An expression of primary lymphedema associated with yellowish coloration of the finger nails and pleural effusions. This syndrome is also caused by same the FoxC2 gene that is responsible to what we think of as regular hereditary lymphedema type II or lymphedema praecox meige syndrome.
Yellow nail syndrome is a very rare disorder often associated with lymphedema of the lower extremeties or leg lymphedema. It is also associated with lung disorders. Other associated indications are rhinosinusitis, pleural effusions, bronchiectasis.
The syndrome is characterized by yellow nails that lack a cuticle, grow slowly and are loose or detached. The nails also become dystrophic with longitudinal or transverse ridging.
There is no treatment or cure specifically for the resolution of the condition. However, there is treatment and management for the underlying lymphedema and treatment for the various complications.
Keywords: Yellow nail syndrome, Empyema, Decortication, Pleural effusion, Edema, Lymphedema, Pleuritis Angiogenesis, Lymphatic vessels
Here is a collection of informational abstracts on the condition.
[Article in French]
Letheulle J, Deslée G, Guy T, Lebargy F, Jego P, Delaval P, Desrues B, Jouneau S.
Service de pneumologie, université de Rennes 1, hôpital Pontchaillou, 2, rue Henri-Le-Guilloux, 35033 Rennes cedex 9, France.
INTRODUCTION: The yellow nail syndrome is a rare disorder described for the first time in 1964. The pathophysiology remains unclear. Its definition is based on a clinical triad of yellow nails, lymphoedema and chronic respiratory disorders including pleural effusions and bronchiectasis.
CASES REPORTS: We describe a retrospective series of five patients diagnosed with the yellow nail syndrome. All the patients were male, aged from 52 to 71 years (median=56). Three patients were diagnosed with the classic triad, whereas the other two had only yellow nails and bronchiectasis. Yellow nails and chronic sinusitis were present in all five patients. We also report atypical manifestations such as a transudative pleural effusion and facial oedema. The yellow nail syndrome was associated with cancer in two cases.
CONCLUSION: More common alternative diagnoses must be excluded. The association with cancer should be explored. The treatment is only symptomatic.
[Article in Polish]
Modrzewska K, Fijołek J, Ptak J, Wiatr E.
Yellow nail syndrome (YNS) is a condition characterized by yellow-green coloration of nails, respiratory manifestations and lymphoedema. This article presents 52-year-old patient with membranous glomerulonephritis, hospitalized at the National Tuberculosis and Lung Diseases Research Institute in Warsaw, because of suspected allergic aspergillosis. Based on clinical and radiological evaluation the diagnosis of YNS was established. Treatment of renal disease did not affect the course of yellow nail syndrome. During the two-year follow-up, despite stable renal parameters we observed the progression of respiratory manifestations (bronchiectasis, pleural effusions).
Cimini C, Giunta R, Utili R, Durante-Mangoni E.
Institute of Internal Medicine, Second University of Naples Medical School, Naples, Italy.
Yellow nail syndrome is a rare cause of edema due to a disordered lymphatic drainage. We recently observed two cases of long-standing, chronic edema, whose nature could not be understood despite innumerable diagnostic procedures. The diagnosis was suspected based on an attentive clinical exam and confirmed by radionuclide lymph scan. Yellow nail syndrome has to be considered in the differential diagnosis in cases of systemic edema, as well as long standing pleural effusions, particularly in patients with bronchiectasis or sinusitis. Clues to diagnosis are the presence of dystrophic, yellowish nails, peripheral lymphedema and relapsing pleural effusions and/or ascites. Long-term control of symptoms is difficult to achieve and may benefit from the judicious use of diuretics and intravenous albumin and by topical alpha-tocopherol. Pleurodesis may be needed. Other pathologic conditions are often associated to yellow nail syndrome and should be ruled out.
Laeknabladid. 2007 Nov
Article in Icelandic
Gunnarsson O, Bjornsson E, Bjornsdottir US, Gudbjartsson T.
