Papillon-Lefevre Syndrome

Background

This is a rare disease, classically diagnosed as a keratoderma. It is an autosomal recessive disorder characterized by focal hyperkeratosis with punctiform accentuation of palmoplantar surfaces with accentuation of creases. The lesions may spread to elbows and knees. The disease has many association but notably deafness and calcification of dura.

OUTLINE

Epidemiology

Laboratory/Radiologic/Other Diagnostic Testing

Gross Appearance and Clinical Variants

Histopathological Features and Variants

Prognosis

Treatment

Commonly Used Terms

Internet Links

EPIDEMIOLOGY CHARACTERIZATION

SYNONYMS Keratosis palmoplantaris with periodontopathy

INCIDENCE/PREVALENCE Rare

AGE Birth

LABORATORY/RADIOLOGIC/
OTHER TESTS
CHARACTERIZATION

RADIOLOGIC

LABORATORY MARKERS

NEUTROPHIL DYSFUNCTION

Papillon-Lefevre syndrome: neutrophil function in 15 cases fron 4 families in Egypt.

Ghaffer KA, Zahran FM, Fahmy HM, Brown RS.

Oral Medicine & Periodontology Department, Faculty of Oral & Dental Medicine, Cairo University, Egypt.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999 Sep;88(3):320-5 Abstract quote
OBJECTIVE: The primary purpose of this study was to investigate the periodontal pathologic cause of Papillon-Lefevre syndrome by comparing, with respect to neutrophil function, probands with Papillon-Lefevre syndrome from 4 families in Egypt, unaffected siblings of the probands, and age-matched and gender-matched control subjects.

STUDY DESIGN: Family histories and clinical dermal and oral manifestations of Papillon-Lefevre syndrome were evaluated for 15 affected members of 4 families with the syndrome, 10 siblings of the probands, and 7 age-matched and gender-matched controls. Phagocytic and intracellular killing (lytic activity) of polymorphonuclear neutrophils was evaluated for all subjects according to a modification of the method of Wilkinson; opsonization was evaluated according to a modification of the methods of Cutler et al. Data were analyzed by means of analysis of variance.

RESULTS: Family pedigrees were plotted, and consanguinity was noted in 3 of the 4 families with Papillon-Lefevre syndrome. The means and SDs for phagocytic killing, lytic activity, and opsonization indices were as follows: probands, 4.76+/-1.99, 0.42+/-0.20, and 0.84+/-0.07; unaffected siblings, 10.4+/-1.3, 3.3+/-0.3, and 0.84+/-0.07; controls, 10.8+/-0.8, 3.5+/-0.6, and 0.85+/-0.05. The phagocytic killing and lytic activity indices demonstrated significance between the probands and both siblings and controls (P<.0005), whereas the opsonization index did not demonstrate significance between groups.

CONCLUSIONS: Significantly decreased neutrophil function in probands with Papillon-Lefevre syndrome was demonstrated with respect to neutrophil phagocytotic and lytic activity but not with respect to opsonization. Therefore, specific neutrophil dysfunction appears to be etiologically involved in this disorder.

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

GENERAL

Atypical familial Papillon-Lefevre syndrome.

Inaloz HS, Harman M, Akdeniz S, Inaloz SS, Isik AG.

Department of Dermatology, University of Wales College of Medicine, Cardiff, UK.
J Eur Acad Dermatol Venereol 2001 Jan;15(1):48-50 Abstract quote
The Papillon-Lefevre syndrome is a rare autosomal recessive disorder. Consanguinity seems a notable prerequisite. Papillon-Lefevre syndrome manifests in the first 6 months of life with rapidly progressive periodontitis and severe alveolar bone destruction leading to early loss of both the deciduous and permanent teeth in association with palmo-plantar hyperkeratosis.

We present two unusual cases of familial Papillon-Lefevre syndrome, one of whom has only late onset of mild skin lesions and the other has severe skin lesions and relatively mild periodontal disease. A number of other cases recently described have also had atypical features.

Papillon-Lefevre syndrome: a case report and review of the literature.

Gonzalez JR, Chabrier L, Rodriguez RJ.

