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Case Report

PapilloneLefevre syndrome mimicking psoriasis e

A rare case report

K. Ramesh a,*, Maya Ramesh b, Karthik Venkataraghavan c

a Professor Department of Pedodontics & Preventive Dentistry, VMSDC, Salem, IndiabReader, Department of Oral Pathology VMSDC, Salem, IndiacProfessor & HOD, College of Dental Sciences, Ahmadabad, Gujarat, india

a r t i c l e i n f o

Article history:

Received 1 March 2012

Accepted 16 May 2013

Keywords:

PapilloneLefevre syndrome

Periodontitis

Hyperkeratosis

Psoriasis

* Corresponding author. 144, Andal Street, T9791842343 (mobile).

E-mail address: drrameshk@gmail.com (K0975-962X/$ e see front matter ª 2013 Indiahttp://dx.doi.org/10.1016/j.ijd.2013.05.003

a b s t r a c t

PapilloneLefevre syndrome is a rare disease characterized by skin lesions caused by palmar-

plantar hyperkeratosis and severe periodontal destruction involving both the primary and

permanent dentitions. It is transmitted as an autosomal recessive condition and consan-

guinity of parents is evident in about one third of the cases. This paper reports a unique case

of a patient with PapilloneLefevre syndrome (PLS) that was earlier mistaken for psoriasis.

The examination revealed severe hyperkeratosis on the hands and feet with associated se-

vere periodontal conditions. The patient was diagnosed with PapilloneLefevre syndrome

and suitable treatment was initiated.

ª 2013 Indian Journal of Dentistry. All rights reserved.

1. Introduction and to the volar wrists. Involvement of the soles extends to

PapilloneLefevre syndrome (PLS) was first described in the

literature by Papillon and Lefevre in 1924. More than 200 cases

have been reported till today. The syndrome is a rare auto-

somal recessive trait with an incidence between one and four

persons per million. 20e40% of the cases show parental con-

sanguinity.1 No gender predilection is detected till date.2

PapilloneLefevre syndrome is characterized by palmar-

plantar hyperkeratosis, and rapid destruction of the alveolar

bone and periodontium of both the primary and permanent

dentitions, commencing at the time of tooth eruption. Skin

lesions usually present from 6 months to 3 years of age,

approximating the time of tooth eruption. These may start as

diffuse red and scaly patches on the palms of the hands and

soles of the feet. Lesions are well demarcated and predomi-

nantly affect the palms extending to the thenar eminences

hirumal Nagar, Alagapur

. Ramesh).n Journal of Dentistry. Al

the Achilles tendon. There can be occasional involvement of

the eyelids, cheeks, labial commissures, knees, elbows,

thighs, externalmalleoli, toes and dorsal fingers. The soles are

frequently affected more severely than the other regions,

which makes walking difficult.1,2 Periodontal effects appear

almost immediately after tooth eruption when gingivae

become erythematous and edematous. Plaque accumulate in

the deep crevices and halitosis can be present. The primary

incisors are usually affected first and display marked mobility

by the age of 3 years. By the age of 4e5 years, all the primary

teeth are exfoliated and the gingival health comes back to

normal. But the same process is repeated as the permanent

dentition starts to erupt.1 Themajority of the permanent teeth

are lost by the age of 14e15. There is dramatic alveolar bone

destruction, often resulting in atrophied jaws.2 The case

described below is of a 4-year-old girl served to illustrate the

am, Salem, Tamil Nadu 636004, India. Tel.: þ91 427 2444886, þ91

l rights reserved.

i n d i a n j o u rn a l o f d e n t i s t r y 4 ( 2 0 1 3 ) 2 1 1e2 1 4212

periodontal effects of PapilloneLefevre syndrome on the pri-

mary dentition.

Fig. 2 e Hyperkeratosis of the soles of the feet.

2. Case report

A 4-year-old girl reported to the dental clinic with a chief

complaint of loose teeth and discomfort while eating. On

clinical examination all anterior teeth were mobile & skin le-

sions were present.

Family history revealed a consanguineous marriage of the

parents (first cousins), neither ofwhomappeared affected. The

mother reported that the skin lesions started appearing by the

end of one year after birth. They had presumed this to be pso-

riasis & started treatment but did not achieve the desired re-

sults. The patient was referred by a practitioner for a thorough

examination, proper diagnosis and treatment of the condition.

Extra oral examination revealed hyperkeratosis of the palms of

the hands, soles of the feet and the knees (Figs. 1 and 2).

