Yellow Nail Syndrome

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CHEST

OriginaI Research PLEURAL DISEASE

Yellow Nail Syndrome* Analysis of 41 Consecutive Patients Fabien Maldonado, MD; Henry D. Tazelaar, MD, FCCP; Chih-Wei Wang, MD; andJay H . Ryu, MD, FCCP

Background: Yellow nail syndrome (YNS) is a rare condition defined by the presence of yellow nails associated with lymphedema and/or chronic respiratory manifestations. Several aspects of this disorder remain poorly defined. Methods: We sought to clarify the clinical features and course associated with YNS by analyzing 41 consecutive cases evaluated at a tertiary referral medical center. Results: There were 20 men and 21 women; median age at diagnosis was 61 years (range, 18 to 82 years). None had a family history of YNS. All but one patient had chronic respiratory manifestations that included pleural effusions (46%),bronchiectasis (44%),chronic sinusitis (41%), and recurrent pneumonias (22%);26 patients (63%) had lymphedema. Treatment included rotating antibiotic therapy for bronchiectasis, thoracenteses, oral vitamin E, and corticosteroid therapy. Eight patients underwent surgical management of recurrent pleural effusions including pleurodesis and decortication; two additional patients underwent pleurodesis via tube thoracostomy. The yellow nails improved or resolved in 14 of 25 patients (56%)for whom relevant data were available. Median survival of this cohort using the Kaplan-Meier method was 132 months, significantly lower than (p = 0.01) the control population. Among those still alive (20 patients), the disease appeared stable. Conclusions: In most cases, YNS is an acquired disorder and associated respiratory manifestations are generally manageable with a regimen of medical and surgical treatments. Yellow nails improve in about one half of patients, often without specific therapy. (CHEST 2008; 134:375-381) Key words: chylothorax; lymphedema; pleural effusion; yellow nail syndrome Abbreviation: YNS = yellow nail syndrome

ellow nail syndrome (YNS)is a rare disorder first described in 1964 by Samman and White,l consisting of yellow nails with lymphedema and/or chronic respiratory manifestations. The respira-

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*From the Division of PulmonaIy and Critical Care Medicine (Drs. Maldonado and Ryu), Mayo Clinic, Rochester, MN; Division of Anatomic Pathology (Dr. Tazelaar), Mayo Clinic, Scottsdale, AZ;and Department of Pathology (Dr. Wang), Chang Gung Memorial Hospital, Taoyuan, Taiwan. The authors have no conflicts of interest to disclose. Manuscript received January 16, 2008; revision accepted March 11, 2008. Reproduction of this article is rohibited without written permission from the American College ofchest Physicians (www.chestjoumal. org/misc/re rints shtml).

Corresponznce to: Fahien Maldonado, MD, Division of Pulmon a y and Critical Care Medicine, Desk East 18, Mayo Clinic, 200 First S t SW, Rochester, MN 55905; e-mail: [email protected] DOI: 10.1378/chest.08-0137 www.chestjournal.org

tory manifestations are diverse and include pleural effusion, bronchiectasis, rhinosinusitis, chronic cough, or recurrent lung infections.13 The pathophysiology of the syndrome remains unclear, but various anatomic or functional lymphatic drainage abnormalities have been proposed as the underlyng c a u ~ e . l . ~ - ~ More recently, microvasculopathy with protein leakage has been suggested as a more likely culprit.7-9 Some authors have classified YNS as a hereditary disorder, transmitted in an autosomal dominant fashion, while others have linked YNS to a variety of underlying diseases including connective tissue disease, malignancy, immunodeficiency states, endocrine disorders including diabetes mellitus and thyroid dysfunction, or as an adverse drug effect.2.10 In this study, we attempted to clarify the clinical feaCHEST r 134I 2 r AUGUST, 2008

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tures and course of patients with YNS by retrospectively assessing 41 consecutive cases evaluated at a tertiary referral medical center.

