Yellow Nail Syndrome

Yellow nail syndrome (YNS) is a rare disorder, in which there is a triad of:

• Nail discolouration and nail dystrophy
• Lymphoedema
• Pleural effusions¹ (alternatively, 'chronic respiratory problems' is used by some authors in the definition²)

Other associated features have also been reported. It was first described by Samman in 1964.³

It is very rare, with around 100 published cases.

• 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.^2,5
• The cause and underlying pathogenesis of the nail changes is uncertain.⁶
• The cause of lymphoedema is unknown, but it may be functional or secondary lymphatic disorder rather than a primary one.⁷

• Age of onset varies, and has been reported from antenatal to 65 years.
• The different clinical features of the syndrome may occur at wide intervals. Patients may not present with the the classical triad of symptoms.¹

Nail features^1,4

• Typically the nails are slow-growing with a yellowish discoloration.⁵
• Various other nail changes have been described, including onycholysis, ridging, thickening, over-curvature and absence of the lunula.

Lymphoedema

The lymphoedema can be widespread, including peripheral oedema (usually lower limb), pleural effusions and ascites.⁴ Facial and laryngeal oedema have also been reported.⁵

Respiratory disorders^4,8

Various respiratory conditions may occur:

• Pleural effusions (usually an exudate), which may be recurrent or massive:
  • Idiopathic
  • Chylothorax
  • Secondary to infection
• Bronchiectasis
• Chronic sinusitis⁹
• Bronchial hyper-responsiveness
• Recurrent pneumonia¹

Other possible associated clinical features

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

• Chylous ascites^10,11
• Intestinal lymphangiectasia¹⁰
• Non-immune hydrops and chylothorax in a fetus and neonate whose mothers had yellow nail syndrome^5,12
• Thyroid abnormalities¹
• Immunological abnormalities, e.g. IgA deficiency¹
• Various other conditions have also been reported in patients with YNS^1,4

• 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.

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:
  • Topical vitamin E (in dimethyl sulphoxide); both ingredients seemed helpful.¹³
  • Oral vitamin E.¹⁴
  • Oil applied to the nails (in this case, topical vitamin E was not beneficial).¹⁵
  • Itraconazole pulse therapy.¹⁴
  • Oral zinc supplementation.¹⁶
• For lymphoedema: oral zinc supplementation.¹⁶
• For pleural effusions:⁸
  • 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).¹¹
    • Octreotide, a somatostatin analogue, has been used successfully to treat chylous pleural effusion.¹⁷
  • Surgical treatment may be required:
    • Pleurodesis^18,19 or pleurectomy.
    • Pleuroperitoneal or pleurovenous shunt.
  However, there are potential complications of surgical treatment (see below).
• Chylous ascites:
  • In one case, this was successfully treated by a diet low in fat, with added medium-chain triglycerides (as explained above).¹¹
  • Octreotide has been reported as beneficial.¹⁷
• Rhinosinusitis: In one review, conventional treatments were generally unhelpful, but functional endoscopic sinus surgery seemed more useful.⁹

• Massive pleural effusions can be life-threatening.^4,19
• Surgical treatment of pleural effusions may have complications:
  • In one case, a pleuroperitoneal shunt led to severe oedema and abdominal distention.
  • Pleurodesis can lead to hypoventilation.¹⁹
• Repeated loss of chyle from drainage of the pleural effusions can lead to malnourishment.
• Lymphoedema can affect quality of life.

There is little mention of prognosis in the literature. However, a number of case reports describe patients in their sixties and seventies.^1,4,8,19 The most problematic complication seems to be large, recurrent pleural effusions.

Spontaneous resolution of the nail changes has been described in some patients.²