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\begin{document}

\title{Yellow Nail Syndrome In an Elderly Sudanese Female: A Case Report}



\author[1]{Abdelmuniem Ahmed}%
\author[1]{Mohamed  Y. Yousif}%
\author[1]{Isam  Abdelmageed}%
\author[2]{ Moh. Eljack}%
\author[3]{Khabab  Mohamed Ahmed}%
\author[3]{Malaz Tarig AbdAlla Mohamed}%
\author[1]{Sulieman  Abdelkareim G. Mohammed}%
\author[4]{Elhadi  B. Salih}%
\author[1]{Dina H. Osman}%
\affil[1]{University of Gezira Faculty of Medicine}%
\affil[2]{Medani Heart Centre}%
\affil[3]{University of Khartoum Faculty of Medicine}%
\affil[4]{Republic of Sudan Federal Ministry of Health}%


\vspace{-1em}



  
  \date{May 26, 2024}


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\selectlanguage{english}
\begin{abstract}
Yellow nail syndrome is a rare lymphatic abnormality without a clear
pathogenesis. Hereby, we report A 70-year Sudanese female 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).%
\end{abstract}%



\sloppy


\textbf{Yellow Nail Syndrome In an Elderly Sudanese Female: A Case
Report}

Abdelmuniem Ahmed\textsuperscript{1}, Mohamed Y.
Yousif\textsuperscript{2}, Isam Abdelmageed\textsuperscript{3}, Moh.
Mah. Fadelallah Eljack\textsuperscript{4}, Khabab Abbasher Hussien
Mohamed Ahmed\textsuperscript{5}, Malaz Tarig AbdAlla
Mohamed\textsuperscript{6}, Sulieman Abdelkareim G.
Mohammed\textsuperscript{7}, Elhadi B. Salih\textsuperscript{8}, Dina H.
Osman\textsuperscript{9}

\textbf{Affiliations}

\begin{enumerate}
\tightlist
\item
  Physiology department, Faculty of Medicine, University of Gezira,
  Gezira, Sudan, monem33246@hotmail.com
\item
  Resident Physician, Sudanese medical specialisation board, Khartoum,
  Sudan, www.\emph{mohamedyousif1993@gmail.com}
\item
  Consultant chest physician, Hasahesa teaching hospital, Gezira, Sudan,
  Drisamyassin@hotmail.com
\item
  University of Bakht Alruda, Faculty of Medicine, Medical Doctor at
  Medani Heart Centre, Medani, Sudan, ORCID: 0000-0002-2370-9368,
  m.mahmmoud96@gmail.com
\item
  University of Khartoum, Faculty of Medicine, Khartoum, Sudan, ORCID:
  0000-0003-4608-5321,\emph{Khabab9722@gmail.com}
\item
  University of Khartoum, Faculty of Medicine, Khartoum, Sudan, ORCID:
  0000-0001-7310-196X,\emph{Malaztarig@gmail.com}
\item
  Physiology department, Faculty of Medicine, University of Gezira,
  Gezira, Sudan,\emph{Suliemanabdelkareim33128@gmail.com}
\item
  Medical officer, federal ministry of health, Khartoum,
  Sudan,\emph{elhadi2811@hotmail.com}
\item
  University of Gezira, Faculty of Medicine, Gezira,
  Sudan,\emph{Dinakhater97@gmail.com}
\end{enumerate}

\textbf{Corresponding Author:}

Dr. Khabab Abbasher Hussien Mohamed Ahmed

Email: Khabab9722@gmail.com

Mobile: 00249907712134

ORCID: 0000-0003-4608-5321

Sudan, Khartoum State, Postal code: 11111

\textbf{Abstract}

Yellow nail syndrome is a rare lymphatic abnormality without a clear
pathogenesis. Hereby, we report A 70-year Sudanese female 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).

\textbf{Keywords:} Yellow nail syndrome; Acute respiratory distress
syndrome; Lymphedema; Edema; ARDS

\textbf{Key Clinical message:}

Whenever common causes are excluded; the co-existence of recurrent
respiratory affection and non-pitting edema in patients of more than 40
years should raise suspicion of yellow nail syndrome even in absence of
sinusitis, bronchiectasis or positive family history.

\textbf{Introduction:}

Yellow nail syndrome is a very rare disorder that has been noticed since
1927 (1). It affects both sex equally, with age of more than 40 years is
typical (2). The exact pathogenesis remains unclear but lymphatic system
anatomical and functional abnormalities remain as the predominant
theory, while other hypotheses suggest autoimmune, cancer and
paraneoplastic roles (3). Also a very rare familial case has been
reported (1).

