Recent developments in the diagnosis, treatment, and management of Papillon-Lefèvre Syndrome.

DATA SOURCES: A systematic search of PubMed, LIVIVO, and Ovid was conducted up to March 2021. These databases were searched for relevant clinical studies on periodontal treatment success in individuals with Papillon-Lefèvre syndrome (PLS). STUDY SELECTION: Clinical studies reporting successful treatment outcomes defined as the loss of four or fewer permanent teeth due to periodontitis and the arrest of periodontitis or probing depths of 5 mm or less in individuals with PLS followed up for ≥24 months were included, and data extracted. DATA EXTRACTION AND SYNTHESIS: Twelve studies reporting on nine PLS patients met the inclusion criteria. The extracted main outcomes in the studies reporting successful periodontal treatment in PLS were as follows: (1) clinical and genetic diagnosis of PLS; (2) age at baseline; (3) initial dental, periodontal parameters, and microbiological assessment, if available; (4) description of disease progression and applied therapies; and (5) outcome and follow-up. RESULTS: Twelve studies reporting nine individuals were included. The timely extraction of affected or all primary teeth, compliance with oral hygiene instructions, supra- and subgingival debridement within frequent supportive periodontal care intervals, and adjunctive systemic antibiotic therapy in most patients affected a halt in disease progression. Suppression of Aggregatibacter actinomycetemcomitans below detection limits was associated with periodontal stabilization. CONCLUSIONS: An intensive, multidisciplinary approach with strict compliance may enable the decelerated progression of PLS-associated periodontitis. The early diagnosis of PLS and the suppression of A. actinomycetemcomitans below the detection level might be critical factors for treatment success. It required significant effort and patient compliance. The study emphasized the importance of timely interventions, oral hygiene maintenance, regular professional dental care, and, in some cases, systemic antibiotics.

"Oral Manifestations of Patients with Inherited Defect in Phagocyte Number or Function" a systematic review.

INTRODUCTION: Inherited phagocyte defects are one of the subgroups of primary immunodeficiency diseases (PIDs) with various clinical manifestations. As oral manifestations are common at the early ages, oral practitioners can have a special role in the early diagnosis. MATERIALS AND METHODS: A comprehensive search was conducted in this systematic review study and data of included studies were categorized into four subgroups of phagocyte defects, including congenital neutropenia, defects of motility, defects of respiratory burst, and other non-lymphoid defects. RESULTS: Among all phagocyte defects, 12 disorders had reported data for oral manifestations in published articles. A total of 987 cases were included in this study. Periodontitis is one of the most common oral manifestations. CONCLUSION: There is a need to organize better collaboration between medical doctors and dentists to diagnose and treat patients with phagocyte defects. Regular dental visits and professional oral health care are recommended from the time of the first primary teeth eruption in newborns.

Papillon-Lefèvre syndrome: Oral aspects and treatment.

Papillon-Lefèvre syndrome (PLS) is a rare disorder characterized by diffuse palmoplantar erythematous, fissured hyperkeratosis, and aggressive periodontal disease that starts in the early periods of childhood. Periodontal disease occurs with the early loss of deciduous teeth at the age of 2 to 4 years, followed by the loss of permanent teeth during adolescence. Prosthodontics management of PLS patients is very complex and sometimes requires invasive therapeutic treatments. Early diagnosis is essential for correct treatment management avoiding the possibility that patients are early edentulous. Management could be a conventional periodontal treatment and pharmacological therapy but in severe cases, digital techniques, could be help the clinician for increased patient comfort and minimized tissue damage.

CTSC compound heterozygous mutations in two Chinese patients with Papillon-Lefèvre syndrome.

