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Ochronosis

Last updated Dec. 11, 2018

Approved by: Maulik P. Purohit MD, MPH

DoveMed.com

Microscopic pathology image showing Ochronosis.


What are the other Names for this Condition? (Also known as/Synonyms)

  • Alkaptonuric Ochronosis
  • Endogenous Ochronosis
  • Exogenous Ochronosis

What is Ochronosis? (Definition/Background Information)

  • Ochronosis is a rare skin condition marked by blue or black discoloration. Individuals, who use skin-lightening agents containing hydroquinone (excessively) are at the highest risk for developing the condition
  • Ochronosis may be exogenous or endogenous, meaning that it can develop from external or internal factors
    • Exogenous Ochronosis: It is most commonly caused by the prolonged usage of topical skin agents that contain hydroquinone. Hydroquinone is used to lighten dark patches of skin
    • Endogenous Ochronosis: It commonly develops in association with alkaptonuria, a rare genetic disorder characterized by urine that becomes black, when left standing over time
  • The most common symptom of Ochronosis is dark blue-black or grey-blue patches of skin in the affected area. Although, the condition most commonly affects the skin, the cartilage of the ears and sclera (white structure) of eyes can also get affected
  • Ochronosis is mainly diagnosed by examination of skin biopsies and a dermoscopy, which is an examination of the skin using a skin surface microscope
  • Complications of Ochronosis, especially in endogenous cases, can include prolonged blue-black color of the skin and sore joints, due to a buildup of pigment that get deposited in bones and cartilage
  • Treatment methods for this skin condition include preventive measures, stopping the usage of skin-lightening agents containing hydroquinone, sunscreen application, and treatment for alkaptonuria in endogenous cases
  • The prognosis of Ochronosis is generally good and the symptoms are known to subside with proper treatment. However, if it is associated with alkaptonuria, Ochronosis is likely to develop into a lifelong condition with no cure

Who gets Ochronosis? (Age and Sex Distribution)

  • Ochronosis is a rare skin condition reported worldwide. It is known to affected individuals of all ages and both genders
  • The disorder occurs without racial or ethnic bias
  • However, the condition is more common in individuals with dark skin, because of a higher usage of skin-lightening agents/creams

What are the Risk Factors for Ochronosis? (Predisposing Factors)

Some risk factors for developing Ochronosis include:

  • Prolonged or excessive use of skin-lightening agents that contain hydroquinone in concentrations of 2% or higher. The risk also includes an application of such compounds over a large area of the body or in large quantities
  • Prolonged sun-exposure: Individuals with outdoor occupations are especially at risk, due to increased sun-exposure
  • Having a pre-existing condition called alkaptonuria (an uncommon genetic disorder)
  • Presence of melasma, a skin condition in which brown or dark patches appear most commonly on facial skin, for which hydroquinone-based treatments are prescribed

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Ochronosis? (Etiology)

Ochronosis can either be caused by internal (endogenous) factors or external (exogenous) factors.

  • Endogenous Ochronosis is caused by a genetic disorder called alkaptonuria
    • Mutations in the HDG gene cause Alkaptonuric Ochronosis
    • The HDG gene codes for the enzyme homogentisate 1,2-dioxygenase (HDG)
    • Mutation(s) in this gene renders the enzyme HDG inactive, resulting in the accumulation of homogentisic acid (HGA) in liver
    • Accumulated HGA gets into blood and is excreted in urine. The HGA is oxidized by oxygen in air and turns into benzoquinone acetate (BQA)
    • BQA forms dark pigments that can accumulate in connective tissues, resulting in Ochronosis
    • This condition is inherited in an autosomal recessive manner, in which an individual must possess both copies of a causative gene in the defective form in all his/her cells for the condition to manifest itself. An affected individual typically inherits one copy of the defective gene from each unaffected parent
  • Exogenous Ochronosis is caused by prolonged usage of topical agents that contain hydroquinone, though substances like phenol and resorcinol may also contribute to it
    • These topical agents can inhibit HGA oxidase, resulting in the accumulation of HGA deep in the skin
    • HGA can then polymerize and form pigment deposits resulting in Ochronosis

What are the Signs and Symptoms of Ochronosis?

The signs and symptoms of Ochronosis include:

  • Grey-blue or blue-black patches of skin, typically in the cheeks, temple, or neck areas
  • Macules (a flat discolored area of skin less than 1 centimeter) with dark caviar-like papules (that are small raised bumps in the skin)
  • Shiny and inelastic appearance of affected skin
  • The skin lesions may develop over 6 months to 3 years, or it may take longer
  • HGA in urine in endogenous cases, result in blackish-brown urine after a few hours of contact with air
  • Bluish-black discoloration of ear cartilage and sclera of the eyes in endogenous cases
  • Arthritis, mainly affecting the shoulders, knees, hip joints, or spine in endogenous cases

How is Ochronosis Diagnosed?

