Case reports have had to fight to justify their role in the hierarchy of clinical data in this age of evidence-based medicine. Jerome Hoffman, MD, argued in a 1999 op-ed piece that case reports generally have limited value, in part because they are often written to emphasize bizarre or unusual clinical findings. (West J Med 1999;170:253.) That the occurrence was rare enough to justify a case report means you'll almost certainly never see it in one of your patients!
Advocates of case reports responded that we'd actually know very little if all we knew were the results of randomized controlled double-blind trials. They pointed out that case reports are an essential tool for identifying unexpected or infrequent (but still important) events and associations, such as side effects of medications after they are approved. A side effect that occurred commonly most likely would have been detected during initial premarketing studies.
But even a rare adverse effect can become important after a drug is released and is used by much larger numbers of patients. As Milos Jenicek, MD, put it in his book Clinical Case Reporting in Evidence-Based Medicine, “Case reports and case series may be the ‘lowest’ or the ‘weakest’ level of evidence, but they often remain the ‘first line of evidence.’ This is where everything begins.”
More than most medical specialties, toxicology relies on case reports to highlight important clinical information. The proliferation of new designer drugs of abuse, for one thing, means that some of the conditions we deal with — MDPV exposure from stimulant “bath salts,” for example — have not been studied because they have not existed until recently. Some of our patients are also quite creative in the substances they use, as in the case I discussed in last year's Special Report of a man who ingested the contents of a sparkle lamp. (See FastLinks.)
The constant stream of new drugs and new medical devices approved by the FDA means that unanticipated adverse effects are often first pointed out in case reports. Not to mention that well-written case reports describing unusual exposures are just fun to read. That said, here are some of the most interesting toxicology case reports published over the last year.
Severe Cobalt Intoxication Following Hip Replacement Revision: Clinical Features and Outcome
Pelclova D, Sklensky M, et al
A 56-year-old man presented complaining of distal paresthesias of his lower extremities, difficulty walking, and markedly impaired hearing, all of which had been progressing over a period of months. His history included a ceramics-on-ceramics hip prosthesis implanted four years earlier, which was revised 20 months before presentation after one of the ceramic elements fractured. The replacement head contained cobalt, chromium, and titanium. His hip had dislocated because 40 percent of the metal head had abraded, and the metal implant was removed.
Workup included an echocardiogram, which showed a large pericardial effusion with early evidence of tamponade. Endocrine tests demonstrated hypothyroidism with increased thyroid-stimulating hormone levels. Neurologic evaluation documented a severe sensory and motor polyneuropathy, diminished deep tendon reflexes, and sensorineural deafness.
Toxicology workup found markedly high levels of cobalt in the blood, pericardial fluid, and cerebrospinal fluid as well as an elevated blood chromium level. The patient was treated with chelation (DMPS [Unithiol]). Many of his symptoms improved, but the severe hearing impairment persisted. The authors could not demonstrate that chelation improved elimination of cobalt or provided clinical benefit.
Cobalt is an essential heavy metal needed to produce vitamin B12, a cofactor in metabolic processes throughout the body, including synthesis of DNA and fatty acids as well as the production of energy. Only trace amounts of cobalt are required; the recommended dietary allowance is between 0.4–2.8 mcg daily depending on age. Vitamin B12 deficiency can cause significant and persistent neurological damage.
An overdose of cobalt can cause significant side effects. Outbreaks of cobalt toxicity are rare but have occurred, most notably in the 1960s when a number of heavy drinkers in the United States and Canada presented with congestive heart failure, pericardial effusion, polycythemia, and lactic acidosis. This syndrome was traced to certain beers to which cobalt sulfate had been added as a foam stabilizer. The mortality of this so-called beer drinkers' cardiomyopathy approached 50 percent.
We are now seeing cases of chronic cobalt toxicity that can be traced to the widespread implantation of hip prostheses made of this metal. These cases often occur when metal structures are used to replace ceramic elements that have fractured. Ceramic debris remaining after the procedure can severely abrade the metal alloy, releasing cobalt and other metals into the surrounding tissues. Cobalt toxicity can also follow use of nonceramic metal-on-metal prosthetic hips.
Manifestations of chronic cobalt toxicity include hearing impairment, cardiomyopathy, pericardial effusion, hypothyroidism, and peripheral sensorimotor deficits. Tinnitus and visual impairment can also occur.
The key take-home lesson: Consider the possibility of chronic cobalt toxicity whenever a patient with a metal prosthesis presents with vision or hearing impairment, peripheral weakness or paresthesia, or new cardiac abnormalities, even if symptoms related to the hip are absent. Such a patient should be evaluated carefully by a neurologist and a toxicologist.
The Case of the Masquerading Octane Booster (Abstract)
Deutsch CM, et al
A 50-year-old man with chronic obstructive pulmonary disease called the local poison center saying he felt “shaky.” He described ingesting a one-ounce bottle of LHP Liquid Horsepower (Manhattan Oil, New Braunsfels, TX) after mistaking it for the type of energy booster sold over-the-counter in convenience stores. Rather than being a consumable caffeine-based stimulant such as 5-hour ENERGY, LHP is a fuel additive designed to boost the octane rating of gasoline.
