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.

Yellow Nail Syndrome Patients with Diffuse Panbronchiolitis-like Pulmonary Manifestation.

Yellow nail syndrome (YNS) is a rare clinical syndrome characterized by a triad of yellow thick nail, lymphedema and respiratory diseases. We experienced 2 cases of YNS with diffuse panbronchiolitis (DPB)-like pulmonary manifestation. Since YNS might be hidden to those who have been diagnosed with DPB, physicians should be alert to recognize nail signs of YNS in case of DPB refractory to macrolide therapy. We hereby review previous case reports of YNS and discuss its pulmonary manifestations.

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 after allogeneic haematopoietic stem cell transplantation in two patients with multiple myeloma.

OBJECTIVE AND IMPORTANCE: Yellow nail syndrome (YNS) is a rare disorder of unknown aetiology characterized by the triad of yellow nails, lymphoedema and respiratory manifestations. About 200 cases have been reported, but a lot of patients probably elude proper diagnosis because of both variability of symptoms and ignorance of this syndrome by many physicians. The pathogenesis remains unclear, and could involve functional lymphatic abnormalities, microvasculopathy or lymphocyte deficiency, but none of these hypotheses seems fully satisfactory. CLINICAL PRESENTATION: We report for the first time two cases of YNS associated with multiple myeloma relapsing after non-myeloablative haematopoietic cell transplantation (HCT). In these two cases, onset or worsening of YNS symptoms followed graft-versus-host disease (GvHD) manifestations. INTERVENTION: Corticosteroids given to treat GvHD also improved YNS manifestations. CONCLUSION: YNS after HCT might be a microvascular manifestation of endothelial GvHD and corticosteroids might be an effective treatment.

Yellow nail syndrome: clinical experience in a series of 21 patients.

BACKGROUND AND OBJECTIVES: The pathogenesis and the therapy of the yellow nail syndrome (YNS) are poorly defined. Our aim was to assess the clinical features, associated diseases and response to treatment of patients with YNS, to help clinicians to better diagnose and treat YNS patients. PATIENTS AND METHODS: We studied the medical records of all patients with YNS diagnosed at the Outpatient Nail Clinic of the University of Bologna in the last 28 years. All patients were re-evaluated to assess the evolution of the disease. RESULTS: We diagnosed YNS in 21 patients; average age was 57 ± 12.3 years at the time of diagnosis. In most patients YNS involved all 20 nails. Sixteen patients had chronic respiratory manifestations and 6 had lymphedema; 12 patients had other concomitant diseases. Ten of the 20 patients treated had a good nail response to systemic vitamin E 1 200 IU/day, while other symptoms were not modified. CONCLUSIONS: YNS is a rare disorder in which the nail alterations are often the symptom that leads to medical consultation. Due to its association with potential serious comorbidity, physicians should be able to diagnose and order further investigations to assess presence of lymphedema and/or lung disease.

Yellow nail syndrome: dystrophic nails, peripheral lymphedema and chronic cough.

A case involving a 41-year-old man with yellow nail syndrome (YNS) is reported. YNS is a rare disorder characterized by yellow, dystrophic nails, peripheral lymphedema and bronchiectasis with recurrent lower respiratory tract infections. YNS is often misdiagnosed because the syndrome is not well known. An interdisciplinary approach is required to recognize and collate the components of the syndrome accurately. Correct diagnosis is of utmost clinical importance because YNS can occur secondary to malignancies and autoimmune disorders. Hence, the diagnosis of YNS must prompt further investigation.

Yellow nail syndrome in a medical clinic.

Yellow nail syndrome is a very rare clinical entity usually diagnosed from a combination of yellow dystrophic nails, lymphoedema and respiratory diseases. The aetiology is not known though dysfunctional hypoplastic lymphatics is speculated. Most cases occur sporadically but few cases may be associated with systemic diseases or may be inherited. This report documents another case in a 56-year old Caribbean female who presented with a six-year history of recurrent respiratory symptoms and later yellow dystrophic nails and lymphoedema. She responded well to vitamin E and oral fluconazole. We also did a short literature review of yellow nail syndrome.

