Psoriasis: current perspectives with an emphasis on treatment

doi:10.1016/S0002-9343(99)00284-3

The American Journal of Medicine

Volume 107, Issue 6, December 1999, Pages 595-605

https://doi.org/10.1016/S0002-9343(99)00284-3 Get rights and content

Abstract

An individualized treatment regimen is necessary for each patient with psoriasis because of the diverse nature of the disease. The manifestation of psoriasis, the severity and extent of the lesions, and the medical history and lifestyle of the patient are important factors that determine the selection of treatment, but in general therapies with the fewest side effects are preferred. First-line topical treatments are corticosteroids, calcipotriene, and tazarotene. If topical treatments are unsuccessful, phototherapy with ultraviolet B or photochemotherapy with psoralens plus ultraviolet A (PUVA) are the next choices. If psoriasis fails to respond to an adequate trial of topical therapy or phototherapy, systemic therapies including methotrexate, acitretin, or cyclosporin should be initiated. Because the regimens involved in systemic and phototherapy are complex and require frequent dose adjustments and specialized equipment, the patient should be referred to a dermatologist when topical therapy is not effective.

Section snippets

Epidemiology

Psoriasis affects about 0.1% to 3% of the world’s population (1), with men and women being equally affected. The prevalence of psoriasis is greatest in northern, colder climates. In the United States alone, prevalence of psoriasis is 1% to 2%, with a yearly incidence of 250,000 new cases (2), about 10 cases per 1,000 persons (3). The National Center for Health Statistics reported that there were 2.25 million visits to ambulatory care facilities during 1996 for psoriasis, compared with almost 19

Quality of life and cost issues

In general, most people underestimate the social and psychological impact of psoriasis, which can be debilitating. Its unsightliness can be detrimental to a patient’s quality of life. The degree of handicap imposed by psoriasis is comparable with that of other chronic diseases, such as diabetes and asthma. In one study of 369 patients with severe psoriasis, only 150 were working. Of those, 59% had lost an average of 26 days of work during a 1-year period as a result of their condition (8). Of

Clinical presentation and pathophysiology

Psoriasis is characterized by hyperkeratosis and thickening of the epidermis as well as by increased vascularity and infiltration of inflammatory cells in the dermis. The most common form is psoriasis vulgaris, which is generally referred to as chronic plaque psoriasis (Figure 1). Its features include silvery, scaly, erythematous plaques, ordinarily found on the scalp, elbows, knees, and buttocks. The plaques are well demarcated, and pinpoint bleeding may occur when a scale is removed (Auspitz

Complications

Psoriasis can also affect the scalp, hair, and nails. Fingernails and toenails are affected in up to 10% of patients with psoriasis vulgaris, and some patients experience hair loss (17). Nail psoriasis is one of the common causes of onycholysis.

Complications may also be specific to the subtype of psoriasis. Patients with severe cases of erythrodermic psoriasis may have hypothermia and hypoalbuminemia secondary to skin exfoliation. Cardiac failure, pneumonia, and renal failure can occur. Between

Treatment of psoriasis: mild-to-moderate disease

There is presently no cure for psoriasis. Currently available treatments are capable of suppressing or ameliorating the disease. The goal of treatment is to decrease the severity and extent of cutaneous lesions so that they no longer interfere substantially with a patient’s employment, social life, or well-being. The majority of patients do not obtain a treatment-free remission, and continuing maintenance therapy is required. The currently available treatment modalities for psoriasis can be

Treatment of psoriasis: severe disease

When treating more severe or extensive psoriasis, with more than 15% to 20% of the body surface area affected, topical treatment is no longer practical, both in terms of cost and patient compliance with the frequent application of topical agents over a large area. When psoriasis is severe, recalcitrant, or extensive, systemic therapy becomes necessary. These treatment regimens are often complex, and they may require specialized equipment and frequent monitoring. Most patients should be referred

Treatment choice

The decision to change from one form of therapy to another in the management of psoriasis is complex. Considerations include the disease severity and type of psoriasis (eg, topical treatments for mild psoriasis and systemic treatments for more severe cases), the failure to respond to first-line therapies, the ability of the patient to understand and cooperate with the necessary restrictions associated with using systemic agents, and the toxicity of systemic agents versus topical treatments.