We describe a 77 year old man with a prior history of recurrent airway infections, who presented with a history of cough, dyspnea and increased mucous production that had lasted several months. On chest X-ray a pleural effusion was observed. Subsequent thoracocentesis demonstrated an exudate with predominant eosinophils. An infectious cause was ruled out. The pleural effusion subsequently recurred and he was admitted for pleural biopsy, which revealed chronic pleuritis. On physical examination yellow nails on fingers and toes were noted. Subsequently, after exclusion of other diseases, a diagnosis of yellow nails syndrome was established. He was treated with corticosteroids, which were tapered over 6 months. One year later the eosinophilia had subsided, however the pleural effusion remained, although on a much smaller scale. Key words: pleural effusion, recurrent respiratory tract infections, yellow nails, sinusitis. Correspondence: Eythornór Björnsson, firstname.lastname@example.org.
Intern Med. 2007
Yamagishi T, Hatanaka N, Kamemura H, Nakazawa I, Hirano Y, Kodaka N, Miura A, Kitahara A, Sawata T, Hosaka K, Sanno K.Department of Respiratory Medicine, Toho University Ohashi Medical Center, Tokyo. email@example.com
Key words: chemical pleurodesis, lymphedema, OK-432, pleural effusion, yellow nail
A 70-year-old female presented with yellow discoloration of the nail beds of all fingers and toes, as well as bilateral pleural effusions. The patient was diagnosed as having the yellow nail syndrome based on the triad of yellow nails, lymphedema, and pleural effusions. The patient's intractable bilateral pleural effusion was treated with pleurodesis using OK-432. The treatment prevented the accumulation of pleural fluid for a long period of time. Pleural effusion associated with yellow nail syndrome is thought to be difficult to treat; however, this patient's excellent clinical course suggests that pleurodesis with OK-432 could be used to treat the disease in the future.
Br J Dermatol. 2007 Jun
Hoque SR, Mansour S, Mortimer PS. Department of Dermatology, St Helier Hospital, Carshalton, Surrey, UK. Shamali.Hoque@epsom-sthelier.nhs.uk
BACKGROUND: Yellow nail syndrome (YNS) is characterized by the triad of characteristic nail changes, chronic respiratory disorders and primary lymphoedema. Over 100 cases have been published, most of which have been sporadic. Despite this, YNS is classified as a dominantly inherited lymphoedema with variable expression. There have been only a few published reports where a positive family history (FH) has been documented in cases of YNS.
OBJECTIVES: To conduct a retrospective survey investigating the genetic basis of YNS.
METHODS: The notes of 11 patients diagnosed with YNS were examined for documentation of a positive FH, and in addition a postal questionnaire was sent to these patients.
RESULTS: Only one of the 11 patients had a relevant FH. In addition, four patients had complete recovery of their nail changes.
CONCLUSIONS: This is the first retrospective study of YNS to document clear remission of nail changes. The lack of a positive FH in the majority of patients in our study, the late onset of the disease and recovery of nail changes in our patients suggest that YNS may not be primarily a genetic disease as it is currently classified.
British Journal of Dermatology
A number sign (#) is used with this entry because yellow nail syndrome, included in the classification of dominantly inherited lymphedema (see 153200), can be caused by mutation in the forkhead family transcription factor gene MFH1 (FOXC2; 602402).
Samman and White (1964) delineated the yellow nail syndrome, reporting on 13 cases. The nails are typically slow growing and excessively curved, with a yellowish discoloration. They frequently show ridging due to interrupted growth. Onycholysis can occur in one or more nails. Wells (1966) described a family with 8 cases in 4 sibships of 2 generations. In the proband, who had yellow nails, lymphedema began in the legs at the age of 51. At times edema also affected the genitalia, hands, face, and vocal cords. Lymphangiograms were interpreted as showing primary hypoplasia of lymphatics. Zerfas and Wallace (1966) described a sporadic case with onset of lymphedema at age 10. Recurrent pleural effusion occurred in some cases.
Govaert et al. (1992) reported a girl who was born at 33 weeks' gestation with nonimmune hydrops and a recurrent left chylothorax to a mother with the yellow nail syndrome. The nonimmune hydrops in this case was diagnosed on a 29-week ultrasound examination. Slee et al. (2000) reported a case of a newborn infant who, at 23 weeks' gestation, was found to have hydrops on antenatal ultrasonography; bilateral chylothorax was found at delivery. The mother had the yellow nail syndrome, with typical nail changes, and bronchiectasis. The infant had a recurrent cough, possibly preceding early onset of bronchiectasis.
