Is psoriasis a T-cell disease?

The etiology and pathogenesis of psoriasis--one of the most common chronic, inflammatory, hyperproliferative skin disorders of man--have long fascinated dermatologists, pathologists and biologists alike. Here, we have a model disease that offers to study neuroectodermal-mesenchymal interactions in the widest sense possible. Epithelial, endothelial, and hematopoietic cells as well as neurons projecting into the skin apparently all interact with each other to generate the characteristic psoriatic lesion. For decades, the ongoing controversy on the molecular nature, choreography and hierarchy of these complex interactions e.g. between epidermal keratinocytes, T cells, neurotrophils, endothelial cells and sensory nerves has served as a driving force propelling investigative dermatology to ever new horizons. This debate has not only been at the heart of our quest to develop more effective forms of therapy for this socially crippling disease, but it also has profoundly influenced how we view the skin as a whole: the numerous competing theories on the pathogenesis of psoriasis published so far also are reflections on the evolution of mainstream thought in skin biology over the last decades. These days, conventional wisdom infatuated with a T-cell-centered approach to inflammatory skin diseases-- portrays psoriasis as an autoimmune disease, where misguided T lymphocyte activities cause secondary epithelial abnormalities. And yet, as this CONTROVERSIES feature reminds us, some authoritative "pockets of academic resistance" are still quite alive, and interpret psoriasis e.g. as a genetically determined, abnormal epithelial response pattern to infectious and/or physicochemical skin insults. Weighing the corresponding lines of argumentation is not only an intriguing, clinically relevant intellectual exercise, but also serves as a wonderful instrument for questioning our own views of the skin universe and its patterns of deviation from a state of homeostasis.

Antimicrobial treatment of psoriasis.

At the Problem Psoriasis Clinic at the University of Tennessee, Memphis, we use an antimicrobial approach for the treatment of psoriasis. This method is described for patient history, physical examination, and laboratory tests as well as treatment.

Psoriasis is a visible manifestation of the skin's defense against micro-organisms.

The recent discovery that human epidermal cells themselves make and secrete the components necessary for activation of the alternative complement pathway appears to provide an explanation for how human skin is ordinarily able to avoid colonization by molds and other organisms. It also helps clarify the mechanisms underlying clinical and laboratory findings seen in chronic mucocutaneous candidiasis, dandruff, and psoriasis. Psoriasis seems best explainable as a visible, late stage of the inflammatory sequelae of activation of the alternative complement pathway in the epidermis.

Microorganisms and psoriasis.

It has been suggested previously that psoriasis is best explained as a distinctive inflammatory response to a variety of microbial stimuli, all acting primarily through activation of the alternative complement pathway. For the past several years we have conducted a "Problem Psoriasis Clinic" based on that premise. Patients are questioned, examined, and subjected to microbiologic laboratory investigations in an attempt to identify possibly relevant microorganisms, and then are treated with antibiotics. This article lists the most commonly found microorganisms in psoriasis patients and describes the usual treatment for each. Results obtained with this approach compare favorably with those achieved with more usual anti-psoriasis treatments. We recommend that a microbiologic investigation and a trial of antimicrobial treatment should precede any plan to treat psoriasis patients with anything more than the simplest topical agents.

Efficacy of bimolane in the Malassezia ovalis model of psoriasis.

Bimolane, an analog of razoxane has been used in China with comparable efficacy but less toxicity than razoxane in the treatment of psoriasis. In an attempt to characterize further its mode of action it was administered both systemically and topically in the Malassezia ovalis animal model of psoriasis. Intravenous methotrexate and topical 0.1% betamethasone valerate were also used as positive control treatments. The animal model of psoriasis was effectively treated by bimolane, both systemically and topically, and also by parenteral methotrexate and topical betamethasone valerate. The time course of bimolane's effect with this model was different from methotrexate's suggesting the possibility of a different mode of action. Because bimolane, like razoxane, is an ethylene diamino tetraacetate acid (EDTA) derivative, it is possible that its effects on this reaction relate to its chelating properties and that inhibition of complement activation is important to its mode of action.

Complement activation in psoriasis.

Plasma from 16 patients with psoriasis and 12 healthy control subjects were measured for iC3b, C4d, and Bb fragments generated by complement activation. Plasma concentrations for iC3b, C4d, and Bb fragments were found to be significantly increased in the patients with psoriasis. The highest concentrations of these complement activation fragments were seen in patients with erythrodermic pustular psoriasis, psoriatic arthritis, and Reiter's syndrome. The serum concentrations of complement components and regulatory proteins were normal or elevated in almost all samples.

Magnolia grandiflora dermatitis.

A patient is described who had allergies to several sesquiterpene lactone-containing plants, but the reaction to Magnolia grandiflora was extremely severe. The condition was a chronic lichenified dermatitis that was unresponsive to treatment but cleared with protective measures. Primary allergy to Magnolia is rarely reported, even though some studies of cross-reactivity suggest that sensitivity is far from rare.

Complement phenotypes in patients with psoriasis.

Phenotype frequencies for the complement proteins C4A, C4B, Bf (factor B) and C3 were performed for 49 Caucasian patients with psoriasis. The C4*A6 allele was present in 26.6% of the patients as compared to 5.4% of healthy regional Caucasian controls, p less than 0.001, relative risk = 6.28. The C4*A6 allele is known to be in linkage disequilibrium with the HLA B17 allele and to produce a non-functional gene product when it occurs with the B17 allele. HLA B17 is known to be associated with psoriasis in many Caucasian populations. Additional findings in the present study were a significant reduction in the C4B*2 allele frequency, a non-significant increase in the Bf*F allele frequency and no difference for Bf or C3 phenotype frequencies in the patients with psoriasis as compared to the controls.

Bf and C4 phenotypes in patients with psoriasis.

Phenotype frequencies for the complement proteins Bf (factor B), C4A and C4B were performed in a sample of 49 Caucasian patients with psoriasis followed in Memphis, Tennessee. The genes for these proteins are located in the major histocompatibility complex between the HLA-B and HLA-DR loci. Bf phenotype frequency did not differ significantly for the patients as compared to regional controls. The C4*A6 allele was present in 26.6% of the patients as compared to 5.4% of the controls, p less than 0.001, relative risk = 4.93. The C4*A6 allele is known to be in linkage disequilibrium with the HLA B17 allele and produces a functionally defective gene product. The role, if any, of C4*A6 in the pathogenesis of psoriasis is uncertain.

Microbial associations of 167 patients with psoriasis.

Microbial findings were analyzed from a group of 167 patients with psoriasis in an attempt to discover specific associations. Positive findings include associations between Malassezia ovalis and scalp/ear/face psoriasis and between bacteria and bodyfold, nailfold, and gluteal/rectal psoriasis.