Ochronosis is a syndrome caused by the accumulation of homogentisic acid in connective tissues. The condition was named after the yellowish (ocher-like) discoloration of the tissue seen on microscopic examination. Macroscopically, though, the affected tissues appear bluish-grey because of a light-scattering phenomenon known as the Tyndall effect. The condition is most often associated with alkaptonuria, but can occur from exogenous administration of phenol complexes such as hydroquinone. It was first described by Rudolf Virchow in 1865. Types
The two types of ochronosis are endogenous and exogenous. The endogenous variety is an autosomal-recessive disease, known as alkaptonuria, that is caused by a lack of homogentisate oxidase enzyme. Exogenous ochronosis is an avoidable dermatitis that can be caused by the topical application of compounds such as hydroquinone or phenols. It was first seen in 1912, when a patient who used phenol on a leg ulcer was found by Beddard and Plumtre to have this condition. Hydroquinone-induced exogenous ochronosis was found in 1975 by Findlay, who observed the condition in patients who used skin lightening creams containing the compound.The three clinical stages of exogenous ochronosis are:
Erythema and mild hyperpigmentation
Hyperpigmentation and "caviar-like" lesions
Papulonodular lesions

Signs and symptoms
Skin: The pigment is deposited throughout the skin, but only becomes apparent in certain locations, where the concentration is great enough to be seen clinically. This usually occurs in areas where connective tissue is thick (joints, tympanic membrane) or close to the surface of the skin (thenar and hypothenar eminences and the sides of the fingers).
This may be due to aesthetic or social-standing reasons, in areas where a lighter skin tone is considered to be a sign of wealth or beauty. Also, skin-lightening creams containing compounds such as hydroquinone are commonly used to help with hyperpigmentation disorders such as melasma.Hydroquinone is the compound most frequently used in skin-whitening products. Due to concerns about its side effects, it was almost banned by the FDA in 2006, as  medical issues of carcinogenicity and reports of disfiguring ochronosis existed. In the European Union hydroquinone has been banned in cosmetic creams since 2000.Long-term use of creams containing this compound may lead to exogenous ochronotic lesions. The duration of use is directly proportional to the risk of developing the condition, with most cases occurring after years of use. Around 10–15 million skin lightening products are sold annually, with Japan being the major buyer. Pathophysiology
Ochronosis occurs because of deposition of phenols (such as homogentisic acid and hydroquinone) as plaques in the matrix of cartilage. The pigments can also be incorporated into collagen and elastin fibers. In the skin, the pigment alters the structure of the fibers, causing enlargement and curling. The embedded pigments also form crosslinks with pigment depositions in adjacent fibers, stabilizing and reducing the elastic recoil of the fibers. This results in hardening of elastic structures, increasing their rigidity and brittleness. Once ruptured, the exposed pigments cause a foreign body reaction and inflammation. This pigment deposition also invokes deposition of hydroxyapatite, the mineral responsible for bone calcification, further hardening the connective tissue.