Department of Dermatology, University of Puerto Rico, School of Medicine, San Juan.
P R Health Sci J 1997 Sep;16(3):279-81 Abstract quote
Papillon-Lefevre syndrome is a rare autosomal recessive syndrome associated with palmoplantar keratoderma and early onset periodontal disease that results in loss of the teeth.

Actinomyces Actinomycetemcomitans causing periodontal damage, and alterations in the polymorphonuclear leukocyte function have been postulated or probable pathogenetic mechanism.

Early recognition of this entity as well as a multidisciplinary management may help in the prognosis of these cases.

The Papillon-Lefevre syndrome: keratosis palmoplantaris with periodontopathy. Report of a case and review of the cases in the literature.

Haneke E.
Hum Genet 1979 Sep 2;51(1):1-35 Abstract quote
The Papillon-Lefevre syndrome (PLS) is an autosomal recessive trait characterized by diffuse transgredient palmar-plantar keratosis (PPK) and premature loss of both the deciduous and permanent teeth. In most cases, the PPK is noted within the first 3 years of life.

The periodontal lesions begin shortly after the start of both the primary and the permanent dentitions. The teeth are affected in the order of their eruption, exhibiting inflammation of the periodontal tissue, bleeding of the gums, pocket formation, loosening, and finally spontaneous exfoliation without showing definite signs of root resorption. After an edentulous interval, the same process begins anew shortly after the second dentition.

Ectopic intracranial calcifications, mental retardation, and increased susceptibility to infections have often been seen in PLS patients and may thus be regarded as facultative signs.

HISTOLOGICAL TYPES CHARACTERIZATION

GENERAL Keratoderma

PROGNOSIS CHARACTERIZATION

DENTAL

Osseointegrated implants in a patient with Papillon-Lefevre syndrome. A 4 1/2-year follow up.

Ullbro C, Crossner CG, Lundgren T, Stalblad PA, Renvert S.

Department of Dentistry, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
J Clin Periodontol 2000 Dec;27(12):951-4 Abstract quote
BACKGROUND: The Saudi female reported in this study was diagnosed with Papillon-Lefevre syndrome. She had lost all her teeth, including third molars, at the age of 18 years.

METHOD: She was wearing full dentures for 7 years, before 5 titanium implants were installed in the mandible.

RESULTS: 4 1/2 years after the implant installation, the treatment was clinically and radiographically successful. Neither A. actinomycetemcomitans nor P. gingivalis were detected at any of the implants. This very encouraging result does not differ from what is generally reported in edentulous medically healthy patients.

CONCLUSION: The use of implants could considerably enhance future therapeutic options for the severely dentally compromised patients with Papillon-Lefevre syndrome.

TREATMENT CHARACTERIZATION

GENERAL

ANTIBIOTICS

Combined systemic and local antimicrobial therapy of periodontal disease in Papillon-Lefevre syndrome. A report of 4 cases.

Rudiger S, Petersilka G, Flemmig TF.

Department of Periodontology, School of Dental Medicine, University of Wurzburg, Germany.
J Clin Periodontol 1999 Dec;26(12):847-54 Abstract quote
4 patients, 2 pairs of siblings, suffering from Papillon-Lefevre syndrome were treated for periodontal disease. Following extraction of hopeless teeth, the children received scaling and adjunctive systemic antibiotics (metronidazole and amoxicillin for 7 to 10 days).

In addition, they performed supragingival pulsated jet irrigation with 0.06% chlorhexidine digluconate 1 x daily. In 2 siblings, A. actinomycetemcomitans was suppressed subgingivally below detectable levels, pocket probing depths were reduced to 4 mm or less, and plaque and bleeding indices were low. No further disease progression was seen over a 3-year-period. Another female patient also showed clinical improvement and suppression of subgingival A. actinomycetemcomitans and B. forsythus up to the 9-month-follow-up, while her sister showed further attachment loss over the course of 4 years.

The present case reports indicated that in some patients suffering from Papillon-Lefevre syndrome periodontal disease may be arrested by means of (i) oral hygiene instruction, (ii) extraction of severely diseased teeth, (iii) scaling, (iv) systemic antibiotics and (v) long-term antimicrobial irrigation.

RETINOIDS

Systemic retinoid medication and periodontal health in patients with Papillon-Lefevre syndrome.