MATERIALS AND METHODS Forty-one patients with YNS diagnosed at the Mayo Clinic, Rochester over a 36-year period from January 1, 1970, to December 31, 2005 were identified by a computer-assisted search of medical records. One of these 41 patients was included in a previously published report” on chylothorax from this institution. This study was approved by the institutional review board of the Mayo Foundation.

Diagnostic Criteria The diagnosis was based on the presence of characteristic yellowish nail discoloration (Fig 1) associated with lymphedema and/or chronic respiratory manifestations including pleural effusions, bronchiectasis (defined by the presence of dilated bronchi on CT or chest radiography), or chronic sinusitis. Potential causes of these manifestations other than YNS were absent.

Clinical Data Collection and Analysis Data extracted from the medical records included the demographics, clinical presentation, laboratory results, radiologic findings, echocardiography, and pulmonary function results whenever available. Presenting features were recorded from the first encounter at the Mayo Clinic that led to a diagnosis of YNS. Follow-up data were collected regarding subsequent clinical course and response to treatment. Pleural effusions were categorized as transudative or exudative using the criteria described by Light et al.12 Pulmonary function results were categorized as obstructive or restrictive, and categorized for severity using the criteria outlined in the American Thoracic and European Respiratory Society statement on interpretation of pulmonary function results.’? Original pathology slides from lung and pleura were reviewed when available. Cumulative survival probabilities were estimated using the Kaplan-Meier method and compared with

the general life expectancy for the US white population for persons of like age, sex, and calendar year of birth using a one-sample log-rank test.

RESULTS Derrulgraphic and Clinical Features Demographic and clinical characteristics of the 41 patients included in this study are outlined in Table 1. The study population included 20 men and 21 women. Median age of the patients at diagnosis of YNS was 61 years (range, 18 to 82 years). Only one patient was an active smoker at diagnosis, and 20 patients had a previous smoking history. None had a family history of YNS. No relevant environmental or occupational exposures, eg, inhalational injuries, were identified. Twenty-six patients (63%) presented with lymphedema as the main manifestation. All but one patient had chronic respiratory manifestations that included pleural effusions, bronchiectasis, chronic sinusitis, recurrent pneumonias, and chronic cough (Table 1). Seventeen patients (41%) had undergone thoracentesis at least once. Results from thoracentesis were available for 16 patients (39%): 15 patients had an exudative pleural effusion with a predominant lymphocytosis, and included 5 patients with chylothorax. One remaining patient had a transudative effusion. Two patients reported significant weight loss; no other constitutional symptoms were reported. Symptoms had been present for a median duration of 1 year before diagnosis (range, 5 months to 22 years). Four patients had a history of malignancy: one had a remote history of cured bladder cancer, one had undergone a nephrectomy for renal cell carcinoma 10 years before presentation, and another had a

Table 1-Demographic and Clinical Features of 41 Patients With YNS* Characteristics

Data

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FIGURE 1. Thickened yellowish nails of a 53-year-old man, a nonsmoker, with YNS.The fungal culture result of a nail sample was negative. Ima e courtesy of the Department of Dermatoloa, Mayo Clinic, Rocfester, MN. 376

Median Range Gender Male Female Manifestations Yellow nails Lymphedema Chronic cough Pleural effusions Bronchiectasis Chronic sinusitis Recurrent pneumonias

61 18-82 20 (49) 21 (51) 41 (100) 26 (63) 23 (56) 19 (46) 18 (44) 17 (41) 9 (22)

*Data are presented as No. (%) unless otherwise indicated. Original Research

history of cured breast cancer 9 years before. Lung adenocarcinoma (TSNOMO) was diagnosed in the one remaining patient at the time of YNS diagnosis and the patient underwent a left lower lobectomy. Associated conditions also included ischemic heart disease (three patients), thromboembolic disease (two patients), cerebral aneurysm (one patient), hypogammaglobulinemia (one patient), pancytopenia (one patient), sarcoidosis and Raynaud phenomenon (one patient), polymyalgia rheumatica (one patient), bullous stomatitis (one patient), eosinophilia-myalgia syndrome (one patient), anhydrosis (one patient), pectus excavatum (one patient), and possible allergic bronchopulmonary aspergillosis (one patient).

