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.