The poison center recommended medical evaluation. The patient's vital signs on arrival at the hospital were normal, with an oxygen saturation of 94%. He had developed a cough and upper respiratory tract irritation. Chest x-ray showed no acute changes. Three hours after ingestion, the patient had a seizure that terminated after treatment with a benzodiazepine. The remainder of his hospital course was notable for fluorescent red diarrhea. No further seizure activity was reported, and he was discharged one day after admission.
LHP contains methylcyclopentadienyl manganese tricarbonyl (MMT), a compound marketed since the 1970s as a gasoline additive to replace the octane-boosting properties of tetraethyl lead. MMT has been shown to be neurotoxic in mice and produce seizure activity, but virtually no data are available on toxicity from human ingestion.
The authors of this case abstract point out that some automotive additives look quite similar to energy shots, products that typically contain caffeine, vitamins, amino acids, and other ingredients. These stimulants themselves can produce toxicity if consumed in quantity.
A Case of Infantile Star Anise Toxicity
Madden GR, Schmitz KH, et al
Pediatr Emer Care
A 3-month-old previously healthy girl was brought to the emergency department after her parents observed possible seizure activity. The parents described an episode of vomiting followed by eye rolling and twitching of the child's arms and legs. The child had been colicky earlier in the evening, and they had added tea brewed with star anise to her formula.
The child had normal vital signs a little more than two hours after this incident, but was noted to have a gray and ashen appearance, though that improved with stimulation and supplemental oxygen. Results from basic blood tests (including blood culture), cerebrospinal fluid analysis, noncontrast head CT, and urine drug screen were all unremarkable. She was observed overnight, and discharged the next day. An EEG one month later was normal, and the neurology service concurred with the diagnosis of neurotoxicity secondary to star anise ingestion.
Some cultures consider tea brewed with star anise to be a cure for colic in infants. The Chinese star anise (Illicium verum) — a spice commonly used in many cuisines — is an eight-pointed fruit generally considered safe for human consumption. It contains, however, compounds called veranisatins that can cause neurologic and gastrointestinal toxicity if large amounts are ingested. Products labeled as Chinese star anise also can be contaminated with material from the closely related Japanese star anise (Illicium anisatum), a fruit containing the much more toxic compound anisatin. These poisons appear to act as noncompetitive γ-aminobutyric acid (GABA) antagonists. The U.S. Food and Drug Administration advised in 2003 that adults and children refrain from consuming any teas brewed from star anise.
Manifestations of star anise toxicity include irritability, abnormal limb movements, nystagmus, vomiting, and seizures. Symptoms typically resolve within 24 hours. The authors of this case report note that the infant received a mega-workup, including lumbar puncture and head CT, and point out that some of the medical tests were not without risk. They suggest that “consideration can be given to limiting the workup for certain stable, well appearing infants with a clear history of recent star anise ingestion.”
Alcoholic Ketoacidosis Coincides with Acute Marchiafava-Bignami Disease — A Case Report
Chen MH, Cheng CA
Am J Emerg Med
2012 Feb 3 [Epub ahead of print]
A 53-year-old man with a history of chronic alcoholism was referred to the emergency department because of decreased level of consciousness. He had been binge drinking three days earlier. He was described as semi-comatose, malnourished, and dehydrated.
Physical examination showed limb rigidity with bilateral positive Babinski signs. Laboratory evaluation showed a high-anion-gap metabolic acidosis (HCO3 7.9 mmol/L), ketonemia, and an ethanol level that was essentially zero. A head MRI showed findings consistent with Marchiafava-Bignami disease (MBD). The working diagnosis was alcoholic ketoacidosis coinciding with MBD. The patient was treated with hydration, dextrose, and vitamin B complex. His neurological abnormalities resolved by the second hospital day, and he was discharged on day 12.
Marchiafava-Bignami disease — a progressive neurological syndrome — is a rare condition seen in chronic alcoholics. Only about 200 cases have been reported in the medical literature. MBD presents with impaired consciousness and multifocal nonspecific neurological deficits, especially upper motor neuron signs. Head MRI was characterized by evidence of demyelination, necrosis, and atrophy of the corpus callosum. MBD can be fatal, and the diagnosis is often delayed or missed. The exact pathologic mechanism has not been described, but may involve malnutrition or vascular abnormalities. The authors of this case report note that the differential diagnosis of impaired sensorium in an alcoholic should include intoxication, Wernicke encephalopathy, alcohol withdrawal, hepatic encephalopathy, central pontine myelinolysis, and MBD.
MBD is rare, but Dr. Chris Nickson in the superb Australian emergency medicine blog Life in the Fast Lane has pointed out an additional important reason emergency physicians should be aware of the condition. When trying to admit an intoxicated alcoholic patient — who obviously needs hospitalization but does not have a specific diagnosis — to a reluctant in-service doctor who thinks it is his main job to “be a wall,” it can be immensely useful to remark nonchalantly: “I know he sounds like just another drunk off the street, but you'll remember that chap with Marchiafava-Bignami Disease; he was exactly the same.”
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© 2012 Lippincott Williams & Wilkins, Inc.
- Read Dr. Gussow's special report on the ingestion of the contents of a sparkle lamp from last year at http://bit.ly/ToxFiles.
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- Visit Dr. Gussow's blog at www.thepoisonreview.com.
- Read all of Dr. Gussow's past columns at http://bit.ly/GussowToxRounds.
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