Yellow Nail Syndrome: Analysis of 23 Consecutive Patients and Effect of Combined Fluconazole-Vitamin-E Treatment.

INTRODUCTION: Yellow nail syndrome (YNS), a very rare disorder of unknown etiology, is characterized by a triad associating yellow nails, respiratory manifestations, and lymphedema. YNS treatment remains non-codified. METHOD: This retrospective study was conducted from January 2008 to December 2022 in a single tertiary department exclusively dedicated to lymphatic diseases. All consecutive patients with YNS were included. RESULTS: Thirteen men and 10 women were included. Three patients had yellow nails at birth or during childhood. For the other 20 patients, median (Q1-Q3) age at first sign was 50.8 (43-61) years, with first-YNS-sign-to-diagnosis interval of 17 (10-56) months. For 4 patients, YNS was associated with primary intestinal lymphangiectasia. The first YNS sign was chronic cough (45.5%), followed by yellow nails (27.3%), chronic sinusitis (18.2%), and lymphedema (9.1%). At first consultation for all patients, 69.6% had the complete triad, all had yellow nails and cough, 82.6% had chronic sinusitis, and 69.6% had lymphedema. Twelve patients' lymphedema involved only the lower limb(s), 2 the lower and upper limbs, and 2 the lower and upper limbs and face. Nineteen (82.6%) patients were prescribed fluconazole (100 mg/day [n = 8] or 300 mg/week [n = 11]) combined with vitamin E (1,000 mg/day) for a median of 13 months. Responses were complete for 4 (21.1%) patients, partial for 8 (42.1%), and therapeutic failures for 7 (36.8%). CONCLUSIONS: YNS is a rare disease that almost always starts with a chronic cough. Despite inconstant efficacy, fluconazole-vitamin E in combination can be prescribed to treat yellow nails.

Bilateral axillary web syndrome in a patient with primary lymphoedema of upper limbs and non-Hodgkin lymphoma.

Primary lymphoedema, axillary web syndrome (AWS) and yellow nail syndrome may be related. Mr B is a 66-year-old gentleman with genital lymphoedema and lymphoedema of all four extremities. In 2023, he was diagnosed with non-Hodgkin lymphoma and also underwent cardiac surgery. In November 2023, he completed an inpatient rehabilitation at the Földi clinic in Germany, where he received intensive treatment for his lymphoedema and was also diagnosed with bilateral AWS. The presence of AWS in a patient with primary lymphoedema and no history of axillary surgery is unique. Although AWS typically presents after axillary surgery, this case highlights that it can also occur in patients without lymph node surgery. While the precise cause of this presentation of AWS is not known, it may be connected to yellow nail syndrome or potentially the recent chemotherapy treatment. This article will describe the clinical case, highlighting the need for further research on AWS present in primary lymphoedema.

Effectiveness of clarithromycin in patients with yellow nail syndrome.

BACKGROUND: Yellow nail syndrome (YNS) is a rare disease characterized by the triad of thickened, slow-growing yellow nails, lymphedema, and chronic respiratory manifestations. The cause of YNS is not known; however, it is suggested to be due to a congenital lymph abnormality. Since YNS is accompanied by chronic bronchial infection in more than half of patients, we hypothesized that treatment with clarithromycin (CAM) could be effective. We therefore evaluated the effectiveness of CAM against nail discoloration and respiratory manifestation in patients with YNS. METHODS: We conducted an observational study involving 5 patients with YNS who were treated at our institution between January 2005 and January 2016. CAM was prescribed for every patient. Patient demographic information, comorbidities, medications, chest radiographs, and clinical data such as nail color were extracted to evaluate clinical outcome. RESULTS: Mean patient age was 71.6 years, and 2 patients (40%) were male. Four patients had sinusitis, and 2 had rheumatoid arthritis. Regarding respiratory manifestations, 4 patients had sinobronchial syndrome and 2 had pleural effusion. Nail discoloration improved in every patient after CAM treatment. Four patients also experienced improvement in their respiratory manifestations. CONCLUSIONS: In patients with YNS, the anti-inflammatory activity of macrolides might improve their systemic inflammation. This improvement could help to reduce lymphedema and promote nail growth. TRIAL REGISTRATION: Ethical approval was provided by the institutional review board of the National Center of Global Health and Medicine (NCGM-G-002143-00), in January 2017. This study is retrospectively registered for UMIN Clinical Trial Registry ( UMIN000028514 ) in August 4th, 2017.