OBJECTIVES: To identify the molecular basis of Papillon-Lefèvre syndrome in two Chinese families. METHODS: Peripheral blood and mouth swab samples were obtained, from which genomic DNA and RNA were isolated. Sanger sequencing was employed to identify the mutations. mRNA expression was tested by real-time quantitative PCR. Evolutionary conservation, pathogenicity prediction and impact of protein structures of the mutations were conducted with bioinformatics tools and homology modelling. HEK293 cells were transfected with plasmids expressing wild-type or mutated CTSC. CTSC protein expression level and enzyme activity were explored. RESULTS: Mutation analysis revealed two novel compound heterozygous mutations, the c.190-191insA and c.1211-1212delA in patient 1 and the c.716A>G and c.757+1G>A in patient 2. In both patients, the levels of CTSC mRNA were significantly lower than in their relatives. Homology modelling analysis predicted that the mutations affect the structure and stability of the protein, and in vitro study showed that the CTSC proteins containing the mutations c.190-191insA and c.1211-1212delA, which result in truncated versions of protein, display impaired enzyme activity. The protein containing c.716A>G mutation showed quite similar enzyme activity compared to wild-type CTSC. CONCLUSION: Our data support the molecular mechanism of PLS and enlarge the scope of CTSC gene mutations related to PLS.

[Recurrent European missense mutation in a Hungarian pedigree with Papillon-Lefèvre syndrome]. / Rekurrens európai misszensz mutáció egy magyar Papillon-Lefèvre szindrómában szenvedo családban.

Papillon-Lefèvre syndrome, a rare disease with autosomal recessive inheritance, is characterized by aggressive periodontitis and palmoplantar hyperkeratosis. Mutations of the cathepsin C gene are responsible for the development of the disease. In this study, we aimed to describe in details the clinical symptoms and to determine the underlying genetic abnormality in two Hungarian siblings affected by Papillon-Lefèvre syndrome. The siblings are under regular dental and dermatological care since their symptoms appeared, but, due to the fact that genetic analysis of Papillon-Lefèvre syndrome has been available for one or two years in Hungary, their mutation screenings were just recently performed. We have identified a homozygous missense mutation on the cathepsin C gene, which is an already published mutation and was originally reported from Germany. Our investigations would like to draw attention to a rare disease, Papillon-Lefèvre syndrome, in which first symptom can be the aggressive periodontitis, and in which genetic testing and for helping child-bearing and family planning is now available.

Abnormal profiles of cathepsin C secreted in urine of Papillon Lefevre syndrome patients.

BACKGROUND: Papillon Lefevre syndrome (PLS) is an autosomal recessive disorder that results from a mutated gene that encodes a lysosomal peptidase known as cathepsin C (CTSC). The clinical presentation of PLS involves mainly palmoplantar keratosis and periodontitis with a variable degree of severity. SUBJECTS: and methods: Our study included ten patients with a broad spectrum of palmoplantar keratosis and periodontitis severity. CTSC variants were detected by Sanger sequencing. CTSC protein secreted in urine was detected by western blotting. RESULTS: Five patients have missense variants, Four have nonsense variants, and one has splice variants in CTSC. The activation products of cathepsin C protein (Heavy and light chains) were absent in all patients' urine samples except one with a significantly reduced level compared to the controls. The dimeric form of CTSC protein was found in all the studied cases. The monomeric form was found in five cases. The products of proteolytic activation of CTSC by other cathepsins (L and S) were found in the urine samples of five of the patients. Each patient had a characteristic pattern of accumulated CTSC protein maturation/activation substrates, intermediates, and products. 40% of the patients had the activation products of other lysosomal cathepsins. CONCLUSION: Urinary CTSC in PLS patients could be used as a diagnostic biomarker for the biochemical screening of the disease. Different variants in CTSC result in different profiles of CTSC secreted in the urine of PLS patients. The profiles of secreted CTSC in urine could be correlated to the severity of palmoplantar keratosis.

Multidisciplinary management of Papillon-Lefevre syndrome as a result of consanguineous marriage.

Papillon-Lefevre syndrome (PLS) is a rare autosomal recessive syndrome, and consanguinity has been reported in 20%-40% of cases. It is characterised by palmoplantar hyperkeratosis associated with severe early-onset periodontitis and premature loss of primary and permanent teeth. This report describes a case of PLS in a female patient with consanguineously married parents. The patient reported mobile upper front teeth. Clinical examination revealed presence of marked palmoplantar hyperkeratosis.Symmetric, well-demarcated, yellowish, keratotic and confluent plaques were seen on the skin of her palms and soles. Intraoral periodontal examination revealed erythematous gingiva with generalised periodontal pockets. Generalised mobility of teeth was present with clinically missing lower anterior teeth. Based on clinical and radiographic feature and the patient's medical, dental and family history, a diagnosis of PLS was made.

