Ochronosis
Encyclopedia
Ochronosis is the syndrome caused by the accumulation of homogentisic acid in connective tissue
s. The phenomenon was first described by Rudolf Virchow
in 1865. The condition was named after the yellowish (ocher-like) discoloration of the tissue seen on microscopic examination. However, macroscopically the affected tissues appear bluish grey because of a light scattering phenomenon known as the Tyndall effect
. The condition is most often associated with alkaptonuria
but can occur from exogenous administration of phenol
complex
es like hydroquinone
.
Exogenous ochronosis is an avoidable dermatitis, that can be caused by the topical application of compounds such as hydroquinone or phenols .
It was first seen in 1912, when a patient who used phenol on a leg ulcer was found to have this condition by Beddard and Plumtre
Hydroquinone induced exogenous ochronosis was found by Findlay in 1975, who observed the condition in patients who used skin lightening creams containing the compound
There are three clinical stages of exogenous ochronosis
Skin lightening products are still prevalent in many parts of the world . Reasons for this may be due to aesthetic or social standing reasons, in areas where a lighter skin tone is considered to be a sign of wealth or beauty .
As well, skin-lightening creams containing compounds such as hydroquinone are commonly used to help with hyperpigmentation disorders such as melasma .
Hydroquinone is the compound most frequently used in skin whitening products. Due to concerns about its side affects, it was almost banned by the FDA in 2006, as there were medical issues of carcinogenicity and reports of disfiguring ochronosis . In the European Union Hydroquinone has been banned in cosmetic creams since 2000.
Long term use of creams containing this compound may lead to exogenous ochronotic lesions. The duration of the use is directly proportional to the risk of developing the condition with most cases being after years of use .
Around 10-15 million skin lightening products are sold annually, with Japan being the major buyer
The majority of the lesions will be seen on areas of the body that get the most sun.
However, some studies show that treatment may be possible with a Q-switched alexandrite (755 nm) laser
It is recommended that individuals with this disorder stop using hydroquinone containing compounds. It is important to be aware of this as dermatologists may think the symptoms a patient is exhibiting are a melasma, and prescribe a hydroquinone containing cream .
(such as homogentisic acid and hydroquinone) as plaques in the matrix of cartilage. The pigments can also be incorporated into collagen and elastin fibers. In the skin, the pigment alters the structure of the fibers causing enlargement and curling. They come to closely resemble fibers seen in biopsies of solar elastosis.
The embedded pigments also form cross-linkages with pigment depositions in adjacent fibers, stabilizing and reducing the elastic recoil of the fibers. This results in hardening of elastic structures increasing their rigidity and brittleness. Once ruptured, the exposed pigments cause a foreign body reaction and inflammation. This pigment deposition also invokes deposition of hydroxyapatite, the mineral responsible for bone calcification, further hardening the connective tissue.
The pigment can also be excreted by glandular cells in apocrine
and ceruminous sweat glands as well as breast and prostate tissue. This results in darkly pigmented sweat and breast milk. Excretion of the pigment is only found in endogenous ochronosis and should not occur from topical phenols.
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
s. The phenomenon was first described by Rudolf Virchow
Rudolf Virchow
Rudolph Carl Virchow was a German doctor, anthropologist, pathologist, prehistorian, biologist and politician, known for his advancement of public health...
in 1865. The condition was named after the yellowish (ocher-like) discoloration of the tissue seen on microscopic examination. However, macroscopically the affected tissues appear bluish grey because of a light scattering phenomenon known as the Tyndall effect
Tyndall effect
The Tyndall effect, also known as Tyndall scattering, is light scattering by particles in a colloid or particles in a fine suspension. It is named after the 19th century physicist John Tyndall. It is similar to Rayleigh scattering, in that the intensity of the scattered light depends on the fourth...
. The condition is most often associated with alkaptonuria
Alkaptonuria
Alkaptonuria is a rare inherited genetic disorder of phenylalanine and tyrosine metabolism. This is an autosomal recessive condition that is due to a defect in the enzyme homogentisate 1,2-dioxygenase , which participates in the degradation of tyrosine...
but can occur from exogenous administration of phenol
Phenol
Phenol, also known as carbolic acid, phenic acid, is an organic compound with the chemical formula C6H5OH. It is a white crystalline solid. The molecule consists of a phenyl , bonded to a hydroxyl group. It is produced on a large scale as a precursor to many materials and useful compounds...
complex
Complex (chemistry)
In chemistry, a coordination complex or metal complex, is an atom or ion , bonded to a surrounding array of molecules or anions, that are in turn known as ligands or complexing agents...
es like hydroquinone
Hydroquinone
Hydroquinone, also benzene-1,4-diol or quinol, is an aromatic organic compound that is a type of phenol, having the chemical formula C6H42. Its chemical structure, shown in the table at right, has two hydroxyl groups bonded to a benzene ring in a para position. It is a white granular solid...
.
Exogenous Ochronsis
There are two types of ochronosis: enogenous and exogenous. The endogenous variety is an autosomal recessive disease, that is caused by a the lack of homogenistic oxidase enyme .Exogenous ochronosis is an avoidable dermatitis, that can be caused by the topical application of compounds such as hydroquinone or phenols .