Radiologic Findings Chest radiographic results were available for 40 patients. Pleural effusions were identifiable in 19 patients (48%).Other radiographic findings included bibasilar interstitial infiltrates (five patients), patchy alveolar infiltrates (five patients), bronchiectasis (three patients), and bilateral apical fibrosis (two patients). Seven patients had a normal-appearing chest radiograph (18%). Chest CT scan results were available for 38 patients (Table 2). Bronchiectasis was present in 18 patients (47%) and most commonly involved both lower lobes (29%). Pleural effusion was noted in 18 patients (47%), more often bilateral than unilateral. Other CT findings included localized parenchymal infiltrates, intrathoracic lymphadenopathy, and pericardial effusion. Chest CT scan was normal in three patients (8%).Lymphoscintigraphy was obtained in two patients and showed delayed lymphatic drainage in both lower extremities with no activity beyond the groin in one patient, and minimal delay in the right leg but normal lymphatic function of the left leg in the second patient.

Table "hest

CT Findings*

Characteristics Bronchiectasis Unilateral Bilateral upper lobes Bilateral lower lobes All lobes Pleural effusions Bilateral Unilateral Localized parenchymal infiltrates Intrathoracic lymphadenopathy Pencardial effusion Normal *CT was not available in 3 of 41 patients www.chestjournal.org

Echocardiography Results Echocardiography was performed in 10 patients, and findings were normal in 4 patients. Abnormalities included mild pulmonary hypertension in three patients, mild-to-moderate pericardial effusion in two patients, mild diastolic dysfunction in one patient, and mild restrictive physiology in one patient.

Pulmonay Function Studies Pulmonary function studies were performed in 35 patients (85%).An obstructive pattern was the sole abnormality in 15 patients (43%). Obstructive abnormality ranged in severity from borderline (4 patients, 27%), mild to moderate (10 patients, 29%), to severe (5 patients, 33%). All of those patients with severe obstructive abnormality had evidence of bronchiectasis on CT i m a p g . A restrictive pattern was found in five patients (14%) and was mild (three patients) or severe (two patients with a history of prior pleurodesis); three of these patients had bilateral pleural effusions. A mixed obstructive-restrictive pattern was found in two patients (6%). An isolated decrease in the diffusing capacity was present in two patients (6%).Pulmonary function results were normal in eight patients (23%).

Laboratoy Results Laboratory data were available for 39 patients. Albumin levels were obtained in 31 patients and were within normal range in 30 patients (97%) and mildly decreased in 1 patient (3.0 g L ) . No proteinuria was found in 13 patients who had a urinalysis performed. Sixteen patients had serum Ig levels measured, and 12 patients (75%)had normal results. Two patients had mildly decreased IgM levels, one patient had mildly decreased IgG level, and another patient had an IgG subclass deficiency. Antinuclear antibody levels were normal in four of five patients; the remaining patient had an elevated titer at 1:160 along with an elevated sedimentation rate and a history of Raynaud phenomenon.

No. (%)

Bronchoscopy Results Twelve patients (29%) underwent a bronchoscopy. Ten patients (83%)had a normal examination; extrinsic compression of the right lower lobe was noted in 2 remaining patients, and was thought to result from pleural effusions. Bronchoscopic lung biopsies obtained in one patient revealed no abnormalities. Bronchoscopic specimens for microbiological studies were obtained in five patients and were positive in three patients: findings included Staphylococcus aureus and Haemophilus influenzae, Haemophilus inCHEST I 134 I 2 I AUGUST, 2008