Although it's only found in 27\%\_60\% of patients The diagnosis depends
on the presence of 2 out of; characteristic nail changes, respiratory
tract infection and lymphedema. The latter occurs in up to 80\% of cases
and may be the first sign (1). The common Nail changes that have been
described include nail discoloration (pale yellow to dark green), nail
hyperkeratosis with loss of the lunula, onycholysis, proximal nail-fold
erythema over curvature, cross-ridging, very hard and difficult-to-trim
nail , increased nail thickness, and slowed longitudinal growth (1,3).
Respiratory manifestations that are encountered include pleural
effusion, bronchiectasis, chronic cough and frequent sinusitis (1).The
condition may resolve spontaneously especially when it is paraneoplastic
or cancerous (1).

Oral vitamin E, and fluconazole showed a good response, while
intralesional steroids, oral zinc sulphate, and subcutaneous
immunoglobulins showed promising data (1). Although The prognosis
appears to be favourable; it requires extensive research.

\textbf{Case Presentation:}

A 70-year Sudanese female, diabetic and hypertensive with a past history
of ischemic stroke 7 years ago resulted in residual right-side weakness;
presented complaining of fever and altered level of consciousness for 2
days with history of recurrent productive cough and recurrent right
lower limb swelling for months. There is no family history of similar
condition, or connective tissue disease. The patient is neither a smoker
nor alcohol consumer. Her current medications included Glimepiride 4 mg
and Losartan 50 mg.

Clinical examination revealed awake, confused patients (GCS 14/15) ,
otherwise clear neurological examination, BP 150/90 mmhg, pulse was 80
beats per minute, SPo2 on 99\% of room air. There was yellowish
discoloration of her nails in both upper and lower extremities
associated with separation from the nail beds (Figure 1 and 2). Chest
examination revealed a right-side stony dullness, decreased air entry
and diminished vocal resonance. Also, a pitting right lower limb oedema.

Laboratory investigations showed random blood glucose of 44 mg/dl,
positive Blood Film for Malaria, normal Renal and Liver function tests.
Chest radiograph revealed a moderate right sided pleural effusion
(Figure 3). Therapeutic thoracentesis was done with 2 litres of a
straw-coloured fluid removed, sent for microscopic examination which
showed a hemorrhagic background pleural fluid, that's made of mixed
mononuclear inflammatory cells with lymphocytic predominance and it was
containing 3.0 g/dl proteins and 57.5 mg/dl glucose.

Diagnosis of yellow nail syndrome with pleural effusion and complicating
pneumonia was made.

The patient managed with Quinine infusion 600 mg T.D.S, 3rd generation
cephalosporin, vitamin E and prophylactic dose of heparin, however the
condition deteriorate progressively and the patient passed away on the
fifth day of admission due to acute respiratory distress syndrome
(ARDS).

\textbf{Discussion:}

Yellow nail syndrome was first discovered in 1927, but the first case
series of the disease was presented by Samman and White in 1964 (4).
Thirteen cases were presented sharing the common features of thickened
yellow nails with growth rates slower than normal (\textless{}0.25
mm/week) in comparison to( 0.5-1.2 mm\textbackslash{}week) in normal
individuals(4). Lymphedema presented in 10 out of the 13 cases, along
with respiratory manifestations consistent with pleural effusion,
bronchiectasis, and chronic sinusitis, which are late manifestations of
the syndrome. Most cases of YNS are sporadic (5). With very little
evidence supporting the hypothesis that YNS is an inheritable condition.
Despite that, rare familial cases were reported with a doubted autosomal
dominant transmission pattern. Very few juvenile cases of the disease
were reported (6,7). In this section, we discuss the intersections of
this patient's YNS presentation with cases reported in literature.

The presentation of this case is relatively late, as the patient
presented at 70 years old. Patients of YNS usually present between their
4\textsuperscript{th} and 6\textsuperscript{th} decade of life(8).
However, like known cases in literature(9,10), this case presents the
classic triad of yellow nail syndrome consisting of: yellow and
thickened nails (figure 1, figure 2), respiratory manifestations (figure
3), and lymphedema (figure 1 and 2). And like other cases of YNS, the
case was diagnosed clinically, as Yellow nail syndrome's diagnosis is a
clinical one (2). And as suggested by Hiller et al, can be made with two
of the three known manifestations of the disease, as the observation of
these signs may resolve overtime (11). Nonetheless, a diagnosis of the
condition can't be made in the absence of nail abnormalities (2). And
hence, based on the look of the patient's nails, chest radiograph, and
lower limb swelling the diagnosis was confirmed.

