Eugene M. Farber

The Natural History of Psoriasis in 5,600 Patients

The natural history of psoriasis was studied through a questionnaire survey of 5,600 patients throughout the United States. The mean age of onset of psoriasis was 27.8 years. 36% of the respondents reported familial occurrence of the disease. At the time of study, the lower extremities were indicated as being the most often affected; trunk, elbow, and scalp were next, knee and face were cited less frequently. Fingernails were involved in half of the patients at some time during the period of their disease. In the majority of patients, hot weather and sunlight had a beneficial effect. One third of the females also indicated improvement during the course of pregnancy. Remissions were reported in 39% of the patients.

Stress, symmetry, and psoriasis: Possible role of neuropeptides

The role of stress as a triggering factor in the exacerbation of psoriasis and the clinically symmetric distribution of psoriatic plaques suggested a possible role for neuropeptides in the etiopathogenesis of psoriasis. Several observations by other investigators involving substance P suggested to us a possible role for substance P as a modulator of the inflammatory response in psoriasis. A hypothesis for the role of substance P that would account for the temporal onset with stress, the clinical symmetry of lesions, and the histopathologic features of psoriasis is presented.

Drugs in exacerbation of psoriasis.

Drugs that have been associated with the precipitation or exacerbation of psoriasis include lithium, beta adrenergic receptor blocking agents, and antimalarials. The withdrawal of corticosteroids has been reported to activate pustular psoriasis. Nonsteroidal anti-inflammatory drugs, such as indomethacin, have recently been reported to exacerbate psoriasis, although additional well-controlled studies are still needed. Drugs used for treatment of psoriasis will sometimes cause a flare because of irritation, phototoxicity, or hypersensitivity reaction resulting in a Koebner phenomenon. Because psoriasis is a very complex disease and its activity is often unpredictable, clinical studies on adverse drug effects on psoriasis have been difficult to conduct. This review evaluates clinical, histologic, and biochemical evidence in the literature for drug-associated onset or exacerbation of psoriasis.

Psoriatic Keratinocytes Express High Levels of Nerve Growth Factor

Many investigators have reported proliferation of terminal cutaneous nerves and upregulation of various neuropeptides (substance P, vasoactive intestinal polypeptide, calcitonin gene-related peptide) in psoriatic lesions. Nerve growth factor promotes growth of nerves and causes upregulation of neuropeptides like substance P and calcitonin gene-related peptide. In this study we investigated the expression of nerve growth factor in psoriatic lesions, non-lesional psoriatic skin, lichen planus and normal control skin. Immunoperoxidase staining was applied on cryosections prepared from snap-frozen biopsy specimens. The primary antibody used was a polyclonal anti-NGF-beta antibody. Nerve growth factor was detected only in the keratinocytes. In psoriatic tissue the number of keratinocytes per square millimeter of epidermis positive for nerve growth factor was 84.7 +/- 46.3 compared to 44.8 +/- 29.9, 18.9 +/- 11.8 and 7.5 +/- 16.9, respectively, in non-lesional psoriatic skin, normal skin and lichen planus. Increased expression of nerve growth factor substantiates larger numbers of terminal cutaneous nerves and upregulations of substance P and calcitonin gene-related peptide in psoriatic lesions. In addition, nerve growth factor is mitogenic to keratinocytes, activates T-lymphocytes and can induce migration of inflammatory cellular infiltrates, histological features characteristic of psoriasis.

