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Nails: The Window to the Nose? Update on Yellow Nail Syndrome

Yellow nail syndrome (YNS) is a rare disorder characterized by typical nail alterations variably associated with lymphedema and respiratory disease. It mainly affects individuals over 50 years of age, although rare pediatric cases have been reported [1-14]. Nail discoloration (chromonychia) varies from pale yellow to dark greenish, with enhanced transverse curvature and onycholysis. The nail plate is thickened, making the nails very Nails: The Window to the Nose? Update on Yellow Nail Syndrome

The pathogenesis is still obscure, with most of the literature deriving from case reports and few investigations. The most common lung conditions associated with YNS are pleural effusion and bronchiectasis, although other respiratory disorders such as recurrent pneumonias, bronchitis, and chronic sinusitis have been included as diagnostic criteria [2,3]. The course of the nail disease does not necessarily parallel that of the associated conditions. We hereby report a case of YNS with severe nasal septum deviation and chronic rhinosinusitis that completely resolved after surgical treatment of the respiratory disease and oral administration of vitamin E, together with a comprehensive review of the literature regarding this peculiar entity.    [2]. However, a recent case-control study on 17 YNS patients with lower and/or upper limb lymphedema found a significantly higher rate of lymphatic morphological abnormality and reduced regional nodal uptake compared to healthy controls, concluding that YNS should be considered as a lymphatic phenotype [23]. As

YNS was first described in 1964 by
Samman and White, who reported the association between typical nail findings and lymphedema [16]. Two years later, Emerson added pleural effusion as a further diagnostic criterion [17]. Later

Associated Conditions
The occurrence of lymphedema ranges between 29% and 80%, being the first sign of the syndrome in approximately one-third of cases [2,3,19].
Clinical characteristics are the same as those of primary lymphedema, most commonly occurring on lower limbs, although facial edema and upper limb lymphedema have been rarely reported [16,23]. Prevalence of pleural effusions is approximately 14%-16% in YNS, with the prevalent clinical manifestation being chronic cough, and bronchiectasias are present in approximately 44% of patients [2]. Acute or chronic sinusitis is frequently observed (14%-83%), mainly affecting the maxillary and ethmoid sinus [1][2][3]19,21,22]. CT scans usually show mucosal thickening with enlargement of turbinates and fluid levels. underwent combined treatment with both rhinoseptoplasty and oral vitamin E supplementation, suggesting that a multidisciplinary therapeutic approach may be more likely to lead to a cure than a single medicine or treatment.
Further research is indeed required in order to investigate the potential of the above-mentioned therapeutic strategies and provide higher levels of evidence for the treatment of YNS. This report aims to emphasize the role of the dermatologist in detecting systemic conditions, sometimes hidden behind what seems to be a mere aesthetic concern.
We believe that our case is of special interest as the correct diagnosis led to appropriate therapeutic strategies, resulting in the complete resolution of both the nail alterations and associated respiratory condition. Careful anamnesis regarding medical history and associated conditions should always be performed in order not to miss an opportunity to provide patients with proper care.
Regarding systemic treatment, oral zinc sulfate supplementation (300 mg/day) resulted in improvement of lymphedema and nail alterations, but no effect on pulmonary manifestations was observed [51]. Triazole antifungals such as itraconazole showed to exert limited effects on affected nails; however, combination treatment with pulsed oral fluconazole and oral α-tocopherol resulted in significant improvement of nail alterations [3,[52][53][54][55]. The therapeutic effect may be exerted by a combination of the azole antifungals' stimulation of linear nail growth and the vitamin E antioxidant properties that prevent colorless lipid precursor to be transformed into lipofuscin pigment responsible of nail yellowing [54,56,57].
Oral vitamin E is traditionally prescribed also as monotherapy. Because of its efficacy for chronic lower respiratory tract infections, clarithromycin (CAM) theoretically makes a suitable candidate as therapeutic agent in YNS. Apart from a single case report in 2011, a recent observational study on 5 YNS subjects with respiratory manifestations reported significant improvement of nail discoloration in parallel with improvement of respiratory symptoms after oral administration of CAM [58,59]. The initial dosage was 200 mg/day, but therapeutic effects were not observed until the dosage was increased to 400 mg/day, suggesting that the activity of CAM in YNS may be dose-dependent. The therapeutic effect may be exerted by both antibacterial and anti-inflammatory activity of CAM, improving both lymphatic drainage around nails with resolution of discoloration and reducing water and mucus secretion in the respiratory tract [60][61][62].
Treatment for chronic rhinosinusitis is not specific for YNS patients; however, global response to medications such as oral antibiotics or topical intranasal steroids or decongestants is poor, making surgical procedures often necessary.
A few cases of YNS with sinobronchial syndrome in which treatment with CAM led to resolution of both nail and respiratory manifestations have been reported [58,59]. A case of a patient affected by YNS with rhinosinusitis cured with combination treatment with triamcinolone injection, oral vitamin E, oral fluconazole, and robust medical regimen for rhinosinusitis has been reported, although the variety of treatment administered makes it is difficult to assess the relevance of each agent in the resolution of symptoms [50]. A single case of YNS with rhinosinusitis whose nail manifestations were dramatically improved after endoscopic sinus surgery has been reported [63].

Conclusions
To our knowledge, this is the fourth report regarding successful treatment of YNS manifestations in a patient with chronic rhinosinusitis, and the second one observing resolution of YNS symptoms after sinus surgery. Notably, our patient Review | Dermatol Pract Concept 2020;10(2):e2020031