Finegold et al. (2001) found a mutation in the FOXC2 gene (602402.0007) in a family with Meige lymphedema (153200), and also in a family with yellow nail syndrome. The authors observed 4 overlapped phenotypically defined lymphedema syndromes: Meige lymphedema, lymphedema-distichiasis syndrome (153400), lymphedema and ptosis (153000), and yellow nail syndrome, but not Milroy disease (153100). The authors stated that the phenotypic classification of autosomal dominant lymphedema does not appear to reflect the underlying genetic causation of these disorders.
1. Finegold, D. N.; Kimak, M. A.; Lawrence, E. C.; Levinson, K. L.; Cherniske, E. M.; Pober, B. R.; Dunlap, J. W.; Ferrell, R. E. : Truncating mutations in FOXC2 cause multiple lymphedema syndromes. Hum. Molec. Genet. 10: 1185-1189, 2001. PubMed ID : 11371511 2. Govaert, P.; Leroy, J. G.; Pauwels, R.; Vanhaesebrouck, P.; De Praeter, C.; Van Kets, H.; Goeteyn, M. : Perinatal manifestations of maternal yellow nail syndrome. Pediatrics. 89: 1016-1018, 1992. PubMed ID : 1594340 3. Samman, P. D.; White, W. F. : The 'yellow nail' syndrome. Brit. J. Derm. 76: 153-157, 1964. PubMed ID : 14140738 4. Slee, J.; Nelson, J.; Dickinson, J.; Kendall, P.; Halbert, A. : Yellow nail syndrome presenting as non-immune hydrops: second case report. Am. J. Med. Genet. 93: 1-4, 2000. PubMed ID : 10861674 5. Wells, G. C. : Yellow nail syndrome with familial primary hypoplasia of lymphatics, manifest late in life. Proc. Roy. Soc. Med. 59: 447 only, 1966. PubMed ID : 5933133 6. Zerfas, A. J.; Wallace, H. J. : Yellow nail syndrome with bilateral bronchiectasis. Proc. Roy. Soc. Med. 59: 448 only, 1966. CONTRIBUTORS George E. Tiller - updated : 10/22/2001 Victor A. McKusick - updated : 7/10/2000 CREATION DATE Victor A. McKusick : 6/2/1986
Pediatr Dermatol. 2006 Jul-Aug;23
Lambert EM, Dziura J, Kauls L, Mercurio M, Antaya RJ.
Yale University School of Medicine, New Haven, Connecticut 06520-8059, USA.
Yellow nail syndrome is an uncommon disorder characterized by dystrophic nails, lymphedema, and respiratory disease. It has rarely been reported in children and this is the first report of congenital yellow nails in siblings. The purpose of this study was to determine whether topical vitamin E applied to the nail plates and periungual skin would affect the growth rate or appearance of the fingernails in patients with congenital yellow nail syndrome. This study was the first trial of a treatment for this entity in children and the largest randomized double blind trial to date. We found that vitamin E solution had no significant effect (p = 0.84) on fingernail growth or the global appearance score (p = 1.0) when compared with placebo. The average growth rates and global assessment scores improved and onycholysis and onychomadesis decreased from baseline with both vitamin E and placebo treatment, although these were not primary end points of the study. Topical vitamin E did not result in a statistically significant improvement when compared with oil alone for the treatment of the nails in our three patients with yellow nail syndrome. However, it is interesting and perhaps clinically useful that both vitamin E and placebo oil improved the condition of the nails.
A 70-year-old woman with yellow nail syndrome and right-sided pleural effusion, lower extremity edema, and hypoalbuminemia was followed for 18 months. She reported an 8-year history of asthma. She had four children (3 boys and 1 girl). Dystrophy, changes in color and shape of nails both hands and foot, along with lower extremity edema was observed in the daughter and two of her sons. One son had asthma. The patient reported that her grandmother had similar nail abnormality and lower extremity edema. Other family members and patient's grandchildren were healthy. This report demonstrates a case of familial yellow-nail syndrome.
The yellow nail syndrome (YNS), first described in 1964 by Samman and White, is characterized by the presence of dystrophic, thickened, and slow-growing yellow nails in association with peripheral edema. It is a rare condition with fewer than 100 reported cases.
