, companies do not have to submit safety or efficacy data to the Food and Drug Administration. Instead, the manufacturer is entrusted with the task of creating manufacturing practice guidelines that ensure its dietary supplements are safe and contain the ingredients listed on the label.7 Studies have found significant variation between brands, as well as toxic components and unlabeled active compounds in some herbal products.5,6,8 In November 2004, the FDA announced an initiative to improve scientific evaluations of new dietary ingredients and regulatory actions against those deemed to be unsafe or making false claims.9 The strategy for improving safety among products with existing ingredients centers on gradual improvement of the evidence base and increased public awareness through education. Second, herbal remedies can easily be purchased over the counter or via the Internet; no mechanism guarantees that the patient’s medication list is reviewed for potential drug interactions. Fewer than 20% of “e-pharmacies” selling St. John’s wort for the treatment of depression inquired whether the patient was also taking a selective serotonin reuptake inhibitor, a class of antidepressants known to have a significant drug interaction with this popular herbal preparation. Approximately 10% of these retailers advised patients to see a physician before self-medicating.10 Finally, patients may neglect to mention herbal remedies when a medication history is taken.2 In both 1990 and 1997, less than 40% of patients using complementary and alternative therapies disclosed this fact to their physicians.3 Possible explanations include patient perception that over-
483 the-counter remedies need not be reported, fear of stigmatization, or omission of questions about unconventional medicine from the history. Many patients might be using several of these agents. Our patient had been taking both valerian root and kava kava to treat his depression, but both also are used for insomnia. Side effects of valerian root include dizziness, nausea, headache, and somnolence, while kava kava can cause tremor, depression, headache, drowsiness, cognitive impairment, ataxia and sedation.5 Complete knowledge of his medications might have elicited the correct diagnosis during the first hospitalization, reducing morbidity and the duration of illness. While data on side effects associated with individual herbal remedies is accumulating, the possible consequences of using several herbals concurrently are largely unknown. A thorough medication history, including specific questions about the use of alternative and complementary medicine, is critical if an accurate diagnosis is to be reached, particularly when the symptoms and signs don’t fit into the usual medical paradigms.
MANAGEMENT Once we were aware of the patient’s use of herbal medications, all testing and treatment was stopped. Over the next 2 days, his physical and neurological status returned to his baseline. He was discharged with instructions to follow-up with his primary care physician. His symptoms did not recur.
References 1. Winslow LC, Shapiro H. Physicians want education about complementary and alternative medicine to enhance communication with their patients. Arch Intern Med. 2002;162:1176-1181. 2. Busse JW, Heaton G, Wu P, Wilson KR, Mills, EJ. Disclosure of natural product use to primary care physicians: A cross-sectional survey of naturopathic clinic attendees. Mayo Clin Proc. 2005;80:616623. 3. Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA. 1998;280:1569-1575. 4. Rhee SM, Garg VK, Hershey CO. Use of complementary and alternative medicines by ambulatory patients. Arch Intern Med. 2004;164: 1004-1009. 5. DeSmet PA. Health risks of herbal remedies: an update. Clin Pharmacol Ther. 2004;76:1-17. 6. DeSmet PA. Herbal remedies. N Engl J Med. 2002;347:2046-2056. 7. US Food and Drug Administration Center for Food Safety and Applied Nutrition. Overview of dietary supplements. Available at http:// www.cfsan.fda.gov/⬃dms/ds-oview.html. Accessed November 19, 2004. 8. Eisenberg DM. Advising patients who seek alternative medical therapies. Ann Intern Med. 1997;127:61-69. 9. US Food and Drug Administration. FDA announces major initiatives for dietary supplements. Available at http://www.fda.gov/bbs/topics/ news/2004/NEW01130.html. Accessed November 19, 2004. 10. Bessell TL, Anderson JN, Silagy CA, Sansom LN, Hiller JE. Surfing, self-medicating and safety: buying non-prescription and complementary medicines via the Internet. Qual Saf Health Care. 2003;12:88-92.