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Ochronosis

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

Background

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.

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Pathophysiology

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.

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Epidemiology

Frequency

United States

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

International

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]

Race

Alkaptonuria is seen in persons of all races.

Sex

The incidence of alkaptonuria is equal in both sexes.

Age

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.

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Contributor Information and Disclosures
Author

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.

Coauthor(s)

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.

References
  1. Felbor U, Mutsch Y, Grehn F, Müller CR, Kress W. Ocular ochronosis in alkaptonuria patients carrying mutations in the homogentisate 1,2-dioxygenase gene. Br J Ophthalmol. 1999 Jun. 83(6):680-3. [Medline].

  2. Zatkova A. An update on molecular genetics of Alkaptonuria. Journal of Inherited Metabolic Disease. December 2011. 34:1127-1136. [Medline].

  3. Natural history of alkaptonuria revisited: Analyses based on scoring systems. Ranganath LR, Cox TE. Journal of Inherited Metabolic Diseases. December 2011. 34:1141-1151. [Medline].

  4. Zhao BH, Chen BC, Shao de C, Zhang Q. Osteoarthritis? Ochronotic arthritis! A case study and review of the literature. Knee Surg Sports Traumatol Arthrosc. 2009 Jul. 17(7):778-81. [Medline].

  5. Gurkanlar D, Daneyemez M, Solmaz I, Temiz C. Ochronosis and lumbar disc herniation. Acta Neurochir (Wien). 2006 Aug. 148(8):891-4; discussion 894. [Medline].

  6. Butany JW, Naseemuddin A, Moshkowitz Y, Nair V. Ochronosis and aortic valve stenosis. J Card Surg. 2006 Mar-Apr. 21(2):182-4. [Medline].

  7. Yoshikai M, Murayama J, Yamada N. Aortic valve regurgitation in alkaptonuria. J Heart Valve Dis. 2004 Sep. 13(5):863-5. [Medline].

  8. Vilboux T, Kayser M, Introne W, et al. Mutation spectrum of homogentisic acid oxidase (HGD) in alkaptonuria. Hum Mutat. 2009 Dec. 30(12):1611-9. [Medline]. [Full Text].

  9. Bruce S, Tschen JA, Chow D. Exogenous ochronosis resulting from quinine injections. J Am Acad Dermatol. 1986 Aug. 15(2 Pt 2):357-61. [Medline].

  10. Bongiorno MR, Aricò M. Exogenous ochronosis and striae atrophicae following the use of bleaching creams. Int J Dermatol. 2005 Feb. 44(2):112-5. [Medline].

  11. Findlay GH, Morrison JG, Simson IW. Exogenous ochronosis and pigmented colloid milium from hydroquinone bleaching creams. Br J Dermatol. 1975 Dec. 93(6):613-22. [Medline].

  12. Hoshaw RA, Zimmerman KG, Menter A. Ochronosislike pigmentation from hydroquinone bleaching creams in American blacks. Arch Dermatol. 1985 Jan. 121(1):105-8. [Medline].

  13. Zawar VP, Mhaskar ST. Exogenous ochronosis following hydroquinone for melasma. J Cosmet Dermatol. 2004 Dec. 3(4):234-6. [Medline].

  14. Balaban B, Taskaynatan M, Yasar E, Tan K, Kalyon T. Ochronotic spondyloarthropathy: spinal involvement resembling ankylosing spondylitis. Clin Rheumatol. 2006 Jul. 25(4):598-601. [Medline].

  15. Koçyigit H, Gürgan A, Terzioglu R, Gürgan U. Clinical, radiographic and echocardiographic findings in a patient with ochronosis. Clin Rheumatol. 1998. 17(5):403-6. [Medline].

  16. Perrone A, Impara L, Bruni A, Primicerio P, Marini M. Radiographic and MRI findings in ochronosis. Radiol Med. 2005 Oct. 110(4):349-58. [Medline].

  17. Cortes Hernandez J, Ruiz-Oliva Ruiz F, Alonso Colmenares JI, Alvarez Ruiz S, Caton Santaren B, Alcorta Armentia MP. [Ochronotic arthropathy: the value of bone scintigraphy in alkaptonuria]. Rev Esp Med Nucl. 2004 May-Jun. 23(3):189-92. [Medline].

  18. Bhangle S, Panush RS, Berman E, Schumacher HR. Clinical images: Synovial fluid clues to ochronosis. Arthitis & Rheumatism. Feb 2012. 64:473-473. [Medline].

  19. Charlin R, Barcaui CB, Kac BK, Soares DB, Rabello-Fonseca R, Azulay-Abulafia L. Hydroquinone-induced exogenous ochronosis: a report of four cases and usefulness of dermoscopy. Int J Dermatol. 2008 Jan. 47(1):19-23. [Medline].

  20. Mishra SN, Dhurdat RS, Deshpande DJ, Nayak CS. Diagnostic utility of dermatoscopy in hydroquinone induced ochronosis. International Journal of Dermatology. April, 2013. 52:413-417. [Medline].

  21. Gonul M, Cakmak SK, Kilic A, Gul U, Heper AO. Pigmented coalescing papules on the dorsa of the hands: pigmented colloid milium associated with exogenous ochronosis. J Dermatol. 2006 Apr. 33(4):287-90. [Medline].

  22. Turgay E, Canat D, Gurel MS, Yuksel T, Baran MF, Demirkesen C. Endogenous ochronosis. Clin Exp Dermatol. 2009 Dec. 34(8):e865-8. [Medline].

  23. Suwannarat P, O'Brien K, Perry MB, Sebring N, Bernardini I, Kaiser-Kupfer MI, et al. Use of nitisinone in patients with alkaptonuria. Metabolism. 2005 Jun. 54(6):719-28. [Medline].

  24. Diven DG, Smith EB, Pupo RA, Lee M. Hydroquinone-induced localized exogenous ochronosis treated with dermabrasion and CO2 laser. J Dermatol Surg Oncol. 1990 Nov. 16(11):1018-22. [Medline].

  25. Lang PG Jr. Probable coexisting exogenous ochronosis and mercurial pigmentation managed by dermabrasion. J Am Acad Dermatol. 1988 Nov. 19(5 Pt 2):942-6. [Medline].

  26. Bellew SG, Alster TS. Treatment of exogenous ochronosis with a Q-switched alexandrite (755 nm) laser. Dermatol Surg. 2004 Apr. 30(4 Pt 1):555-8. [Medline].

  27. Introne WJ, Perry MB, Troendle J, Tsilou E, Kayser MA, Suwannarat P, et al. A 3-year randomized therapeutic trial of nitisinone in alkaptonuria. Molecular Genetics and Metabolism. 2011. 103:307-314. [Medline].

  28. Braconi D, Laschi M, Amato L, Bernardini G, Millucci L, Marcolongo R, et al. Evaluation of anti-oxidant treatments in an in vitro model of alkaptonuric ochronosis. Rheumatology. 2010. 49:1975-1983. [Medline].

  29. Faria B, Vidinha J. Impact of chronic kidney disease on the natural history of alkaptonuria. Nephrology Dialysis Transplantation Plus. August 2012. 5:352-355.

 
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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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