Ochronosis Clinical Presentation

  • Author: Craig G Burkhart, MD, MPH; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Feb 28, 2012
 

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.[3] 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.[4]

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Physical

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 maculOchronosis 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.[5] Lower back, hip, and knee pain and stiffness are not uncommon.

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.[6, 7]

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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 African blacks 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 been reported, even when using 2% hydroquinone products. With exogenous ochronosis, the arthropathy seen with alkaptonuria does not occur.

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Contributor Information and Disclosures
Author

Craig G Burkhart, MD, MPH  Clinical Professor, Department of Medicine, Section of Dermatology, The University of Toledo College of Medicine; Clinical Assistant Professor, Department of Dermatology, Ohio State University College of Medicine

Craig G Burkhart, MD, MPH is a member of the following medical societies: American Academy of Dermatology, Ohio State Medical Association, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Coauthor(s)

Craig N Burkhart, MD, MSBS  Assistant Professor, Department of Dermatology, University of North Carolina at Chapel Hill

Craig N Burkhart, MD, MSBS is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, and American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Catharine Lisa Kauffman, MD, FACP  Georgetown Dermatology and Georgetown Dermpath

Catharine Lisa Kauffman, MD, FACP is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Royal Society of Medicine, Society for Investigative Dermatology, and Women's Dermatologic Society

Disclosure: Nothing to disclose.

Richard P Vinson, MD  Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association

Disclosure: Nothing to disclose.

Warren R Heymann, MD  Head, Division of Dermatology, Professor, Department of Internal Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

References

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Ochronosis revealing a perioral bluish black macular eruption after hydroquinone use.
Periorbital discoloration due to excessive use of topical bleaching preparations containing hydroquinone.
Upon microscopic examination, amber-colored, oval structures are detected in the mid-to-upper dermal tissues (hematoxylin and eosin, original magnification X40).
Upon higher magnification (of Image 3), ochronosis reveals homogenization and swelling of collagen bundles (hematoxylin and eosin, original magnification X100).
 
 
 
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