The manifestations of YNS have been extended to include pleural effusion [2, 3], bronchial hyperresponsiveness , bronchiectasis , chronic bronchitis, chronic sinusitis, and lymphedema (most frequently of the lower extremity). Most cases reported are idiopathic, however the syndrome has been described in association with malignancy . Familial occurrence of YNS also has been reported (5).
We present a patient with familial YNS associated with pulmonary findings, lymphedema, and hypoproteinemia in a 70-year-old woman; manifestations of this syndrome were also present in her three siblings.
A 70-year-old woman was admitted for evaluation of a right-sided pleural effusion. She had a history of dyspnea and asthma for 8 years and was treated with an anti-asthmatic drug. On examination her temperature was 36.5°C, blood pressure 120/70 mm, respiratory rate 28 breaths/minute, and pulse 93 beats/minute. Examination of the chest revealed dullness on percussion, with decreased breath sounds in the lower half of the right lung, bilateral expiratory wheezing, and pitting edema of the legs. All 20 nails showed a yellowish discoloration with thickening of the nail plates and disappearance of the cuticles (Fig. 1). Nail growth was almost totally arrested.
Laboratory studies showed the following: WBC of 15,600/ml (80 % neutrophils, 18 % lymphocytes, 2 % monocytes); a hemoglobin level of 15.2 g/dl, and a platelet count of 380,000/ml. The total protein level was 5.5 g/dl (normal: 6.4 to 8.4 g/dl); asparate aminotransferase, 35 U/L (normal: 0 to 33 U/L); alanine aminotransferase and alkaline phosphatase was normal. The erythrocyte sedimentation rate was 3 mm/hour. Urinalysis showed a pH of 8, negative for albumin, and no cells. Chest X-ray showed a right sided pleural effusion (Fig. 2). A thoracentesis yielded yellow fluid; with a lactate dehydrogenase level of 315 U/L (normal 100-500 U/L); protein content was 2.2 g/dl; glucose content was 79 mg/dl; pleural fluid total cell was 3780/ml (white blood cell 3680/ml with neutrophils 94 % and lymphocytes 6 %). Concomitant serum lactate dehydrogenase was 341 U/dl. Cytologic examination did not reveal malignant cells, and the results of acid fast bacillus study and culture were negative. The PPD test was negative. Arterial blood gas value on room air revealed a pH of 7.36, a carbon dioxide partial pressure of 47.6 mm Hg, and oxygen partial pressure of 64.1 mm Hg and HCO3 26.4 mmol/l. Computed tomographic (CT) scan of the chest demonstrated bronchiectasis and fibrotic changes in anterior segment of the right upper lobe (Fig. 3).
After 18-months followup the patient was hospitalized again, this time with bilateral pleural effusions, worsening of lower extremity edema, and ascites. Treatment with furosemide, intravenous albumin, and low-salt regimen was begun. The pedal edema subsided and the patient was discharged. After 3 months her condition deteriorated, and the patient was readmitted because of exacerbation of ascites, extremity edema, and progressive bilateral pleural effusions. Despite treatment for respiratory failure with mechanical ventilation and aspiration of large pleural fluids, the patient died of nosocomial pneumonia and a complication of mechanical ventilation.
The patient had four children (3 boys and 1 girl). She was related to her husband before the marriage (the husband was the son of paternal aunt and she was the daughter of a paternal uncle). The 36-year-old daughter and 33- and 40-year old sons had manifestations of this syndrome. They were noted to have changes in color and shape of fingernails and toenails (Figs. 4-6). The 33-year-old son also had asthma. The patient reported similar nail abnormalities and lower extremity edema in her grandmother. Other family members and the patient's grandchildren were healthy.
It appear that familial YNS is present in grandmother and three children of patient. Two siblings have been described who manifested signs of both the syndrome and immunologic deficiency; however, this familial occurrence is unique among the case reported to date .
