Abstract
Background: Papillon-Lefèvre Syndrome is a rare autosomal
recessive disorder characterized by the presence of palmoplantar
hyperkeratosis and severe periodontitis leading to premature loss of
dentition. Triangular lunulae is a feature considered pathognomonic for
an entirely unrelated condition, the Nail and Patella Syndrome, and has
not been previously reported together with Papillon-Lefèvre Syndrome.
Case Summary: A 16-year-old girl presenting with a long-term
history of palmoplantar hyperkeratosis extensive loss of dentition and a
short-term history of pyogenic infection of the right big toe. The
examination of the patient revealed a rare finding of triangular lunulae
on all fingernails. The patient was diagnosed clinically as a case of
Papillon-Lefèvre Syndrome. Evaluation of other family members allowed
early diagnosis of the syndrome in another sibling and the timely
initiation of treatment to prevent similar morbidity as in the primary
patient.
Conclusion: Triangular lunulae, considered pathognomonic for
Nail-Patella Syndrome, may also be a feature of other syndromes, such as
the case here.
Keywords: triangular lunulae, Papillon-Lefèvre syndrome, case
report
Key Clinical Message: Triangular lunulae, considered
pathognomonic for Nail-Patella Syndrome, may also be a feature of other
syndromes, such as the case here. Papillon-Lefèvre syndrome is a rare
genodermatosis associated with significant morbidity. Consanguinity is
an established high-risk factor. Early diagnosis and treatment can
mitigate the morbidity in affected individuals and societal awareness
around consanguinity can help reduce the burden of the disease in
populations where the practice is common.
Introduction: First described by Papillon and Lefèvre in 1924
[1], Papillon-Lefèvre Syndrome (PLS) is a rare, autosomal recessive
disorder [2] characterized by the presence of palmoplantar
hyperkeratosis and frequent bacterial infections, particularly severe
periodontitis resulting in early loss of deciduous and, eventually,
permanent teeth [2-3]. The prevalence of the PLS is reported to be
1-4 cases per million individuals [4]. Skin changes are the earliest
to appear, usually within the first year of life, with diffuse,
erythematous, palmoplantar hyperkeratosis being the most commonly noted
presentation [3]. Additional features may include dural and choroid
plexus calcifications, hyperkeratotic plaques on the elbows and knees,
pseudo-ainhums around digits, and infrequently, mental retardation [3,
4]. PLS is caused by a mutation in the CTSC gene encoding a lysosomal
protease, cathepsin C [5]. The gene is widely and strongly expressed
in immune cells, such as neutrophils and macrophages, and also at sites
mainly affected in PLS, including the palms, soles, knees, and
keratinized gingiva in the oral cavity, elucidating the mechanisms
underlying the symptomatology that is observed [5]. Aberrations in
the normal functioning of cathepsin C in neutrophils in PLS have been
noted to result in their excessive recruitment to periodontal tissue
which, paired with their reduced antimicrobial ability due to the
protease deficiency, leads to the classical, severe periodontitis that
is noted in the disorder and which is the main reason for the premature
exfoliation of primary and secondary teeth [6]. Besides
periodontitis, infections of other sites are also common in patients
with PLS, including pyogenic skin infections, abscesses in internal
organs such as the kidneys and liver, and recurrent respiratory and
urinary tract infections [7]. An allelic variant of PLS, Haim-Munk
syndrome is also characterized by the cardinal features of PLS, namely,
palmoplantar hyperkeratosis and premature periodontal destruction but
with the addition of onychogryphosis, acro-osteolysis, and
arachnodactyly [8].
Nail and Patella Syndrome is a distinct clinical entity, a rare
autosomal dominant condition comprising variable nail, skeletal, and
systemic anomalies, including patellar hypoplasia and agenesis, elbow
dysplasia, radial head dislocation, characteristic iliac horns, nail
abnormalities, nephropathy and glaucoma [9]. Though nail
abnormalities are variable, triangular lunulae in the fingernails are
considered pathognomonic for the condition [10]. So far, the
presentation of triangular lunulae has not been reported with other
conditions. Identifying the feature in our patient with PLS is the first
report of its nature.