Lundgren T, Crossner CG, Twetman S, Ullbro C.

Department of Dentistry, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia.

J Clin Periodontol 1996 Mar;23(3 Pt 1):176-9 Abstract quote
Periodontal health in relation to systemic retinoid medication was evaluated retrospectively in patients with Papillon-Lefevre Syndrome (PLS). The material consisted of 18 children/young adults ranging from 8 to 28 years of age, all with a confirmed diagnosis of PLS. 9 participants, comprising a medication group, had been on long-term (range 1.5-9 years) retinoid medication for their cutaneous lesions. The remaining 9 served as controls.

Regardless of whether or not retinoid medication was received, every patient experienced an early and devastating periodontitis, with atypical edematous and erythematous gingiva, suppuration from deep gingival pockets and premature loss of teeth. No correlation could be found between the severity of skin involvement and the severity of periodontal involvement. An improvement with age could be seen for the cutaneous lesions but not for the periodontal condition. Systemic medication with retinoids had a favorable therapeutic effect on cutaneous lesions, and no severe complication/side effect could be seen after several years of continuous use.

However, from the results of this study it can be concluded that, at least in a situation with poor compliance of daily oral home-care, no positive effect on the periodontal health in patients with PLS could be seen by the retinoid medication.

Papillon-Lefevre syndrome. Successful treatment with oral retinoids in three patients.

el Darouti MA, Al Raubaie SM, Eiada MA.

Department of Dermatology, Cairo University Faculty of Medicine, Egypt.
Int J Dermatol 1988 Jan-Feb;27(1):63-6 Abstract quote
Papillon-Lefevre syndrome is a rare autosomal recessive disorder of palmoplantar keratinization in which there is a unique association of the palmoplantar hyperkeratosis and premature loss of both deciduous and permanent teeth.

We report three patients with papillon-lefevre syndrome who showed a remarkable degree of improvement after treatment with an oral retinoid.

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Eight Edition. Mosby 1996.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

Commonly Used Terms

Basic Principles of Disease
Learn the basic disease classifications of cancers, infections, and inflammation

Commonly Used Terms
This is a glossary of terms often found in a pathology report.

Diagnostic Process
Learn how a pathologist makes a diagnosis using a microscope

Surgical Pathology Report
Examine an actual biopsy report to understand what each section means

Special Stains
Understand the tools the pathologist utilizes to aid in the diagnosis

How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate

Internet Links

Last Updated 4/7/2003

TREATMENT	CHARACTERIZATION
GENERAL
ANTIBIOTICS
Combined systemic and local antimicrobial therapy of periodontal disease in Papillon-Lefevre syndrome. A report of 4 cases. Rudiger S, Petersilka G, Flemmig TF. Department of Periodontology, School of Dental Medicine, University of Wurzburg, Germany.	J Clin Periodontol 1999 Dec;26(12):847-54 Abstract quote 4 patients, 2 pairs of siblings, suffering from Papillon-Lefevre syndrome were treated for periodontal disease. Following extraction of hopeless teeth, the children received scaling and adjunctive systemic antibiotics (metronidazole and amoxicillin for 7 to 10 days). In addition, they performed supragingival pulsated jet irrigation with 0.06% chlorhexidine digluconate 1 x daily. In 2 siblings, A. actinomycetemcomitans was suppressed subgingivally below detectable levels, pocket probing depths were reduced to 4 mm or less, and plaque and bleeding indices were low. No further disease progression was seen over a 3-year-period. Another female patient also showed clinical improvement and suppression of subgingival A. actinomycetemcomitans and B. forsythus up to the 9-month-follow-up, while her sister showed further attachment loss over the course of 4 years. The present case reports indicated that in some patients suffering from Papillon-Lefevre syndrome periodontal disease may be arrested by means of (i) oral hygiene instruction, (ii) extraction of severely diseased teeth, (iii) scaling, (iv) systemic antibiotics and (v) long-term antimicrobial irrigation.
RETINOIDS
Systemic retinoid medication and periodontal health in patients with Papillon-Lefevre syndrome. Lundgren T, Crossner CG, Twetman S, Ullbro C. Department of Dentistry, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia.	J Clin Periodontol 1996 Mar;23(3 Pt 1):176-9 Abstract quote Periodontal health in relation to systemic retinoid medication was evaluated retrospectively in patients with Papillon-Lefevre Syndrome (PLS). The material consisted of 18 children/young adults ranging from 8 to 28 years of age, all with a confirmed diagnosis of PLS. 9 participants, comprising a medication group, had been on long-term (range 1.5-9 years) retinoid medication for their cutaneous lesions. The remaining 9 served as controls. Regardless of whether or not retinoid medication was received, every patient experienced an early and devastating periodontitis, with atypical edematous and erythematous gingiva, suppuration from deep gingival pockets and premature loss of teeth. No correlation could be found between the severity of skin involvement and the severity of periodontal involvement. An improvement with age could be seen for the cutaneous lesions but not for the periodontal condition. Systemic medication with retinoids had a favorable therapeutic effect on cutaneous lesions, and no severe complication/side effect could be seen after several years of continuous use. However, from the results of this study it can be concluded that, at least in a situation with poor compliance of daily oral home-care, no positive effect on the periodontal health in patients with PLS could be seen by the retinoid medication.
Papillon-Lefevre syndrome. Successful treatment with oral retinoids in three patients. el Darouti MA, Al Raubaie SM, Eiada MA. Department of Dermatology, Cairo University Faculty of Medicine, Egypt.	Int J Dermatol 1988 Jan-Feb;27(1):63-6 Abstract quote Papillon-Lefevre syndrome is a rare autosomal recessive disorder of palmoplantar keratinization in which there is a unique association of the palmoplantar hyperkeratosis and premature loss of both deciduous and permanent teeth. We report three patients with papillon-lefevre syndrome who showed a remarkable degree of improvement after treatment with an oral retinoid.

