Papillon-Lefevre disease

Papillon-Lefèvre Syndrome (PLS): A Rare Genetic Disorder

Papillon-Lefèvre syndrome (PLS) is a rare genetic disorder that affects the skin and teeth. It is characterized by:

• Diffuse palmoplantar hyperkeratosis: Thickening of the skin on the soles and palms, causing redness and discomfort [3][4].
• Rapidly progressive periodontitis: A severe and destructive disease affecting both primary and permanent teeth, leading to premature loss [6][9].
• Autosomal recessive inheritance: PLS is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition [2][12].

Causes and Symptoms

PLS is caused by mutations in the cathepsin C (CTSC) gene. The symptoms of PLS typically appear between 1-5 years of age, although they can start at any time during childhood or even later in life [10]. The disease progresses rapidly, leading to significant discomfort and disability.

Treatment and Management

While there is no cure for PLS, treatment focuses on managing the symptoms and slowing down the progression of periodontal disease. This may involve antibiotics, pain management, and dental care to preserve remaining teeth [11].

Prevalence and Diagnosis

PLS is a rare condition, with an estimated prevalence of 1-4 per million people. It affects both males and females equally and has no racial or ethnic preference. Diagnosis is typically made through clinical examination, medical history, and genetic testing.

Overall, Papillon-Lefèvre syndrome is a complex and challenging condition that requires early diagnosis and management to improve quality of life for affected individuals.

Papillon-Lefèvre syndrome (PLS) is a rare genetic disorder characterized by severe periodontitis affecting both baby and adult teeth, along with skin manifestations.

Common signs and symptoms:

• Abnormal fingernails
• Atrophy of alveolar ridges (shrinking of gum ridges)
• Gingivitis (inflamed gums)
• Palmoplantar keratoderma (thickening of the soles and palms)
• Periodontal disease affecting both primary and permanent teeth
• Redness, thickening, and fissuring of the skin on the palms and soles
• Severe destructive periodontal disease

Additional symptoms:

• Hypotrichosis (sparse hair on the scalp and body) [7]
• Dirty colored skin [7]
• Very fragile nails that easily break off [7]

It's worth noting that not all individuals with PLS will experience all of these symptoms, and some may have mild or late-onset periodontal disease. However, in many cases, the syndrome is accompanied by enhanced susceptibility to cutaneous and systemic infections.

References: [4] [5] [8]

Papillon-Lefèvre syndrome (PLS) diagnosis can be challenging due to its rarity and similarity in clinical signs with other conditions. However, several diagnostic tests can help confirm the diagnosis.

Clinical Signs: The first step in diagnosing PLS is to identify the characteristic clinical signs, which include:

• Palmoplantar hyperkeratosis
• Periodontitis leading to tooth loss
• Absence of third molars and multiple other permanent teeth

These symptoms typically become apparent between 1-5 years of age.

Diagnostic Tests: The following tests can help confirm the diagnosis of PLS:

• Molecular Genetic Testing: This test can detect mutations in the CTSC gene, which is responsible for PLS. According to [2], molecular genetic testing can confirm a diagnosis.
• Dental Radiography: Dental radiographs (x-rays) can show atrophy of the alveolar bone and absence of third molars and multiple other permanent teeth, as seen in [3] and [5].
• Neutrophil Function Tests: These tests can reveal anomalies of chemotaxis and phagocytosis, which are characteristic of PLS. According to [4], neutrophil function tests can help confirm the diagnosis.
• Genetic Testing: Genetic testing can detect mutations in the CTSC gene and confirm the diagnosis. According to [7] and [8], genetic testing is often performed to confirm the diagnosis.

Other Tests: In addition to these diagnostic tests, hematological and biochemical tests may be performed to rule out other conditions that may present with similar symptoms.

It's essential to note that a combination of clinical signs and diagnostic tests can help confirm the diagnosis of PLS. However, a definitive diagnosis can only be made through molecular genetic testing.

References:

[2] Fergelot P, et al. Analysis of urinary cathepsin C for diagnosing Papillon-Lefèvre syndrome. FEBS J. 2016;283:498-509

[3] by T Phull · 2023 · Cited by 1 — The radiograph also revealed the absence of third molars along with multiple other permanent teeth.

[4] Diagnosis is based on clinical signs. Dental radiography shows atrophy of the alveolar bone. Neutrophil Function Tests were performed in the laboratory.

[7] Papillon-Lefevre syndrome (PLS), classified as ectodermal dysplasia, is an autosomal recessive condition related to the cathepsin C (CTSC) gene mutation.