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Juenzae and Moraxella catarrhalis, and Mycobacterium avium complex and Pseudorrwnas aeruginosa, respectively. Thoracic Procedures As already noted, 17 patients (41%) had undergone at least one thoracentesis. Eleven patients (27%) underwent additional procedures for diagnostic and/or therapeutic purposes. Five patients had a thoracotomy, and included decortication and pleurectomy in four patients and a lobectomy (adenocarcinoma of the lung) in one patient. One of these patients also had thoracic duct ligation performed for chylothorax. Four other patients underwent video-assisted thoracoscopic surgery for pleurodesis (talc pleurodesis in three patients, mechanical pleurodesis in one patient). Two additional patients underwent chemical pleurodesis performed via a chest tube. Pleural biopsy specimens were available for current review in seven patients (17%) and revealed chronic fibrosing pleuritis in all, characterized by collagenous thickened pleura associated with chronic inflammatory cells and lymphoid aggregates. No specific histopathologic findings of lymphatic abnormalities, eg, lymphatic ectasia, were seen. Underlying lung parenchyma showed respiratory and follicular bronchiolitis in one patient and organizing pneumonia in another patient.

Medical Therapy Medical therapy included rotating antibiotic therapy for bronchiectasis (16 of 18 patients with bronchiectasis, 39% of all patients), vitamin E for the yellow nails (8 patients, 20%), and postural therapy and/or compression stockings for lymphedema (8 patients, 20%). Other treatments for lymphedema included diuretics (three patients) and low-salt diet (two patients). Two patients with chronic sinusitis underwent sinus surgery. Follow-up information was available for 37 patients (90%) with a median interval of 78 months (range, 5 to 236 months). Seventeen of these patients (46%) died after a median interval of 82 months (range, 12 to 236 months). A Kaplan-Meier survival curve for this cohort is shown in Figure 2; estimated median survival was 132 months. Compared to a control population of like age, gender, and calendar year of birth, patients with YNS had decreased survival (p = 0.01). All patients in the study cohort and comparison control population were white. The cause of death was unknown except in two patients who died from arrhythmia and metastatic cancer of unknown origin, respectively. Twenty patients were alive after a median follow-up period of 82 months (range, 5 to 230 months). 378

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FIGURE2. Kaplan-Meier survival curve of subjects with YNS compared general life expectancy.

The yellow nails improved or resolved in 14 of 25 patients (56%) for whom follow-up data were available. Nail improvement occurred without specific therapy in nine patients; five patients were receiving vitamin E therapy. In all nine patients with improved nails receiving no specific therapy, the improvement appeared to be associated with better control of their respiratory manifestations (pleural effusion and/or bronchiectasis). Among 11 patients whose yellow nails persisted, 3 patients were receiving vitamin E therapy (combined with biotin and zinc therapy in 2 patients). Lymphedema resolved in 2 of 22 patients for whom follow-up data were available, and appeared to be associated with better control of recurrent respiratory infections. Lymphedema persisted without noticeable change in the remaining patients and was managed with compression stocking, bandage wraps, exercise, and low-salt diet. Of 20 patients still living, 2 patients had resolution of respiratory symptoms but the remaining 18 patients had persistent exertional dyspnea and/or productive cough. Two of the latter patients were receiving supplemental oxygen therapy during with exertion, but none of the patients described a progressive decline in respiratory status. Most patients were able to maintain stability with a regimen that usually consisted of intermittent antibiotic therapy for exacerbations of bronchial or sinus symptoms, bronchial hygiene measures (postural drainage, chest physiotherapy, flutter valve), and bronchodilators. One patient noted symptomatic benefit from the use of nebulized N-acetylcysteine.