The

Conclusions

Despite the wide range of treatment options, there is currently no cure for psoriasis. Current treatments for psoriasis work to attenuate the mechanisms that cause it. Because psoriasis is not usually life-threatening, the degree of psychological and social morbidity accompanying psoriasis is often underestimated, which may result in less-than-optimal care. The selection of an appropriate therapy must take into account patient preference and lifestyle, response to previous treatment, and

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Anti-proliferative and anti-inflammatory effects of 3β,6β,16β-Trihydroxylup-20(29)-ene on cutaneous inflammation
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Citation Excerpt :
Facing the complex nature of the disease, most of treatments often do not show satisfactory outcomes. Drug tolerance, side effects, toxicity and inconvenience are the main drawbacks of the available therapies (Gottlieb, 2005; Linden and Weinstein, 1999). In light of the difficulties, there is growing interest in the development of new therapies and drugs to treat inflammatory skin disorders in a safe and effective way (Stern et al., 2004).
3β,6β,16β-Trihydroxylup-20(29)-ene (TTHL) is a triterpene isolated from the flowers of Combretum leprosum, a plant used in folk medicine in the north of Brazil for the treatment of skin disorders.
In the present study, TTHL was evaluated as a potential topical anti-inflammatory and anti-proliferative agent through in vivo and in vitro models.
Anti-inflammmatory and anti-proliferative effects of TTHL were assessed using Swiss mice in acute and chronic models of skin inflammation induced by 12-O-tetradecanoylphorbol-acetate (TPA) application. Anti-proliferative activity was proved through in vitro experiments with the HaCaT human keratinocyte cell line.
Treatment with TTHL inhibited inflammatory parameters such as oedema formation and cellular infiltration in acute and chronic models. In the chronic model, TTHL also inhibited epidermal hyperproliferation, as evidenced by reduction of epidermis thickness and proliferating cell nuclear antigen expression. The anti-proliferative effect was confirmed by the capability of TTHL in reducing the proliferation and inducing cell apoptosis of HaCaT cells. Suggesting a mechanism of action, TTHL showed activation of corticosteroid receptors, but without the induction of corticosteroid-related cutaneous side effects.
Our results demonstrate consistent anti-inflammatory and anti-proliferative activity and assign TTHL as a valuable tool in the development of a new treatment for skin inflammatory and proliferative diseases, such as psoriasis.
Physico-chemical characteristics of methotrexate-entrapped oleic acid-containing deformable liposomes for in vitro transepidermal delivery targeting psoriasis treatment
2012, International Journal of Pharmaceutics
Citation Excerpt :
Psoriasis is a chronic autoimmune disease predominantly appeared on the skin and joint manifestations. It occurs when immune system mistakes the skin cells such as a pathogen, and transmits faulty signals that speed up the growth and division of skin cells, resulting in a well-defined erythematous together with red and white hues of scaly patches appearing on the top layer of the epidermis (Andrew et al., 2004; Linden and Gerald, 1999). Patients with psoriasis experience the increased levels of stress, anxiety, depression and anger.
This study aimed to investigate the physico-chemical characteristics and in vitro permeability of methotrexate (MTX)-entrapped deformable liposomes prepared from phosphatidylcholine (PC) and oleic acid (OA), comparing with those of MTX-entrapped conventional liposomes prepared from PC and cholesterol (CH). Two formulations of MTX-entrapped PC2:CH1 and PC9:CH1 liposomes and one formulation of MTX-entrapped PC2.5:OA1 liposomes were prepared. The size, size distribution, zeta potential, thermal properties, entrapment efficiency, stability, and in vitro permeability across a porcine skin of the MTX-entrapped liposomes were evaluated. All liposome formulations showed a narrow size distribution with the size range of 80–140 nm which is appropriate for the skin permeability. The percentage of MTX loading, entrapment efficiency and the stability of MTX-entrapped PC2:CH1 and PC9:CH1 liposomes were slightly higher than those of MTX-entrapped PC2.5:OA1 liposomes. However, the MTX-entrapped PC2.5:OA1 liposomes enhanced the skin permeability characterized by the higher concentration and flux of MTX diffused across or accumulated in the epidermis and dermis layers of porcine skin. The enhanced permeability of MTX-entrapped PC2.5:OA1 liposomes was explained by 2 mechanisms: (1) the deformable and elasticity characteristics of OA-containing liposomes and (2) a property as a skin penetration enhancer of OA. This suggested that the PC2.5:OA1 deformable liposome was one of promising candidates to enhance the permeability of MTX for the treatment of psoriasis.
