To the Editor: Punctate palmoplantar keratoderma type I (Brauer-Buschke-Fischer syndrome or PPKP1) is one of a group of heterogeneous disorders characterized by abnormal keratinization of the palms and soles. It is an autosomal dominant genodermatosis, and lesions appear within the first 2 decades of life. Molecular genetic studies have shown loss-of-function mutations in AAGAB, encoding α- and γ -adaptin-binding protein p34, located at locus 15q22. 1 Since PPKP1 is a rare disease, no standardized treatment has been established. Therapeutic approaches are based on traditional systemic retinoids (e.g., acitretin), although a successful response is not always seen. We describe a 41-year-old Caucasian woman with a 20-year history of hyperkeratotic lesions on the palms and soles. She complained of pruritus and pain, as well as difficulty walking and performing manual activities. Previous treatments, which included various keratolytic creams/ointments and potent topical steroids, did not produce a significant improvement. Similar skin lesions were present in her brother and grandmother. Dermatologic examination demonstrated multiple, yellow-gray crater-like hyperkeratotic papules on the palms and soles. The papules coalesced to form diffuse plaques of approximately 1 to 2 cm in diameter, especially over pressure points on the feet (Fig 1, A). There was no keratoderma transgrediens. Histopathology of a skin biopsy specimen from a palm lesion revealed marked hyperkeratosis, parakeratosis, and mild acanthosis without any change in the dermis, consistent with a diagnosis of PPKP1. Molecular studies were not performed due to lack of availability. Routine hematologic investigations were normal and pregnancy test was negative. Oral alitretinoin 30 mg/day was administered for 8 months as a trial of treatment. Contraceptive therapy was initiated 1 month earlier and continued for 10 months. Almost complete clinical remission of PPK was achieved after 8 months of treatment (Fig 1, B). No local or systemic adverse events were observed. Two months into the follow-up period the patient had not experienced any recurrence. An “8-months-on, 4-months-off” protocol for alitretinoin therapy was planned. Traditional systemic retinoids are used for treatment of PPK by many authors.2 and 3 We elected not to treat with acitretin because of its long-lasting teratogenicity (3 years after stopping treatment) and the need for long-term contraception.4 Alitretinoin (9-cis-retinoic acid) is a new retinoid, with immunomodulatory and anti-inflammatory effects, which binds to retinoic acid receptors A and X. It regulates keratinocyte differentiation with fewer adverse events than traditional retinoids and requires only 1 month of contraception once therapy is completed. 5 We therefore consider oral alitretinoin to be a useful alternative treatment for women of childbearing age who suffer with PPKP.

Alitretinoin: A new treatment option for hereditary punctate palmoplantar keratoderma (Brauer-Buschke-Fischer syndrome)

RAONE, BEATRICE;PATRIZI, ANNALISA
2014

Abstract

To the Editor: Punctate palmoplantar keratoderma type I (Brauer-Buschke-Fischer syndrome or PPKP1) is one of a group of heterogeneous disorders characterized by abnormal keratinization of the palms and soles. It is an autosomal dominant genodermatosis, and lesions appear within the first 2 decades of life. Molecular genetic studies have shown loss-of-function mutations in AAGAB, encoding α- and γ -adaptin-binding protein p34, located at locus 15q22. 1 Since PPKP1 is a rare disease, no standardized treatment has been established. Therapeutic approaches are based on traditional systemic retinoids (e.g., acitretin), although a successful response is not always seen. We describe a 41-year-old Caucasian woman with a 20-year history of hyperkeratotic lesions on the palms and soles. She complained of pruritus and pain, as well as difficulty walking and performing manual activities. Previous treatments, which included various keratolytic creams/ointments and potent topical steroids, did not produce a significant improvement. Similar skin lesions were present in her brother and grandmother. Dermatologic examination demonstrated multiple, yellow-gray crater-like hyperkeratotic papules on the palms and soles. The papules coalesced to form diffuse plaques of approximately 1 to 2 cm in diameter, especially over pressure points on the feet (Fig 1, A). There was no keratoderma transgrediens. Histopathology of a skin biopsy specimen from a palm lesion revealed marked hyperkeratosis, parakeratosis, and mild acanthosis without any change in the dermis, consistent with a diagnosis of PPKP1. Molecular studies were not performed due to lack of availability. Routine hematologic investigations were normal and pregnancy test was negative. Oral alitretinoin 30 mg/day was administered for 8 months as a trial of treatment. Contraceptive therapy was initiated 1 month earlier and continued for 10 months. Almost complete clinical remission of PPK was achieved after 8 months of treatment (Fig 1, B). No local or systemic adverse events were observed. Two months into the follow-up period the patient had not experienced any recurrence. An “8-months-on, 4-months-off” protocol for alitretinoin therapy was planned. Traditional systemic retinoids are used for treatment of PPK by many authors.2 and 3 We elected not to treat with acitretin because of its long-lasting teratogenicity (3 years after stopping treatment) and the need for long-term contraception.4 Alitretinoin (9-cis-retinoic acid) is a new retinoid, with immunomodulatory and anti-inflammatory effects, which binds to retinoic acid receptors A and X. It regulates keratinocyte differentiation with fewer adverse events than traditional retinoids and requires only 1 month of contraception once therapy is completed. 5 We therefore consider oral alitretinoin to be a useful alternative treatment for women of childbearing age who suffer with PPKP.
Beatrice Raone; Roberta Raboni; Annalisa Patrizi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/388186
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