DISCUSSION The initial description of YNS in 1964 by Samman and Whitel included 13 subjects with dystrophic Original Research

slow-growing nails and lymphedema. On the basis of lymphangographic studies obtained in four of these patients, they hypothesized that the nail changes and lymphedema may result from dysfunctional lymphatic drainage. Since this initial description, > 100 cases of YNS have been described in the literature, mostly consisting of isolated case reports or limited case series. Since the underlying pathophysiology is poorly understood, the dagnosis of YNS remains essentially clinical in nature and one of exclusion. The diagnosis of YNS is usually established by the classical triad of yellow dystrophic and/or slow growing nails, lymphedema, and respiratory manifestations in the absence of other more likely explanations.1.2.7All three criteria may not be simultaneously present, and the presence of two of them has been judged to be sufficient for diagno~is.~ For the purpose of our study, we required the presence of yellow nails in association with lymphedema and/or respiratory manifestations including pleural effusions (chylous or nonchylous), bronchiectasis, rhinosinusitis, chronic cough, or recurrent respiratory infections in the absence of another likely cause. These criteria were more stringent than those used in many previous studies. Multiple clinical associations have been reported with YNS. The most common associations include connective tissue disease, malignancy, immunodeficiency states, drugs, and several endocrine disorders includmg diabetes mellitus and thyroid dysfunction.2~3,sJOOther associations have included obstructive sleep apnea,l4 myocardial infarction,l" hemochromatosis,l6 Guillain-Barrk syndrome,'7 xanthogranulomatous pyelonephritis18 and tuberc u l o ~ i swith , ~ ~most of these associations described in isolated case reports. More recently, an association with low serum protein states has been reported, presumably supporting the hypothesis that microvasculopathy with protein leakage may be an important contributor to the lymphedema observed in YNS.7.s In our study, there was no evidence that hypoproteinemia was the cause for YNS.We noted a variety of other disorders coexisting in our YNS patients. For example, four of our patients had a history of malignancy; the history was remote for three of them. One patient was found to have lung adenocarcinoma at the time of diagnosis of YNS, an association that has been previously described.20 His symptoms did not improve after lobectomy despite prolonged survival (13-year follow-up). Only three patients had a history of connective tissue disease, including Raynaud phenomenon, polymyalgia rheumatica, and eosinophilia-myalgia syndrome, making it difficult to conclude there is an association. However, it is interesting that the original description of www.chestjournal.org

yellow nails included patients with Raynaud disease. I Most patients tested had normal Ig studies and had no clinical or laboratory evidence of immunosuppressed state. In addition, there was no evidence of recurrent infections except for those likely related to the presence of bronchiectasis. In our study, no particular association or theme appeared to emerge regarding the etiology of YNS. A role for heredity with an autosomal dominant pattern of inheritance had previously been suggested, but a recent study1" on this issue cast serious doubts on this proposition. We also did not find evidence of any hereditary pattern of transmission in our study. Family histories were well documented in all of our patients and were negative for YNS or symptoms suggestive of YNS. Lymphatic dysfunction is thought to be involved in the pathogenesis of YNS. Five of our 16 patients (31%) with pleural fluid analysis had chylothorax, a conmtion caused by abnormal lymphatic drainage." This relatively high rate of chylothorax in patients with YNS in this study argues against a coincidental association. However, examination of pleural biopsies obtained in our patients failed to reveal any specific histopathologic evidence of lymphatic abnormalities. If impaired lymphatic drainage can explain the lymphedema and pleural effusions frequently encountered in YNS, the etiology of other manifestations, namely the yellow nails and other respiratory manifestations (sinusitis and bronchiectasis), is more difficult to understand. Nailfold capillaroscopy studies in YNS have occasionally shown dilated and tortuous capillary loops, a finding suggestive of microangiopathy as the cause for the nail changes.8 An interesting feature of YNS noted in our study is the reversibility of the nail changes. This observation would support the hypothesis that lymphatic abnormalities may be functional rather than structural and modifiable over time.5 Some of our patients seemed to associate improvement in their nails with better control of their respiratory symptoms, particularly recurrent infections. One of our patients noticed significant improvement of the yellow nails after starting decongestive physiotherapy, a phenomenon that had been previously described.21 The role of vitamin E therapy in the management of yellow nails remains unclear. Five of eight patients treated with oral vitamin E therapy had improvement in their nails. However, the majority of patients with improved nails were not receiving vitamin E. The evidence for vitamin E in YNS is anecdotal and initially based on positive experiences in patients with other dermatologc conditions assumed to result from deficient microvascularity.22 The occurrence of bronchiectasis and chronic sinusitis in YNS are also difficult to explain. Primary CHEST I 134 I 2 I AUGUST, 2008

