Revisiting the Koebner Phenomenon

Abstract

Nerve growth factor (NGF) influences the key pathological events of psoriasis: keratinocyte proliferation, angiogenesis, and T-cell activation. We have systematically examined the kinetics of NGF expression, keratinocyte proliferation, and migration of T lymphocytes in the epidermis in Koebner-induced developing psoriatic plaques. In skin traumatized by the tape-stripping method (n ‫؍‬ 12), a marked up-regulation of NGF in Koebner-positive lesions (n ‫؍‬ 7) was observed 24 hours after trauma. Synthesis of NGF reached its maximum level in the 2nd week. Furthermore, cultured keratinocytes from nonlesional skin of psoriasis patients produced 10 times higher levels of NGF compared with keratinocytes from healthy individuals. To substantiate the in vivo effect of NGF secreted by keratinocytes in psoriatic plaques, we studied psoriatic plaques and normal human skin in a SCID-human skin xenograft model. The transplanted psoriatic plaques demonstrated marked proliferation of NGF-R (p75)-positive nerve fibers compared with only a few nerves in the transplanted normal human skin. Our results demonstrate that 1) in a developing psoriatic lesion, up-regulation of NGF together with keratinocyte proliferation are early events and precede epidermotropism of T lymphocytes; 2) keratinocytes in patients with psoriasis are primed to produce elevated levels of NGF; and 3) NGF synthesized by these keratinocytes is functionally active.

Nailing down the Genetic and Immunological Basis for Psoriatic Disease

“…The histological findings of microdamage at normal entheses are reminiscent of the Koebner responses that are well known to dermatologists in the setting of both skin psoriasis and nail disease [20,21]. The recognition of the functional integration between the nail and enthesis including the bone therefore offers a better understanding of rare psoriatic disease variants, such as acral pustular psoriasis, that have been reported with resorptive osteolysis (deep Koebner phenomenon) [22].…”

Reactive Oxygen Species in Psoriasis and Psoriasis Arthritis: Relevance to Human Disease

“…Different environmental triggers like infection (from bacteria, fungi and viruses) [2,3], medications (lithium, antimalarials and nonsteroidal anti-inflammatory drugs) [2,4,5], obesity [6] and stress [7] initiate or worsen this complex, multifactorial syndrome in genetically prone individuals. Ps patients are at a great risk of developing a number of comorbid conditions including diabetes mellitus, hypertension, coronary heart disease, inflammatory bowel disease, lymphoma and depression [8].…”

Human papilloma virus infection and psoriasis: Did human papilloma virus infection trigger psoriasis?

“…The uniqueness of psoriatic keratinocytes is not well established, but a high level of NGF is reported in the psoriatic prone skin as compared to normal skin; psoriatic skin primed to make the increased level of NGF. [12] We, hereby conclude that this case may have developed due to primary HPV infection triggering psoriatic lesions, or the association could be a mere coincidence. The patient after clearance of skin and genital lesions was lost to follow-up.…”