Intraoral examination revealed that all the primary teeth were

present. Oral hygiene was poor. The upper and the lower an-

teriors showed plaque accumulation, gingival recession, juve-

nile periodontitis and mobility (Figs. 3 and 4). Periodontal

abscesses were seen associated with the lower right and left

first and second primary molars (Figs. 5 and 6). Radiographic

examination (orthopantomogram) confirmed the presence of

generalized destruction of the alveolar bone around the pri-

mary dentition with generalized horizontal bone loss. Tooth

buds of permanent teeth were seen below the deciduous teeth

(Fig. 7). From the presenting conditions, a diagnosis was made

of PapilloneLefevre syndrome. Because of the severe peri-

odontal destruction, periodontal treatment was initiated. The

patientwasput undermedications andwas recalled for scaling

and curettage. The patient is currently kept under periodic re-

view to initiate suitable treatment at an appropriate time.

3. Discussion

PapilloneLefevre syndrome is evident in 1e4 persons per

million population and the disease carriers are thought to be

2e4 per thousand persons.3 In most cases, dermatologic

Fig. 1 e Hyperkeratosis of the palms of the hand.

manifestations become evident in the first three years of life.

Some patients describe worsening of the symptoms in winter

mimicking the manifestations of psoriasis.

The oral manifestations consist of advanced periodontitis

involving both deciduous and permanent dentitions and

develop soon after the eruption of teeth. A rapid loss of

attachment is seen with the teeth lacking osseous support.

Radiographically teeth appear to float in soft tissues. Without

aggressive therapy, loss of teeth is inevitable. Alveolarmucosa

becomes normal when teeth are absent. Aggregatibacter acti-

nomycetemcomitans has been related to the periodontal

destruction. Although a hereditary component and leukocyte

Fig. 3 e Plaque accumulation and gingival recession in

upper anteriors.

Fig. 4 e Plaque accumulation and gingival recession in

lower anteriors.

Fig. 6 e Periodontal abscesses in relation to lower right first

and second primary molars.

i n d i a n j o u r n a l o f d e n t i s t r y 4 ( 2 0 1 3 ) 2 1 1e2 1 4 213

dysfunction can be demonstrated, it appears that an infection

with A. actinomycetemcomitans is necessary for the periodontal

component to develop. Leukocyte dysfunction may be

induced by infectionwithA. actinomycetemcomitans, secondary

to the generated leukotoxins.3

3.1. Histopathology

Sloan et al studied the gingiva of a 3-year-old Iranian boy

suffering from PapilloneLefevre syndrome was examined by

light and electron microscopy. Deep pockets associated with

predominantly Gram-negative plaque were present. The

gingival lesionwas dominated by plasma cells, many of which

Fig. 5 e Periodontal abscesses in relation to lower left first

and second primary molars.

were degenerate. Russell bodies were a prominent feature. No

defect of epithelium was detected.4 As this patient was not

willing for incisional biopsy, the histopathologic picture of

this patient is not available.

3.2. Pathophysiology

In subjects with PapilloneLefevre syndrome there is defective

cathepsin C production. The gene for cathepsin C lies on

chromosome 11. Cathepsin C is a lysosomal protease and it is

distributed to many tissues. Cathepsin C is involved in the

activation of T cells. The exact biochemical defect leading to

periodontal disease is still unclear. In 1942, Wannenmacher

suggested that PapilloneLefevre syndrome was due to a

combination of ecto and mesodermal malformations. Saaha-

net al suggested that a functional imbalance of collagenolytic

activity in the periodontal ligament was responsible for peri-

odontitis in PapilloneLefevre syndrome. In 1984, VanDyke

suggested that neutrophils from an individual with Papil-

loneLefevre syndrome exhibit decreased receptor affinity for

chemotaxins such as formyl peptides. Page RC et al in sug-

gested defective cementum formation to be the cause for

periodontitis in PapilloneLefevre syndrome. PapilloneLefevre

syndrome is associated with myeloperoxidase deficiency, low

integrin expression, defective phagocytosis and chemotaxins.

Neutrophils from individuals with PapilloneLefevre syn-

drome exhibit decreased affinity for chemotaxins.5

Fig. 7 e Orthopantomogram showing horizontal bone loss

in the primary dentition with permanent tooth buds.

i n d i a n j o u rn a l o f d e n t i s t r y 4 ( 2 0 1 3 ) 2 1 1e2 1 4214

Hattab et al, reported four cases of PapilloneLefevre syn-

drome affecting two Jordanian families with eight children. In

all patients there was a relationship between increased

severity of skin lesions and seasonal variations and intensified

periodontal destruction. Lass et al in three multiplex families,

one Ethiopian and two German, demonstrated linkage of

PapilloneLefevre syndrome with chromosome 11q13-q14.

