Yellow nail syndrome is a rare disorder of the nail, which is usually accompanied by lymphoedema (swelling of parts of the body caused by blockage or damage to the drainage of the lymphatic system). It may also be associated with recurrent pleural effusions (fluid collection in space surrounding the lungs) and less commonly bronchiectasis (chronic, abnormal dilation of the bronchi in the lungs), chronic bronchitis and sinus infections.
Yellow nail syndrome, also known as “primary lymphedema associated with yellow nails and pleural effusion”, is a very rare medical syndrome that includes pleural effusions, lymphedema (due to under development of the lymphatic vessels) and yellow dystrophic nails. Approximately 40% will also have bronchiectasis. It is also associated with chronic sinusitis and persistent coughing. It usually affects adults.
NORD gratefully acknowledges Fabien Maldonado, MD, Assistant Professor of Medicine, Consultant, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota, for assistance in the preparation of this report.
Yellow nail syndrome (YNS; OMIM 153300, ORPHA662) is a very rare disorder that almost always occurs after 50 years of age but a juvenile or familial form has also been observed. YNS is diagnosed based on a triad associating yellow nail discoloration, pulmonary manifestations (chronic cough, bronchiectasia, pleural effusion) and lower limb lymphedema.
Chronic sinusitis is frequently associated with the triad. YNS etiology remains unknown but a role of lymphatic impairment is usually evoked. YNS is more frequently isolated but may be associated in rare cases with autoimmune diseases, other clinical manifestations implicating lymphatic functions or cancer and, hence, is also considered a paraneoplastic syndrome.
YNS management is symptomatic and not codified. YNS can resolve spontaneously. Oral vitamin E alone or even better when associated with triazole antifungals may achieve partial or total disappearance of nail discoloration. Pleural effusion can be treated surgically, with decortication/pleurectomy or pleurodesis.
Antibiotic prophylaxis is prescribed for bronchiectasia with chronic sputum production. Lymphedema treatment is based on low-stretch bandages and the wearing of elastic compression garments combined with skin care, exercises and, as needed, manual lymph drainage
Although its name implies it is a cosmetic issue, yellow nail syndrome is actually a complex, potentially painful disorder that affects multiple body systems. It usually appears in people over age 50.
Yellow nail syndrome is considered to be very rare, with less than 400 cases published in medical literature. It is estimated to occur in fewer than 1 in every 1 million people.
The condition has been noted worldwide in both men and women and, though unusual, it can affect children and newborns.
Signs and symptoms
The characteristic finding associated with yellow nail syndrome is the development of yellow, thickened, and excessively curved nails with almost complete stoppage of nail growth. Loss of the strip of hardened skin at the base and sides of a fingernail (cuticles) may also occur. Separation of the nails from the nail bed (onycholysis) may cause the nails to fall out.
Some individuals may develop infection of the soft tissue around edge of the nails (paronychia). Any nail (both toenails and fingernails) may be affected. Unlike the nails in similar, related disorders, the nails of individuals with yellow nail syndrome generally remain clear (translucent) and smooth as opposed to not transparent (opaque) and rough.
The nails are markedly thickened with yellow to yellow-green discoloration of the nails. They grow slowly, at a rate of 0.25 mm/week or less. The nails may have ridges and increased side-to-side curvature, reduction of the white crescent and detachment of the nail from the nailbed. The nail changes may change over time.
Most people with yellow nail syndrome (four fifths) have lymphedema; it is symmetrical and typically affects both legs. It is the first symptom of the condition in about a third. Involvement of the arms and face is more unusual, as is lymphedema of the abdomen with ascites (fluid collection in the abdominal cavity) and fluid collection around the heart.
Various lung problems can occur in people with yellow nail syndrome. Many experience cough and shortness of breath. Forty percent of cases develop pleural effusions, which are collections of fluid in the pleural cavity (the space that contains the lungs and normally only has a minimal amount of fluid in it). About half of all people with yellow nail syndrome have either recurrent chest infections or a chronic lung condition known as bronchiectasis which causes chronic production of sputum with episodes of worsening. Forty percent of people with yellow nail syndrome have chronic sinusitis.
Yellow nail syndrome has been associated with some drugs, e.g. penicillamine, bucillamine and gold sodium thiomalate.
