Ochronosis

Ochronosis is a condition characterized by the deposition of a dark ochronotic pigment in connective tissues, leading to blue-black discoloration and tissue fragility. It is most commonly associated with endogenous ochronosis in the setting of alkaptonuria, and it can also arise from long-term use of certain skin-lightening agents, causing exogenous ochronosis.

Endogenous ochronosis results from a deficiency of the enzyme homogentisate 1,2-dioxygenase in the tyrosine degradation pathway. This leads to accumulation of homogentisic acid (HGA), which oxidizes and deposits as a dark pigment in cartilage, skin, sclera, and heart valves. Urine from affected individuals often darkens on standing or exposure to air due to oxidation of HGA. Clinical manifestations include ochronotic arthropathy with early degeneration of the spine and large joints, back pain, reduced mobility, and characteristic discoloration of ear cartilage and sclera.

Diagnosis is supported by elevated urinary homogentisic acid levels and, when appropriate, tissue biopsy showing ochronotic pigment deposition. Imaging may reveal characteristic calcification of intervertebral discs and early osteoarthritis in affected joints.

Management is supportive, as there is no cure. Dietary restriction of phenylalanine and tyrosine can reduce HGA production in some cases. Nitisinone may lower HGA levels but requires careful monitoring for adverse effects. For exogenous ochronosis, caused by prolonged use of hydroquinone or related agents, the primary step is discontinuation of the offending product, with sun protection and, in some cases, laser therapy to reduce pigment.