Fischer et al, conducted a primary genome wide search by

homozygositymapping in a large consanguineous family with

four affected siblings. Homozygosity and linkage was

demonstrated in region 11q14 of chromosome.5

Toomes et al believe that the syndromemay be genetically

determined and have demonstrated loss-of-function muta-

tions affecting both alleles of the lysosomal protease

cathepsin C gene in patients with PLS. The cathepsin C gene,

which is located on chromosome 11q14.1-q14.3 has endo-

peptidase activity and is expressed in epithelial regions

commonly affected by PLS including palms, soles, knees, and

keratinized oral gingiva. It is also expressed at high levels in

various immune cells including polymorphonuclear leuko-

cytes, macrophages, and their precursors. Ryu et al believe

that the severe periodontal destruction seen in Papil-

loneLefevre syndrome may be a result of loss of function

mutation in the cathepsin C gene and subsequent dysregula-

tion of localized polymorphonuclear leucocytes in inflamed

periodontal tissues.6

Hart et al, reported mutations in cathepsin C gene in pa-

tients with PapilloneLefevre syndrome from five different

countries.5

A closely related disease, HaimeMunk syndrome also ex-

hibits palmoplantar keratosis, progressive periodontal dis-

ease, recurrent skin infections and several skeletal

malformations. In this syndrome, the skin manifestations are

more severe and the periodontal disease is milder. This also

exhibit mutation of the Cathepsin C gene and has been shown

to represent an allelic variant of PapilloneLefevre syndrome.3

Severe periodontal and alveolar bone destruction in children

necessitate that the life-threatening disorders should be

excluded. These differential diagnosis include leukemia and

neutropenias, where loosening of the teeth is an associated

feature, along with extensive gingivitis, hemorrhage and ul-

ceration. Other disorders where premature loss of primary

and/or permanent teeth occur include hypophosphatasia,

Langerhan’s cell histiocytosis, ChediakeHigashi syndrome,

acrodynia and acatalasia.7,8

3.3. Treatment modalities

Various treatment modalities have been suggested,

including: early extraction of all primary teeth to eliminate

all pathogens involved and allow the remaining teeth to

erupt without infection. A multidisciplinary approach is

necessary in the management of these patients. The skin

manifestations can be treated with emollients. The

administration of oral retinoids is the mainstay of hyper-

keratosis and periodontitis. The periodontal disease may be

arrested by improving oral hygiene, extraction of severely

diseased teeth, scaling, systemic antibiotics and long term

antimicrobial irrigation. But inspite of extensive peri-

odontal therapy and antibiotics, the disease progresses in

many patients until all the teeth are lost. The use of im-

plants can be considered if the remaining alveolar bone is

sufficient, for severely dentally compromised patients.

Rigorous oral hygiene, chlorhexidine mouth rinses,

frequent professional prophylaxis and periodic appro-

priate antibiotic therapy are necessary for long term

maintenance.3

Conflicts of interest

All authors have none to declare.

r e f e r e n c e s

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2. Papillon MM, Lefevre P. Deux cas de keratodermie palmaire etplantaire symetrique familiale (maladie de Meleda) chez lefrere et la soeur: coexistence dans les deux cas d’alterationsdentaires grave. Bulletin de la Societe Francaise de Dermatologie etde Syphiligraphie. 1924;31:82e84.

3. Neville Brad W, Damm Douglas D, Allen Carl M, Bouquot JerryE. Oral and Maxillofacial Pathology. 2nd ed. W B SaundersCompany; 2002.

4. Sloan P, Soames JV, Murray JJ, Jenkins WM. Histopathologicaland ultrastructural findings in a case of PapilloneLefevresyndrome. J Periodontol. 1984 Aug;55(8):482e485.

5. Rathod Varsha J, Joshi Nilesh V. PapilloneLefevre Syndrome: areport of two cases. J Indian Soc Periodontol. 2010 OctDec;14(4):275e278.

6. Sachdeva Shabina, Kalra Namita, Kapoor Pranav.PapilloneLefevre syndrome: report of a case and itsmanagement. J Clin Exp Dent. 2012;4(1):e77e81.

7. Galanter DR, Bradford S. Case report e hyperkeratosispalmoplantaris and periodontosis the PapilloneLefevresyndrome. J Periodontal. 1969;1:40e47.

8. Patel SJ, Umarji RH. PapilloneLefevre syndrome e a casereport. J Indian Acad Oral Med Radiol. 2004;16:306e310.