Chest pains prompt admission to the hospital, where diagnostic testing triggers new symptoms. 

Ms. K, age 58, experienced intermittent chest pain for five hours prior to presenting at the hospital. Her left-sided chest discomfort, which occurred at rest, radiated to her neck and lasted only a few minutes at a time. There were no alleviating or aggravating factors. The patient reported that similar chest discomfort four years earlier had prompted a treadmill stress test, with negative results.

In addition to the most recent pain, Ms. K noted shortness of breath and nausea. Her chest discomfort was nonpleuritic, did not change with position, and was not reproducible by palpation. Two days earlier, she had walked seven to eight city blocks without symptoms.

Past medical history included hypercholesterolemia and hypertension with no other significant diagnoses. Ms. K had never smoked cigarettes or used illegal drugs. She was, however, in the habit of drinking two to three beers a day and had done so for 40 years. Her current medications included metoprolol, aspirin, hydrochlorothiazide, a multivitamin, and potassium chloride. She was not on any estrogen replacement therapy. 

IN-HOUSE WORKUP

1 Our patient's chest discomfort waxed and waned until it resolved completely without any specific therapy about two hours after she arrived. The initial three sets of cardiac enzyme determinations were negative, and the ECG showed some flattening of the T waves in the V5 and V6 leads. CT angiography found no evidence of a pulmonary embolus but did reveal fatty infiltration of the liver. Mrs. K was admitted for evaluation of her chest pain.

Thirty-six hours after admission, during a dobutamine echocardiographic stress test, Ms. K achieved maximal heart rate. The test was negative for stress-induced cardiac ischemia. The working diagnosis at this point was costochondritis.

Two hours after the echocardiogram, however, Ms. K be-came disoriented, light-headed, and weak. At the same time, she experienced diffuse abdominal pain and reddish urine.

An urgent CT of the abdomen was negative for pancreatitis, intra-abdominal abscess, hemorrhage, or any other acute intra-abdominal process. Liver function tests showed aminotransferases and g-glutamyltransferase as high as 2,000 units/L each. Lipase, amylase, and cardiac enzymes (CK and troponin I) remained at normal levels. There was no serologic evidence of hepatitis B or C infection, and serum lead and acetaminophen levels were unremarkable. The urine contained no blood (specifically no RBCs) or myoglobin, but its color became more and more like that of cranberries.

When questioned, Ms. K recalled one episode of red urine 20 years ago during a period of great emotional stress. The physician then said there was no evidence of hematuria or myoglobinuria. That episode of red urine lasted four days and resolved without treatment. 

PHYSICAL EXAM FINDINGS

2 Eight hours after the echocardiogram, Ms. K's vital signs were temperature 97.9°F, pulse 102 beats per minute, respiratory rate 16 breaths per minute, and BP 112/72 mm Hg. Melasma overlay both cheeks. Heart sounds were audible, rate was slightly tachycardic, rhythm was regular; no murmurs, rubs, or clicks were heard. Lungs were clear to auscultation bilaterally. The abdomen was soft and nontender, with normal bowel sounds.

Extremities displayed an intention tremor bilaterally. On neurologic examination, Ms. K was awake and alert and fully oriented to person, place, and time. Cranial nerves II through XII were intact. Strength was +5/5 globally, and reflexes were +2/4 in all extremities. Coordination, gait, and sensation to light touch and temperature were intact.

PUTTING TOGETHER THE CLUES

3 Ms. K's urinalysis revealed elevated levels of uroporphyrinogen. Given the plasma and urine porphyrin results, we diagnosed porphyria cutanea tarda (PCT). The most common presenting sign of PCT is fragility of sun-exposed skin after mechanical trauma, leading to erosions and bullae, typically on the hands and forearms and occasionally on the face or feet. Pigmentary changes include melasmalike hyperpigmentation of the face. Indurated, waxy, yellowish plaques that resemble lesions of scleroderma can develop over the chest and back but are most prominent in the pre-auricular and nuchal areas. A urine sample often has a tea- or wine-colored tint.1

Ms. K's attack of acute porphyria occurred immediately after she received dobutamine, a potent exogenous catecholamine. The antihypertensive drugs a-methyldopa and clonidine are considered unsafe for patients with a history of porphyria. This is most likely due to the drugs' selective blockade of certain receptors or possibly to a rebound effect resulting in increased catecholamine release that can induce a porphyric attack.2 Such increases can also lead to hypertension and tachycardia.

Other possible causes for elevated catecholamine levels are (1) increased release of norepinephrine (NE) and epinephrine due to pathologic changes within the sympathetic nervous system itself, (2) impaired metabolism of catecholamines, (3) impaired reuptake of NE by the adrenergic neurons, or (4) some combination of these mechanisms.2

After following Ms. K, we hypothesize that dobutamine stress tests may induce acute attacks of porphyria in suscep-tible patients. Dobutamine might also have caused the liver enzyme elevations by reducing hepatic blood flow to the point of inducing liver ischemia. The chest pain that brought her to the emergency department was attributed to costochondritis.

DISCUSSION

4 The etiology of a porphyria attack is as important as the type of porphyria a patient suffers. At her six-week follow-up, Ms. K was asymptomatic, although her urinary and plasma uroporphyrinogen levels remained elevated, indicating inhibition of the heme synthetic enzyme uroporphyrinogen decarboxylase (UROD).

Most patients susceptible to porphyria are fine unless something triggers an attack. Porphyria becomes problematic only when acute attacks do not respond to conservative measures, such as removing the precipitating agent, giving IV fluid, controlling pain with opiates, and relieving nausea and vomiting with a phenothiazine. More serious attacks can cause total body paralysis, requiring mechanical ventilation. Hematin infusion is indicated to sustain life and interrupt the attack.2  

Porphyria is a disease of genetics, exposure, and precipitants.2 Ms. K was unaware of other family members with the disorder. None of the jobs she had held exposed her to toxins known to precipitate porphyria, e.g., the insecticide dioxin.

Susceptible patients must be aware of medications that could induce their porphyria and should wear a medical alert tag indicating their comorbid condition. Moreover, we urge clinicians planning to use a catecholamine stress test in patients with porphyria to proceed with caution.

Dr. Brodkin is a hospitalist with Aurora Healthcare in Kenosha, Wis. Dr. Rafiq is a gastroenterology fellow at John H. Stroger Jr Hospital of Cook County in Chicago, where Dr. Das is firm chief of internal medicine and Dr. Telfer is a hematologist.

References

1. Beal MF, Atuk NO, Westfall TC, Turner SM. Catecholamine uptake, accumulation, and release in acute porphyria. J Clin Invest. 1977;60:1141-1148. 

2. Porphyria cutanea tarda. Available at emedicine.com/DERM/topic344.htm, accessed November 5, 2008.