Case History and Clinical Examination: A 16-year-old girl, the
second eldest of four daughters to parents who were first-degree
cousins, was referred to the dermatology clinic at Khyber Teaching
Hospital, Peshawar, Pakistan with a 3-months-long complaint of a small,
soft outgrowth from the lateral periungual skin fold of the right
big-toe that appeared spontaneously as an erythematous papule and grew
slowly in size with time, eroding the adjacent nail plate and ultimately
exuding purulent discharge. On further inquiry, the patient’s mother
reported a history of persistent and progressively worsening thickening,
scaling, and fissuring of the palms and soles that was first noticed
when the patient started walking at the age of one. Initially, the
complaint was restricted to the palms and soles but later progressed to
involve the dorsal surfaces of the hands and feet. The skin complaints
were accompanied by frequent swelling and friability of the gums which
became more noticeable and pronounced when the patient began to
prematurely lose her primary dentition by the age of two, which had
sprouted normally. The gum complaints subsided once all deciduous teeth
were lost, only to reappear with the eruption of secondary dentition.
Consequently, the patient also lost most of her secondary dentition by
the age of 11. The patient also had a history of recurrent, focal skin
infections over the years, primarily on the scalp, that were slow to
resolve and would frequently lead to ulceration. However, these lesions
were responsive to topical and oral antibiotics. There was also a
history of progressively worsening dystrophy of the nails of the fingers
and toes and thickened, scaly plaques on the elbows and knees that had
resolved a few years back to leave behind atrophic, hypopigmented skin.
According to the mother, there were no ante- or postnatal complications,
and the patient was otherwise healthy and achieved her developmental
milestones on time. Over the years, the patient had had numerous
outpatient visits to dental and dermatological clinics, however, a firm
diagnosis was not made, resulting in interrupted and mostly symptomatic
medical management. The youngest sister of the patient, age 9 years, was
also found to be following an almost identical sequence of symptoms as
the patient, including palmoplantar thickening, loss of secondary
dentition, and frequent slow-healing, scalp infections.
On examination, the patient had diffuse palmoplantar erythema,
thickening, and scaling that extended confluently onto the dorsal
aspects of the hands and feet. Multiple areas of fissuring were noted on
the palms and soles (Figures 1 & 2).
Concentric band-like thickening of the skin of the fingers was also
observed (Figure 3A) resulting in accentuation of the pulp of the soft
tissue between the interphalangeal joints. The fingernails showed an
exaggerated longitudinal curvature, an enlarged triangular lunula
(Figures 2A & 3B), multiple pits and horizontal grooves, and slight
distal discoloration (Figure 3B).
The right big toenail had a 1x1cm soft, fluctuant, exophytic growth with
purulent exudate and crusting arising from the left, lateral periungal
skin fold and involving the lateral nail bed (Figure 4A). Both big-toe
nails showed yellow discoloration and multiple horizontal and
longitudinal grooves. The second and fifth toenails of the left foot
showed onychogryphosis while the remainder of the toenails of the left
foot showed mild dystrophy (Figure 4B). The second to fifth toenails of
the right foot were normal (Figure 4A). Triangular lunulae were not
noted in the toenails.
Oral cavity examination revealed signs of mild gingival inflammation of
the right, lower side. Two upper molars, a single left lower molar, and
a loose right upper incisor were the only teeth noted (Figure 5). The
elbows had bilaterally symmetrical hypopigmented, atrophic plaques
(Figure 6A) whereas the knees showed similar plaques without atrophy
(Figure 6B). No abnormality of the hair was noted. A systemic
examination was also unremarkable.
