Ochronosis Clinical Presentation

Updated: Mar 07, 2017
  • Author: Paul N Skiba; Chief Editor: Dirk M Elston, MD  more...
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Presentation

History

Alkaptonuria is often recognized at birth when parents note discoloration of the urine.

Nevertheless, many patients with this metabolic disorder are symptomless until ochronotic changes occur with bluish black pigmented patches in the sclera developing in patients aged 30-39 years. [6] These ocular discolorations are located between the corneal margin and the inner canthus.

The fourth decade often marks the onset of thickening and blue-black or gray-blue discoloration of the ear cartilage.

Other body locations that frequently display the alteration in skin hue are the eyelids, the forehead, the cheeks, the axillae, the genital region, the nail beds, the buccal mucosa, the larynx, the tympanic eardrum, and the tendons (most easily demonstrated by the patient making a fist).

Ochronotic arthropathy develops later with arthritic symptoms. [7]

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Physical Examination

Dark urine noted in diapers is usually the presenting manifestation of this entity.

For those cases of alkaptonuria not diagnosed in infancy, black cerumen and axillary pigmentation may be noted before age 10 years.

Gray-black scleral pigmentation in the configuration of small, dark rings is noted in the third decade.

Ear cartilage alterations in the fourth decade include discoloration with a grayish blue hue, followed by structural changes with stiffness, contour irregularities, and calcification. Note the images below.

Ochronosis revealing a perioral bluish black macul Ochronosis revealing a perioral bluish black macular eruption after hydroquinone use.
Periorbital discoloration due to excessive use of Periorbital discoloration due to excessive use of topical bleaching preparations containing hydroquinone.

Ochronotic discoloration can also be detected on the nasal tip, the costochondral junctions, the extensor tendons of the hands, the cheeks, the fingernails, and the buccal mucosa.

Arthritic signs of ochronotic arthropathy develop in the third and fourth decades. Narrowing of the joint spaces and disk calcifications occur. [14] Lower back, hip, and knee pain and stiffness are not uncommon. Inflammation, calcification, and rupture of tendons and ligaments may also occur. [15]

The clinical discoloration of the skin is a result of the formation of ochronotic pigment granules in the dermis and in the apocrine glands. Thus, the ochronotic changes of cartilaginous and tendinous structures are best appreciated in regions in which the overlying skin is of minimal thickness, such as the ears, the nasal tip, and the extensor tendons of the hands.

Accumulation of this pigment in cardiac tissue can lead to an inflammatory reaction and progressive heart valve dysfunction, with aortic stenosis being the most common, but in rare cases aortic regurgitation may also be observed. [16, 17]

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Causes

Alkaptonuria is a genetic disorder related to a deficiency of homogentisic acid oxidase. [8]

Ochronotic pigmentation can develop from medications. Similar skin and cartilage alterations can be induced by quinacrine administration and at sites of quinine injections. [9] Quinines directly inhibit homogentisic acid oxidase. Carbolic acid topical applications to cutaneous ulcers have also induced ochronotic skin alterations.

Exogenous ochronosis has been reported with topical applications of phenol and hydroquinones to the skin. [10, 11, 12, 13] In the case of hydroquinone, it is reported that 35% of black Africans exhibit ochronotic skin changes when using a 6-8% hydroquinone preparation over a prolonged period. Indeed, the prevalence among users of these skin lighteners has been stated to be 69% in a South African study. In African Americans, this cutaneous adverse effect of hydroquinones has also been reported, even when using 2% hydroquinone products. With exogenous ochronosis, the arthropathy seen with alkaptonuria does not occur.

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Complications

Complications of alkaptonuria include arthropathy and possible cardiovascular disease (see Prognosis).

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