Eponym: Papillon-Lefevre syndrome.

Papillon-Lefevre Syndrome (PLS) is a very rare autosomal recessive disorder characterized by palmoplantar hyperkeratosis and severe early onset periodontitis, affecting the primary and permanent dentition. The syndrome was first described by Papillon and Lefevre in 1924. Genetic, immunologic, and microbiologic factors are suggested as responsible for the initiation and progression of the disease. A point mutation of cathepsin C gene has recently been detected in PLS. A multidisciplinary approach is important for management .The prognosis has improved with the early recognition of the syndrome, effective professional supervision, and home care.

Pyogenic liver abscess and peritonitis due to Rhizopus oryzae in a child with Papillon-Lefevre syndrome.

Papillon-Lefevre syndrome (PLS) is an autosomal recessive disease that is characterized by symmetric palmoplantar keratodermatitis and severe periodontal destruction. Mutations in the cathepsin C gene (CTSC) have recently been detected in PLS. Immune dysregulation, due to a mutation in CTSC, increases the risk of pyogenic infections in PLS patients. A child with PLS is presented here with liver abscesses and peritonitis caused by Rhizopus oryzae. His liver abscess and peritonitis were cured with amphotericin B without surgical care. This is the first case in the literature liver abscess due to Rhizopus oryzae in a child with PLS.

Renal abscess in Papillion-Lefèvre syndrome.

A 5-year-old female with Papillon-Lefèvre syndrome presented with renal mass. A radiological diagnosis of malignancy was made; however, partial nephrectomy revealed granulomatous disease indicative of chronic infection. Although liver abscess is an emerging complication in patient with Papillon-Lefèvre syndrome, this case represents the first renal abscess described in such patients.

Papillon-Lefevre syndrome.

Papillon-Lefevre syndrome is a very rare syndrome of autosomal recessive inheritance characterized by palmoplanter hyperkeratosis of the skin and severe periodontal disease extending to destruction of the alveolar bone surrounding deciduous and permanent teeth as they erupt leading to precocious loss of dentition. Although the exact pathogenesis of this syndrome is still unknown immunologic, microbiologic, and genetic bases have been proposed. Here we report a case of Papillon-Lefevre syndrome. The patient had generalized plaque accumulation along with halitosis, mobile teeth with periodontal pocket with pus exudation. Blood & biochemical report was within normal limit with a low CD3+ and CD4+.

Two patients with Papillon-Lefèvre syndrome without periodontal involvement of the permanent dentition.

Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive genodermatosis characterized by palmoplantar keratoderma and severe periodontitis leading to premature loss of primary and permanent teeth. PLS is caused by loss-of-function mutations in CTSC, lacking functional cathepsin C, which impairs the activation of neutrophil serine proteases. Precise pathogenesis of periodontal damage is unknown. Patient 1 presented with well-demarcated, transgredient, diffuse, palmoplantar keratoderma and psoriasiform lesions from the age of 2 years. Based on severe and recurrent periodontal inflammation, his dentist had diagnosed PLS at the age of 3 years and provided a strict oral hygiene regimen with repeated adjunct antibiotic therapies. Oral acitretin 10 mg/day along with tretinoin ointment at the age of 9 greatly improved palmoplantar keratoderma. Aged 18 years, the patient exhibited an intact permanent dentition and absence of periodontal disease. Patient 2, a 30-year-old man, suffered from transgredient, diffuse, palmoplantar keratoderma with fissuring from the age of 2 months, marked psoriasiform plaques on elbows and knees, and nail dystrophy. Intriguingly, without specific dental treatment, teeth and dental records were unremarkable. He was referred with a suspected diagnosis of psoriasis. Both patients were otherwise healthy, blood tests and sonography of internal organs were within normal limits. Panel sequencing revealed loss-of-function mutations in CTSC, c.322A>T (p.Lys108Ter) and c.504C>G (p.Tyr168Ter) in patient 1 and homozygous c.415G>T (p.Gly139Ter) in patient 2. The final diagnosis of unusual PLS was made. PLS should be considered in palmoplantar keratoderma lacking periodontitis or tooth loss.

Keratosis palmoplantaris associated with early-onset periodontitis: a case report.

