|Year : 2007 | Volume : 1 | Issue : 2 | Page : 77-80|
Alkaptonuria is a rare inherited autosomal recessive metabolic disorder, caused by the deficiency of homogentisate 1, 2 dioxygenase enzyme. The three major features of alkaptonuria are the presence of homogentisic acid in the urine, ochronosis (bluish-black pigmentation in connective tissue) and arthritis of the spine and large joints. In this report, we describe a 48-year-old female who presented with advanced arthritic degenerative changes in her both shoulders and benefited from bilateral shoulder resurfacing. The bilateral shoulder resurfacing has not been reported in the literature before. The literature, clinical, radiological and histological features along with differential diagnosis and management of this rare condition are reviewed in this article.
Keywords: Alkaptonuria, homogentisic acid, ochronosis, resurfacing
|How to cite this article:
Azhar A, Khan R, Smyth H. Ochronotic arthritis. Int J Shoulder Surg 2007;1:77-80
Alkaptonuria is a rare autosomal recessive disorder, caused by the deficiency of homogentisate 1, 2-dioxygenase, an enzyme that converts homogentisic acid (HGA) to maleylacetoacetic acid in the tyrosine degradation pathway. The estimated incidence is lower than 1:250 000 and most common in certain areas of Eastern Europe.  Alkaptonuria frequently presents as triad of arthritis, dark urine and bluish discoloration of cartilage.  This bluish-black pigmentation of the connective tissue, such as cartilage, skin and sclera is called ochronosis. Ochronosis was first described by Virchow in 1866. During post-mortem, Virchow found pigmentation of the tissues caused by the deposition of ochre-colored granules.  The most incapacitating complication of alkaptonuria is severe progressive degenerative arthropathy mainly affecting the axial and weight bearing joints, associated with extra-articular manifestations. 
The literature on arthroplasty in this disease is limited to a few case reports, mainly describing hip and knee replacements [Table – 1]. We report a case with bilateral shoulder resurfacing which, to our knowledge, has never been reported before.
A 48-year-old female, a known case of alkaptonuria, was referred to the orthopaedic clinic in mid-2000 for the assessment of her both shoulders. Her main complaint was bilateral painful and stiff shoulders, interfering severely with her activities of daily living. She was also having some pain in her both knees. She was taking regular analgesia without any benefit and was unable to sleep due to pain. Her urine used to turn dark when left in the air for a while and her sweat used to stain her clothes; otherwise she was well and asymptomatic till 2000, when her both shoulders started to give her pain and stiffness. The pain and stiffness was gradually becoming worse.
During physical examination, she had a painful and very restricted range of movements of both shoulders [Table – 2] whereas both knees had satisfactory range of motion. She was assessed on the Disabilities of the Arm, Shoulder and Hand (DASH) Score andth preoperatively it was 64 on the left and 58 on the right shoulder. Radiographs revealed severe arthritic changes in both shoulders [Figure – 1],[Figure – 2] and mild changes in her both knees. Examination of the urine showed a high level of homogentisic acid.
Initially we tried manipulation under anesthesia along with steroid injections thrice, which was unsuccessful. She had left and right shoulder resurfacing (Copeland) in May 2002 and in September 2002 respectively. Her postoperative recovery period was uneventful and she was discharged after a few days from the hospital on both occasions. Recently she has been seen in the clinic with no complaints regarding the shoulders, with good range of movements
[Table – 3] and radiologically there are no signs of loosening [Figure – 3],[Figure – 4]. She was re-assessed on the DASH Score and it is 43 on both shoulders, whichth is less than preoperative scores (left 64, right 58). She has some bluish pigmentation on her right sclera, new onset of neck and lower back stiffness along with pain. The pain in both knees has increased in the last few years but it is still bearable and settles with analgesia.
There is no positive family history for alkaptonuria. In the past, she had multiple surgeries to her left dysplastic hip and subsequently she had total hip replacement in January 2000. She also had caesarean section 30 years ago and left breast lumpectomy in 1999.Four years postoperatively, the patient has good range of motion in both shoulders and is pain free. She is being followed-up in orthopaedic and metabolic clinics regularly.
Ochronotic arthropathy is a manifestation of long standing alkaptonuria resulting from deposition of ochronotic pigments within the articular cartilage. The presence of joint disease in alkaptonuria was first pointed out by Albrecht and Zdarek in 1902 and two years later Osler clinically diagnosed ochronosis for the first time in two alkaptonuric brothers.  The patients suffering from this disease are usually asymptomatic until they present with arthritis of the main joints or as low back pain and stiffness. The initial presentation of our patient was with stiff and painful shoulders. The tendency for alkaptonuria to affect the shoulder joints further distinguishes it from osteoarthritis.  The arthritis is usually so severe that the patient is crippled with pain and cannot carry out routine activities. The most common age for onset of clinical symptoms of ochronotic arthropathy is in the fourth decade. 
The extra-articular manifestations are pigmentation of the ears, sclerae and skin, darkening of the urine after long exposure to air, aortic stenosis, prostatic, urethral and renal calculi, rarely prostatitis, nephrocalcinosis and renal failure.  The radiological features in the joints include narrowing or loss of joint space, subchondral bone sclerosis with few cystic lesions, no osteophytes and fragmentation and ossification of loose bodies. In the spine, the features are compression and narrowing of the disc spaces with dense calcification and vacuum phenomenon predominantly in the dorsolumbar region, fusion of vertebral bodies and spondylosis with small or absent osteophytes. Sacroiliac joints and symphysis pubis joint space also become narrow and calcified.  The macroscopic appearance of the involved tissue usually shows pigmentation, which varies from brown to black. Microscopically, in the hyaline cartilage there is deposition of ochre-coloured granules, more marked in the deeper layers. In the synovium, there is thickening, granule deposition, calcification and presence of small islands of cartilage.  The differential diagnosis of this disease mainly includes osteoarthritis, ankylosing spondylitis, rheumatoid arthritis and calcium pyrophosphate arthropathy. Discal calcification in the spine can also mimic hyperparathyroidism, hemochromatosis, amyloidosis, diffuse idiopathic skeletal hyperostosis (DISH) or surgical spinal fusion.
The course and prognosis of the disease depend on the severity of the alkaptonuria. Currently there is no specific treatment for alkaptonuria and management is usually conservative.  In our case, the patient is being treated symptomatically and had bilateral shoulder resurfacing for painful stiff shoulders.
Four years on, our patient is very happy with the shoulder resurfacing. She is pain-free with good range of movements. In conclusion, ochronotic arthropathy is a rare condition with widespread premature degenerative disease associated with peripheral arthritis. In our opinion, joint arthroplasty is one of the treatment options to improve the quality of the patient’s life and so far no complications have been reported in the literature.
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[Figure – 1], [Figure – 2], [Figure – 3], [Figure – 4]
[Table – 1], [Table – 2], [Table – 3]