Ochronosis

Ochronosis is a relatively rare hereditary disease that is associated with metabolic disorders in the body. A person diagnosed with ochronosis has a deficiency of the enzyme homogentisinase: this causes intra-tissue deposits of homogentisic acid. Externally, this is manifested by a change in the shade of the skin, cornea, etc.

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Epidemiology

Ochronosis is considered a genetic disease and is rarely detected. According to the latest statistics, ochronosis is diagnosed in one case out of 25 thousand.

It was found that the highest percentage of ochronosis cases is registered in the Czech Republic, Slovakia and the Dominican Republic.

Hereditary ochronosis more often affects the male population.

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Causes ochronosis

Ochronosis is a genetic enzyme deficiency that occurs in a baby in utero, provided that the baby has a mutated parental gene.

The organic substance homogentisic acid is formed after the decomposition of phenylalanine to form tyrosine and hydroxyphenylpyruvic acid.

During metabolic processes, homogentisic acid in a healthy person is gradually transformed into maleyl-acetoacetic acid, fumaryl-acetoacetic acid, as well as fumaric and acetoacetic acids. But in the presence of a mutated gene, amino acid metabolism stops at the stage of homogentisic acid formation.

In people with ochronosis, the following risk factors influence the production of the enzyme homogentisinase:

• nucleotide substitutions;
• splicing mutation, when the nucleoside phosphate G is changed to A or T;
• insertional nucleotide insertions;
• combined mutations (nucleotide insertions in combination with deletions).

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Pathogenesis

As a result of mutational changes in genes during ochronosis, homogentisic acid, which has stopped its metabolic reactions, is transformed into the pigment substance alkapton, a type of quinone polyphenol.

Alkapton begins to be excreted in large quantities through the urinary system (about 5-7 g daily). The residual amount of pigment gradually accumulates in the tissues, which explains their darkening and fragility.

Joints, cartilages, mucous tissues, ligaments, and sclera suffer more than others. Heart valves, myocardium, and vascular endothelium also change.

The accumulation of pigment in ochronosis leads to the formation of stones - deposits in the prostate and kidneys. Later, inflammatory reactions join in, primarily in the joints.

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Symptoms ochronosis

The first signs of ochronosis are detected already in the neonatal period: due to the high level of alkapton, the urine becomes very dark, even brown and dark brown.

Additional symptoms of ochronosis appear much later – after several decades, when the content of alkapton in tissues reaches its maximum. For example, damage to cartilage tissue and joints is detected after the age of 30.

General signs of ochronosis are as follows:

• The patient's skin darkens, especially on the face, neck, stomach and groin.
• The auricles acquire a bluish tint and become denser.
• In the area of the sclera, dark-colored inclusions and spots become noticeable.
• Diseases of the joints and spine appear. This can be noticed by the difficulty of movement in the joints, dull pain in the back (especially during physical exertion).
• Painful sensations occur when swallowing food or even saliva, which is the result of the deposition of alkapton in the laryngeal cartilages.
• Diseases of the vessels and vascular valves appear.
• Stones form in the kidneys and, in men, in the prostate gland.

Stages

The accumulation of pigment in the tissues of the joints during ochronosis eventually leads to the development of arthrosis and deformations. Joint pathology occurs in certain stages:

• swelling, which is a sign of reactive synovitis;
• crepitus;
• limited motor function;
• development of flexion contracture.

Most often, ochronosis affects the hip joints, shoulders, knees, as well as the pubic symphysis and sacral region.

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Forms

There are several types of ochronosis:

• Genetic ochronosis, inherited in an autosomal recessive manner. It is formed as a result of a gene mutation with a disruption in the production of the enzyme responsible for the breakdown of tyrosine and phenylalanine.
• Symptomatic ochronosis. Occurs with an acute deficiency of ascorbic acid in the body.

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Complications and consequences

Ochronosis can be complicated by the following painful conditions:

• formation of kidney stones, development of pyelonephritis - an inflammatory process of bacterial etiology, which occurs with an increase in temperature, pain in the lower back;
• stiffness of the spine and joints, up to and including complete loss of motor function;
• heart valve disease, cardiac insufficiency.

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Diagnostics ochronosis

In order to diagnose ochronosis, it is necessary to examine the patient and prescribe a number of diagnostic procedures and studies.

• Examination of the patient allows to pay attention to the main symptoms of the disease. In this case, the color of the urine has an important diagnostic value.
• Urine tests using enzyme-linked spectrophotometry and chromatography can help assess the level of homogentisic and benzoquinoacetic acid.
• Genetic tests – PCR – will help identify the defective gene.
• An X-ray of the spinal column will allow visualization of calcifications, narrowing of intervertebral spaces and vertebral sclerosis.
• Instrumental diagnostics of joints (ultrasound and X-ray) demonstrates a decrease in joint spaces, the presence of osteophytes, and changes in the structure of cartilaginous and soft tissues. Additionally, arthroscopy may be prescribed to confirm cartilaginous pigmentation in ochronosis.
• Ultrasound of the prostate and kidneys confirms or excludes the presence of deposits.
• Aortography and echocardiography will indicate the presence of pathologies of the cardiovascular system.
• Laryngoscopy will allow you to examine the shade of the laryngeal cartilages.
• A puncture with collection of synovial fluid will allow detection of alkapton.

In addition, it is important to distinguish between genetic and symptomatic ochronosis, since the symptomatic one completely disappears on its own after the cause of its occurrence is eliminated (for example, when replenishing the lack of ascorbic acid).

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Differential diagnosis

Differential diagnosis of ochronosis is also carried out with porphyria, hematuria, and melaninuria.