Yellow Nail Syndrome Presenting With a Pericardial Effusion: A Case Report and Review of the Literature.

Yellow nail syndrome (YNS) is a constellation of clinical findings including at least 2 of the 3 features of thickened yellow nails, respiratory tract involvement, and lymphedema. We report the case of a middle-aged man presenting with dystrophic, thickened yellow nails; an idiopathic pericardial effusion in the absence of pleural effusion(s); and unilateral apical bronchiectasis found on computed tomography of the chest. This represents a unique presentation of YNS as the first report of a patient with YNS and a pericardial effusion in the absence of pleural effusions and lymphedema and is the 11th case report of YNS with pericardial effusion.

[Respiratory manifestations of yellow nail syndrome: report of two cases and literature review].

Objective: To describe the clinical characteristics of respiratory manifestations of yellow nail syndrome. Methods: We conducted a retrospective analysis of 2 patients with respiratory diseases associated with yellow nail syndrome. Their clinical and chest radiological data were collected. We searched PubMed, Wanfang and CNKI databases with the keywords "yellow nail syndrome, yellow nail and lung" in Chinese and English. And the relevant literatures, including 6 articles in Chinese and 81 articles in English, were reviewed. Results: Our 2 patients were male, one 60 years old and the other 76. Typical yellow nails were present in their fingers, and one of them also showed toe yellow nails. One patient was admitted for refractory respiratory infection and he was diagnosed with diffuse bronchiectasis. The respiratory symptoms could be relieved with antibiotics according to the results of sputum microbiological analysis. The other patient was admitted for cough and exertional dyspnea, and refractory pleural effusions were revealed bilaterally. He received repeated effusion drainage by thoracentesis, and Octreotide was tried recently. A total of 373 cases were reviewed in Chinese and English literatures. Pleural effusions (152 cases) and diffuse bronchiectasis (121 cases) were the most common reported respiratory manifestations. Lymphoedema was present in almost all cases with pleural effusion associated with yellow nail syndrome, and the effusion was usually exudative and lymphocyte predominant. Pleurodesis and decortication were effective for them. But, somatostatin analogues had been tried effectively for these patients recently. On the other hand, literatures showed that diffuse bronchiectasis in yellow nail syndrome was less severe than idiopathic diffuse bronchiectasis, and might benefit from long-term macrolide antibiotics. Conclusions: Yellow nail syndrome is a very rare disorder. Besides yellow nail, respiratory manifestations are the main clinical presentations. Diffuse bronchiectasis and recurrent pleural effusions are the common manifestations.

Bronchiectasis in yellow nail syndrome.

BACKGROUND AND OBJECTIVE: Yellow nail syndrome (YNS) is a rare and poorly described disease process. In this case-control study, clinical features and findings on HRCT were compared with idiopathic bronchiectasis (IBx). METHODS: A review of all patients attending an adult bronchiectasis clinic between 2007 and 2013 identified 25 YNS patients. IBx patients were matched in a 2:1 ratio for age, duration of symptoms and gender. RESULTS: Median age of onset was 53 years. There were 12 male and 23 Caucasian YNS patients. Respiratory manifestations included chronic productive cough (100%), chronic rhinosinusitis (88%), pleural effusions (20%) and lymphoedema (12%). Chest symptoms preceded yellow nails in the majority (68%). Abnormal nails persisted at follow-up in 23 of 25 patients but improved in 14. In both disorders, there was symmetrical, predominantly lower lobe bronchiectasis on HRCT. Extent (P = 0.04), severity (P = 0.03) and bronchial wall thickness (P = 0.05) scores were lower in YNS, with less upper and middle lobe disease. Multivariate analysis showed an independent association with increased mucus plugging in YNS. There was a similar prevalence of Pseudomonas aeruginosa infection and mild lung function abnormalities. CONCLUSION: Bronchiectasis in YNS is less severe than IBx but is associated with increased mucus plugging, onset is in middle age and there is no female predominance. Treatment targeted at improved secretion clearance may improve both chest and nail symptoms, with consideration of long-term macrolide antibiotics.

