eMedicine Specialties > Dermatology > Metabolic Diseases

Ochronosis: Differential Diagnoses & Workup

Author: Craig G Burkhart, MD, MPH, Clinical Professor, Department of Medicine, Section of Dermatology, Medical College of Ohio at Toledo; Clinical Assistant Professor, Department of Dermatology, Ohio University School of Medicine
Coauthor(s): Craig N Burkhart, MD, MSBS, Assistant Professor, Department of Dermatology, University of North Carolina at Chapel Hill
Contributor Information and Disclosures

Updated: Dec 30, 2008

Differential Diagnoses

Argyria
Arsenical Keratosis

Workup

Laboratory Studies

  • Most laboratory testing for alkaptonuria detects the alterations in the urine. Increased urinary levels of HGA are characteristic of this metabolic disorder.
    • Elevated levels of HGA in the urine, blood, and other tissues can be determined by specific enzymatic and colorimetric tests, direct spectrophotometric methods, high-performance liquid chromatographic testing, and molecular techniques.
    • Other simple urinary studies include darkening of urine with the addition of sodium hydroxide, black reaction with FeCl3, and blackening of photographic emulsion paper with alkali added to urine.

Imaging Studies

In patients with ochronotic arthropathy, radiography and MRI help identify characteristic and diagnostic features, including articular space narrowing up to osseous ankylosis, calcifications, osteophytosis, and reactive sclerosis of the articular surfaces.9 Bone scintigraphy can be useful in evaluation, correlation with the clinical course, and follow-up of such patients.10

Procedures

Dermoscopy has proved useful in exogenous ochronosis. In addition to melasma findings, dermoscopy reveals amorphous densely pigmented structures obliterating some follicular openings.11

Histologic Findings

Skin biopsy samples with hematoxylin and eosin staining reveal yellowish brown pigmented bodies in the dermis that represent altered widened elastic fibers, as well as in macrophages, endothelial cells, apocrine glands, and epidermal basement membranes. The deposits do not lose their pigmentation after 3 days in 10% H2 O2. Furthermore, the ochronotic pigment reacts with all routine stains for melanin. Such deposits can also be seen in cartilage and elastic tissue.

Exogenous ochronosis reveals ochronotic collagen fibers leading to the formation of ochronotic colloid milium.12 The dermal cell infiltrate is variable but often granulomatous. Transfollicular elimination of these ochronotic fibers has been reported.

More on Ochronosis

Overview: Ochronosis
Differential Diagnoses & Workup: Ochronosis
Treatment & Medication: Ochronosis
Follow-up: Ochronosis
Multimedia: Ochronosis
References
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References

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

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

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

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

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

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

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

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

  10. 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. May-Jun 2004;23(3):189-92. [Medline].

  11. 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. Jan 2008;47(1):19-23. [Medline].

  12. 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. Apr 2006;33(4):287-90. [Medline].

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

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

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

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

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

  18. Fernandez-Canon JM, Granadino B, Beltran-Valero de Bernabe D, Renedo M, Fernandez-Ruiz E, Penalva MA, et al. The molecular basis of alkaptonuria. Nat Genet. Sep 1996;14(1):19-24. [Medline].

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  22. Jordaan HF, Van Niekerk DJ. Transepidermal elimination in exogenous ochronosis. A report of two cases. Am J Dermatopathol. Aug 1991;13(4):418-24. [Medline].

  23. Keller JM, Macaulay W, Nercessian OA, Jaffe IA. New developments in ochronosis: review of the literature. Rheumatol Int. Mar 2005;25(2):81-5. [Medline].

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  26. Mannoni A, Selvi E, Lorenzini S, Giorgi M, Airo P, Cammelli D, et al. Alkaptonuria, ochronosis, and ochronotic arthropathy. Semin Arthritis Rheum. Feb 2004;33(4):239-48. [Medline].

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  28. O'Brien WM. Biochemical, pathologic and clinical aspects of alkaptonuria, ochronosis and ochronotic arthropathy. Am J Med. 1963;34:813-9.

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  30. Suzuki Y, Oda K, Yoshikawa Y, Maeda Y, Suzuki T. A novel therapeutic trial of homogentisic aciduria in a murine model of alkaptonuria. J Hum Genet. 1999;44(2):79-84. [Medline].

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Further Reading

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Keywords

alkaptonuria, bluish black discoloration of tissue, exogenous ochronosis, exposure to hydroquinone, homogentisic acid oxidase, homogentisic acid, HGA

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Contributor Information and Disclosures

Author

Craig G Burkhart, MD, MPH, Clinical Professor, Department of Medicine, Section of Dermatology, Medical College of Ohio at Toledo; Clinical Assistant Professor, Department of Dermatology, Ohio University School 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.

Medical Editor

C Lisa Kauffman, MD, FACP, Professor, Chief, Division of Dermatology, Departments of Medicine and Pathology, Georgetown University Medical Center
C 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.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University 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.

Managing Editor

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

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine 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, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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