The diagnosis of Ochronosis is made through the following tests and exams:

  • A complete physical examination and review of one’s personal and family medical history 
  • Assessment of symptoms
  • Analysis of a skin biopsy of the affected areas: The skin is analyzed under a microscope for the presence of yellow-brown banana-shaped deposits in the deep layers of the skin
  • Dermoscopy: In this technique, a specialized microscope that can be used on skin without surgically removing tissue is used. It allows for the viewing of specific patterns unique to Ochronosis
  • Use of reflectance confocal microscopy (RCM): This is a specialized type of dermoscopy that allows for the non-invasive viewing of deeper layers of the skin, that is not possible with other methods
  • Blood and urine tests to diagnose underlying alkaptonuria

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Ochronosis?

Complications of Ochronosis are determined by whether an individual is having the endogenous or exogenous type of the disorder. Some possible complications may include:

  • Prolonged presence of bluish-black patches of skin (with both Exogenous or Endogenous Ochronosis)
  • Prolonged arthritis (endogenous)
  • Cardiovascular or renal complications resulting from the build-up of pigment in tissues, which may be life-threatening (endogenous)
  • Complications of underlying alkaptonuria

How is Ochronosis Treated?

The treatment for Ochronosis is difficult. The effectiveness of treatment has been shown as being inconsistent with little to varying degrees of success rate. The treatment options may include:

  • Preventive measures including the use of alternative measures for skin-lightening:
    • The best treatment option for Ochronosis is limiting the usage of skin-lightening agents, especially those agents with a high concentration of hydroquinone
    • Use of sun protection, such as sunscreen, hats, sun-goggles, and protective clothing, can limit damage to the skin from sunlight
    • Use of low-potency creams, such as topical retinoid acid, glycolic acid, and corticosteroids, to improve pigmentation
    • Using high doses of vitamin E and C - both vitamins act as de-pigmentating agents
    • Use of antioxidants that work well with vitamin E and C to provide protection from light
    • Chemical peeling of the skin using glycolic acid or tricarboxylic acid
  • Dermabrasion therapy: CO2 laser resurfacing of the skin and Q-switched laser treatments are both methods of dermabrasion therapy used to treat Ochronosis
  • Cryotherapy, where freezing temperatures are used to treat the skin condition
  • Treatment to prevent complications of Alkaptonuric Ochronosis: Antalgics (pain-reducers), anti-inflammatory medications, and surgery are commonly used to treat arthritic symptoms and valvular heart disease in those with Alkaptonuric Ochronosis

How can Ochronosis be Prevented?

Some methods for prevention of Exogenous Ochronosis include:

  • Avoiding excessive or long-term usage of skin-lightening agents that contain concentrations of hydroquinone higher than 2% (recommendations to use concentrations lower than 1%)
  • Avoiding excessive sun exposure to limit damage to the skin

Currently, there are no specific methods or guidelines to prevent Alkaptonuric Ochronosis, since it is a genetic condition.

  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks before planning for a child
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as alkaptonuria
  • Regular medical screening at periodic intervals with tests, scans, and physical examinations are recommended

What is the Prognosis of Ochronosis? (Outcomes/Resolutions)

The prognosis of Ochronosis may be positive or negative, depending on whether it is endogenous or exogenous and the treatment methods used. Some possible outcomes of Ochronosis include:

  • Improvement of symptoms, including skin pigment following suitable treatment
  • The presence of continued symptoms even after proper treatment
  • Continued Ochronosis and associated symptoms through lack of proper treatment, or through association with alkaptonuria, which is a life-long condition having no cure
  • Life-threatening cardiovascular or renal complications associated with Alkaptonuric Ochronosis may develop in some individuals

Additional and Relevant Useful Information for Ochronosis:

  • Alcoholic skin-lightening agents containing hydroquinone have shown to be more likely to cause Ochronosis than other cream types
  • Ochronosis has been confused for melasma, which paradoxically is treated with the use of topical skin agents containing hydroquinone, to lighten the pigmentation of the skin. This can cause Ochronosis to worsen
  • Ochronosis was thought to only affect dark-skinned individuals, although cases reported in fair-skinned people are becoming more common

What are some Useful Resources for Additional Information?


References and Information Sources used for the Article:


Helpful Peer-Reviewed Medical Articles:


Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: July 24, 2017
Last updated: Dec. 11, 2018