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ciliary dyskinesia as a cause for recurrent sinopulmonary infections in YNS has been investigated and refuted.23 Immune deficiencies as described in previous case reports2J0,N could account for these manifestations but were not manifest in our patients. Impaired lymphatic drainage in the bronchi and bronchioles has been suggested as a cause for recurrent infections and development of bronchiectasis.22.z Hypoplastic lymphatic vessels have been observed in a minority of biopsies, and may relate to few genetically predisposed YNS subjects. Enlarged lymphatic vessels at a microscopic level have also been described.5.6.26 However, we were unable to document lymphatic abnormalities histopathologically in our study cohort. Although our study describes the largest number of patients with YNS to date, we were limited by the retrospective nature of this study. We were able to ascertain the vital status on most patients, but detailed follow-up data regarding the evolution of clinical manifestations and causes of deaths were frequently not available. The diagnosis of YNS is ascertained on a clinical basis, and it is likely that less florid cases escaped diagnosis. Interestingly, yellow and/or dysplastic nails appeared to be the most inconsistent diagnostic criterion, resolving in about one half of our patients over a course of several years. The pathogenesis of YNS remains obscure. The presence of lymphedema in almost two thirds of patients, along with the significant number of chylothoraces observed in our study, suggests a role of impaired lymphatic drainage in the pathogenesis of YNS.However, we wonder whether systemic inflammatory state induced by recurrent respiratory tract infections may be the initiating factor for abnormal lymphatic physiology and clinical manifestations. YNS is likely an acquired disorder in most patients because we find no clear evidence for an inherited pattern. Although association of YNS with a variety of disorders has been reported, we find no consistent association in this study. Based on our data, following recommendations seem reasonable in the management of patients with YNS. Optimal control of bronchiectasis with bronchopulmonary hygiene measures (postural drainage, chest physiotherapy, use of flutter valve, inhaled bronchodilator if indicated), influenza and pneumococcal immunizations, and prompt treatment of complicating respiratory infections are advisable. None of our patients required lung resection for management of bronchiectasis. The management of pleural effusion occurring in patients with YNS should be tailored to the size, persistence, and clinical effects of the effusion. Those patients with recurrent symptomatic accumulation of pleural effusion may require pleurodesis or other surgical ma380

neuvers. Ten of our 18 patients eventually underwent pleurodesis (surgical or via chest tube) or pleurectomy. Better control of respiratory manifestations appeared to be associated with improvement in the nails of our patients. Although the efficacy of vitamin E remains unclear, it seems reasonable to offer this option to patients who are troubled by their nail manifestations. Lymphedema can be managed in most patients with a regimen that consists of gradient pressure garments, exercise, bandage wraps, and manual lymphedema drainage or external pneumatic compression as needed. Overall, our results sugest that the manifestations of YNS can be managed with currently available means in most patients and progressive respiratory insufficiency appears to be uncommon.

