Yellow nail syndrome

What is yellow nail syndrome?¹

Yellow nail syndrome is a very rare disorder of unknown aetiology that almost always occurs after 50 years of age but a juvenile or familial form has also been reported. Yellow nail syndrome is diagnosed based on a triad associating:

• Yellow nail discoloration.

• Pulmonary manifestations (chronic cough, bronchiectasis, pleural effusion).

• Lower limb lymphoedema.

Chronic sinusitis is frequently associated with the triad.

How common is yellow nail syndrome? (Epidemiology)

It is very rare with only around 150 published cases.² Men and women are equally affected.^{2 3}

Causes of yellow nail syndrome (aetiology)^{2 4}

• Both familial and sporadic cases have been reported.

• YNS has been classified as a dominantly inherited lymphoedema with variable expression. However, this classification and aetiology have been disputed, suggesting it may not be a genetic disease.^{5 6}

• The cause and underlying pathogenesis of the nail changes are unknown.

• The cause of lymphoedema is unknown, but the lymphatic abnormality may be congenital or acquired, or related to associated conditions. It may be caused by structural or functional abnormality.

Clinical features

• It usually presents after 50 years of age.

• The different clinical features of the syndrome may occur at wide intervals. Patients may not present with the classical triad of symptoms.

Nail features⁴

• Typically, the nails are slow-growing with a yellowish discoloration. They may appear to have stopped growing. They appear thicker.

• Usually nails remain smooth, but there may be ridging, overcurvature or loss of cuticles

• All nails may be affected.

• Onycholysis may affect one or more nails.

Lymphoedema⁴

• Swelling occurs in around 80% and most often affects the legs.

• Hands, face and genitals may be affected.

• It is non-pitting.

• Lymphoedema typically occurs after the nail changes, often after an interval of some months.

Respiratory disorders³

Various respiratory conditions may occur:

• Pleural effusions most commonly (usually an exudate), which may be recurrent or massive:
  

  • Idiopathic.

  • Chylothorax.

  • Secondary to infection.

• Bronchiectasis.

• Chronic sinusitis.

• Bronchial hyper-responsiveness.

• Recurrent pneumonia.

Associated clinical features

The following have also been reported; note that these are case reports only, so the link to YNS is uncertain:

• Chylous ascites.

• Intestinal lymphangiectasia.

• Non-immune hydrops and chylothorax in a fetus and neonate whose mothers had YNS.

• Thyroid abnormalities.

• Malignancies.

• Immunological abnormalities - eg, immunoglobulin A (IgA) deficiency.

• A number of other associations have been reported, but all are likely to be spurious.^{2 3}

Assessment and diagnosis of yellow nail syndrome^{2 7}

• The diagnosis is made clinically, once other causes have been excluded.

• Be aware that the different clinical features of the syndrome may occur at wide intervals.

• The absence of nail changes does not exclude the diagnosis, if other causes of pleural effusions and lymphoedema have been excluded.

Management of yellow nail syndrome^{1 8}

There is no specific treatment for YNS. Standard treatments can be used for lymphoedema, pleural effusions and bronchiectasis. In addition, the following treatments have been reported as helpful in individual cases:

For nails^{4 9}

• Nail changes may resolve spontaneously without treatment.

• Topical vitamin E (in dimethyl sulfoxide); both ingredients seemed helpful.

• Oral vitamin E supplementation.

• Oil applied to the nails (in this case, topical vitamin E was not beneficial).

• Itraconazole pulse therapy.

• Oral zinc supplementation.

For lymphoedema

Oral zinc supplementation.

For pleural effusions¹⁰

• Medical treatment:
  

  • Diuretics and low-fat diet are possible treatments, but may be inadequate. (A low-fat diet with added medium-chain triglycerides reduces the load on the lymphatics, because medium-chain triglycerides are absorbed into the portal venous system, whereas long-chain fatty acids are absorbed into the intestinal lymphatics.)

  • Octreotide, a somatostatin analogue, has been used successfully to treat chylous pleural effusion.¹¹

• Surgical treatment may be required:
  

  • Pleurodesis or pleurectomy.

  • Pleuroperitoneal or pleurovenous shunt.

Complications of yellow nail syndrome¹⁰

• Massive pleural effusions can be life-threatening.^{12 13}

• Surgical treatment of pleural effusions may have complications:
  

  • A pleuroperitoneal shunt led to severe oedema and abdominal distention in one reported case.

  • Pleurodesis can lead to hypoventilation.¹³

• Repeated loss of chyle from drainage of the pleural effusions can lead to malnourishment.

• Lymphoedema can affect quality of life.

Prognosis³

• Nail changes may resolve in up to half of cases.

• Respiratory changes are usually manageable with medical and surgical regimens. Progressive respiratory insufficiency is uncommon.

• The most problematic manifestation seems to be large, recurrent pleural effusions.