Characteristics of patients with yellow nail syndrome and pleural effusion.

Yellow nail syndrome (YNS) can be associated with a pleural effusion (PE) but the characteristics of these patients are not well defined. We performed a systematic review across four electronic databases for studies reporting clinical findings, PE characteristics, and most effective treatment of YNS. Case descriptions and retrospective studies were included, unrestricted by year of publication. We reviewed 112 studies (150 patients), spanning a period of nearly 50 years. The male/female ratio was 1.2/1. The median age was 60 years (range: 0-88). Seventy-eight percent were between 41-80 years old. All cases had lymphoedema and 85.6% had yellow nails. PEs were bilateral in 68.3%. The appearance of the fluid was serous in 75.3%, milky in 22.3% and purulent in 3.5%. The PE was an exudate in 94.7% with lymphocytic predominance in 96% with a low count of nucleated cells. In 61 of 66 (92.4%) of patients, pleural fluid protein values were >3 g/dL, and typically higher than pleural fluid LDH. Pleurodesis and decortication/pleurectomy were effective in 81.8% and 88.9% of cases, respectively, in the treatment of symptomatic PEs. The development of YNS and PE occurs between the fifth to eighth decade of life and is associated with lymphoedema. The PE is usually bilateral and behaves as a lymphocyte-predominant exudate. The most effective treatments appear to be pleurodesis and decortication/pleurectomy.

[Yellow nail syndrome: two pediatric case reports]. / Syndrome des ongles jaunes : deux cas pédiatriques.

BACKGROUND: Yellow nail syndrome (YNS) is a combination of specific nail dystrophy (yellowish or green nails, transverse ridging, increased curvature with "a hump" and distal onycholysis), lymphoedema and respiratory tract involvement (mainly bronchial hyper-responsiveness, recurrent pneumonia, bronchiectasis and pleural effusion), with or without sinusitis. This rare condition is most often seen in middle age. We report two pediatric cases. PATIENTS: A 9-year-old boy had 20 yellow nails and lymphedema of the lower and upper left limbs. He was born at 32 weeks of gestation. At birth, he had fetal hydrops with bilateral chylothorax. Since then, he presented bronchopulmonary dysplasia. In his first year of life, he had recurrent nasopharyngitis and serosal otitis. Lymphoscintigraphy was not performed. A 14-year-old boy had 10 yellow toenails and 2 yellow fingernails. He was born at 36 weeks of gestation with fetal hydrops. He had recurrent serosal otitis and asthma attacks. Lymphoscintigraphy showed lymphatic hypoplasia, especially of the left limbs. DISCUSSION: These two children have the classic triad of YNS, including yellow nails, lymphedema and respiratory tract involvement. Thirteen cases have been reported in children from birth to 10 years of age, three of whom were siblings, thus suggesting genetic predisposition. In most cases lymphoscintigraphy showed hypoplasia and/or ectasia of lymphatic vessels. These lymphatic abnormalities may be responsible for nail changes as seen in Turner's syndrome. The prognosis of YNS in adults may be serious because of the pulmonary tract involvement. However, it is not known in children. CONCLUSION: Yellow dystrophic nails in children may be associated with lymphedema and respiratory tract involvement, as in adults, and this condition should therefore be investigated in cases of YNS.

Control of pleural effusion with prednisolone in a patient with yellow nail syndrome: A case report.

