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 (<0.25
mm/week) in comparison to( 0.5-1.2 mm\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
4th and 6th 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´ 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.