Epidemiology
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS	Keratosis palmoplantaris with periodontopathy
INCIDENCE/PREVALENCE	Rare
AGE	Birth

LABORATORY/RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
RADIOLOGIC
LABORATORY MARKERS
NEUTROPHIL DYSFUNCTION
Papillon-Lefevre syndrome: neutrophil function in 15 cases fron 4 families in Egypt. Ghaffer KA, Zahran FM, Fahmy HM, Brown RS. Oral Medicine & Periodontology Department, Faculty of Oral & Dental Medicine, Cairo University, Egypt.	Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999 Sep;88(3):320-5 Abstract quote OBJECTIVE: The primary purpose of this study was to investigate the periodontal pathologic cause of Papillon-Lefevre syndrome by comparing, with respect to neutrophil function, probands with Papillon-Lefevre syndrome from 4 families in Egypt, unaffected siblings of the probands, and age-matched and gender-matched control subjects. STUDY DESIGN: Family histories and clinical dermal and oral manifestations of Papillon-Lefevre syndrome were evaluated for 15 affected members of 4 families with the syndrome, 10 siblings of the probands, and 7 age-matched and gender-matched controls. Phagocytic and intracellular killing (lytic activity) of polymorphonuclear neutrophils was evaluated for all subjects according to a modification of the method of Wilkinson; opsonization was evaluated according to a modification of the methods of Cutler et al. Data were analyzed by means of analysis of variance. RESULTS: Family pedigrees were plotted, and consanguinity was noted in 3 of the 4 families with Papillon-Lefevre syndrome. The means and SDs for phagocytic killing, lytic activity, and opsonization indices were as follows: probands, 4.76+/-1.99, 0.42+/-0.20, and 0.84+/-0.07; unaffected siblings, 10.4+/-1.3, 3.3+/-0.3, and 0.84+/-0.07; controls, 10.8+/-0.8, 3.5+/-0.6, and 0.85+/-0.05. The phagocytic killing and lytic activity indices demonstrated significance between the probands and both siblings and controls (P<.0005), whereas the opsonization index did not demonstrate significance between groups. CONCLUSIONS: Significantly decreased neutrophil function in probands with Papillon-Lefevre syndrome was demonstrated with respect to neutrophil phagocytotic and lytic activity but not with respect to opsonization. Therefore, specific neutrophil dysfunction appears to be etiologically involved in this disorder.

HISTOLOGICAL TYPES	CHARACTERIZATION
GENERAL	Keratoderma