Yellow nail syndrome (YNS) can induce bilateral exudative pleural effusion; however, to the best of our knowledge, no standard treatment for YNS has been established. The present study describes a patient with YNS for whom the pleural effusion was controlled by prednisolone. A 73-year-old man was referred to the University of Tsukuba Hospital (Ibaraki, Japan) complaining of shortness of breath, which was diagnosed as being due to bilateral pleural effusion. Based on the presence of yellowing and growth retardation of the toenails, lymphedema, bilateral exudative pleural fluid of unknown etiology, and lymphatic congestion on lymphoscintigraphy, the patient was diagnosed with YNS. The pleural fluid was predominantly lymphocytic and responded to systemic steroid administration [prednisolone 30 mg/day (0.5 mg/kg) for 2 weeks, with subsequent weekly tapering]. The general condition of the patient and their dyspnea also improved with treatment. These findings indicated that systemic steroid administration should be considered as one of the treatment options for patients with YNS who are reluctant to undergo chest drainage or pleurodesis due to the potential for a decrease in their ability to perform daily activities and respiratory function.

Four-Year Follow-Up of a Case of Yellow Nail Syndrome With IgM Deficiency.

Yellow nail syndrome is a rare condition occurring sporadically, with an extremely low prevalence rate. This syndrome classically presents with a triad of lower extremity edema, yellow nails, and mucosal issues such as pleural effusion and/or chronic sinusitis. Two out of the three features are deemed sufficient to diagnose a person with yellow nail syndrome. We present a rare case of yellow nail syndrome that began with chronic leg swelling and later progressed to the development of an asymptomatic pleural effusion and finally discoloration of nails. In our case, the patient did have a significant recent history of a total knee replacement with a titanium implant. Of note was the chronology of events including leg edema and asymptomatic pleural effusion which were present even before the titanium knee implant. The third feature of the hardening and yellow discoloration of the nails was found to have developed following the knee replacement. Interestingly, on further evaluation, he was found to have IgM deficiency.

Nail disorders to be kept in mind.

Recognizing and diagnosing the most common nail diseases is essential, to be able to guide patients and provide appropriate treatment. However, uncommon nail disorders should not be neglected, in order to avoid inadequate treatment and above all to ensure that no severe underlying disorder, with severe prognosis, is overlooked.

Selective IgG2-deficiency in yellow nail syndrome.

IgG2-deficiency increases susceptibility to recurrent pulmonary infections and the risk for bronchiectasis. Isolated IgG2-deficiency has not been previously described in Yellow Nail Syndrome (YNS).

Recurrent Pericardial Effusions and Pericarditis Due to Yellow Nail Syndrome.

A 79-year-old woman presents with recurrent pericardial and pleural effusions for several years. She was noted to have exudative pleural effusions and bilateral nailbed discoloration. The constellation of her presenting symptoms and existing physical examination findings revealed a diagnosis of yellow nail syndrome, a rare cause of recurrent pericardial effusions. (Level of Difficulty: Advanced.).

Cryptosporidiosis in Yellow Nail Syndrome - A Rare Case Report.

BACKGROUND: Cryptosporidium species infection causes malabsorption and severe diarrhea in immunocompromised hosts. Association of Yellow Nail Syndrome (YNS) and Cryptosporidiosis is rare and has not been reported till date. Immunity can also be affected in this case of YNS is associated with autoimmune disorders. CASE PRESENTATION: Here, we describe a case of persistent diarrhea in an 8 month old YNS patient. Modified Ziehl-Neelsen staining and Saffranine-Methylene blue revealed oocyts of Cryptosporidium species. Following appropriate treatment, the patient's symptoms improved and the patient was discharged in a hemodynamically stable condition. DISCUSSION: Cryptosporidiosis is a significant cause of morbidity and mortality in immunocompromised patients. YNS per se as well as treatment including steroids leads to immunosuppression in individuals making them susceptible host for opportunistic infections like Cryptosporidiosis. CONCLUSION: Clinicians should be aware of the condition and screen for Cryptosporidiosis in any immunocompromised patients with diarrheal symptoms, as parasitic infection like this are opportunistic in them.

