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  • Author: Craig G Burkhart, MD, MPH; Chief Editor: Dirk M Elston, MD  more...
Updated: Aug 19, 2015


Ochronosis is the bluish black discoloration of certain tissues, such as the ear cartilage and the ocular tissue, seen with alkaptonuria, a metabolic disorder. Additionally, ochronosis can occasionally occur from exposure to various substances such as phenol, trinitrophenol, resorcinol, mercury, picric acid, benzene, hydroquinone, and antimalarials.



Ochronosis was defined by Virchow who histologically described the connective tissue in alkaptonuria, given the cartilage's ochre, or yellow, hue under the microscope.

Alkaptonuria is a rare autosomal recessive metabolic disorder caused by deficiency of homogentisic acid oxidase, the only enzyme capable of catabolizing homogentisic acid (HGA). Alkaptonuria features a defect in the biochemical pathway by which phenylalanine and tyrosine are normally degraded into fumaric and acetoacetic acid. The genetic defect is autosomal recessive and is mapped to the HGO gene on arm 3q1, and 18 genetic missense mutations are known to cause homogentisic acid oxidase aberrations.[1] This deficiency results in accumulation and deposition of HGA in cartilage, causing the characteristic diffuse bluish black pigmentation. These affected connective tissue become weak and brittle with time, leading to chronic inflammation, degeneration, and osteoarthritis.

Exogenous ochronosis, in which bluish black pigmentation of cartilage is noted iatrogenically by exogenous agents, has been seen after exposure to noxious substances, including phenol, trinitrophenol, benzene, and hydroquinone.




United States

Alkaptonuria is a rare autosomal recessive disease with a prevalence of 1 case per 1 million population.


Alkaptonuria occurs worldwide, with the highest frequency seen in Slovakia and Dominican Republic, in which the prevalence approaches 1 case per 19,000 inhabitants.[2]


Alkaptonuria is seen in persons of all races.


The incidence of alkaptonuria is equal in both sexes.


Alkaptonuria is present at birth and is often diagnosed by discoloration of the diapers. Up to 25% of patients with alkaptonuria do not have the characteristic dark urine staining, and many patients remain undiagnosed until adulthood.

Contributor Information and Disclosures

Craig G Burkhart, MD, MPH Clinical Professor, Department of Medicine, Medical College of Ohio; Clinical Assistant Professor, Department of Medicine, Ohio University College of Osteopathic Medicine

Craig G Burkhart, MD, MPH is a member of the following medical societies: Association of Military Dermatologists, American College of Aesthetic and Cosmetic Physicians; American Society of Aesthetic/Cosmetic Physicians, Michigan Dermatological Society, Academy of Medicine of Toledo and Lucas County, Ohio Dermatological Association, American Academy of Dermatology, Ohio State Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.


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

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

Disclosure: Nothing to disclose.

Specialty Editor Board

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, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Warren R Heymann, MD Head, Division of Dermatology, Professor, Department of Internal Medicine, Rutgers New Jersey Medical School

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

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

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

Disclosure: Nothing to disclose.

Additional Contributors

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, Royal Society of Medicine, Women's Dermatologic Society, American Medical Association, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

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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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