The syndrome of yellow nails and lymphedema was first described by Samman and White in 1964 . Later, Emerson added pleural effusion as a frequent feature of the disease. The diagnosis is based on the characteristic triad of yellow nails, lymphedema, and respiratory involvement. However, these three alterations are simultaneously present in only 27 percent of cases . In 1986 Nordkild and associates reviewed the reports of the 97 patients described in the literature . The median age at onset was 40 years, however, the age of onset varies widely; for example, lymphedema may be present at birth or become manifest at the age 65. Yellow nails were present in 89 percent of the patients, 80 percent had lymphedema of varying severity, and 36 percent had pleural effusion. In 29 percent of patients, the initial symptom was related to pleural effusion.
Patients often give a history of recurrent attacks of bronchitis and may have chronic sinusitis, bronchiectasis, and recurrent pneumonia. Of the twelve patients reported from the Mayo Clinic, eight had recurrent pleural effusion and five had bronchiectasis; in this series, the first manifestation of the syndrome was either lymphedema or yellow nails, pleural effusion appearing somewhat later in all cases. The pleural effusion is usually exudative, either idiopathic or secondary to infection or chylothorax. The pleural fluid characteristically contains a high percentage of lymphocytes .
The pathogenesis of the bronchiectasis is unknown, although it is frequently associated with sinusitis; in one patient the bronchiectasis was confined to the upper lobes . The YNS has been reported in association with thyroid disease , hypogammaglobulinemia , nephrotic syndrome , protein-losing enteropathy , obstructive sleep apnea , and xanthogranulomatous pyelonephritis .
Many nail alterations have been described in association with YNS as follows: thickening, hardening, longitudinal over-curvature, total or distal yellow discoloration, loss of cuticle, transverse ridging associated with variations in the ungual growth rate, and onycholysis that may lead to shedding. Erythema and edema of the proximal nail fold or chronic paronychia also may be present . The nail growth is slow (0.1-0.25 mm/week, normal 0.5-2 mm/week) . Dermatophytic superinfection had been reported rarely .
The pathogenesis of nail abnormalities remains unknown. Lymphatic vessel alterations may play a role in some cases. DeCoste et al. hypothesized that primary sclerosis of the stroma could lead to lymphatic obstruction . The slower ungual growth may be a result of slow lymphatic flow. In 7-30 percent of cases, there is a spontaneous partial or total remission [1, 16]. But relapse often occurs. Nail improvement is often concomitant with improvement of the respiratory pathology [4, 15]. Defective lymph drainage and lymphedema is attributed to hypoplasia (sometimes atresia) of the lymphatics, defects that can be demonstrated by peripheral lymphangiography. Impaired lymphatic function has been considered an underlying abnormality in YNS, and perhaps even the primary problem. In YNS, edema results from and imbalance between capillary filtration and lymph flow.
Lymphedema, by definition, is edema due to a reduction in lymph flow. Many chronic edema are of mixed etiology, i.e., attributed to impaired lymph flow in the face of raised filtration rate. The reversibility of the edema suggests that any lymphatic insufficiency is functional and not structural. The widespread nature of fluid accumulation in YNS, including peripheral edema, pleural effusions and ascites, also suggest a functional rather than an anatomic disorder. There is no evidence to suggest that other factors influencing edema, such as salt or water imbalance, or hapoproteinemia, play a part in the genesis of YNS. Although lymphedema may be associated with YNS, the reversible nature of the edema excludes a primary structural abnormality in YNS and suggest that lymphatic involvement is secondary, and probably functional, in nature .
An inflammatory component, which could alter both blood flow and capillary permeability has not been excluded in the pathogenesis of the edema in the YNS. Interestingly, topical vitamin E, which has been used to treat nail in YNS, has and anti-inflammatory action [13, 16].
In summary, this report shows a case of familial YNS with implications of genetic factors in the pathogenesis of the disease. On the basis of this observation, it appears essential that family history be considered in the characterization of the disease.
Martin Riedel, MD
From Deutsches Herzzentrum, Technische Universität München, Munich, Germany.
