A 38-year-old man comes to the office due to pain in multiple joints. He has a 5-year history of lumbar pain and a 2-year history of bilateral knee pain. The patient works in construction and his pain is worst after a long day on his feet. He has taken ibuprofen intermittently, but the pain is no longer tolerable. The patient has a paternal aunt with osteoarthritis. Physical examination shows blue-black spots on his sclerae and diffuse darkening of the auricular helices. Which of the following is the most likely cause of this patient's arthritis?

Question

A 38-year-old man comes to the office due to pain in multiple joints.  He has a 5-year history of lumbar pain and a 2-year history of bilateral knee pain.  The patient works in construction and his pain is worst after a long day on his feet.  He has taken ibuprofen intermittently, but the pain is no longer tolerable.  The patient has a paternal aunt with osteoarthritis.  Physical examination shows blue-black spots on his sclerae and diffuse darkening of the auricular helices.  Which of the following is the most likely cause of this patient's arthritis?

Quizplus · Accepted Answer

11ec160b_36f8_3434_9249_cf2e3fb9bb3b_MD0001_00 Alkaptonuria is a relatively benign childhood disorder that is marked by severe arthritis in adult life. This autosomal-recessive disorder is caused by deficiency of homogentisic acid dioxygenase, which normally metabolizes homogentisic acid into maleylacetoacetate. Accumulated homogentisic acid causes pigment deposits in connective tissue throughout the body. During adulthood, these blue-black deposits become apparent in the sclerae and ear cartilage. Deposits also occur in the large joints and spine, causing ankylosis, motion restriction, and significant pain. A distinctive characteristic of alkaptonuria is that the urine of these patients turns black when exposed to air due to oxidization of homogentisic acid. (Choice B) Hyperuricemia can cause acute monoarticular gouty arthritis due to urate crystal deposition in joints (usually the great toe or knee). These acute attacks resolve in days to weeks and are not associated with connective tissue hyperpigmentation. (Choice C) Osteoarthritis is due to combined genetic, metabolic, and mechanical factors that result in defects in articular cartilage. Polyarticular joint involvement of the fingers (including Heberden and Bouchard nodes), knees, hips, and spine classically occur. Joint pain typically peaks in the afternoon or evening after activity, but osteoarthritis is not associated with the blue-black deposits. (Choice D) Reactive arthritis can occur following enteric or genitourinary infections with organisms such as Salmonella, Shigella, Campylobacter, and Chlamydia. The typical pattern is asymmetric involvement of lower extremity joints accompanied by enthesitis (inflammation at insertion of tendons), conjunctivitis, and urethritis. Reactive arthritis has no associated skin findings in contrast to alkaptonuria. (Choice E) Albinism is caused by defects in biosynthesis and distribution of melanin. Melanocytes synthesize melanin from tyrosine via the enzyme tyrosinase. Educational objective: Alkaptonuria is an autosomal-recessive disorder caused by a deficiency of homogentisic acid dioxygenase, an enzyme involved in tyrosine metabolism. Excess homogentisic acid causes diffuse blue-black deposits in connective tissues. Adults have sclerae and ear cartilage hyperpigmentation along with osteoarthropathy of the spine and large joints. __________ References: Alkaptonuria. (http://www.ncbi.nlm.nih.gov/pubmed/20301627) Alkaptonuria. (http://www.ncbi.nlm.nih.gov/pubmed/25003018)

A 38-Year-Old Man Comes to the Office Due to Pain