REFERENCES 1 Samman PD, White WF. The “yellow nail” syndrome. Br J Dermatol 1964; 76:153-157 2 Cordasco EM Jr, Beder S, Coltro A, et al. Clinical features of the yellow nail syndrome. Cleve Clin J Med 1990;57:472-476 3 Hiller E, Rosenow EC 111, Olsen AM. Pulmonary manifestations of the yellow nail syndrome. Chest 1972; 61:452-458 4 Beer DJ, Pereira W Jr, Snider GL. Pleural effusion associated with primary lymphedema: a perspective on the yellow nail syndrome. Am Rev Respir Dis 1978; 117:595-599 5 Bull RH, Fenton DA, Mortimer PS. Lymphatic function in the yellow nail syndrome. Br J Dermatol 1996; 134:307-312 6 Solal-Celigny P, Cormier Y, Fournier M. The yellow nail syndrome: light and electron microscopic aspects of the pleura. Arch Pathol Lab Med 1983; 107:183-185 7 Battaglia A, di Ricco G , Mariani G, et al. Pleural effusion and recurrent broncho-pneumonia with lymphedema, yellow nails and protein-losing enteropathy. Eur J Respir Dis 1985; 66:65-69 8 D’Alessandro A, Muzi G , Monaco A, et al. Yellow nail syndrome: does protein leakage play a role? Eur Respir J 2001; 17:149-152 9 Nougue J, Nougue-Channarond M, Parant M, et al. The yellow-nails syndrome: apropos of 2 cases; review of the literature [in French]. Ann Dermatol Venereol 1983; 110: 827-832 10 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; 156:1230-1234 11 Doerr CH, Allen MS, Nichols FC 111, et al. Etiology of chylothorax in 203 patients. Mayo Clin Proc 2005; 80:867870 12 Light RW, Macgregor MI, Luchsinger PC, et al. Pleural effusions: the diagnostic separation of transudates and exudates. Ann Intern Med 1972; 77:507513 13 Pellegrino R, Vie@G , Brusasco V, et d . Interpretative strategies for lung function tests. Eur Respir J 2005; 26948-968 14 Gubinelli E, Fiorentini S, Cocuroccia B, et d.Yellow nail syndrome associated with sleep apnoea. J Eur Acad Dermatol Venereol2005; 19:650-651 15 Scott J. Cardiac infarction and yellow nail syndrome [letter]. Proc R Soc Med 1974; 67:323 16 Di Stefano F, Vema N, Balatsinou L, et al. Genetic hemochromatosis with normal transferrin saturation in a man with cholangiocarcinoma and yellow nail syndrome. J Gastroenterol Hepatol 2003; 18:1221-1222 Original Research

17 Woollons A, Darley CR. Yellow nail syndrome following Guillain-Barre syndrome. Chn Exp Dermdtol 1997; 22:25%254 18 Danenberg HD, Eliashar R, Flusser G, et al. Yellow nail syndrome and xanthogranulomatous pyelonephritis. Postgrad Med J 1995; 71:110-111 19 Pang SM. Yellow nail syndrome resolution following treatment of pulmonay tuberculosis. Int J Dermatol 1993; 32:605-606 20 Vonk Noordegraaf A, Paul MA, Boonstrd AB, et al. “Palm reading” as a diagnostic aid [in Dutch]. Ned Tijdschr Geneeskd 2004; 148:53-56 21 Szohoky G, Lakatos B, Husz S, et al. Improvement in lymphatic function and partial resolution of nails after complex decongestive physiotherapy in yellow nail syndrome. Int J Dermatol 2005; 44:501-503

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22 Awerhuch MS. The yellow nail syndrome, bronchiectasis and Rayndud’s disease: a relationship. Med J Aust 1976; 2 m9 -8 3 0 23 Miro AM, Vasudevan V, Shah H. Ciliary motility in two patients with yellow nail syndrome and recurrent sinopulmonary infections. Am Rev Respir Dis 1990; 142:890-891 24 Bokszczanin A, Levinson AI. Coexistent yellow nail syndrome and selective antibody deficiency. Ann Allergy Asthma Immunol 2003: 91:496500 25 Wiggins J, Strickland B, Chung KF. Detection of bronchiectasis by high-resolution computed tomography in the yellow nail syndrome. Clin Radio1 1991; 43:377379 26 Bilen N, Bayramgurler D, Devge C, et al. Lymphoscintigraphy in yellow nail syndrome. Int J Dermdtol 1998; 37:444-446

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