Keratosis palmoplantaris associated with periodontopathy or Papillon Lefevre syndrome is a very rare genetic disorder with autosomal recessive mode of inheritance and is characterized by hyperkeratosis of the palms and soles and early onset of a severe destructive periodontitis. The clinical presentation, differential diagnosis, therapeutic and periodontal management of an 8-year old male child diagnosed with this syndrome is discussed.

Resolution of eosinophilic granuloma after minimal intervention. Case report and review of literature.

Langerhans cell histiocytosis (LCH), previously known as histiocytosis X, is a rare, proliferative disorder in which the accumulation of pathologic Langerhans cells leads to local tissue infiltration and destruction. The incidence of LCH is estimated to be one case per 200,000 children per year. The role of the dentist is important in early and accurate evaluation, staging and diagnosis of LCH, because it may mimic more common diseases, such as juvenile periodontitis and osteomyelitis. There are multiple treatment options, but the response is unpredictable. The aim of this paper is to give a short, introductory overview on current diagnostic and treatment strategies for LCH in the oral and maxillofacial region and to present a case of LCH that mimicked juvenile periodontitis and was resolved following extraction of affected teeth. The history, radiological appearance, differential diagnosis, histopathology and treatment options for the patient are discussed.

Partial expression of Papillon-Lefèvre Syndrome.

Papillon- Lefèvre Syndrome (PLS) is a rare autosomal recessive trait, which is transmitted with an estimated frequency of one to four per million individuals. It is characterized by palmar plantar keratosis and severe early-onset periodontitis affecting both deciduous and permanent dentition. In this report, we present clinical, microbiological and leukocyte function test findings of a thirty-five year-old patient with symptoms typical of Papillon-Lefèvre Syndrome except for premature loss of deciduous and permanent dentition. The patient exhibited palmar plantar keratosis and an isolated, moderately deep periodontal pocket in the third quadrant. No anaerobic bacteria were isolated from the plaque culture. The neutrophil function test revealed defective chemotaxis and phagocytosis while intracellular killing and respiratory burst were normal.

New lesions on the knees with palmoplantar keratoderma.

A 40-year-old Latin American woman presented for evaluation with a 5-week history of redness, thickened skin, and itching of the knees, as well as persistent redness and thickened skin of the palms and soles consistent with Papillon-Lefèvre syndrome (PLS). The article discusses the clinical presentation and treatment of PLS.

Papillon-lefevre syndrome with congenital hepatic fibrosis.

Papillon Lefevre syndrome (PLS) is a rare autosomal recessive disorder, which is characterized by palmar-plantar hyperkeratosis, periodontitis, and premature loss of dentition. We report a 16 years old girl with PLS. The patient presented at 08 years of age with complaints of corn on the feet and hands, and failure to thrive. On examination, her upper primarily canines were loose, she had severe periodontitis, eruption of permanent teeth, diffuse eritematous and hyperkeratotic palms and soles that suggested the syndrome. During the follow-up, the patient was diagnosed to have congenital hepatic fibrosis (CHF) when she was 16 years old, while she was being investigated for the etiology of her splenomegaly and pancytopenia. We report a patient with PLS associated with CHF, an association that has not been previously described. Abbreviations-HbsAg: Hepatitis B virus surface antigen, Anti Hbs: Antibody against Hepatitis B surface antigen, Anti Hbc IgM: Antibody against Hepatitis B cor antigen immunglobulin M, Anti dsDNA: Antibody against double stranded deoksiribonucleic acid, Anti HCV: Antibody against Hepatit C virus, Anti HIV: Antibody against human immun deficiency virus, AST: Aspartat amino transferase, ALT: Alanin amino transferase, Gamma-GT: Gamma glutamyl transferase, LDH: Lactate dehydrogenase & MRI: Magnetic resonance imaging.

Papillon-Lefevre syndrome: two case reports.

Papillon-Lefevre syndrome is a rare autosomal recessive disorder in which there is palmoplantar keratinization and premature loss of both deciduous and permanent teeth. The palmoplantar keratoderma typically has its onset between the ages of 1 and 4 years and severe periodontitis starts at the age of 3 or 4 years. An early diagnosis of the syndrome can help preserve the teeth by early institution of treatment, using a multidisciplinary approach. We present two cases of the syndrome having all of the characteristic features.