Dermatology: Practical and Conceptual


Review  |  Dermatol Pract Concept 2020;10(2):e2020031 1

Dermatology Practical & Conceptual

Introduction

Yellow nail syndrome (YNS) is a rare disorder characterized 

by typical nail alterations variably associated with lymph-

edema 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 yel-

low 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

Laura Vollono,1 Marco Adriano Chessa,2 Antonio Bruno,3 Michela Starace,2  
Aurora Alessandrini,2 Bianca Maria Piraccini2

1 Dermatology Unit, Department of Medicina dei Sistemi, Tor Vergata University, Rome, Italy

2 Dermatology Unit, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy

3 Radiology Unit, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy

Key words: yellow nail syndrome, lichen planus, arrested nail growth, respiratory disease

Citation: Vollono L, Chessa MA, Bruno A, Starace M, Alessandrini A, Piraccini BM. Nails: the window to the nose? Update on yellow nail 
syndrome. Dermatol Pract Concept. 2020;10(2):e2020031. DOI: https://doi.org/10.5826/dpc.1002a31

Accepted: December 6, 2019; Published: April 3, 2020

Copyright: ©2020 Vollono et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, 
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: None.

Competing interests: The authors have no conflicts of interest to disclose.

Authorship: All authors have contributed significantly to this publication.

Corresponding author: Dr. Marco Adriano Chessa, Dermatology, Department of Experimental, Diagnostic and Specialty Medicine, 
University of Bologna, Via Massarenti, 1-40138 Bologna, Italy. Email: marco.adriano.chessa@gmail.com

Background: Yellow nail syndrome is a rare condition characterized by typical nail alterations and 
variable presence of lymphedema and respiratory disease. The pathogenesis is still obscure, with most 
of the literature deriving from case reports and few investigations. The most reported respiratory 
conditions associated with yellow nail syndrome are pleural effusion and bronchiectasis, whereas 
association with rhinosinusitis is rarer.

Objectives: To describe a case of yellow nail syndrome and to provide a literature review regarding 
this disorder, discussing pathogenetic hypothesis, associated conditions, and therapeutic options.

Patients/Methods: A 49-year-old man presented with arrested growth and alterations of his nails, 
without any history of previous trauma or inflammation but with a severe nasal septum deviation and 
a history of chronic rhinosinusitis. A diagnosis of yellow nail syndrome was made.

Results: Six months after undergoing rhinoseptoplasty and treatment with oral vitamin E, the pa-
tient’s nails were cured.

Conclusions: This case emphasizes the role of the dermatologist in detecting systemic conditions. 
The correct diagnosis led to complete resolution of both nail alterations and associated respiratory 
disorders.

ABSTRACT

https://doi.org/10.5826/dpc.1001a30
mailto:marco.adriano.chessa@gmail.com


2 Review  |  Dermatol Pract Concept 2020;10(2):e2020031

hard and difficult to trim (scleronychia) 

and the lunula is obscured by nail hyper-

keratosis. Nail growth rate is half that 

of normal nails, with disappearing of 

cuticles. Differential diagnosis includes 

onychomycosis, drug-induced nail dis-

coloration, trauma, chronic paronychia, 

and acquired pachyonychia [15].

The pathogenesis is still obscure, 

with most of the literature deriving from 

case reports and few investigations. The 

most common lung conditions associ-

ated with YNS are pleural effusion and 

bronchiectasis, although other respira-

tory disorders such as recurrent pneu-

monias, 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 asso-

ciated conditions. We hereby report a 

case of YNS with severe nasal septum 

deviation and chronic rhinosinusitis that 

completely resolved after surgical treat-

ment of the respiratory disease and oral 

administration of vitamin E, together 

with a comprehensive review of the lit-

erature regarding this peculiar entity.

Case Report

A 49-year-old man presented to our 

Nail Clinic with arrested growth rate 

and alterations of his nails that started 

6 months prior. His medical history 

was unremarkable, except for chronic 

rhinosinusitis. Dermatological exam-

ination revealed increased transverse 

curvature, onycholysis, yellow-green 

discoloration, and nail fold swelling. 

Notably, the cuticles were lacking (Fig-

ure 1, A and B). He denied any previous 

trauma or manipulation of his nails. 

Routine nail fungal culture was nega-

tive. Neither swelling of the limbs nor 

facial edema was observed. Based on 

the clinical picture and medical history, 

a head CT scan was performed, which 

detected a severe nasal septum devia-

tion compromising the airway (Figure 

1C). Chest x-ray was unrevealing. A 

diagnosis of YNS with chronic rhinosi-

nusitis was made. The patient under-

Figure 1. Nail alterations characteristic of yellow nail syndrome. (A,B) Absence of the cu-

ticles and nail fold swelling are key to diagnosis. (C) Head CT scan revealing type II septal 

deviation (Mladina classification) associated with unilateral spur compromising the airway 

(arrow, left) and secondary hypoplasia of the right middle nasal turbinate (arrow, right). 

(D,E) Improved appearance of the nails 1 year after rhinoseptoplasty and oral vitamin E 

supplementation.



Review  |  Dermatol Pract Concept 2020;10(2):e2020031 3

parietal pleura and subcutaneous tissue 

of YNS patients.

