Middle-Aged Man With Lower Extremity Pain and Edema

A 54-year-old man is admitted to the hospital because of worsening lower extremity swelling and knee and ankle pain and stiffness. These symptoms have made walking very difficult for the past month.

HISTORY
For 18 years, the patient has had hypertension, for which he takes a β-blocker. Otherwise, he has been healthy. He has no known drug allergies. He has smoked 1 pack of cigarettes every 3 days for the past 21 years and drinks alcohol in moderation. He denies intravenous drug use. He lives alone and works as a security guard-although for the past month his symptoms have prevented him from performing his job.

PHYSICAL EXAMINATION
Temperature is 38.1^oC (100.6^oF); heart rate, 104 beats per minute with regular rhythm; respiration rate, 18 breaths per minute; blood pressure, 160/100 mm Hg; and oxygen saturation, 97%. Lungs are clear. There are no oral lesions. Abdomen is normal; results of a digital rectal examination are heme-negative. You note 1+ pitting edema in the lower extremities. Right knee is warm with effusion; left knee is normal. Both ankles are warm and swollen, but the left ankle is more erythematous and edematous and is tender on palpation. Strength is normal throughout, but gait is slow and stiff because of pain in the ankles and knee.

LABORATORY AND IMAGING RESULTS
Blood urea nitrogen level is 11 mg/dL; creatinine level, 1.6 mg/dL; albumin level, 3.5 g/dL; calcium level, 12.1 mg/dL; and phosphorus level, 2.9 mg/dL. White blood cell count is 10,800/μL, and hemoglobin level is 11.1 g/dL. Radiographs of the ankles and right knee show effusion and soft tissue swelling. Aspiration of the knee yields 30 mL of joint fluid, which is sent for analysis.

Which of the following tests is (are) most likely to identify the pathophysiology that underlies the patient’s clinical and laboratory findings?A. Measurement of rheumatoid factor titer.
B. Serial blood cultures.
C. Measurement of serum parathyroid hormone level (and ionized calcium level).
D. Twenty-four–hour urine collection to assess uric acid excretion. CORRECT ANSWER: C
The patient presents with a variety of clues to his diagnosis and underlying pathophysiology. The asymmetry of the inflammatory arthritis in his lower extremities, the absence of symptoms in his hands and fingers, and the lack of a history of morning stiffness appear to rule out rheumatoid arthritis. Thus, choice A is incorrect. This man had a low-grade fever on admission as well as a slightly elevated white blood cell count.

Septic arthritis is always a concern in a patient with inflammatory arthritis and fever. However, the clinical findings here are not typical of this entity. Open trauma to a joint and intravenous drug use are both strong risk factors for septic arthritis; neither is present. Moreover, the patient does not seem to have rheumatoid arthritis, which is also recognized as a risk factor for comp-licating septic arthritis. The number of affected joints (at least 3 with arthritis and effusion) and their location (all in the lower extremities) are unusual as well. Even bacteremic seeding would be unlikely to involve only lower extremity joints. Thus, serial blood cultures (choice B) are unlikely to yield a diagnosis. The involvement of the lower extremities-particularly the feet-in this man’s arthritis is a strong clue that his condition is crystal-induced. Analysis of the joint fluid reveals positive birefringent crystals; this finding is diagnostic of calcium pyrophosphate deposition disease, or pseudogout. The crystals seen in gout, by contrast, are the needle-like negatively birefringent crystals of uric acid. Because joint fluid analysis establishes pseudogout as the cause of the patient’s arthritis, studies related to uric acid metabolism (choice D) are unnecessary. Moreover, studies of uric acid metabolism are not the ideal choice for diagnosing gout. They would be performed later in a patient’s evaluation, if at all

What is needed is further study of the patient’s calcium metabolism (choice C). Although pseudogout can be idiopathic, it can also be associated with hyperparathyroidism. This patient has a slightly elevated serum calcium level (even after adjustment for the albumin level) and a slightly low serum phosphorus level. These findings alone suggest a high parathyroid hormone (PTH) level; when coupled with the presentation of pseudogout seen here, they justify investigation for PTH abnormalities.

Outcome of this case. After the patient’s acute symptoms are treated with NSAIDs and corticosteroid injections in the involved joints, serum PTH is measured- in addition to serum ionized calcium for the greatest interpretative accuracy.¹ The intact PTH level is 123 pg/mL (normal, less than 20 pg/mL), and the ionized calcium level is normal; these values are consistent with primary hyperparathyroidism. Weekly alendronate is prescribed to control his hypercalcemia; he will be followed up at an endocrinology clinic. A technetium Tc 99m sestamibi scan of his neck to localize a parathyroid adenoma and a surgical consultation are planned. The results of the scan and the patient’s subacute clinical course will determine whether surgery is warranted.

References:

REFERENCES

1.

Marx SJ. Hyperparathyroid and hypoparathyroid disorders.

N Engl J Med.

2000;343:1863-1875.

2.

Silverberg SJ, Shane E, Jacobs TP, et al. A 10-year prospective study of primaryhyperparathyroidism with or without parathyroid surgery.

N Engl J Med.

1999;341:1249-1255.