Examination of the younger sister of the patient revealed plantar
thickening and scaling, increased dental spacing with signs of gingival
inflammation, and an ulcerated plaque on the scalp with alopecia (Figure
7).
Methods: Biochemical and radiological workup was unremarkable.
This included an ultrasound of the abdomen and pelvis, a skull X-ray,
and an X-ray of the hands and feet to rule out liver and renal
abscesses, intracranial calcifications, and acro-osteolysis,
respectively. A genetic analysis could not be done given the
nonavailability of the facility in Pakistan. Work-up did not identify
features consistent with Nail and Patella syndrome.
Results and Conclusion: Based on the history and examination, a
clinical diagnosis of Papillon-Lefèvre Syndrome was made. The patient
and family were counseled regarding the diagnosis in both the patient
and her sister and its implications and prognosis. The patient was
started on oral Isotretinoin, antibiotics, a topical combination of a
Vitamin D analog and steroids, and emollients. Surgery and Dentistry
departments were involved in the management of the right big toe
granulation tissue and dental rehabilitation, respectively.
Papillon-Lefèvre syndrome is a rare genodermatosis associated with
significant morbidity. Consanguinity is an established high-risk factor.
Early diagnosis and treatment can mitigate the morbidity in affected
individuals and societal awareness around consanguinity can help reduce
the burden of the disease in populations where the practice is common.
Discussion: Despite the inability to pursue genetic testing for
a confirmed diagnosis, the abundant clinical evidence in the patient,
supported by the consanguinity of the parents and similar clinical
findings in another sibling helped in establishing the diagnosis of
Papillon-Lefèvre Syndrome. Papillon-Lefèvre Syndrome is a rare autosomal
recessive disorder whose prevalence is estimated at 1-4 cases per
million individuals using statistical analysis [2]. The results of
such estimations depend on the accuracy of the data on consanguinity in
the study population, indicating that the mentioned prevalence may be an
underestimation for populations with higher rates of consanguinity, such
as Pakistan [11]. Higher numbers of PLS in countries with similarly
high rates of consanguinity, for example, Saudi Arabia and India
[12,13], may serve as an indication of the prevalence of the disease
in Pakistan. Early diagnosis and treatment may control the periodontitis
observed in PLS and significantly delay or even stop the loss of teeth.
Rigorous dental care under the supervision of a dentist, stringent oral
hygiene, prophylactic antibiotic cover, and the use of oral retinoids
have all been indicated in the preservation of teeth in PLS [14].
Dental prostheses can significantly reduce morbidity in patients with
extensive teeth loss. Unfortunately, a timely diagnosis was missed in
our patient resulting in loss of almost all teeth. Establishing the
diagnosis in our patient helped us diagnose the younger sibling with PLS
as well, allowing her to seek early treatment. The allelic variant of
PLS, Haim-Munk syndrome, is extremely rare, however, cases have been
reported in Pakistan and in Pakistani origin families [15]. Our
patient had onychogryphosis of her toenails, a feature found in
Haim-Munk syndrome [8] but lacked acro-osteolysis and
arachnodactyly. The remarkable finding noted in our patient was the
presence of a triangular lunula, which is one of the pathognomonic
features of Nail-Patella syndrome [16]. To the best of our
knowledge, literature on PLS has not mentioned the presence of
triangular lunula of nails, which in our patient indicates an extremely
rare finding. The underlying mechanisms behind the development of the
triangular lunulae remain an enigma though its association with median
nail dystrophy has been reported [17]. Identification of the
triangular lunulae in our case opens the possibility of the feature
occurring in other conditions as well.
Author’s Contribution: ZKS, MK, and IU conceived the idea,
collected the patient information, and critically reviewed the
manuscript. ZI was responsible for graphics, and ZI, QAK, BS, and RV
wrote the initial manuscript. All authors reviewed and approved the
final manuscript before submission.
Consent: Written informed consent was taken from the parents of
the patients for publishing this case report and its accompanying
images.