Yellow nail syndrome in a medical clinic / El síndrome de las uñas amarillas en una clínica médica

Yellow nail syndrome is a very rare clinical entity usually diagnosed from a combination of yellow dystrophic nails, lymphoedema and respiratory diseases. The aetiology is not known though dysfunctional hypoplastic lymphatics is speculated. Most cases occur sporadically but few cases may be associated with systemic diseases or may be inherited. This report documents another case in a 56-year old Caribbean female who presented with a six-year history of recurrent respiratory symptoms and later yellow dystrophic nails and lymphoedema. She responded well to vitamin E and oral fluconazole. We also did a short literature review of yellow nail syndrome.

El síndrome de las uñas amarillas es una entidad clínica muy rara, la cual usualmente se diagnostica a partir de una combinación de uñas amarillas distróficas, linfedemas, y enfermedades respiratorias. Se desconoce la etiología, aunque se especula que se debe a vasos linfáticos hipoplásticos disfuncionales. La mayoría de los casos ocurre esporádicamente pero pocos casos pueden asociarse con las enfermedades sistémicas o pueden ser heredados. Este informe documenta el caso de una mujer caribeña de 56 años, que se presentó con antecedentes de síntomas respiratorios recurrentes y más tarde con uñas amarillas distróficas y linfedemas. Durante el tratamiento, respondió bien a la vitamina E y al fluconazol oral. El trabajo también realiza una breve revisión de la literatura del síndrome de las uñas amarillas.

Yellow nail syndrome.

Yellow nail syndrome is an acquired condition of unknown etiology, rarely seen in children, characterized by a triad of thickened yellow nails, primary lymphedema, and respiratory manifestations. We report an 8-year-old girl with this syndrome who showed improvement with Fluconazole, 200 mg once weekly and vitamin E, 1000 IU once daily.

Yellow nail syndrome: treatment with octreotide.

INTRODUCTION: The yellow nail syndrome (YNS) is the triad of 'yellow' nails, peripheral oedema and pleural effusions. For diagnosis, which is clinical, at least two of these findings are necessary. Also typical is a long-standing chronic cough often caused by low-grade bronchiectases. The pleural effusions often require pleurodesis. The pathogenesis is probably a dysfunction of the lymphatic system (1, 2). Octreotide regulates the release of growth hormone and thyrotropin, and also has effects on the gastro-intestinal tract, where it inhibits glandular secretion, neurotransmission, smooth-muscle contraction and absorption of nutrients. Adverse effects are nausea, abdominal cramps, diarrhoea, malabsorption of fat and flatulence (3). Because of the inhibition of absorption of fats and other nutrients, octreotide has been useful in chylothorax from many different causes (4). The pleural effusion in YNS is usually an exudate, but in rare cases a frank chylothorax. One such case with successful octreotide treatment has been described in the literature (5). OBJECTIVE: The aim of this report was to investigate the effect of octreotide treatment on a patient with YNS with pleural exudates not resulting from chylothorax. METHODS AND RESULTS: A 62-year-old man with typical YNS presented with bilateral large pleural effusions (Fig. 1). He had suffered from repeated pneumonia for many years, and 10 years earlier mild bronchiectases were diagnosed and yellow nails were noted. From the right pleura, 1750-mL clear yellowish fluid was removed and a few days later, 1300 mL was removed from the left side. During the next few weeks, repeated thoracocenteses on both sides were necessary for the palliation of his dyspnoea, and the total amount of removed fluid was more than 10 L. The pleural fluid showed a low cholesterol value, 1.2 mmol/L (serum, 3.5), a fairly high albumin level, 19.0 g/L [serum, 25 g/L (normal, 36-45)], and no triglycerides. Octreotide was administered, initially 0.5 mg subcutaneously twice daily to make sure that there were no side effects, then the long-acting drug, 30 mg given every fourth week. There was a subjective improvement after the first week, and even though he still has pleural effusions bilaterally, he no longer needs palliative thoracocenteses and can live a normal life. His nails are better, as is the oedema. He is satisfied with his treatment and does not wish to have any pleurodesis. The observation time is now 6 months, and no adverse side effects have been seen so far. CONCLUSION: Octreotide can be tried in cases of YNS before more aggressive therapies are started. However, the best results are probably achieved in the rare cases where the effusion is a chylothorax. The other symptoms, such as yellow nails and oedema, also seemed to improve but evaluation is difficult because even normally, there are variations over time with these symptoms. Pleurodesis will probably be necessary in the future for our patient despite his octreotide treatment. Further studies are warranted in this rare disease.