[Yellow nail syndrome. A case report with postmortem study]. / Síndrome de las uñas amarillas. Presentación de un caso con estudio autópsico.

Yellow nail syndrome is a rare disease of unknown aetiology. Patients with YNS have a characteristic yellowish-coloured nails, pulmonary alterations and primary lymphedema. To the best of our knowledge, only a few reports of autopsy findings in these patients have been published. Its aetiology possibly involves a primary malformation of larger lymph vessels. We describe autopsy findings not previously associated with yellow nail syndrome, such as expansion of mediastinal lymph-nodes and splenic sinusoids. The present autopsy reveals hitherto unreported findings associated with YNS, such as alterations in splenic sinusoids and mediastinal lymph-node sinuses.

Amlodipine as a Suggested Cause of Yellow Nail Syndrome: A Case Report.

Yellow nail syndrome (YNS) is a rare disorder initially described in 1964. It is characterized by a classical triad: yellow nails, lymphedema, and respiratory manifestations. We present a 71-year-old woman who presented with progressive dyspnea. Medical history includes hypertension treated with amlodipine. Examination showed bilateral lower extremity non-pitting edema, yellowish discoloration of nails, and bilateral pleural effusion. Thoracentesis demonstrated chylous effusion. The presumptive diagnosis was YNS. Assuming amlodipine as a cause of interstitial edema, it was stopped, and the symptoms improved gradually. After two months, amlodipine was restarted externally, and the dyspnea relapsed. Amlodipine was discontinued again. After two years of amlodipine cessation, the patient remained well without symptoms. The progression and resolution of symptoms point to amlodipine as a suggested cause of YNS. Paying attention to the prescribed drugs was the key to diagnosing and resolving serious complications.

Rapidly Progressive Bronchiectasis and Pulmonary Fibrosis in Yellow Nail Syndrome with Possible Association with Selective IgM Deficiency.

A 67-year-old man with a history of IgM deficiency and pulmonary fibrosis and bronchiectasis was admitted for management of worsening symptoms. Investigations revealed exudative pleural effusion with rapidly progressive bronchiectasis. Although a potential trigger of bronchiectasis and pulmonary fibrosis was not identified despite extensive work-up by several physicians in the past, a bedside observation of yellow dystrophic nails on all extremities revealed the diagnosis. This case report helps to remind clinicians of a rare medical disorder of still uncertain aetiology and no available cure. This case is consistent with a few previous case reports that suggest a potential association with selective immunoglobulin deficiency. LEARNING POINTS: Yellow nail syndrome is a rare condition characterized by the classic triad of respiratory, nail and lymphatic involvement.Diagnosis remains clinical with no confirmatory tests available; the absence of yellow nails does not preclude the diagnosis.An association with selective IgM deficiency has been infrequently reported.

Yellow nail syndrome in an elderly sudanese female: A case report.

Yellow nail syndrome is a rare lymphatic abnormality without clear pathogenesis. Hereby, we report a 70-year-old Sudanese female patient who presented with recurrent cough, recurrent lower limb swelling, and yellowish nail discoloration diagnosed as yellow nail syndrome but unfortunately passed away due to acute respiratory distress syndrome (ARDS).

Yellow nail syndrome accompanied by minimal-change nephrotic syndrome: A case report.

BACKGROUND: In most cases of yellow nail syndrome (YNS), the classic triad of yellow nails, lymphedema and respiratory manifestations rarely manifest simultaneously. Therefore, diagnosis is delayed or frequently missed. CASE SUMMARY: We report a 62-year-old YNS patient presenting with bilateral pleural, pericardial and peritoneal effusions who, 2 mo later, developed minimal-change nephrotic syndrome. After treatment with vitamin E, clarithromycin and prednisone for 3 mo, effusions in the chest, pericardium and abdominal cavity decreased while urine protein levels returned to within normal ranges. CONCLUSION: Clinicians should consider the possibility of YNS for patients presenting with multiple serous effusions and nephrotic syndromes.