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The American College of Physicians (ACP) established its evidence-based clinical practice guidelines program in 1981. The ACP clinical practice guidelines and guidance statements follow a multistep development process that includes a systematic review of the evidence, deliberation of the evidence by the committee, summary recommendations, and evidence and recommendation grading.

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A 47-year-old man is evaluated for a 10-year history of slowly progressive joint pain of the shoulders, hands, wrists, and knees. He has progressive enlargement of the joints and mild stiffness throughout the day; pain is worse with use and better with rest. He reports no redness or swelling. He also notes fatigue. He takes ibuprofen as needed. Family history is notable for his father who has diabetes mellitus and arthritis.

On physical examination, vital signs are normal. BMI is 28. Limited range of motion of the shoulders is noted. There is bony enlargement of the second and third metacarpophalangeal (MCP) joints bilaterally and all proximal interphalangeal (PIP) joints, wrists, and knees. There are no effusions, warmth, or redness of any joint.

Laboratory studies, including complete blood count, erythrocyte sedimentation rate, blood urea nitrogen, calcium, creatinine, electrolytes, magnesium, phosphorus, and thyroid-stimulating hormone, are normal except for a fasting glucose level of 120 mg/dL (6.7 mmol/L).

Radiographs of the hands show hook-like osteophytes on the radial aspect of the second and third MCP heads bilaterally and mild osteoarthritis of the wrists, PIP joints, and shoulders; there are no erosive changes. A knee radiograph is shown.


Which of the following is the most appropriate management?

Measurement of serum transferrin is appropriate for this patient who has osteoarthritis (OA) involving atypical joints, including the metacarpophalangeal (MCP) joints and wrists. His radiographs show chondrocalcinosis in the knees and hook-like osteophytes on the radial aspect of the MCP heads, consistent with calcium pyrophosphate deposition (CPPD)-induced OA. CPPD is usually idiopathic, trauma induced, or familial, and it increases in prevalence with advancing age. However, in a younger patient who also has other metabolic problems such as diabetes mellitus and skin bronzing, it is important to consider the possibility of hemochromatosis. Other causes of CPPD include conditions leading to hypercalcemia such as hyperparathyroidism, hypomagnesemia, familial hypocalciuric hypercalcemia, and hypophosphatasia. Acromegaly and Wilson disease may also be associated with CPPD. This patient does not have any clinical or laboratory evidence of these other disorders and should therefore be screened for hemochromatosis with a serum transferrin level, the most sensitive screening test for this disorder. Patients with a serum transferrin measurement greater than 45% should be tested for the HFE genotype, which will confirm the diagnosis.

Anti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with rheumatoid arthritis, which is characterized by symmetric polyarthritis involving small, medium, and large joints and associated with prolonged (>60 minutes) morning stiffness. Examination reveals soft, boggy, or fluctuant swelling and tenderness at involved joints. Plain radiographs may reveal periarticular osteopenia, erosions, and symmetric joint-space narrowing. These findings are not present in this patient; therefore, testing for anti-CCP antibodies is not indicated.

Antinuclear antibody testing is a screening and diagnostic tool used in systemic lupus erythematosus (SLE). Although SLE can involve arthralgia and arthritis affecting the hands, wrists, and knees, it is not associated with chondrocalcinosis or hook-like osteophytes on the MCP heads.

Measurement of this patient's parathyroid hormone level is unnecessary because his serum calcium is normal, arguing against hyperparathyroidism as a cause of his CPPD-induced arthropathy.

Key Point

  • Hemochromatosis should be considered as a cause of osteoarthritis in younger patients with involvement of atypical joints or characteristic findings on imaging, such as evidence of calcium pyrophosphate deposition in the joints and hook-like osteophytes on the radial aspect of the metacarpophalangeal heads.
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