The case was a sporadic case. No similar signs of the disease were
reported in the patient's family. Patients also presented with ankle and
foot oedema, as in the majority of the cases reported by Samman and
White in their thirteen case series report (9) and 9 out of 17 cases
presented by Bull et al (12). No rhinosinusitis was reported in this
patient's condition.

The diseases known to be associated with YNS are malignancies,
immunodeficiency states, connective tissue diseases, diabetes mellitus,
thyroid dysfunction, hemochromatosis, obstructive sleep apnea,
Guillain--Barre\selectlanguage{ngerman}´ syndrome, xanthogranulomatous pyelonephritis,
tuberculosis, myocardial infarction, nephrotic syndrome, exudative
enteropathy, hypoalbuminemia, and drugs (thiol compound therapy) (2).
Comorbidities of patients presenting in this case intersects with this
group in diabetes mellitus only. The patient also had hypertension and
had a history of stroke. Hypertension is a comorbidity that was reported
for other patients with YNS (13,14) although no association between the
two conditions has been confirmed yet. In a case of an 65 year old man
with hypertension and stroke, it was also suggested that the syndrome
might be linked to the patient's cardiac pacemaker (14). However, all of
these hypotheses are questionable..

The therapeutic thoracentesis of the patient showed a straw-colored
fluid of two litres, which can expected in a pleural effusion patient
and is consistent with the patient's presentation with fever, as lower
respiratory tract infections, pneumonias, and bronchiectasis present in
half of YNS patients(2,15). And hence as indicated by her symptoms, the
patient had pneumonia.

Generally, analysis of pleural fluid of YNS patients is characterised by
being transudative, with high protein content (2,16). Analysis of this
patient's pleural fluid showed mixed mononuclear inflammatory cells with
lymphocytic predominance. With 3.0 g/dl protein and 57.5 mg/dl glucose
content. Previous findings in literature entail that lymphocytic
predominance is the rule when it comes to cellular analysis (8). The
patients pleural fluid is also exudative by protein criteria and
transudative by cholesterol and lactate dehydrogenase criteria as with
previously known cases in Maldonaldo et al in which he performed high
yield analysis of pleural fluid of 41 patients (8).

Patient's chest radiograph shows moderate right sided pleural effusion
(figure 3). This radiographic finding is particularly similar to a case
reported by Maldonaldo et al where the patient's pleural effusion was
bilateral but particularly larger in the right chest (2).

Although not all known cases of yellow nail syndrome present with
lymphedema, some cases do indeed present without it (9,12). The
likelihood of the lymphadenopathic theory of the disease still prevails.
The presentation of this case can be regarded as supportive of this
theory, although confirmatory integrity of this theory still remains a
question under investigation.

Cases of YNS's respiratory manifestations are treated with postural
drainage, other pulmonary hygiene measures, and antimicrobials (2).
Treatment of pleural effusion depends on the severity of the effusion.
Therapeutic thoracentesis might suffice in management. With pleurodesis
coming as an option for recurrent effusion patients (2). The use of
topical steroids or vitamin E has been described though the evidence
supporting their use remains scarce (8,17).

No definitive treatment for YNS was confirmed until now. However,
several treatment regimens for the disease were proposed in literature,
but they remain as treatment efforts for individual cases. Fluconazole,
vitamin E, and topical steroids have been the most popularly used
treatments for YNS. But their ascribed treatment properties are still
under question due to scarcity of supportive evidence (8,17,18). Another
effort by Algain et al (18) suggested terbinafine and topical minoxidil
as curative treatments for the disease that promote the formation and
enhance barriers and thus reduce peripheral swelling in a first of its
form remarks. Like many other cases with the disease (2), this case was
managed with supportive treatments to ameliorate the severity of the
symptoms. Specifically, regarding the patient's treatment for YNS, along
with the therapeutic thoracentesis, she was treated with vitamin E. The
patient took Glimepiride 4 mg and Losartan 50 mg. For her diabetes and
hypertension, quinine for her Malaria, 3rd generation cephalosporin for
her pneumonia, and a dose of heparin as prophylaxis for her
hypertension. Despite efforts, the patient's condition deteriorated
quickly and she passed away due to an episode of acute respiratory
distress syndrome (ARDS). Up to our knowledge, there is no published
literature linking yellow nail syndrome to a specific fatal
complication.