Treatment ochronosis

There is currently no adequate treatment regimen for ochronosis. Scientists continue to work to find a drug that can replace the missing enzyme substance in the body.

Due to the lack of specific treatment for ochronosis, the doctor can only prescribe symptomatic therapy aimed at reducing painful manifestations. For example, if ochronosis affects the joints and spine, the following medications can be used:

• Non-steroidal anti-inflammatory drugs (indomethacin, diclofenac, etc.).
• Steroid drugs with a long-lasting effect (administered intra-articularly for severe pain, but no more than 1-2 times a year).
• Medicines based on hyaluronic acid (for significant joint damage).
• Chondroprotective drugs that prevent the destruction of cartilage tissue.
• Muscle relaxants that relieve muscle tension in the spinal column.
• Antispasmodics (for damage to the urinary system).
• Vitamins – in particular, vitamin C, which participates in the processes of tyrosine breakdown and prevents the deposition of metabolic products in tissues during ochronosis. Ascorbic acid is prescribed in high doses – 500-600 mg/day.

Surgical treatment – joint replacement – is used only in cases of significant deformation, which leads to loss of motor function in ochronosis.

	Method of administration and dosage	Side effects	Special instructions
Diclofenac	For ochronosis, tablets are taken in the amount of 25-50 mg up to three times a day, after meals.	Abdominal pain, dyspepsia, headache.	The tablets can be prescribed to children from six years of age.
Chondroxide	For ochronosis, ointment or gel is applied to the affected joints up to 3 times a day.	Rarely – allergic reactions.	The drug is not used to treat mucous membranes.
Drotaverine	The tablets are taken for ochronosis, 40-80 mg three times a day, for spasms and pain.	Dizziness, dyspepsia, allergy.	The drug may cause a decrease in blood pressure.
Mydocalm	For ochronosis, tablets are taken at 50-150 mg up to three times a day, with a gradual increase in dosage.	Myasthenia, headache, low blood pressure, abdominal discomfort.	The drug can be used in children from 3 years of age.

Physiotherapy treatment

In case of ochronosis, which is accompanied by joint damage, magnetic therapy can help, during which local heating of not only the joint but also the nearest muscles and ligaments occurs. The procedure helps to stimulate blood circulation, eliminate swelling, increase cellular immunity, and activate the tissue restoration mechanism.

Ultrasound treatment is a procedure that directly affects the course of ochronosis, as it improves nutrition and blood supply to tissues. Ultrasound helps reduce signs of inflammation and restore cartilage tissue.

In addition to magnetic therapy and ultrasound treatment, a good effect in ochronosis can be expected from hydrogen sulfide and radon baths. Such baths enhance blood circulation, improve the quality and quantity of synovial fluid, and facilitate the work of the cardiovascular system.

Folk remedies

If a patient with ochronosis is found to have kidney and joint damage, he can be recommended to use folk remedies to relieve unpleasant symptoms. Folk remedies will not completely eliminate such a disease as ochronosis, but they can improve the patient's well-being.

• Every morning, on an empty stomach, you should drink 50 ml of fresh radish juice.
• In spring, at the height of the birch sap season, it is necessary to drink it daily without restrictions. At other times of the year, you can replace the sap with an infusion of corn silk.
• High-quality homemade vinegar for ochronosis can be taken every morning on an empty stomach, 1 teaspoon, dissolved in 200 ml of water. Duration of intake is 1 month. The remedy is not suitable for those people who have problems with the digestive organs.
• Bay leaf decoction has a beneficial effect on joints in case of ochronosis. To prepare it, take 20 g of bay leaf, place in boiling water (300 ml) and keep on low heat for several minutes, then cover with a lid and leave until cool. This medicine should be drunk before going to bed. A new fresh decoction is prepared every day.

Herbal treatment

For the adjuvant treatment of ochronosis, herbs are often used that have analgesic, anti-inflammatory, strengthening, bactericidal and virus-static properties.

• Elderberry flowers 10 g, birch leaves 40 g, willow bark 40 g are infused in 1 liter of boiling water. Drink half a glass 4 times a day before meals.
• Elderberry flowers 10 g, nettle leaves 30 g, parsley rhizome 30 g, willow bark 30 g are infused in 1 liter of boiling water. Take half a glass 4 times a day before meals.
• Birch leaves 20 g, nettle leaf 20 g, violet grass 20 g are brewed in 500 ml of boiling water. Take half a glass up to 6 times a day before meals.

During the day, with ochronosis, it is recommended to drink vitaminized tea based on currant leaves and rose hips. It is advisable to drink such a drink at least 2 times a day.

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Homeopathy

The use of homeopathic remedies for ochronosis - both monopreparations and composite homeopathic compositions - allows you to achieve a stable period of relief. An additional advantage of such treatment is the absence of side effects and addiction to medications. However, only an experienced doctor who specializes in homeopathy can prescribe such drugs.

• If you are bothered by burning and pain in your joints, Apis will help.
• If joint pain occurs only during physical activity, Bryonia is prescribed.
• For arthritis and significant metabolic disorders, Phytolyaka is used.
• For joint deformations due to arthritis, Sulfur is prescribed.
• Dulcamara helps with pain associated with weather changes.

The listed drugs are usually taken for a long time, over several months. More precise information can be obtained from the attending homeopathic physician.

Prevention

Since ochronosis is considered a genetic disease, there are no specific measures for its prevention.

The benefits of conducting medical genetic counseling at the pregnancy planning stage are currently being considered.

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Forecast

Ochronosis is considered an incurable pathology with a chronic course. The disorders that occur in the body are irreversible.

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