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

Epidemiology⁴

It is very rare with only 100 published cases.

Aetiology

• 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 are uncertain.⁶
• The cause of lymphoedema is unknown, but it may be functional or secondary lymphatic disorder rather than a primary one.⁷

Clinical features

• 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, overcurvature 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

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.^10,11
• Intestinal lymphangiectasia.¹⁰
• Nonimmune hydrops and chylothorax in a fetus and neonate whose mothers had YNS.^5,12
• Thyroid abnormalities.¹
• Immunological abnormalities, e.g. immunoglobulin A (IgA) deficiency.¹
• Thoracic surgery.¹³

Assessment and diagnosis^1,6

• 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

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 sulfoxide); both ingredients seemed helpful.¹⁴
• Oral vitamin E.¹⁵
• Oil applied to the nails (in this case, topical vitamin E was not beneficial).¹⁶
• Itraconazole pulse therapy.¹⁵
• Oral zinc supplementation.¹⁷

For lymphoedema

Oral zinc supplementation.¹⁷

For pleural effusions⁸

• 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.¹⁸
• Surgical treatment may be required:
  • Pleurodesis^19,20 or pleurectomy.
  • Pleuroperitoneal or pleurovenous shunt.

There are potential complications of surgical treatment: (see Complications, 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.¹⁸
• Rhinosinusitis: conventional treatments were generally unhelpful in one review, but functional endoscopic sinus surgery seemed more useful.⁹

Complications⁸

• Massive pleural effusions can be life-threatening.^4,20
• 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.²⁰
• Repeated loss of chyle from drainage of the pleural effusions can lead to malnourishment.
• Lymphoedema can affect quality of life.

Prognosis

There is little mention of prognosis in the literature. However, a number of case reports describe patients aged in their sixties and seventies.^1,4,8,20 The most problematic complication seems to be large, recurrent pleural effusions.

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

Document references

1. Nakielna EM, Wilson J, Ballon HS; Yellow-nail syndrome: report of three cases. Can Med Assoc J. 1976 Jul 3;115(1):46-8. [abstract]
2. Hoque SR, Mansour S, Mortimer PS; Yellow nail syndrome: not a genetic disorder? Eleven new cases and a review of the literature. Br J Dermatol. 2007 Jun;156(6):1230-4. Epub 2007 Apr 25. [abstract]
3. Samman PD, White WF; The "Yellow nail" syndrome. Br J Dermatol. 1964 Apr;76:153-7.
4. Razi E; Familial yellow nail syndrome. Dermatology Online Journal 2006, 12 (2):15.
5. Yellow Nail Syndrome, Online Mendelian Inheritance in Man (OMIM)
6. Simon RW, Bundi B; Yellow nails, chronic cough, and edema. Am J Med. 2010 Feb;123(2):125-6.
7. Bull RH, Fenton DA, Mortimer PS; Lymphatic function in the yellow nail syndrome. Br J Dermatol. 1996 Feb;134(2):307-12. [abstract]
8. Tanaka E, Matsumoto K, Shindo T, et al; Implantation of a pleurovenous shunt for massive chylothorax in a patient with yellow nail syndrome. Thorax. 2005 Mar;60(3):254-5. [abstract]
9. Varney VA, Cumberworth V, Sudderick R, et al; Rhinitis, sinusitis and the yellow nail syndrome: a review of symptoms and response to treatment in 17 patients. Clin Otolaryngol Allied Sci. 1994 Jun;19(3):237-40. [abstract]
10. Duhra PM, Quigley EM, Marsh MN; Chylous ascites, intestinal lymphangiectasia and the 'yellow-nail' syndrome. Gut. 1985 Nov;26(11):1266-9. [abstract]
11. Tan WC; Dietary treatment of chylous ascites in yellow nail syndrome. Gut. 1989 Nov;30(11):1622-3. [abstract]
12. Govaert P, Leroy JG, Pauwels R, et al; Perinatal manifestations of maternal yellow nail syndrome. Pediatrics. 1992 Jun;89(6 Pt 1):1016-8. [abstract]
13. Banta DP, Dandamudi N, Parekh HJ, et al; Yellow nail syndrome following thoracic surgery: a new association? J Postgrad Med. 2009 Oct-Dec;55(4):270-1. [abstract]
14. Williams HC, Buffham R, du Vivier A; Successful use of topical vitamin E solution in the treatment of nail changes in yellow nail syndrome. Arch Dermatol. 1991 Jul;127(7):1023-8. [abstract]
15. Luyten C, Andre J, Walraevens C, et al; Yellow nail syndrome and onychomycosis. Experience with itraconazole pulse therapy combined with vitamin E. Dermatology. 1996;192(4):406-8. [abstract]
16. Lambert EM, Dziura J, Kauls L, et al; Yellow nail syndrome in three siblings: a randomized double-blind trial of topical vitamin E. Pediatr Dermatol. 2006 Jul-Aug;23(4):390-5. [abstract]
17. Arroyo JF, Cohen ML; Improvement of yellow nail syndrome with oral zinc supplementation. Clin Exp Dermatol. 1993 Jan;18(1):62-4. [abstract]
18. Makrilakis K, Pavlatos S, Giannikopoulos G, et al; Successful octreotide treatment of chylous pleural effusion and lymphedema in the yellow nail syndrome. Ann Intern Med. 2004 Aug 3;141(3):246-7.
19. Jiva TM, Poe RH, Kallay MC; Pleural effusion in yellow nail syndrome: chemical pleurodesis and its outcome. Respiration. 1994;61(5):300-2. [abstract]
20. Yamagishi T, Hatanaka N, Kamemura H, et al; Idiopathic yellow nail syndrome successfully treated with OK-432. Intern Med. 2007;46(14):1127-30. Epub 2007 Jul 17. [abstract]

Internet and further reading

• Gregoriou S, Argyriou G, Larios G, et al; Nail disorders and systemic disease: what the nails tell us. J Fam Pract. 2008 Aug;57(8):509-14.

Acknowledgements