Early diagnosis of Ochronosis is difficult because it is a rare disease, few know about it and even who knows hardly consider this diagnose.

Patients in the age group of 30 to 50 years usually look for medical attention not because of the skin or eye blemishes. They go to medical service because of low back pain with no previous history of trauma, being diagnosed with postural or labor low back pain receiving symptomatic treatment. Radiological signs of Ochronosis, if present at this time, are often incipient and nonspecific.

These patients invariably have urinary abnormalities since childhood that are never properly valued because they rarely expose their urine to ambient air, to witness it darkening. If urine is tested¹⁰, AKU will be diagnosed before the emergence of evident Ochronosis manifestations.

However, with the advancing of age and clinical condition, skin blemishes begin to appear and lower back pain gets worse, also affecting other joints such as the hip, knees, and shoulders.

At this stage, significant osteoarthritis, osteoporosis, reduction of intervertebral space, loss of lumbar lordosis, and the typical central calcifications of intervertebral discs, a pathognomonic sign of Ochronotic Arthropathy¹⁰, are already present on spinal radiographs.

In our medical service, we followed the case of a 73-year-old male patient, initially in clinical follow-up because of heart disease, but who began to manifest rheumatological symptoms, which proved to be Ochronosis:

Fig. 3: Lumbar spine lateral and AP radiography of a 73-year-old male, showing the pathognomic aspect of Ochronotic Arthropathy: Central calcifications of intervertebral discs. Osteophytosis and mild osteoarthritis of the plateau vertebral are also noted.

Fig. 4: Thoracic spine lateral and AP radiography of a 73-year-old male, showing the pathognomic aspect of Ochronotic Arthropathy: Central calcifications of intervertebral discs (white arrows). Osteophytosis and mild osteoarthritis of the plateau vertebral are also noted.

Fig. 5: Spinal Ochronotic Arthropathy. A) T2 weighted image and B) T1 weighted image Magnetic Resonance of a 73-year-old male displaying degenerative spine alterations.

Fig. 6: Cervical Ochronotic Arthropathy. A) Computed Tomography bone window image and B) Magnetic Resonance in T2 weighted image displaying degenerative cervical process in a 73-year-old male.

Ochronotic Arthropathy can also affect the sacroiliac joints, pubic symphysis, and large joints, with interarticular space reduction, intra-articular bone fragmentation, tendon calcification that can rupture, and the common osteoarthritis features, as bone sclerosis. Osteophytes are uncommon, as well the involvement of ankle, wrists and small joints¹⁰.

Fig. 7: Hands radiography of a 73-year-old male with distal interphalangeal osteoarthritis due Ochronotic Arthropathy, as can be seen in spotlighted pictures.

Table 2: Radiological manifestations of Ochronotic Osteoarthropathy. Adapted from Resnick D, et al. (1995) Diagnosis of Bone and Joint Disorders. Saunders; 1670-1684.

Tendons affected by Ochronotic Arthropathy usually develop tendinopathy¹⁰ because of intra- and extracellular deposition of ochronotic pigment, making them thickened, inflamed, less sliding, painful, and more susceptible to rupture.

Fig. 8: Wrist ultrassonography of a 73 years-old male exhibiting tendinopathy due Ochronosis. A) Thickened tendons, marked as yellow “t” letters. B) Rupture of radial carpal flexor tendon (yellow arrows).

The typical clinical condition of progressive low back pain, dorsolumbar mobility reduction and large joint arthralgia, associated with radiographic findings, often lead to different diagnostic hypotheses, such as Ankylosing Spondylitis² most commonly.

Table 3: Radiological differences between Ankylosing Spondylitis and Ochronotic Arthropathy. Adapted from Mistry JB, et al. (2013) Alkaptonuria. Rare Dis. 1:e 27475.

If Ochronotic Osteoarthropathy affects small joints, in an atypical manifestation, the diagnosis of Osteoarthritis is usually also considered, especially if there are changes in serum inflammatory markers and if there are joint overload factors for labor or idiopathic reasons.

Table 4: Similarities between peripheral Ochronotic Arthropathy and Osteoarthritis. Adapted from Mistry JB, et al. (2013) Alkaptonuria. Rare Dis. 1:e 27475.

Degenerative Osteoarthritis, as well as other clinical conditions, such as Calcium Pyrophosphate Dihydrate Deposition disease (CPPD), Hemochromatosis, Hyperparathyroidism, and Acromegaly, may present similar radiological features to Ochronotic Osteoarthropathy¹⁰. Degenerative Osteoarthritis is typical of the natural aging process. Hemochromatosis is an arthropathy caused by the iron excess in the organism, that is deposited in joints. Hyperparathyroidism is a disorder of the parathyroid hormone, leading to an increase in the serum calcium caused due osteopenia. Acromegaly is the uncontrolled production of growth hormone, increasing the robustness of bone structures. CPPD is the spectrum of possible manifestations due to calcium pyrophosphate dihydrate salt deposition in joint spaces.

Table 5: Comparison between Ochronotic Arthropathy and Degenerative Aging Osteoarthritis. Adapted from Resnick D, et al. (1995) Diagnosis of Bone and Joint Disorders. Saunders; 1670-1684.

Table 6: Comparison between the pattern of intervertebral calcification in Ochronotic Arthropathy and in some of its differential diagnosis. Adapted from Resnick D, et al. (1995) Diagnosis of Bone and Joint Disorders. Saunders; 1670-1684.

When Ochronotic Arthropathy did not present the rare cardiovascular manifestations, it does not generate mortality, but greatly increases morbidity, reducing patients' life quality. The clinical condition usually advances to a dramatic knee and hip joint osteoarthritis, which can lead to spontaneous fractures of the femoral head¹¹, and at this stage, total hip joint replacement is imperative¹². Knee replacement not rare is also needed too.

Fig. 9: Lateral radiography of the lumbosacral spine of a 73-year-old male showing the right total hip joint replacement, besides the pathognomonic signs of Ochronotic Arthopathy.

Fig. 10: AP knees radiography of a 73-year-old male, showing reduced bone mineralization and his knee replacement, due Ochronotic Arthropathy.

The most common manifestation related to Ochronosis is the brownish blemishes, which are typically more evident in the ocular sclera, auricular cartilage, nail beds and facial skin.

Fig. 11: Photography showing ochronotic pigment (black arrow) in the ocular sclera of a 73-year-old male.

Fig. 12: Photography showing stiffening, thinning and Raynaud's phenomenon in the right hand of a 73-years-old male due Ochronosis

Other less frequent manifestations of Ochronosis is lithiasis by HGA stones, usually as nephrolithiasis, but reports of bladder lithiasis, prostatic lithiasis, sialolithiasis and biliary lithiasis^2,12 were made too.

Likewise grave is the cardiovascular manifestations of Ochronosis, with ochronotic pigment deposition in the aortic sinus, leading to local inflammatory stress and consequent calcification, which may lead to coronary manifestations and valvular heart disease. Heart failure caused by Ochronosis will usually be diagnosed only at an advanced age, along with other typical signs of the Ochronotic disease ¹³.