Psoriasis and Antioxidants: A Literature Review

Wendy Barkin, Esq., V.P.

Source: Theodore Hersh, MD, MACG
Professor of Medicine, Emeritus, Emory University 

No Copyright Infringement Intended

​

Psoriasis is an inflammatory and hyperproliferative skin disease characterized by keratinocyte proliferation and differentiation and cutaneous accumulation of inflammatory polymorphonuclear leukocytes capable of release of toxic oxygen and free radical species. Psoriasis therapy is usually targeted at decreasing psoriatic skin inflammation and keratinocyte hyperproliferation.

 

Seborrheic dermatitis is a papulosquamous inflammatory disease of cutaneous areas rich in sebaceous glands, particularly in the scalp, where its feature is a "scale" which is dry, snowy-white and desquamates (dandruff). Seborrhea is associated with the presence of Pityrosporum yeasts contributing to scalp pruritus, erythema and exudation. Selenium and zinc pyrithione preparations are cornerstones of treatment for these two conditions.

​

The epidermis in psoriatic skin, much like skin which has sustained a significant burn, has increased levels of the enzyme "xanthine oxidase." This enzyme, like phagocytic cells and skin fibroblasts, is capable of generating free oxygen radicals. In an experimental mouse model, an inflammation induced by a specific chemical (TAP) was associated with high xanthine oxidase activity and concomitant epidermal cell hyperplasia. This experimental finding is similar to what occurs in psoriatic skin, where there is a five-fold increase in xanthine oxidase and there is also cellular hyperproliferation. It is not known if this increase in xanthine oxidase is responsible for epidermal hyperplasia in psoriasis, yet in vitro, when fibroblasts in culture are subjected to low hydrogen peroxide levels, there is an increase in epithelial cell proliferation. Consequently, it appears that reducing the quantity of reactive oxygen species by scavenging and neutralizing these free radicals with topical antioxidants will reduce free oxygen radicals in favor of hydrogen peroxide production by the process of dismutation, thereby resulting, at least in part, in arresting the hyperproliferative state in the skin affected by psoriasis.

​

A. PUVA Treatment

Psoralens plus ultraviolet A radiation (PUVA) represent one form of therapy, although there exists a definite increased risk of photocarcinogenesis with this therapy. Like the increased risk of cutaneous carcinomas and melanoma from UV radiation, reactive oxygen and other free radical species may be pathogenetic of these neoplasias. PUVA leads to chromosomal breakage through the formation of transferable clastogenic factors, but this genesis may be inhibited by the enzyme superoxide dismutase.

 

Clastogenic factors have been detected in patients with psoriasis and with other illnesses associated with oxidative stress, where the free radical superoxide is produced by phagocytes in the so-called "respiratory burst reaction" and from the process of lipid peroxidation. These clastogenic factors have been detected in blood of untreated psoriatic patients and are markedly increased during PUVA treatment. Thus, the oxidative stress, particularly during PUVA therapy, may be ameliorated and the risk of photocarcinogenesis decreased by concomitant administration of oral and topical antioxidant preparations, particularly those with superoxide scavengers. These measures represent preventive aspects in the management of patients with psoriasis. (Filipe, P et al, Photochem & Photobiol 66:497, 1997).

​

B. SKALP Levels

Skin-derived anti-leukoproteinase (SKALP) is a potent and specific inhibitor of leukocyte elastase. In a study in Holland, Kuijpers and colleagues showed that there were decreased SKALP levels in skin from patients with pustular psoriasis compared to those samples from plaque psoriasis They postulate that low SKALP levels contribute to an inbalance between elastase and its inhibitor as being pathogenetic in psoriatic pustule formation.

 

Lowering skin inflammation reduces both the numbers of leukocytes and also those of the enzyme elastase locally. This study supports the value of administering local antioxidant compositions to psoriatic skin to bind free radical species in the affected skin surfaces and reduce the inflammation. (Arch Derm Research 288: 641,1996).