Correspondence to Martin Riedel, MD, Deutsches Herzzentrum, Technische Universität München, Lazarettstrasse 36, D-80636 Munich, Germany. E- mail m.rie…@dhm.mhn.de
A 54-year-old woman was referred for evaluation of possible cor pulmonale based on the presence of dyspnea, chronic productive cough, and bilateral leg edema for 8 years. For about 8 years, her nails had been thick, brown-yellowish and would break easily. The nail grew very slowly and sometimes separated from its bed. The appearance of the nails did not change after 7 courses of antimycotic therapy. Physical examination was remarkable for dullness and decreased breath sounds at both lung bases. There was slight symmetric, nonpitting pretibial, ankle, and hand edema (Figure 1). All nails were brown-yellowish, thickened, excessively curved from side-to-side, and had transverse ridging. The lunulae were absent, and there was a distinct hump on the nails (Figure 1). Standard hematological and biochemical tests showed values within the normal ranges. Sinus radiographs revealed shadowing of both maxillary sinuses. The echocardiogram showed a small pericardial effusion (8 mm); there was no sign of constrictive pericarditis or pulmonary hypertension. The chest radiograph revealed bilateral pleural effusions with normal heart and pulmonary vasculature (Figure 2, top). Computed tomography demonstrated normal heart, great vessels and mediastinal structures, and bilateral pleural effusions. There were discrete changes suggestive of bronchiectasis in the left lower lobe. Thoracentesis revealed a clear, straw-colored nonviscous fluid with a protein content of 43.7 g/L. The concentration of glucose, lactic dehydrogenase, and amylase was normal. The white cell count was 5400/mm3 with a predominance of lymphocytes. No malignant cells were found and the culture was negative. The common causes of a transudate (cardiac failure, hepatic cirrhosis, nephropathy, myxedema, or hypoproteinemia) or exudate (lymphoma, metastatic disease, connective tissue disease, infection) were excluded. A diagnosis of pleural effusions secondary to yellow nail syndrome was made. No therapy was prescribed. A control chest radiograph after 7 weeks showed spontaneous reduction of both pleural effusions (Figure 2, bottom). Since the initial presentation the patient has been followed for 8 months and did not require thoracentesis. Chest radiographs have shown stable small pleural effusions.
The yellow nail syndrome is a triad of slow-growing dystrophic yellow nails, lymphedema, and pleural effusions, often associated with pericardial effusion, rhinosinusitis, and bronchiectasis. Our patient presented with most of these signs coexisting simultaneously. The etiology of this syndrome is obscure, although the pathogenesis seems to involve impaired lymphatic drainage. There is no known specific treatment. The pleural fluid often recurs after tapping; pleurodesis is sometimes helpful. This case illustrates the rather benign course of the syndrome over more than 8 years. The entity should be considered in the differential diagnosis of bilateral pleural effusions.
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Battaglia A, di Ricco G, Mariani G, Giuntini C.
A case is reported in whom the triad generalized lymphedema, nail dystrophy, and pleural effusion was associated to protein-losing enteropathy. This combination, not previously described, was also characterized by exacerbations of pleural effusion with recurrent episodes of broncho-pneumonia. Albumin turnover study showed depletion of the total body pool, decreased catabolic rate, and elevated albumin removal through the gastrointestinal tract. During bronchopneumonia, increased capillary permeability due to pleural involvement may worsen the basic deficit of pleural lymphatic drainage.
Publication Types: Case Reports PMID: 3979479 [PubMed - indexed for MEDLINE]
Gupta S, Samra D, Yel L, Agrawal S.
Division of Basic and Clinical Immunology, University of California, Irvine, California.
Yellow nail syndrome (YNS) is a rare disorder of unknown etiology that is characterized by yellow nails associated with lymphedema, and chronic respiratory manifestations. There are no detailed immunological studies in YNS. In this study we present first extensive immunological analysis of both adaptive and innate immunity in two patients with YNS. One patient has common variable immunodeficiency, whereas, second patient has specific antibody deficiency syndrome. Severe lymphopenia, and a striking deficiency of naïve CD4+ and CD8+ T cells and total B cells, and increased transitional B cells were observed. T cell proliferative response to mitogens and antigens were significantly reduced in both patients. Both patients failed to make specific antibody response to pneumococci. Complement, NK cell activity, and neutrophil oxidative burst were normal. Immunoglobulin administration resulted in decreased frequency and severity of infections, and an impressive effect was observed on lymphedema and on the recurrence of pleural effusion. Our data show that YNS is associated with both T and B cell defects. Furthermore, Immunoglobulin may be beneficial in clinical manifestations of lymphedema.