What is ophthalmoarthropathy?
Stickler syndrome refers to a group of disorders of connective tissue. Connective tissue, which is distributed throughout the body, multiple organ systems can be affected. The specific symptoms present in Stickler syndrome often vary greatly from one individual to another. Affected individuals may not have all of the symptoms .The eyes, ears, skeleton and joints are most often affected. Affected individuals may also have distinctive facial features and palate abnormalities.
One of the first signs in Stickler syndrome is nearsightedness (myopia), in which objects close by are seen clearly but objects that are far away appear blurry. Myopia may vary from mild to severe in Stickler syndrome, but generally is not progressive (does not get worse). Myopia may be detectable shortly after birth, but the onset varies and may not develop until adolescence or even adulthood in some cases.
Stickler syndrome is characterized by the following clinical features: vitreoretinal degeneration, myopia, cataracts, retinal holes and detachments, sensorineural hearing loss, a characteristic facial appearance with mid facial flatness, small chin, long philtrum; palatal abnormalities, including cleft palate, bifid uvula or high arched palate; musculoskeletal problems including loose joints, scoliosis, chest deformities, Legg-Calve-Perthe's disease; early onset degenerative osteoarthritis (onset before age 40 years by xray); and mitral valve prolapse. An affected person does not need to have all of these features. In fact, the clinical picture is very variable even among affected people in the same family.
Four distinct forms of Stickler syndrome have been identified in the medical literature based on location of the mutated gene and inheritance pattern and at least one other form exists with an as yet unknown mutation location.
Stickler syndrome was first described in the medical literature in 1965 and 1965 by Gunnar Stickler et al., who called the disorder hereditary progressive arthro-ophthalmopathy. Stickler syndrome refers to a group of disorders of connective tissue. Connective tissue, which is the material between cells of the body that gives the tissue form and strength, is found all over the body. Connective tissue is made up of a protein known as collagen of which there are several different varieties found in the body. Stickler syndrome often affects the connective tissue of the eye, especially in the interior of the eyeball (vitreous humor), the specialized tissue that serves as a buffer or cushion for bones at joints (cartilage) and the ends of the bones that make up the joints of the body (epiphysis).
What are the symptoms for ophthalmoarthropathy?
Flat face symptom was found in the ophthalmoarthropathy condition
Widespread enlargement of the thyroid can expand the gland well beyond its typical size (left) and cause a noticeable bulge in the neck (right).
Common signs and symptoms of Graves' disease include:
- Anxiety and irritability
- A fine Tremor of the hands or fingers
- Heat Sensitivity and an increase in perspiration or warm, moist skin
- Weight loss, despite normal eating habits
- Enlargement of the thyroid gland (goiter)
- Change in menstrual cycles
- Erectile dysfunction or reduced libido
- Frequent bowel movements
- Bulging eyes (Graves' ophthalmopathy)
- Thick, red skin usually on the shins or tops of the feet (Graves' dermopathy)
- Rapid or irregular heartbeat (palpitations)
- Sleep disturbance
Graves' ophthalmopathy Graves'
Graves' ophthalmopathy signs and symptoms include bulging eyes, redness and retracting eyelids.
About 30% of people with Graves' disease show some signs and symptoms of Graves' ophthalmopathy. In Graves' ophthalmopathy, inflammation and other immune system events affect muscles and other tissues around your eyes. Signs and symptoms may include:
- Bulging eyes
- Gritty sensation in the eyes
- Pressure or pain in the eyes
- Puffy or retracted eyelids
- Reddened or inflamed eyes
- Light sensitivity
- Double vision
- Vision loss
Graves' dermopathy Graves'
Rarely, people who have Graves' disease develop a reddish thickening of the skin that resembles the texture of an orange peel (Graves' dermopathy). This results from a buildup of protein in the skin. It often occurs on the shins and on the tops of the feet.
An uncommon manifestation of Graves' disease, called Graves' dermopathy, is the reddening and thickening of the skin, most often on your shins or the tops of your feet.
What are the causes for ophthalmoarthropathy?
Graves' disease is caused by a malfunction in the body's disease-fighting immune system. It's unknown why this happens.
The immune system normally produces antibodies designed to target a specific virus, bacterium or other foreign substance. In Graves' disease — for reasons that aren't well understood — the immune system produces an antibody to one part of the cells in the hormone-producing gland in the neck (thyroid gland).
Normally, thyroid function is regulated by a hormone released by a tiny gland at the base of the brain (pituitary gland). The antibody associated with Graves' disease — thyrotropin receptor antibody (TRAb) — acts like the regulatory pituitary hormone. That means that TRAb overrides the normal regulation of the thyroid, causing an overproduction of thyroid hormones (hyperthyroidism).
Cause of Graves' ophthalmopathy
Graves' ophthalmopathy results from a buildup of certain carbohydrates in the muscles and tissues behind the eyes — the cause of which also isn't known. It appears that the same antibody that can cause thyroid dysfunction may also have an "attraction" to tissues surrounding the eyes.
Graves' ophthalmopathy often appears at the same time as hyperthyroidism or several months later. But signs and symptoms of ophthalmopathy may appear years before or after the onset of hyperthyroidism. Graves' ophthalmopathy can also occur even if there's no hyperthyroidism.
What are the treatments for ophthalmoarthropathy?
