Treatment of Painful Palmoplantar Keratoderma Related to Pachyonychia Congenita Using EGFR Inhibitors
Pachyonychia congenita (PC) is a genodermatosis associated with severe painful palmoplantar keratoderma (PPK) and thickened dystrophic nails caused by autosomal dominant-negative mutations in five genes encoding keratins 6A-B-C, 16, and 17. The mechanical, surgical, or medical options for painful PC...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/4/841 |
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| author | Céline Greco Anne-Charlotte Ponsen Stéphanie Leclerc-Mercier Joël Schlatter Salvatore Cisternino Claude Boucheix Christine Bodemer |
| author_facet | Céline Greco Anne-Charlotte Ponsen Stéphanie Leclerc-Mercier Joël Schlatter Salvatore Cisternino Claude Boucheix Christine Bodemer |
| author_sort | Céline Greco |
| collection | DOAJ |
| description | Pachyonychia congenita (PC) is a genodermatosis associated with severe painful palmoplantar keratoderma (PPK) and thickened dystrophic nails caused by autosomal dominant-negative mutations in five genes encoding keratins 6A-B-C, 16, and 17. The mechanical, surgical, or medical options for painful PC are inefficient. Given ErbB/Her family members’ role in epidermal homeostasis, this study sought to investigate the possibility of treating PC patients with PPK by blocking signaling either with EGFR (Her1) inhibitor erlotinib or lapatinib, a dual EGFR(Her1)/Her2. After 1 month of therapy with oral erlotinib treatment at 75 mg/day, the pain disappeared for patient #1, with partially reduced hyperkeratosis, while increasing the dose to 100 mg/day resulted in painful skin fissures. Therapy replacement with erlotinib cream at 0.2% was inconclusive, and substitution with oral lapatinib at alternating doses of 500 and 750 mg/day achieved a good compromise between pain reduction, symptom improvements, and side effects. Patient #2′s treatment with erlotinib cream failed to display significant improvements. Oral erlotinib started at 75 mg/day then reduced to 25 mg/day because of the formation of an acneiform rash. Treatment considerably improved the patient’s condition, with an almost complete disappearance of pain. Oral Her1 or 1/2 inhibitors reduced pain, improved two PC patients’ quality of life, and offered promising therapeutic perspectives. |
| first_indexed | 2024-03-09T11:07:38Z |
| format | Article |
| id | doaj.art-ef9de45ea23947da94a05a042725ac5a |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T11:07:38Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-ef9de45ea23947da94a05a042725ac5a2023-12-01T00:54:10ZengMDPI AGBiomedicines2227-90592022-04-0110484110.3390/biomedicines10040841Treatment of Painful Palmoplantar Keratoderma Related to Pachyonychia Congenita Using EGFR InhibitorsCéline Greco0Anne-Charlotte Ponsen1Stéphanie Leclerc-Mercier2Joël Schlatter3Salvatore Cisternino4Claude Boucheix5Christine Bodemer6Department of Pain and Palliative Care, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris (AP-HP), 75015 Paris, FranceIMAGINE Institute, Inserm U1163, Université de Paris, 75015 Paris, FranceDepartment of Pathology, Reference Center for Genodermatoses (MAGEC), Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris (AP-HP), 75015 Paris, FranceService Pharmacie, Hôpital Paul Doumer, Assistance Publique Hôpitaux de Paris (AP-HP), 60332 Liancourt, FranceService Pharmacie, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris (AP-HP), 75015 Paris, FranceInserm UMRS-MD-1197, Université Paris-Saclay, 94800 Villejuif, FranceIMAGINE Institute, Inserm U1163, Université de Paris, 75015 Paris, FrancePachyonychia congenita (PC) is a genodermatosis associated with severe painful palmoplantar keratoderma (PPK) and thickened dystrophic nails caused by autosomal dominant-negative mutations in five genes encoding keratins 6A-B-C, 16, and 17. The mechanical, surgical, or medical options for painful PC are inefficient. Given ErbB/Her family members’ role in epidermal homeostasis, this study sought to investigate the possibility of treating PC patients with PPK by blocking signaling either with EGFR (Her1) inhibitor erlotinib or lapatinib, a dual EGFR(Her1)/Her2. After 1 month of therapy with oral erlotinib treatment at 75 mg/day, the pain disappeared for patient #1, with partially reduced hyperkeratosis, while increasing the dose to 100 mg/day resulted in painful skin fissures. Therapy replacement with erlotinib cream at 0.2% was inconclusive, and substitution with oral lapatinib at alternating doses of 500 and 750 mg/day achieved a good compromise between pain reduction, symptom improvements, and side effects. Patient #2′s treatment with erlotinib cream failed to display significant improvements. Oral erlotinib started at 75 mg/day then reduced to 25 mg/day because of the formation of an acneiform rash. Treatment considerably improved the patient’s condition, with an almost complete disappearance of pain. Oral Her1 or 1/2 inhibitors reduced pain, improved two PC patients’ quality of life, and offered promising therapeutic perspectives.https://www.mdpi.com/2227-9059/10/4/841pachyonychia congenitapalmoplantar keratodermapainEGFRtyrosine kinase inhibitors |
| spellingShingle | Céline Greco Anne-Charlotte Ponsen Stéphanie Leclerc-Mercier Joël Schlatter Salvatore Cisternino Claude Boucheix Christine Bodemer Treatment of Painful Palmoplantar Keratoderma Related to Pachyonychia Congenita Using EGFR Inhibitors Biomedicines pachyonychia congenita palmoplantar keratoderma pain EGFR tyrosine kinase inhibitors |
| title | Treatment of Painful Palmoplantar Keratoderma Related to Pachyonychia Congenita Using EGFR Inhibitors |
| title_full | Treatment of Painful Palmoplantar Keratoderma Related to Pachyonychia Congenita Using EGFR Inhibitors |
| title_fullStr | Treatment of Painful Palmoplantar Keratoderma Related to Pachyonychia Congenita Using EGFR Inhibitors |
| title_full_unstemmed | Treatment of Painful Palmoplantar Keratoderma Related to Pachyonychia Congenita Using EGFR Inhibitors |
| title_short | Treatment of Painful Palmoplantar Keratoderma Related to Pachyonychia Congenita Using EGFR Inhibitors |
| title_sort | treatment of painful palmoplantar keratoderma related to pachyonychia congenita using egfr inhibitors |
| topic | pachyonychia congenita palmoplantar keratoderma pain EGFR tyrosine kinase inhibitors |
| url | https://www.mdpi.com/2227-9059/10/4/841 |
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