Moreover, numerous neuropeptides have been identified in the pathophysiology of psoriasis. Farber et al7 first proposed that release of substance P (SP) from cutaneous sensory nerve fibers causes a local neurogenic response that triggers psoriasis in predisposed individuals. The role of SP in psoriasis is unclear, as there have been reports of both higher8 and lower9 levels in involved and noninvolved skin of psoriatic patients compared to skin in healthy individuals. It has been suggested that numerous other neuropeptides, including nerve growth factor (NGF), calcitonin gene-related peptide, and vasoactive intestinal peptide, play a part in psoriasis.2,10 Specifically, NGF prevents apoptosis of keratinocytes11 and is found in higher levels in psoriatic skin compared to controls.12 Calcitonin gene-related peptide has been shown to stimulate keratinocyte proliferation13 and has been found at increased levels in psoriatic skin.14 Vasoactive intestinal peptide-positive nerve fibers in the epidermis and dermis are found in higher quantities in psoriatic plaques compared to nonlesional and normal skin.8
Neuropeptides also might play a role in the itching and Köbner phenomenon that accompany psoriasis. Increased levels of NGF in nonlesional skin of patients with psoriasis is thought to contribute to the development of psoriatic plaques following trauma by inducing an inflammatory response that upregulates other neuropeptides, such as SP and calcitonin gene-related peptide. These neuropeptides induce keratinocyte proliferation, which further increases NGF expression, thus creating a cycle of inflammation and formation of psoriatic lesions.6 Moreover, there is a notable correlation between pruritus severity and density of NGF-immunoreactive keratinocytes, high-affinity NGF receptors, protein gene product 9.5–immunoreactive intraepidermal fibers, and immunoreactive vessels for E-selectin.15
Spontaneous remission of psoriasis after cerebrovascular accident was first reported in 1998.5 Moreover, there have been cases of protective effects from psoriasis and psoriatic arthritis in limbs affected by poliomyelitis.16,17 In cases in which patients regained neurologic function, Zhu et al10 found that recurrence of skin lesions in areas corresponding to nervous system injury also occurred. However, in cases of permanent nerve damage, psoriasis did not return,10 confirming the role of peripheral nerves in the pathogenesis of psoriasis. It is thought that peripheral nerve damage results in decreased secretion of neuropeptides3 and that central nervous system injury also can cause similar downstream effects.10
Other reasons for the patient’s remission also were considered. Although it is possible that the sudden change in the patient’s usual environment could have induced remission of psoriasis, it seems more likely that the stress of the situation would have worsened his symptoms. Medications used during the patient’s hospitalization also were considered as reasons for symptom improvement. One study using a case-control and case-crossover design found psoriasis to be associated with nonsteroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors (odds ratio, 4.0 and 2.1, respectively).18 Atorvastatin has been investigated as a potential treatment of psoriasis, though no therapeutic benefit has been proven.19,20 Heparin has been shown in case reports to improve psoriasis symptoms but was used in addition to standard psoriasis therapies and not as monotherapy.21
A more thorough understanding of which neuropeptides are directly implicated in the neurologic-mediated clearance of psoriasis might contribute to better targeted therapies. For example, infusion of peptide T, a vasoactive intestinal peptide analogue, was shown to have some effect in clearing the skin in 14 psoriasis patients.22 Although this finding has not been replicated, it demonstrates the potential utility of therapies targeted toward the neurologic aspects of psoriasis. More research is needed to evaluate the potential of targeting other neuropeptides for treatment of psoriatic plaques.