The course of the disease is generally known to be benign; the prognosis
of yellow nail syndrome cases shows decreased life longevity in
comparison to control population (2). And although when presented to the
clinic the patient underwent the proper investigations to diagnose the
syndrome and was managed with the up to date known management of the
disease, this late presentation and hence identification of the
patient's condition might have affected her prognosis, along with the
patient's co- morbidities and age which might have further complicated
the condition and our understanding of the progression of the case.

\textbf{Conclusion:}

Yellow nail syndrome is a syndrome that presents with yellow thickened
nails, respiratory manifestations, and lymphedema. In this case, the
patient has presented in the 8\textsuperscript{th} decade of her life as
a sporadic case with the classic triad of the disease with no
complications. Patients' pleural profile and chest radiograph matched
that of patients in existing literature. Also, the case had a history of
hypertension, diabetes, and stroke. Although diabetes has been noted to
be associated with yellow nail syndrome. There is no conclusive evidence
regarding its relation to hypertension despite a number of noted cases
up until now. Patient passed away after an episode of acute respiratory
distress syndrome (ARDS). No similar reports of this specific case of
death were found in literature.

\textbf{Declarations:}

\textbf{Consent to participate:}

Both verbal and written consents to participate and to publish this
information were obtained from the patient.

\textbf{Consent to publish:}

Consent for publication was obtained from all authors.

\textbf{Availability of data and materials:}

The datasets used and \textbackslash{} or analysed during the current
study are available from the corresponding author on reasonable request.

\textbf{Competing interests:}

The authors have no conflict of interest to declare.

\textbf{Funding:}

The authors received no funding for this work.

\textbf{Authors contribution:}

AA, MYY and IA: Took history, did investigations and participated in
writing first draft.

MMF, KAH and MTA: Wrote first and final drafts.

SAG, EBS and DHO: wrote and revised final draft.

All authors contributed significantly in the study.

\textbf{Acknowledgment:}

Not applicable.

\textbf{References:}

1. Vignes S, Baran R. Yellow nail syndrome: a review. Vol. 12, Orphanet
Journal of Rare Diseases. BioMed Central Ltd.; 2017.

2. Maldonado F, Ryu JH. Yellow nail syndrome. Vol. 15, Current Opinion
in Pulmonary Medicine. 2009. p. 371--5.

3. Soong LC, Haber RM. Yellow Nail Syndrome Presenting With a
Pericardial Effusion: A Case Report and Review of the Literature. J
Cutan Med Surg {[}Internet{]}. 2018;22(2):190--3. Available from:
https://doi.org/10.1177/1203475417738970

4. Samman P, White WF. of Dermatology. Br J Dermatol.
1964;76(April):153--7.

5. Kulo\selectlanguage{romanian}ǧlu Z, \selectlanguage{ngerman}Üstünda\selectlanguage{romanian}ǧ G, Kirsa\selectlanguage{ngerman}çlio\selectlanguage{romanian}ǧlu CT, Kansu A, Bingol-Kologlu M,
Vargun R, et al. Successful living-related liver transplantation in a
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6. Razi E. Familial yellow nail syndrome. Dermatol Online J. 2006
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7. Lambert EM, Dziura J, Kauls L, Mercurio M, Antaya RJ. Yellow nail
syndrome in three siblings: A randomized double-blind trial of topical
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8. Maldonado F, Tazelaar HD, Wang CW, Ryu JH. Yellow nail syndrome:
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9. SAMMAN PD, WHITE WF. THE ``YELLOW NAIL'' SYNDROME. Br J Dermatol.
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10. SAMMAN PD, STRICKLAND B. Abnormalities of the finger nails
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11. Hiller E, Rosenow EC, Olsen AM. Pulmonary manifestations of the
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from: http://dx.doi.org/10.1378/chest.61.5.452

12. Bull RH, Fenton DA, Mortimer PS. Lymphatic function in the yellow
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14. Suzuki T, Tokuda Y, Kobayashi H. The development of yellow nail
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15. Wiggins J, Strickland B, Chung KF. Detection of bronchiectasis by
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16. Runyon BA, Forker EL, Sopko JA. Pleural-fluid kinetics in a patient
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17. Szolnoky G, Lakatos B, Husz S, Dobozy A. Improvement in lymphatic
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