Yellow nail syndrome is occasionally associated with the accumulation of fluid in the membranes surrounding the lungs and lining the chest cavity (pleural effusion). Pleural effusions can cause shortness of breath, chest pain and a cough.
Additional respiratory problems may occur in yellow nail syndrome such as chronic infection and inflammation of the main air passages (bronchial tubes) out of the lungs (bronchitis), destruction and widening of the small air passages out of the lung (bronchiectasis), ongoing inflammation of the membranes that line the sinus cavities (sinusitis) and/or chronic inflammation or infection of the lungs (recurrent pneumonias). Individuals with yellow nail syndrome may have a history of respiratory problems before developing characteristic nail findings.
Individuals with yellow nail syndrome often have swelling of the arms and legs due to the accumulation of a fluid known as lymph (peripheral lymphedema). The legs are especially affected in yellow nail syndrome. The onset of lymphedema may occur around puberty. Areas affected by lymphedema may feel heavy or tight. Decreased flexibility may develop in the hands, feet, wrists or ankles if lymphedema is present in the corresponding arm or leg. The skin on areas affected by lymphedema may become hardened or thickened.
Yellow nail syndrome is usually diagnosed after a thorough evaluation of a person’s symptoms. The telltale signs of this rare condition include:
- Nail changes: The fingernails or toenails may be yellow, thickened, and have a very strong curve. The nails often stop growing altogether and may separate from the nail bed and fall out.
- Pleural effusion: This is the buildup of fluid between the membranes that line the lungs and chest cavity. Pleural effusion often causes chest pain, cough, and shortness of breath.
- Chronic respiratory infections: These conditions can include sinus infections, cough, bronchitis, or pneumonia.
- Lymphedema in the arms and legs: Lymphedema is a buildup of lymph fluid, which usually moves throughout the body to help fight infection. If it becomes blocked, it can cause swelling, heaviness, tightness, and problems moving the affected limb. In yellow nail syndrome, the lymphedema usually affects one or both legs.
A diagnosis of yellow nail syndrome is typically made if the person has the telltale nail symptoms combined with lymphedema and a respiratory problem.
The cause of yellow nail syndrome remains unknown. Lymphatic impairment or reduced lymphatic drainage has been proposed, as it may explain lymphedema, pleural effusion, or nail discoloration. However, it is hard to justify as a cause for bronchiectasia and sinusitis. Additionally, lymphatic impairment is not easy to confirm.
While most cases of yellow nail syndrome occur randomly, a few cases have run in families. While this suggests that genetic factors may play a role in some cases, no known genetic factors have been identified.
The exact cause of yellow nail syndrome is not known. Most cases seem to occur randomly, for no apparent reason (sporadically). Some researchers believe that yellow nail syndrome is a sporadic, acquired condition. However, some sources in the medical literature currently classify yellow nail syndrome as a primary genetic disorder.
Some cases of yellow nail syndrome have run in families suggesting that, in these cases, genetic factors may play a role in the development of the disorder. Some researchers have speculated that yellow nail syndrome is inherited as an autosomal dominant trait, although the evidence for this remains scarce.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease.
The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.
Some reports in the medical literature have linked some cases of yellow nail syndrome to mutations of the FOXC2 gene. This gene is known to cause a similar disorder called lymphedema-distichiasis syndrome. Some researchers believe that the only primary lymphedema disorder caused by mutation of this gene is lymphedema-distichiasis syndrome and that individuals with yellow nail syndrome linked to this gene may have been misdiagnosed.
Yellow nail syndrome has occurred with greater frequency than would be expected in individuals with certain forms of cancer, immunodeficiency syndromes, nephrotic syndrome, thyroid disease, and rheumatoid arthritis. In individuals with rheumatoid arthritis and yellow nail syndrome, researchers believe certain drugs used to treat the arthritis (thiol drugs) play a role in the development of yellow nail syndrome.
Many of the symptoms of yellow nail syndrome are commonly associated with malfunction of the lymphatic system including yellow nails, lymphedema, and breathing (respiratory abnormalities). The lymphatic system is a circulatory network of vessels, ducts, and nodes that filter and distribute certain protein-rich fluid (lymph) and blood cells throughout the body.