It was first seen in 1912, when a patient who used phenol on a leg ulcer was found to have this condition by Beddard and Plumtre
Hydroquinone induced exogenous ochronosis was found by Findlay in 1975, who observed the condition in patients who used skin lightening creams containing the compound
There are three clinical stages of exogenous ochronosis
- erythema and mild hyperpigmentation
- hypergimentation and ‘’caviar-like’’ lesions
- papulo-nodular lesions
Causes of Exogenous Ochronosis
Exogenous ochronosis can be caused from long term usage of certain ‘’skin lightening products’’, even if the hydroquinone is in amounts as small as 2% .Skin lightening products are still prevalent in many parts of the world . Reasons for this may be due to aesthetic or social standing reasons, in areas where a lighter skin tone is considered to be a sign of wealth or beauty .
As well, skin-lightening creams containing compounds such as hydroquinone are commonly used to help with hyperpigmentation disorders such as melasma .
Hydroquinone is the compound most frequently used in skin whitening products. Due to concerns about its side affects, it was almost banned by the FDA in 2006, as there were medical issues of carcinogenicity and reports of disfiguring ochronosis . In the European Union Hydroquinone has been banned in cosmetic creams since 2000.
Long term use of creams containing this compound may lead to exogenous ochronotic lesions. The duration of the use is directly proportional to the risk of developing the condition with most cases being after years of use .
Around 10-15 million skin lightening products are sold annually, with Japan being the major buyer
Symptoms of Exogenous Ochronosis
Symptoms include :- yellow-brown, banana-shaped fibers
- caviar-like papules
- brown-grey or blue-black hyperpigmentation
The majority of the lesions will be seen on areas of the body that get the most sun.
Treatment of Exogenous Ochronosis
Hydroquinone-induced exogenous ocrhonosis is an avoidable dermatosis that is exceedingly difficult to treat.However, some studies show that treatment may be possible with a Q-switched alexandrite (755 nm) laser
It is recommended that individuals with this disorder stop using hydroquinone containing compounds. It is important to be aware of this as dermatologists may think the symptoms a patient is exhibiting are a melasma, and prescribe a hydroquinone containing cream .
Pathophysiology
Ochronosis occurs because of deposition of phenolsPhenols
In organic chemistry, phenols, sometimes called phenolics, are a class of chemical compounds consisting of a hydroxyl group bonded directly to an aromatic hydrocarbon group...
(such as homogentisic acid and hydroquinone) as plaques in the matrix of cartilage. The pigments can also be incorporated into collagen and elastin fibers. In the skin, the pigment alters the structure of the fibers causing enlargement and curling. They come to closely resemble fibers seen in biopsies of solar elastosis.
The embedded pigments also form cross-linkages with pigment depositions in adjacent fibers, stabilizing and reducing the elastic recoil of the fibers. This results in hardening of elastic structures increasing their rigidity and brittleness. Once ruptured, the exposed pigments cause a foreign body reaction and inflammation. This pigment deposition also invokes deposition of hydroxyapatite, the mineral responsible for bone calcification, further hardening the connective tissue.
The pigment can also be excreted by glandular cells in apocrine
Apocrine
Apocrine is a term used to classify exocrine glands in the study of histology. Cells which are classified as apocrine bud their secretions off through the plasma membrane producing membrane-bound vesicles in the lumen. This method is also called decapitation secretion...
and ceruminous sweat glands as well as breast and prostate tissue. This results in darkly pigmented sweat and breast milk. Excretion of the pigment is only found in endogenous ochronosis and should not occur from topical phenols.
Symptoms
- Skin: The pigment is deposited throughout the skin but only becomes apparent in certain locations where the concentration is great enough to be seen clinically. This usually occurs in areas where connective tissue is thick (joints, tympanic membrane) or close to the surface of the skin (thenar and hypothenar eminences and the sides of the fingers). In exogenous ochronosis, the hyperpigmentation is localized to the area where the inciting agent is applied. Intradermal nevi can appear like blue nevi.
- Eye: The most obvious change is darkening around the palpebral fissure. The cornea can become hyperpigmented if exposed to phenol vapors.
- Cartilage: Darkening and hardening of ear cartilage is a prominent feature of ochronosis. Nasal cartilage is also frequently involved. The voice can be affected by hardening of the laryngeal cartilage. Stiffening of the ribs with decreased lung function has also been reported. The intravertebral cartilage is also more prone to herniation.
- Connective tissue: Hardening of tendons and ligaments can predispose them to rupture. Color changes in the joints can be observed clinically. ArthropathyArthropathy-Scope:Arthritis is a form of arthropathy that involves inflammation of one or more joints, while the term arthropathy may be used regardless of whether there is inflammation or not.Spondylarthropathy is any form of arthropathy of the vertebral column....
is common due to chronic inflammation and microruptures. - Heart valves: Stenosis can results from the increased rigidity of the connective tissue as well as chronic inflammation.
Treatment
Treatment is predominantly preventative. Avoidance of topical phenols and diets low in tyrosine. Replacement and repair of damaged tissue is also possible.See also
- AlkaptonuriaAlkaptonuriaAlkaptonuria is a rare inherited genetic disorder of phenylalanine and tyrosine metabolism. This is an autosomal recessive condition that is due to a defect in the enzyme homogentisate 1,2-dioxygenase , which participates in the degradation of tyrosine...
- TyrosinemiaTyrosinemiaTyrosinemia is an error of metabolism, usually inborn, in which the body cannot effectively break down the amino acid tyrosine. Symptoms include liver and kidney disturbances and mental retardation...
- PhenylketonuriaPhenylketonuriaPhenylketonuria is an autosomal recessive metabolic genetic disorder characterized by a mutation in the gene for the hepatic enzyme phenylalanine hydroxylase , rendering it nonfunctional. This enzyme is necessary to metabolize the amino acid phenylalanine to the amino acid tyrosine...
- List of cutaneous conditions