Papillon Lefevre syndrome

Alternate names

Hyperkeratosis palmoplantaris with periodontosis; Keratoris palmoplantaris with periodontopathia; Palmar-plantar hyperkeratosis and concomitant periodontal destruction; Keratosis palmoplantaris with periodontopathia; Palmoplantar keratoderma with periodontosis; Keratosis palmoplantar - periodontopathy; Papillon-Lefèvre syndrome; Keratosis palmoplantar-periodontopathy syndrome

Defintion

Papillon-Lefèvre syndrome (PLS) is a rare ectodermal dysplasia characterized by palmoplantar keratoderma associated with early-onset periodontitis.

Epidemiology

The prevalence is estimated between 1/250,000 and 1/1,000,000 individuals. The male to female ratio is 1:1. PLS is found in all ethnic groups.

Cause

PLS is due to mutations in the CTSC gene (11q14.2) that codes for cathepsin C (also known as dipeptidyl peptidase I), a lysosomal protease playing a role in epidermal differentiation and desquamation and in activation of serine proteases expressed in cells of the immune system. CTSC mutations lead to an almost total loss of cathepsin C activity which seems to result in susceptibility to specific virulent pathogens. It is also suggested that other immune-mediated deficiencies in the host defense mechanism could be involved in the pathogenesis of PLS.

Inheritance

Autosomal recessive inheritance, a 25% chance

Transmission is autosomal recessive. Genetic counseling should be offered to the parents of an affected individual informing them of the 25% chance their offspring has of inheriting the disease causing mutation.

Signs and symptoms

Diffuse palmoplantar keratoderma with erythematous plaques develops between the first and fourth years of life, with the soles being usually more severely affected than the palms. Psoriasiform hyperkeratosis can overflow onto the dorsal surfaces of the hands and feet (transgredient spread) and, less frequently, lesions can be seen on the limbs (knees, elbows). Skin lesions are followed by intense gingivitis that rapidly progresses into periodontitis with alveolar bone lysis and early loss of primary dentition. The skin lesions are aggravated by cold and during episodes of severe periodontitis.

During childhood, the phenomenon of periodontal disease recurs with rapid loss of permanent dentition. Cases of PLS with mild and/or late-onset periodontal disease have been reported occasionally. PLS is accompanied, in half of the patients, by enhanced susceptibility to cutaneous and systemic infections (furunculosis, skin abscesses, pyoderma, hidradenitis suppurativa , respiratory tract infection...). Patients may also present with malodorous hyperhidrosis, follicular hyperkeratosis, nail dystrophy or dural calcifications. The association of PLS with malignant melanoma or squamous cell carcinoma has been reported in very rare occasions.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Abnormal fingernail morphology(Abnormal fingernails)
• Atrophy of alveolar ridges(Shrinking of gum ridges)
• Gingivitis(Inflamed gums)
• Palmoplantar hyperkeratosis(Thickening of the outer layer of the skin of the palms and soles)
• Palmoplantar keratoderma(Thickening of palms and soles)
• Premature loss of primary teeth(Early loss of baby teeth)
• Pustule(Pimple)
• Reduced number of teeth(Decreased tooth count)
• Severe periodontitis

30%-79% of people have these symptoms

• Cerebral calcification(Abnormal deposits of calcium in the brain)
• Chronic furunculosis
• Nail dystrophy(Poor nail formation)
• Recurrent cutaneous abscess formation
• Recurrent respiratory infections(Frequent respiratory infections)

5%-29% of people have these symptoms

• Arachnodactyly(Long slender fingers)
• Cigarette-paper scars('cigarette paper scarring')
• Generalized hirsutism(Excessive hairiness over body)
• Hypertrichosis
• Hypopigmented skin patches(Patchy loss of skin color)
• Liver abscess
• Melanoma
• Osteolysis(Breakdown of bone)
• Sparse body hair
• Squamous cell carcinoma

Diagnosis

Differential diagnosis includes two rare disorders that are allelic variants of PLS, Haim-Munk syndrome and prepubertal/aggressive periodontitis. Other diseases with similar dermatologic features include localized epidermolytic palmoplantar keratoderma (Vörner), mal de Meleda, Howel-Evans syndrome, transgrediens et progrediens palmoplantar keratoderma (Greither's disease) , and keratosis punctata.

Antenatal diagnosis Antenatal diagnosis is theoretically possible but has never been reported.

Treatment

Treatment is based on oral retinoids which attenuate the palmoplantar keratoderma and slow the alveolar bone lysis. Antibiotics, along with oral hygiene and use of mouth rinses, are also recommended for slowing the progression of periodontitis. Ultimately, primary or remaining teeth are extracted and are replaced by dental implants. Antibiotherapy is also used in the treatment of recurrent infections. Etretinate (a synthetic retinoid) shows promising results in the treatment of PLS.

Prognosis

Despite meticulous dental care, all patients eventually become edentulous at the beginning of adulthood. Life expectancy is normal.

NIH genetic and rare disease info

• NIH info on Papillon Lefevre syndrome

Papillon Lefevre syndrome is a rare disease.

Papillon Lefevre syndrome Resources
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