Papillon-Lefèvre Syndrome:A Case Report

Yu-Lei Zhao,Zhao Feng,Bin Hu,Liu-Qing Chen,*

1Department of Dermatology,The Third Hospital of Soochow University,Changzhou,Jiangsu,213003,China,2Department of Dermatology,Wuhan No.1 Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430022,China.

Abstract Introduction:Papillon-Lefèvre syndrome(PLS)is an autosomal recessive disorder characterized by a diffuse palmoplantar hyperkeratosis and early periodontal destruction.Only a few PLS cases are reported by dermatological clinicians due to its rarity.

Keywords:Papillon-Lefvre syndrome,Palmar-plantar hyperkeratosis,Case report

Introduction

Papillon-Lefèvre syndrome(PLS)is an extremely rare autosomal recessive genetic disorder characterized by palmoplantar hyperkeratosis with progressively destructive periodontitis.Genetic,immunologic,and bacterial etiologies have been thought to be involved in the etiopathogenesis of PLS,and parental consanguinity is a contributive factor for this condition.PLS is commonly reported by stomatological doctors because it is usually present with oral lesions,here we describe a 16-year-old Chinese boy,who was born to consanguineous parents and presented with classic skin features of PLS,which may be helpful for comprehensive understanding of this rare disease by dermatological clinician.

Case report

A 16-year-old Chinese boy presented with a history of thickening and flaking of the skin over the palms and soles since 4 years of age.The severity of the skin lesions exhibited seasonal variation and worsened in winter.He had also experienced recurrent episodes of swollen gums with premature loss of teeth.He reported that the teeth had been lost without any noticeable trauma.He had been born to apparently healthy consanguineous parents(cousins).The patient’s medical history showed that he had sought therapeutic intervention for his palmoplantar keratoderma and periodontitis,but the cause of his condition had not been clearly determined and treatment had been unsatisfactory.

Cutaneous examination revealed symmetrically diffuse,erythematous,hyperkeratotic,anddesquamating lesions on both palms and soles.The lesions extended onto the dorsal surfaces of the hands and feet with a clear demarcation separating them from the normal skin(Fig.1A and 1B).Well-circumscribed psoriasiform,erythematous,scaly plaques were present on the bilateral elbows and knees.Intraoral examination revealed swollen gums and gingival inflammation with bleeding upon manipulation(Fig.1C).His hair and nails showed no abnormalities.Histopathological examination of the left palmar lesion revealed changes characteristic of psoriasiform lesions,including parakeratotic hyperkeratosis,hypergranulosis,regular acanthosis,and a dense perivascular lymphohistiocytic infiltration.The results of laboratory examinations were unremarkable.

Figure 1.Clinical presentation of the patient with Papillon-Lefèvre syndrome.(A and B)Diffuse erythematous,hyperkeratotic,desquamating lesions were present on the palms and soles.(C)Intraoral examination revealed swollen gums and gingival inflammation.

Based on the patient’s history,clinical presentation and biopsy findings,a diagnosis of PLS was established.The patient received treatment with oral retinoids and adjunctive systemic antibiotics.His periodontal status was evaluated by dentists,and periodontal therapy in the form of scaling and root planing was performed.

Written informed consent for publication of the clinical details and images was obtained from the patient’s mother.Three months after presentation,he continued to have recurrent gingival inflammation,although his skin lesions improved.He has since been lost to follow-up.

Discussion

Firstly described by the two French physicians-Papillon and Lefèvre in 1927,PLS is a rare genodermatosis of autosomal recessive inheritance with an estimated prevalence of one to four cases per million and an equal sex distribution.1Parental consanguinity was demonstrated in about onethird of previously reported case series.2PLS usually occurs within the first 4 years of life.Clinically,classic manifestations include diffuse transgradient palmoplantar hyperkeratosis and aggressive prepubertal periodontitis.The skin lesions are sharply demarcated and can spread to the lateral side of the palms and soles and dorsal side of the fingers and toes(i.e.,transgrediens).The lesions may also involve the knees and elbows,as in the patient described herein.

Although the exact pathogenesis of PLS remains unclear,this condition has been determined to result from loss-offunction mutations in the cathepsin C gene(CTSC)on chromosome11q14.1-q14.3.Thisgene ishighlyexpressedin immune defense cells and epithelial tissues,3particularly the gingiva and skin of the palms and soles.Mutations in CTSC lead to absent or reduced proteolytic activation of some serine proteases,including neutrophil elastase,proteinase 3,and cathepsin G.4Proteinase 3 has been proven necessary for generation of the cathelicidin antimicrobial peptide LL-37;however,recent studies have demonstrated that LL-37 is reduced in the gingival crevicular fluid and neutrophils of patients with PLS.5-6Thus,lymphocytes and natural killer cells in patients with PLS exhibit impaired cytotoxic lymphocyte function,which may explain the outgrowth of periodontal pathogenic bacteria.Various subgingival microflora,especially Aggregatibacter actinomycetemcomitans,play a vital role in the pathogenesis of PLS.7Further researches on the CTSC-mediated immune defense against periodontal pathogenic bacteria may pave the way for the development of novel therapies for PLS.

Histopathological findings of the skin lesions of patients with PLS are usually nonspecific.The diagnosis is based on the patient’s history and clinical manifestations.The most common differential diagnosis of PLS is Haim-Munk syndrome,which also originates from an identified mutation on the CTSC gene and is characterized by similar palmoplantar hyperkeratosis and prepubertal periodontitis.The additional features of arachnodactyly,acroosteolysis,onychogryphosis,and pes planus help to distinguish Haim-Munk syndrome from PLS.8

PLS frustrates patients psychologically,socially,and aesthetically,and its management is challenging.The skin lesions are usually treated with emollients and keratolytics.Oral retinoids have been shown to improve both the dermatological and oral lesions.9Systemic antibiotics can effectively reduce the active periodontitis.Regular performance of professional tooth scaling and root planing helps to improve the quality of life.

In summary,we have herein described a typical presentation of PLS with both palmoplantar hyperkeratosis and periodontal loss in a patient with parental consanguinity.We have highlighted the rarity of this entity,which provides opportunities to investigate the complex interactions of genetic,immunologic,and microbiological factors involved in pathogenesis of PLS.