Medical Care

Ranganath et al have shown that nitisinone 2 mg daily and 10 mg daily are beneficial in patients with alkaptonuria, with 10 mg displaying a greater decrease in HGA. The authors note that a diet lower in protein would likely improve safety with the higher dose. Nitisinone 10 mg was approved by the European Medicines Agency for adults with alkaptonuria in 2020.^[8] Nitisinone is approved in the United States for the treatment of children with tyrosinemia type I. It acts by inhibiting the enzyme 4-hydroxyphenyl pyruvic acid and therefore can decrease formation of HGA.^[9]

Vitamin E and N-acetyl cysteine have been examined as novel potential therapies to prevent damage to articular cartilage.^[4]Ochronotic arthropathy is treated with physiotherapy, analgesia, rest, and prosthetic joint replacement when necessary.

Exogenous ochronosis caused by topical hydroquinone use has been treated successfully with picosecond laser.^[41]

Surgical Care

With exogenous cutaneous ochronosis induced by topical hydroquinones, carbon dioxide lasers and dermabrasion have been reported to be helpful.^{[5, 6]}Reports have described effective therapy with the Q-switched alexandrite 755-nm laser.^[7]

Arthroscopy has been found to be effective in alleviating joint pain and improving mobility in cases of ochronotic arthropathy.^[4]Knee, hip, shoulder, and other joint replacements may be needed if ochronotic arthropathy progresses substantially. Surgical intervention for prostate and renal stones may also be necessary. Aortic valve replacement is indicated in the case of aortic calcification and stenosis.^[42]

Surgical replacement of cardiac valves may be necessary in cases of ochronosis. Selvakumar et al relate the case of a 72-year-old man with ochronosis and aortic stenosis necessitating aortic valve replacement with a bioprosthetic valve. The authors assert that the stenosis was not secondary to typical, idiopathic calcification but rather to calcification resulting from an inflammation response to the pigments.^[43] Aortic valve replacement in another onchronosis case was performed using a mechanical bileaflet valve.^[44]

Consultations

Consultations with a rheumatologist for the arthropathies that develop should be considered.

An expert in medical genetics may be of assistance in screening families for this autosomal recessive metabolic disorder.

Cardiac assessments, including echocardiography to detect aortic or mitral valve calcification and stenosis, are needed upon entering the fourth decade of life.

Medication

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Media Gallery

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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Author

Paul N Skiba University of North Carolina at Chapel Hill School of Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Christopher Sayed, MD Clinical Assistant Professor of Dermatology, Clinician Educator, Director of Medical Student Education, Director of Hidradenitis Suppurativa Clinic, University of North Carolina at Chapel Hill School of Medicine

Christopher Sayed, MD is a member of the following medical societies: American Academy of Dermatology, American Society for Dermatologic Surgery, Medical Dermatology Society, North Carolina Dermatology Association, Society for Investigative Dermatology, Society for Pediatric Dermatology

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Abbvie, Inc.

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

Craig N Burkhart, MD, MSBS 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, American Medical Association, Royal Society of Medicine, Society for Investigative Dermatology, Women's Dermatologic Society

Disclosure: Nothing to disclose.

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.