Upregulation of RANTES in Psoriatic Keratinocytes: a Possible Pathogenic Mechanism for Psoriasis

Intraepidermal collections of neutrophils and lymphocytes are unique features of the inflammatory reaction of psoriasis. Migration of leukocytes from dermis to the epidermis suggests a role for chemotactic agent(s). In recent years, increased levels of chemokines such as IL-8 , GRO-a and MCP-1 have been reported in the keratinocytes of psoriatic tissue. IL-8 and GRO-alpha belong to a subfamily (C x C) class and MCP-1 is a beta chemokine. In this study, we investigated RANTES, which is a beta chemokine (C-C class); RANTES has been found to be associated with various cell-mediated hypersensitive disorders. We obtained eight skin biopsies from chronic psoriatic plaques, and five biopsies each from non-lesional psoriatic skin, lichen planus, eczematous dermatitis and skin from healthy controls. Snap-frozen samples were cut into 7 microm cryosections and stained with 6 mg/ml of monoclonal anti-RANTES mouse IgG (DNAX, Palo Alto, CA). Standard immunohistochemistry techniques were applied. RANTES was detected only in the keratinocytes. The number of keratinocytes in per mm2 of epidermis stained for RANTES were 116.79+/-98.42 in psoriatic tissues compared to 32.00+/-46.05 (p<0.05), 6.39+/-3.59 (p<0.01), 2.64 +/-1.15 (p<0.01) and 3.53+/-5.26 (p<0.01), respectively, in the non-lesional, lichen planus, eczematous lesions and normal skin. This is the first study to report that the keratinocytes of psoriatic tissue express high levels of RANTES compared to the controls. IL-8 and related molecules (C x C class) are predominantly chemotactic for neutrophils and MCP-1 is a strong chemotactic factor for monocytes. In contrast, RANTES is chemotactic for memory T cells and activated naive T cells. Increased amounts of RANTES as reported here provide an explanation for migration of the activated T cells to the epidermis of the psoriatic lesions. In addition, RANTES activates T cells. These results suggest that RANTES may have a significant role in the inflammatory process of psoriasis. Our findings further substantiate a regulatory role for keratinocytes in the inflammatory process of psoriasis.

The role of cutaneous sensory nerves in the maintenance of psoriasis

This is a case report of two patients with chronic plaque psoriasis in whom cutaneous nerve damage resulted in clearance of the disease at that site. In both patients reappearance of the psoriasis occurred with recovery of cutaneous sensation. The role of cutaneous sensation in the maintenance of skin disorders and, in particular, the role of neuro‐peptides in the pathogenesis of psoriasis are discussed.

Limited application period for dithranol in psoriasis. Preliminary report on penetration and clinical efficacy.

This preliminary study suggests that a 1 h application of dithranol may be effective in the treatment of psoriasis. It is conceivable that short application periods for other topically applied agents, e. g. corticosteroids, may reduce the side‐effects in non‐affected skin, while maintaining the therapeutic benefit in diseased areas.

Mast cell density and IL-8 expression in nonlesional and lesional psoriatic skin.

Abstract

Double-labeled immunofluorescence study of cutaneous nerves in psoriasis

Background and objective In recent years, many reports have suggested an active role of neuropeptides in the pathogenesis of psoriasis. Increased numbers of neuropeptide‐containing nerves positive for substance P (SP), vasoactive intestinal polypeptide (VIP), and calcium gene‐related peptide (CGRP) have been reported in psoriatic tissue. As psoriatic epidermis has a larger mass/volume, however, it is expected to have more nerves and a higher number of neuropeptergic fibers. Therefore, instead of demonstrating a larger number of neuropeptergic fibers, a more significant study is to investigate whether the neuropeptergic fibers are denser in psoriatic tissue. In this study, we applied a double labeled immunofluorescence technique. This method allows the identification of the total number of nerve fibers and the number of nerves positive for specific neuropeptides.

Cellular localization of fractalkine at sites of inflammation: antigen-presenting cells in psoriasis express high levels of fractalkine.

Background Chemokines play a key role in cell trafficking at sites of inflammation. The fractalkine CX3C chemokine is unique in several aspects. Fractalkine is expressed on activated endothelial cells and exists in two forms, either membrane anchored or in a soluble form. The soluble form is a potent chemotactic agent for T cells/monocytes and the anchored form functions as an adhesion molecule. In view of these specific functions fractalkine is capable of controlling the key regulatory mechanisms of cell trafficking at sites of inflammation.