Yellow Nail syndrome

Yellow Nail syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Yellow Nail syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • YNS
  • lymphedema with yellow nails

Disorder Subdivisions

  • None

General Discussion

Yellow nail syndrome is an extremely rare disorder characterized by malformations affecting the fingernails and toenails, abnormalities affecting the lungs and the airways (respiratory tract), and swelling or puffiness in different parts of the body because of the accumulation of protein-rich fluid (lymph) in the soft layers of tissue under the skin (lymphedema). Yellow nail syndrome usually affects older adults. The exact cause of yellow nail syndrome is not known. Occasionally, yellow nail syndrome has been reported to run in families suggesting that genetic factors may play a role in the development of the disorder in these cases.

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.



Yellow nail syndrome is usually 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.

Causes

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.

Affected Populations

Yellow nail syndrome affects males and females in equal numbers. More than 100 cases have been reported in the medical literature. Yellow nail syndrome usually occurs in older adults with most cases occurring in individuals over 50 years of age. Although uncommon, yellow nail syndrome can occur in children.



Yellow nail syndrome was first described in the medical literature in 1964.

Standard Therapies

Diagnosis

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.



Treatment

The treatment of yellow nail syndrome is geared toward the symptoms present in each individual. Treatment may include antibiotic therapy for repeated respiratory infections. The yellowed, malformed nails may improve without therapy. In some cases, the changes may be permanent. Vitamin E has been used to treat nail changes. Corticosteroids have also been used to treat individuals with yellow nail syndrome. Surgical management of respiratory problems such as pleural effusions has been used in some cases.



Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com



The University of Pittsburgh is conducting a Lymphedema Family Study to identify genes responsible for primary (or inherited) lymphedema. For more information contact:



http://www.hgen.pitt.edu/projects/lymph/index.php



Kara Levine, M.S.

Lymphedema Family Study

Department of Human Genetics

University of Pittsburgh

A300 Crabtree Hall, GSPH

Pittsburgh, PA 15261

Phone: (412) 624-4659 or (800) 263-2152

Email: genetics@pitt.edu

(Please be sure to include the word "LYMPHEDEMA" in your subject line)

References

JOURNAL ARTICLES

Maldonado F, Tazelaar HD, Wang CW, Ryu JH. Yellow nail syndrome: analysis of 41 consecutive patients. Chest. 2008;[Epub ahead of print].



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;56:1230-1234.



Lambert EM, Dziura J, Kauls L, Mercurio M, Antaya RJ. Yellow nail syndrome in three siblings: a randomized double-blind trial of topical vitamin E. Pediatr Dermatol. 2006;23:390-295.



Razi E. Familial yellow nail syndrome. Dermatol Online J. 2006;12:15.



Berry FB, Tamimi Y, Carle MV, Lehmann OJ, Walter MA. The establishment of a predictive mutational model of the forkhead domain through the analyses of FOXC2 missense mutations identified in patients with hereditary lymphedema with distichiasis. Hum Mol Genet. 2005;14:2619-27.



Lehuede G, Toussirot E, Despaux J, Michel F, Wendling D. Yellow nail syndrome associated with thiol compound therapy for rheumatoid arthritis. Two case reports. Joint Bone Spine. 2002;69:406-408.



D'Alessandro A, Muzi G, Monaco A, Filiberto S, Barboni A, Abritti G. Yellow nail syndrome: does protein leakage play a role? Eur Respir J. 2001;17:149-152.

Resources

National Lymphedema Network

116 New Montgomery Street

Suite 235

San Francisco, CA 94105

Tel: (415)908-3681

Fax: (415)908-3813

Tel: (800)541-3259

Email: nln@lymphnet.org

Internet: http://www.lymphnet.org



American Lung Association

1301 Pennsylvania Ave NW

Suite 800

Washington, DC 20004

USA

Tel: (202)785-3355

Fax: (202)452-1805

Tel: (800)586-4872

Email: info@lungusa.org

Internet: http://www.lungusa.org



NIH/National Heart, Lung and Blood Institute

P.O. Box 30105

Bethesda, MD 20892-0105

Tel: (301)592-8573

Fax: (301)251-1223

Email: nhlbiinfo@rover.nhlbi.nih.gov

Internet: http://www.nhlbi.nih.gov/



Lymphovenous Canada

8 Silver Ave

Toronto

Ontario, M6R 1X8

Canada

Tel: 4165332428

Email: info@lymphovenous-canada.ca

Internet: http://www.lymphovenous-canada.ca



Lymphatic Research Foundation

40 Garvies Point Road

Glen Cove, NY 11542

USA

Tel: (516)625-9675

Fax: (516)625-9410

Email: lrf@lymphaticresearch.org

Internet: http://www.lymphaticresearch.org



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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