Osler's sign revisited.

A 50-year-old male admitted for arthritis was noted incidentally to have a brownish black discoloration in both eyes, and an ophthalmology opinion was sought. On examination, brownish black pigmented lesions [Figure 1] were seen in both nasal and temporal aspects of the sclera in the interpalpebral region of both eyes. Rest of the ocular examination was normal. On questioning, the patient gave a positive history of blackish discoloration of urine on standing. A urine sample was obtained, and sodium hydroxide was added in drops. The urine showed progressive blackish discoloration, [Figure 2] and after a time, the entire sample turned black. Thus, a diagnosis of alkaptonuria was made based on the triad of scleral pigmentation, arthritis, and black urine.

Figure 1

Brownish black scleral pigmentation

Figure 2

Blackish discoloration of urine after adding sodium hydroxide

DISCUSSION

Alkaptonuria is an autosomal recessively inherited metabolic disorder due to a deficiency in the enzyme homogentisic acid oxidase[1] which results in the accumulation of homogentisic acid. Homogentisic acid is rapidly excreted by the kidneys. Urine, on exposure to air, gives a black color due to the formation of an oxidation product of homogentisic acid. This is usually one the earliest symptoms of the disease. Gradually, homogentisic acid is deposited within cartilage and other collagenous tissues, a condition called ochronosis. Patients may present with brownish black pigmentation of the eyes or ears.

The scleral discoloration is referred to as Osler's sign, which usually starts around the third decade.[2] It is usually seen at the site of insertion of the medial and lateral rectus muscles and is seen in 82% of patients. The scleral pigmentation does not give rise to any visual disturbance. The pigment involves the entire thickness of the sclera and can be either extracellular in location along with collagen fibers, or intracellular within macrophages and fibrocytes.[1]

Arthritis is a common complaint and is usually seen in the spine, hips, and knees. It starts usually in the fourth decade and is the major cause of morbidity associated with the disease. Palmoplantar pigmentation may also rarely occur.[3]

Vitamin C has a possible antioxidant action to reduce the conversion of homogentisic acid to polymers that get deposited in tissues. Nitisinone has been shown to reduce levels of homogentisic acid,[4] but its clinical applications are yet to be fully elucidated.

Most cases are diagnosed when the patients become symptomatic due to the disease. Thus, the awareness of the ocular sign in alkaptonuria can lead to an earlier diagnosis and intervention since scleral pigmentation usually starts in the mid-twenties.