​

C. Alpha-1-antiproteinase and N-Acetyl-L-Cysteine

Oxidants produced by activated phagocytes include superoxide, hydrogen peroxide and hypochlorous acid. A major extracellular target of attack by hypochlorous acid is alpha-1-antiproteinase, the major circulating inhibitor of proteases like the enzyme elastase. Inactivation of the alpha-1-antiproteinases results in elastase dependent hydrolysis of tissue elastin, as in the skin of psoriasis patients and the lungs of those with emphysema. N-Acetyl-L-Cysteine raises intracellular glutathione and also acts as an antioxidant scavenger, thereby protecting the alpha-1-antiproteinases and nullifying the local digestive effects of elastase on cutaneous elastin tissue (Arouma, Free Radic.Biol. Med 6:593,1988).

​

D. AIDS and Glutathione

Patients with AIDS often have complicating dermatoses including desquamating disorders such as psoriasis and seborrhoeic dermatitis. These skin conditions as well as other opportunistic infections tend to increase during the more advanced stages of AIDS, when CD4-T lymphocytes and their glutathione levels are very low. Repletion of HIV seropositive patients with glutathione decreases HIV viral replication, prolongues HIV patient survival and may decrease the risks of developing complicating opportunistic infections and bothersome dermatoses. (Rosatelli et al, Intl. J. Dermat 36:729,1997).

​

E. Selenium

Corrocher and colleagues demonstrated that patients with moderate or severe psoriasis have low blood selenium levels and a concomitant increase in the production of the chemical malondialdehyde, a reflector of free radical damage in the body. (Clin Chim Acta 179: 121,1989).

Harvima and collaborators in Finland supplemented psoriasis patients with oral selenomethionine. Although neither skin selenium levels nor the clinical condition were affected, there was a distinct increase in the numbers of skin CD4 -T lymphocytes, which are able to modulate local immunologic mechanisms. (Acta Derm Vener 73:88, 1993).

Burke and colleagues have demonstrated both in human subjects and experimental animals that topical selenomethionine reduces the degree of UV irradiated damage to the skin. In the murine species, topical selenium also inhibited skin carcinogenesis. Free radical species are implicated in inducing these skin pathologies.

 

Thus, selenomethionine applied topically with its synergistic antioxidant partners will benefit patients with psoriasis, including those undergoing PUVA treatments, both as a preventative of skin cancers and reparative of cutaneous damage. (Photoderm, Photoimmuno 9:52, 1992).

Patients with seborrheic dermatitis have been shown to have low plasma levels of vitamin E, selenium, erythrocyte selenium containing glutathione peroxidase and of poly-unsaturated fatty acids. These low blood levels of nutrients were recorded whether these patients with seborrheic dermatitis were HIV positive or HIV negative.

 

They ascribed these deficiencies to the pathogenesis of seborrheic dermatitis and then patented a reparative shampoo composition, as adjuvant therapy, consisting of selenium, methionine and vitamin E as a protective response to scalp damage caused by the process of lipid peroxidation, (Instituto Dermatologico, San Gallicano, Rome, Italy) (U.S. Patent #5,290,809).

​

Another composition of selenium as the sulfide is a well known component in anti-dandruff shampoos (Rappaport, MJ., Int Med Res. 9:152,1981).

​

Bergbrant stresses that the numbers of the pathogenetic Pitysporum yeasts in seborrheic dermatitis patients is not related to their numbers in the scalps of affected individuals. He ascribes these micro-organisms as etiologic due to altered cell-mediated immunity, akin to the low levels of CD 4 T-lymphocytes which are also glutathione-depleted in patients with AIDS.

 

The Pitysporum ovale species, which is rich in lipase content, causes an inflammatory response in the scalp. There is then an increase in the release of the enzyme elastase from leukocytes which further generates free radicals and induces tissue damage. Impaired immune function, the inflammatory leukocytic reaction, and Pitysporum ovale lipase activity need to be reduced to ameliorate seborrheic dermatitis. (Curr Topics Med Mycol 6:95, 1995).

 

Drugs that reduce sebum and antimycotic therapies, including the anti-infective zinc pyrithione, require addition of adjuvant therapy, as provided from locally administered antioxidants, including glutathione, cysteine, and selenium. These antioxidants neutralize the free radicals and ameliorate the inflammatory reaction while helping to restore immune function.