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NORD is very grateful to 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 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.
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.
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.
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.
Symptoms of the following disorders can be similar to those of yellow nail syndrome. Comparisons may be useful for a differential diagnosis.
Lymphedema-distichiasis syndrome is a rare genetic multisystem disorder characterized by swelling of the legs because of fluid accumulation and the development of extra eyelashes (distichiasis). Distichiasis may range from a few extra lashes to a full set of extra eyelashes. Swelling most often affects both legs (bilateral) and usually occurs around puberty. Additional anomalies sometimes associated with this disorder include cleft palate, droopy eyelids (ptosis), abnormalities of the curved transparent outer layer of fibrous tissue covering the eyeball (cornea), cysts on the spinal cord, an abnormal sensitivity to light (photophobia), and cardiac (heart) defects. Lymphedema-distichiasis syndrome is caused by mutations of the FOXC2 gene and is inherited as an autosomal dominant trait. (For more information on this disorder, choose "lymphedema distichiasis" as your search term in the Rare Disease Database.)
Hereditary lymphedema is a genetic developmental disorder affecting the lymphatic system. It is characterized by abnormal swelling of certain parts of the body. 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. In hereditary lymphedema, lymphatic fluid collects in the soft tissues in and under the skin (subcutaneous) due to obstruction, malformation, or underdevelopment (hypoplasia) of various lymphatic vessels. There are three forms of hereditary lymphedema: congenital hereditary lymphedema or Milroy disease; lymphedema praecox or Meige disease; and lymphedema tarda. Symptoms include swelling (lymphedema) and thickening and hardening of the skin in affected areas. In most cases, hereditary lymphedema is inherited as an autosomal dominant trait. (For more information on this disorder, choose "hereditary lymphedema" as your search term in the Rare Disease Database.)
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.
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.
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
For information about clinical trials sponsored by private sources, contact:
The University of Pittsburgh is conducting a Lymphedema Family Study to identify genes responsible for primary (or inherited) lymphedema. For more information contact:
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
(Please be sure to include the word "LYMPHEDEMA" in your subject line)
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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.
Report last updated: 2012/01/03 00:00:00 GMT+0