[8] The results of routine blood tests and liver function tests were determined to be within the acceptable range.

Treatment Options for Papillon-Lefevre Disease

Papillon-Lefevre disease, a rare genetic disorder, requires prompt and effective treatment to manage its symptoms and prevent further complications. The primary goal of treatment is to alleviate the skin lesions and periodontal destruction associated with this condition.

Oral Retinoids: A Key Treatment Option

Oral retinoids, such as acitretin and etretinate, have been shown to be highly effective in treating Papillon-Lefevre disease. These medications work by reducing inflammation and promoting the growth of new skin cells, thereby alleviating the symptoms of palmar-plantar hyperkeratosis.

• Acitretin has been found to result in excellent improvement of periodontitis, increase in alveolar bone height, and periodontal attachment [9].
• A study published in 2015 reported that treatment with acitretin resulted in almost complete resolution of skin lesions and significant improvement in periodontal health [11].

Other Treatment Options

In addition to oral retinoids, other treatment options may include:

• Emollients, salicylic acid, and urea to address skin lesions
• Antibiotics and oral hygiene measures to manage periodontal disease
• Dimethyl fumarate, which has anti-inflammatory and immune-modulatory effects [5], [7]

Multidisciplinary Approach

A multidisciplinary approach is advisable for treating Papillon-Lefevre disease. This may involve a team of healthcare professionals, including dermatologists, periodontists, and oral surgeons.

• A case report published in 2023 highlighted the importance of scaling, root planing, and systemic drug therapy (amoxicillin-metronidazole) in managing periodontal disease [8].

Clinical Trials

Clinical trials are essential for determining the safety and efficacy of new treatments for Papillon-Lefevre disease. Observational studies can also provide valuable insights into the natural history of this condition.

• The U.S. Food & Drug Administration provides information on clinical trials, including those related to Papillon-Lefevre disease [10].

In conclusion, oral retinoids are a key treatment option for Papillon-Lefevre disease, and other treatments may be used in conjunction with these medications to manage the symptoms of this condition. A multidisciplinary approach is essential for effective management and prevention of further complications.

Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder that can be challenging to diagnose due to its overlapping symptoms with other conditions. The differential diagnosis for PLS includes:

• Acrodynia: Also known as Pinker's disease or Swift's disease, acrodynia is a condition characterized by skin lesions and periodontal disease.
• Hypophosphatasia: A rare genetic disorder that affects bone mineralization and can cause periodontal disease.
• Histiocytosis X: A group of rare disorders caused by abnormal proliferation of histiocytes, which can lead to periodontal disease.
• Cyclic neutropenia: A rare condition characterized by recurring episodes of low white blood cell count, which can increase the risk of infections and periodontal disease.
• Chediak-Higashi syndrome: A rare genetic disorder that affects the immune system and can cause periodontal disease.
• Thost-Uny syndrome: A rare condition characterized by skin lesions and periodontal disease.

These conditions share similar symptoms with PLS, such as palmoplantar hyperkeratosis, periodontal involvement, and skin lesions. Therefore, a comprehensive diagnostic workup is essential to rule out these differential diagnoses and confirm the diagnosis of Papillon-Lefèvre syndrome.

According to [4], the differential diagnosis for PLS includes acrodynia, hypophosphatasia, histiocytosis X, cyclic neutropenia, Chediak-Higashi syndrome, Thost-Uny syndrome, Haim-Munk syndrome, and juvenile periodontitis. [8] also mentions that the differential diagnosis of PLS includes acrodynia or mercury poisoning, hypophosphatasia, and cyclic neutropenia.

It's essential to note that a thorough clinical examination, radiographic findings, and laboratory tests are necessary to confirm the diagnosis of PLS and rule out these differential diagnoses. [11] provides an introduction to PLS, highlighting its autosomal recessive inheritance pattern, characteristic skin lesions, and severe periodontal disease.

References:

[4] Papillon-Lefèvre syndrome is a rare disease characterised by skin lesions caused by palmar-plantar hyperkeratosis and severe periodontal destruction. [8] The differential diagnosis of PLS includes acrodynia or mercury poisoning, hypophosphatasia, and cyclic neutropenia. [11] Introduction. Papillon–Lefèvre syndrome (PLS) was first described by two French physicians, Papillon and Lefèvre, in France.1 It is an autosomal recessive inherited disorder of keratinization,2 characterized by redness, thickening of the soles and palms, and severe destructive periodontal disease affecting both primary and permanent teeth, caused by mutations in cathepsin C (CTSC) gene.3,4 ...