Striate, focal or diffuse palmar and plantar hyperkeratosis (‘keratoderma’) without a red border. Patients usually have no history of skin blistering. Involvement of other skin areas, especially over joints (knuckles, finger joints, elbows, knees) is possible. In Ichthyosis hystrix type Curth-Macklin, hyperkeratosis of palms and soles is extremely severe and debilitating, usually associated with severe contractures of the digits and deep, painful fissures. In Greither disease, NEPPK extends to the extensor surface of the limbs. In contrast to syndromic forms of NEPPK, those due to keratin mutations are not associated with other organ abnormalities.