In the largest series published to 

date, Maldonado et al hypothesized 

that YNS pathogenesis might be due 

to microvasculopathy associated with 

protein leakage, rather than lymphatic 

functional impairment [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 consid-

ered as a lymphatic phenotype [23]. As 

suggested, it seems likely that one given 

unknown factor, genetic and/or extrin-

sic, determines a decline in lymph vessel 

function, leading to peripheral sclerosis 

of subcutaneous tissues and morpholog-

ical abnormality of lymph vessels that 

worsen as the YNS clinical manifesta-

tions become more evident. The role of 

titanium, especially titanium dioxide, 

has been recently evoked, although the 

mere exposure to the agent does not 

seem sufficient to develop the syndrome 

[43-45]. In any case, a detailed expo-

sure history from patients with YNS is 

indeed recommended.

Treatment

A careful review of the literature points 

out that there is no consensus regarding 

YNS treatment, owing to the lack of 

large-scale studies. Treatment is typi-

cally based on anecdotal evidence, case 

reports, or small series. Spontaneous res-

olution without any treatment has been 

observed. Cancer treatment showed 

to lead to resolution of symptoms in 

patients affected by paraneoplastic YNS 

[12]. Topical treatments for nail changes 

such as triamcinolone injections and 

topical α-tocopherol (vitamin E) have 
been proposed, with inconsistent results 

[46-50]. Management of lymphedema 

with manual lymphatic drainage and 

compression bandages is advisable in 

order to prevent irreversible hypertro-

phy of subcutaneous tissue [19].

YNS has been also associated with 

several systemic conditions. Hydrops 

fetalis, primary intestinal lymphangi-

ectasis, and lymphedema-distichiasis 

syndrome has been reported in patients 

with YNS, suggesting lymphatic impair-

ment as a key factor in the development 

of the syndrome [24-26]. Cases of iat-

rogenic YNS following cardiac mitral 

valve replacement, implantation of per-

manent titanium cardiac pacemaker, 

and coronary artery bypass grafting 

have been recently published [27-29]. 

Autoimmune diseases (primarily rheu-

matoid arthritis) and immune deficiency 

have been occasionally associated with 

YNS, partially explaining the proneness 

to chronic infection of the respiratory 

system [30-33]. The hypothesis that 

YNS may be a paraneoplastic syndrome 

derives from reports of malignant dis-

eases diagnosed concurrently or closely 

thereafter in YNS patients [2,3,17,34-

42]. The frequency of association 

between YNS and various types of can-

cer is low and the matter remains con-

troversial; however, a careful anamnesis 

of medical history and possible signs of 

systemic disease is recommended.

Pathogenesis

The etiology of YNS is obscure and inves-

tigations are few. Most of the literature 

is from case reports, and the majority of 

case series include 3 or fewer patients, 

although large series of up to 41 cases 

have been published [1-3,21,23]. Despite 

the paucity of evidence, a unifying lym-

phatic mechanism has been proposed to 

explain the development of lymphedema, 

pleural effusion, and nail alterations in 

YNS. Defective lymphatic drainage may 

be responsible for the sclerosis of the nail 

matrix tissue observed at light micros-

copy examination, with ectatic, endo-

thelium-lined channels embedded in the 

fibrotic stroma, resulting in the clinically 

evident slow growth and thickening of 

the nails. The same mechanisms could 

be held responsible for the sclerosis and 

dilated lymphatic vessels also found in 

went rhinoseptoplasty and treatment 

with oral vitamin E (1,200 IU/day). One 

year later, his respiratory symptoms had 

resolved and his nails appeared com-

pletely cured (Figure 1, D and E).

Discussion

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 

on, other chronic respiratory symptoms 

including sinusitis, bronchitis, recurrent 

pneumonias, pleuritis, and bronchiecta-

sias have been included in the character-

istic pulmonary manifestations of YNS 

[16-20]. Only 2 criteria out of 3 are 

required to diagnose YNS, and the com-

plete triad is reported to be present in 

only 27%-60% of cases [1-3,16,17,19-

22]. The possible interval between the 

first clinical sign (lymphedema, lung 

manifestations) and nail alterations hin-

ders affirmation of the diagnosis; thus 

the condition may be underestimated.

Associated Conditions

The occurrence of lymphedema ranges 

between 29% and 80%, being the 

first sign of the syndrome in approx-

imately 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 manifesta-

tion being chronic cough, and bronchi-

ectasias are present in approximately 

44% of patients [2]. Acute or chronic 

sinusitis is frequently observed (14%-

83%), mainly affecting the maxillary 

and ethmoid sinus [1-3,19,21,22]. CT 

scans usually show mucosal thicken-

ing with enlargement of turbinates and 

fluid levels.



4 Review  |  Dermatol Pract Concept 2020;10(2):e2020031

underwent combined treatment with both rhinoseptoplasty 

and oral vitamin E supplementation, suggesting that a multi-

disciplinary 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 derma-

tologist 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.

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Regarding systemic treatment, oral zinc sulfate supple-

mentation (300 mg/day) resulted in improvement of lymph-

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Treatment for chronic rhinosinusitis is not specific for 

YNS patients; however, global response to medications such 

as oral antibiotics or topical intranasal steroids or deconges-

tants 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 respi-

ratory 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 treat-

ment 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 success-

ful 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 



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