Greco Céline, Ponsen Anne-Charlotte, Leclerc-Mercier Stéphanie, Schlatter Joël, Cisternino Salvatore, Boucheix Claude, Bodemer Christine
Department of Pain and Palliative Care, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris (AP-HP), 75015 Paris, France.
IMAGINE Institute, Inserm U1163, Université de Paris, 75015 Paris, France.
Biomedicines. 2022 Apr 3;10(4):841. doi: 10.3390/biomedicines10040841.
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.
先天性厚甲症（PC）是一种遗传性皮肤病，与严重的掌跖角化病（PPK）和指甲增厚营养不良有关，由编码角蛋白6A - B - C、16和17的五个基因的常染色体显性负性突变引起。针对疼痛性PC的机械、手术或药物治疗方法效果不佳。鉴于表皮生长因子受体（ErbB）/人表皮生长因子受体（Her）家族成员在表皮稳态中的作用，本研究旨在探讨用表皮生长因子受体（EGFR，Her1）抑制剂厄洛替尼或双重表皮生长因子受体（EGFR，Her1）/人表皮生长因子受体2（Her2）抑制剂拉帕替尼阻断信号传导来治疗患有掌跖角化病的PC患者的可能性。在以75毫克/天的剂量口服厄洛替尼治疗1个月后，患者1的疼痛消失，角化过度部分减轻，而将剂量增加到100毫克/天则导致疼痛性皮肤皲裂。用0.2%的厄洛替尼乳膏替代治疗尚无定论，而交替使用500毫克/天和750毫克/天的口服拉帕替尼在减轻疼痛、改善症状和副作用之间取得了较好的平衡。患者2用厄洛替尼乳膏治疗未显示出明显改善。口服厄洛替尼从75毫克/天开始，由于出现痤疮样皮疹，随后减至25毫克/天。治疗使患者病情显著改善，疼痛几乎完全消失。口服Her1或1/2抑制剂减轻了疼痛，改善了两名PC患者的生活质量，并提供了有前景的治疗前景。