The treatment goals for Graves' disease are to stop the production of thyroid hormones and to block the effect of the hormones on the body. Some treatments include:
Radioactive iodine therapy
With this therapy, you take radioactive iodine (radioiodine) by mouth. Because the thyroid needs iodine to produce hormones, the thyroid takes the radioiodine into the thyroid cells and the radiation destroys the overactive thyroid cells over time. This causes your thyroid gland to shrink, and symptoms lessen gradually, usually over several weeks to several months.
Radioiodine therapy may increase your risk of new or worsened symptoms of Graves' ophthalmopathy. This side effect is usually mild and temporary, but the therapy may not be recommended if you already have moderate to severe eye problems.
Other side effects may include tenderness in the neck and a temporary increase in thyroid hormones. Radioiodine therapy isn't used for treating pregnant women or women who are breast-feeding.
Because this treatment causes thyroid activity to decline, you'll likely need treatment later to supply your body with normal amounts of thyroid hormones.
Anti-thyroid medications interfere with the thyroid's use of iodine to produce hormones. These prescription medications include propylthiouracil and methimazole (Tapazole).
Because the risk of liver disease is more common with propylthiouracil, methimazole is considered the first choice when doctors prescribe medication. However, propylthiouracil is the preferred anti-thyroid drug during the first trimester of pregnancy, as methimazole has a slight risk of birth defects. Pregnant women will generally go back to taking methimazole after the first trimester.
When these two drugs are used alone without other treatments, a relapse of hyperthyroidism may occur at a later time. Taking either drug for longer than a year may result in better long-term results. Anti-thyroid drugs may also be used before or after radioiodine therapy as a supplemental treatment.
Side effects of both drugs include rash, joint pain, liver failure or a decrease in disease-fighting white blood cells.
These medications don't inhibit the production of thyroid hormones, but they do block the effect of hormones on the body. They may provide fairly rapid relief of irregular heartbeats, tremors, anxiety or irritability, heat intolerance, sweating, diarrhea, and muscle weakness.
Beta blockers include:
- Propranolol (Inderal, InnoPran XL)
- Atenolol (Tenormin)
- Metoprolol (Lopressor, Toprol-XL)
- Nadolol (Corgard)
Beta blockers aren't often prescribed for people with asthma because the drugs may trigger an asthma attack. These drugs may also complicate management of diabetes.
Surgery to remove all or part of your thyroid (thyroidectomy or subtotal thyroidectomy) also is an option for the treatment of Graves' disease. After the surgery, you'll likely need treatment to supply your body with normal amounts of thyroid hormones.
Risks of this surgery include potential damage to the nerve that controls your vocal cords and the tiny glands located adjacent to your thyroid gland (parathyroid glands). Your parathyroid glands produce a hormone that controls the level of calcium in your blood. Complications are rare under the care of a surgeon experienced in thyroid surgery. You'll need to take thyroid medication for life after this surgery.
Treating Graves' ophthalmopathy
Mild symptoms of Graves' ophthalmopathy may be managed by using over-the-counter artificial tears during the day and lubricating gels at night. If your symptoms are more severe, your doctor may recommend:
- Corticosteroids. Treatment with corticosteroids, such as prednisone, may lessen swelling behind your eyeballs. Side effects may include fluid retention, weight gain, elevated blood sugar levels, increased blood pressure and mood swings.
- Teprotumumab (Tepezza). This medication may be used to treat Graves' ophthalmopathy. It's given through an IV in the arm every three weeks and is given eight times. It can cause side effects such as nausea, diarrhea, muscle spasms and elevated blood sugar levels. As this medication is new, its role in the management of Graves' opthalmopathy isn't yet defined.
- Prisms. You may have double vision either because of Graves' disease or as a side effect of surgery for Graves' disease. Though they don't work for everyone, prisms in your glasses may correct your double vision.
Orbital decompression surgery. In this surgery, your doctor removes the bone between your eye socket (orbit) and your sinuses — the air spaces next to the orbit. This gives your eyes room to move back to their original position.
This treatment is usually used if pressure on the optic nerve threatens the loss of vision. Possible complications include double vision.
- Orbital radiotherapy. This was once a common treatment for this condition, but the benefits aren't clear. It uses targeted X-rays over the course of several days to destroy some of the tissue behind your eyes. Your doctor may recommend this if your eye problems are worsening and corticosteroids alone aren't effective or well tolerated.
Graves' ophthalmopathy doesn't always improve with treatment of Graves' disease. Symptoms of Graves' ophthalmopathy may even get worse for three to six months. After that, the signs and symptoms of Graves' ophthalmopathy usually become stable for a year or so and then begin to get better, often on their own.
What are the risk factors for ophthalmoarthropathy?
Although anyone can develop Graves' disease, many factors can increase the risk of disease, including:
- Family history. Because a family history of Graves' disease is a known risk factor, there is likely a gene or genes that can make a person more susceptible to the disorder.
- Sex. Women are much more likely to develop Graves' disease than are men.
- Age. Graves' disease usually develops in people before age 40.
- Other autoimmune disorders. People with other disorders of the immune system, such as type 1 diabetes or rheumatoid arthritis, have an increased risk.
- Emotional or physical stress. Stressful life events or illness may act as a trigger for the onset of Graves' disease among people who have genes that increase their risk.
- Pregnancy. Pregnancy or recent childbirth may increase the risk of the disorder, particularly among women who have genes that increase their risk.
- Smoking. Cigarette smoking, which can affect the immune system, increases the risk of Graves' disease. Smokers who have Graves' disease are also at increased risk of developing Graves' ophthalmopathy.