Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive genetic disorder caused by cathepsin C deficiency. The syndrome is characterized by palmoplantar keratoderma and destructive periodontal disease, which manifests as gingival inflammation and loss of most primary and permanent teeth.
Cathepsin C is necessary for granzyme B and natural killer cell function, and its deficiency is associated with reduced immunologic response to bacteria. The presence of virulent pathogens, specifically Actinobacillus actinomycetemcomitans, within the mouth has been proposed to contribute to the progression of PLS.
The clinical age of onset is between ages 2 and 3. Consanguinity is a high risk factor for PLS. There is no racial predominance, and men and women are equally affected.
Symptoms and Signs Skin Hyperkeratosis of the palmar and plantar surfaces appears in the first few years of life. The red, scaly, and well-demarcated plaques extend to the margins of the palms and span over the thenar eminence. Lesions on the plantar surface spread to the edges of the sole, reaching to the Achilles tendon (transgrediens). Knees and elbows may manifest hyperkeratotic plaques in some patients. Nail dystrophy has also been reported.
Mouth Gingival inflammation typically coincides with the presentation of palmoplantar hyperkeratosis.
Deciduous teeth are often lost by age 5, after which there is a decrease in gingival inflammation. As permanent teeth begin to appear, the inflammatory process restarts and symptoms recur. By age 16, all permanent teeth, except for the third molars typically, are lost.
Codes
ICD10CM: K05.4 – Periodontosis Q82.8 – Other specified congenital malformations of skin
SNOMEDCT: 40158001 – Papillon-Lefèvre syndrome
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Differential Diagnosis & Pitfalls
Haim-Munk syndrome comprises palmoplantar keratoderma, arachnodactyly, pes planus, acroosteolysis and onychogryphosis. Periodontosis may be seen. Haim-Munk syndrome is allelic to PLS.
Other diffuse hereditary PPKs:
Vorner (epidermolytic) PPK and Unna-Thost (nonepidermolytic) PPK are the result of keratin mutations and show waxy or verrucous white-yellow symmetric hyperkeratosis.
Mal de Meleda is a rare PPK associated with SLURP1 mutations and features stocking-glove distribution of hyperkeratosis with malodor and nail changes.
Vohwinkel syndrome (mutilating PPK) has 2 variants: the classic form associated with deafness and mutations of the connexin gene GJB2 and the loricrin variant associated with loricrin mutations and ichthyosis. The PPK shows a diffuse honeycomb pattern. Additional features include starfish-shaped keratotic plaques on dorsal hands, feet, elbows, and knees as well as constricting digital bands termed "pseudo-ainhum," which may progress to autoamputation.
Richner-Hanhart syndrome is associated with mutations in the gene that encodes tyrosine aminotransferase. Accumulation of tyrosine leads to focal (or diffuse) hyperkeratotic plaques on the hands, feet, elbows, and knees, corneal inflammation / ulceration, and intellectual disability in some cases. Diets low in phenylalanine and tyrosine may prevent complications.
Acquired PPKs:
Keratoderma climactericum – Seen in menopausal women, often associated with obesity or hypertension; pressure points on the soles of the feet are affected first.
PPK as a feature of systemic disease – Hypothyroidism, myxedema, diabetes mellitus, and chronic lymphedema.
Paraneoplastic PPK – Acrokeratosis paraneoplastica of Bazex is associated with squamous cell carcinoma of the upper gastrointestinal tract, and "tripe palms" is associated with pulmonary or gastric malignancies. Other malignancies with associated paraneoplastic PPK include breast, bladder, and skin malignancies; myeloma; mycosis fungoides; and Sézary syndrome.