Researchers believe that in yellow nail syndrome, lymphatic fluid collects in the soft tissues in and under the skin (subcutaneous) due to obstruction, malformation, or underdevelopment (hypoplasia) of various lymphatic vessels. Researchers have also speculated that abnormal of leakage of fluid through very tiny vessels (microvascular permeability) may also contribute to the development of lymphedema in yellow nail syndrome.
A diagnosis of yellow nail syndrome is made based upon a thorough clinical evaluation, a detailed patient history and identification of characteristic findings. The nail changes in yellow nail syndrome are distinct from the nail changes that occur in most other lymphedema syndromes.
You shouldn’t ignore a change in nail color or shape, especially if your nails turn yellow. Yellow nails can indicate a problem with your liver or kidney, diabetes mellitus, fungal infections, or psoriasis, which need to be treated by a doctor.
If you develop yellow nails along with swelling or respiratory problems, see a doctor.
A doctor may diagnose yellow nail syndrome if you exhibit primary symptoms of the condition. Your doctor may also order a pulmonary function test to measure how well your lungs work or take a sample of your nail to check for fungus.
The diagnosis is based on the combination of the symptoms. Generally, people are diagnosed with yellow nail syndrome if they have two or three of the three classical symptoms (yellow nails, lymphedema and lung problems). The nail changes are considered essential for the diagnosis, but they can be subtle.
Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional
Pulmonary function testing can show obstruction of the airways. People with pleural effusions may show evidence of restriction in lung volumes due to the fluid. Analysis of the fluid in pleural effusions generally shows high levels of protein but low levels of cholesterol and lactate dehydrogenase, but about 30% of effusions are chylous (chylothorax) in that they have the characteristics of lymph.
A lymphogram may be performed in people with lymphedema. This can show both under developed (hypoplastic) lymphatic ducts and dilated ducts. Dye may be found in the skin months after the initial test. Scintigraphy of lymph flow (lymphoscintigraphy) shows delays in drainage of lymph (sometimes asymmetrically), although this test can also be normal.
Yellow nail syndrome management aims to address each of the symptoms. Treatment for nail discoloration may include oral vitamin E and/or triazole antifungals. Pleural effusion may be treated with surgery. Antibioticprophylaxis may be prescribed for bronchiectasia with chronic mucus production. Lymphedema treatment may involve low-stretch bandages and elastic compression garments combined with skin care, exercises and manual lymph drainage as needed.
In some cases, yellow nail syndrome goes away on its own or when an underlying, associated condition is treated.
There’s no one treatment for yellow nail syndrome. Treatment addresses specific symptoms of the condition and may include:
- topical or oral vitamin E for nail discoloration
- oral zinc
- antifungal medications
- antibiotics in the case of bacterial sinusitis, lung infections, or excess mucus production
- diuretics, which remove excess fluid
- tube thoracostomy, a procedure to drain fluid from the pleural space
If yellow nail syndrome occurs with an associated disease like cancer, arthritis, or AIDS, symptoms may improve after treating the underlying disease.
To treat lymphedema-distichiasis syndrome, your doctor may recommend manual lymph drainage, which is a specialized massage technique to improve circulation and reduce puffiness. You can also reduce lymphedema at home by wearing elastic compression garments. Compression encourages better lymph flow through your lymphatic vessels.
There’s no way to prevent yellow nail syndrome, but the symptoms can be manageable with medication, fluid removal, and supplementation. As lymph drainage improves, nails may return to a normal color. One study found that nail symptom improvement may occur in 7 to 30 percent of those with yellow nail syndrome.
Because lymphedema can become a chronic condition, some people require ongoing therapy to manage swelling and fluid accumulation.
No precise data are available to determine the exact prevalence of YNS, as fewer than 400 cases have been published in the literature, with an estimated prevalence <1/1,000,000. Cases have been described in all countries worldwide. YNS most often occurs in adults over 50 years old, with no sex predominance. Pediatric forms are very rarely reported YNS may be present at birth (congenital) or develop before the age of 10 years .
A familial form of YNS has very rarely been described , affecting two siblings or a family with eight cases in four sibships over two generations . The very few reported familial cases mimic a dominant inheritance pattern, which is not supported by any genetic evidence . YNS may be associated with intellectual disability, in which case it evokes a more complex syndrome or occurs in cases of consanguinity .
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