Celastrol-induced apoptosis in human HaCaT keratinocytes involves the inhibition of NF-κB activity
2011, European Journal of Pharmacology
Citation Excerpt :
However, because of the complex nature of psoriasis, many therapeutic regimens often fail to produce satisfactory results, largely due to drug tolerance and the associated untoward side effects. There is presently no cure for psoriasis (Linden and Weinstein, 1999). Because of these reasons, many patients often seek help from complementary medicine such as traditional Chinese herbal medicine.
Psoriasis is a chronic inflammatory skin disease affecting 1–3% of the world's population. Traditional Chinese medicines have been extensively used for treating psoriasis with promising clinical results. Celastrol, a triterpenoid isolated from a Chinese herb Celastrus orbiculatus caulis, has been known to have diverse pharmacological effects such as anti-inflammatory, anti-cancer and antioxidant activities. The present study aimed at evaluating the anti-proliferative action of celastrol on cultured HaCaT cells and elucidating the mechanisms of action involved. Celastrol was shown to inhibit HaCaT cells growth with an IC₅₀ value of 1.1 μM as measured by MTT assay. The ability of celastrol to induce apoptosis was studied by flow cytometric and western blot analyses. Celastrol was found to be capable of inducing apoptosis in HaCaT cells as characterized by phosphatidyl-serine (PS) externalization, depolarization of mitochondrial membrane potential and activation of caspase-3. The apoptosis induced by celastrol could be suppressed by Z-IETD-FMK and Z-LEHD-FMK, the respective caspase-8 and caspase-9 inhibitor. In addition, western blot analysis revealed a significant augmentation in the protein expression of Bax and attenuation in Bcl-2, suggesting that the celastrol-induced apoptosis acts through both death receptor and mitochondrial pathways. Moreover, western blot analysis on the expression of Rel/NF-κB demonstrated that the celastrol-mediated apoptosis on HaCaT cells was associated with the inhibition of the NF-κB pathway. Taken together, the present project has for the first time identified celastrol as a naturally occurring compound with potent apoptogenic action on cultured human keratinocytes, rendering it a promising candidate for further development into an anti-psoriatic agent.
Psoriasis exacerbation after hormonotherapy in prostate cancer patient-Case report
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Psoriasis, as the most common inflammatory skin disorder, affects about 2–3% of the world's population. Many non-dermatological conditions have been linked with psoriasis, including cardiovascular diseases, depression, inflammatory bowel disorders, and some cancers, i.e. lung, colon and kidney cancers. Among systemic factors are endocrine and metabolic disturbances as well as many drugs. Erythrodermic psoriasis, the most severe form of the disease, is characterized by diffuse erytrema and scaling, often accompanied by fever, chills, and malaise.
A 57-year-old Caucasian man was admitted for curative radiation therapy of adenocarcinoma of the prostate after 3 months of initial hormonal therapy. The management comprised the combined androgen blockade (CAB). On admission the patient reported escalation of psoriasis symptoms, which he had been treated for since 2002. Due to a mild course of the disease he had not required any systemic treatment ever before, even during aggravation periods. The last exacerbation started appearing a month after hormonal therapy implementation. The cutaneous eruptions, already existing, become larger with new foci revealing, mainly on upper and lower limbs. During radiotherapy planning, there appeared a diffuse erythema and scaling on hands and feet with accompanying pruritis. We decided to start the previously planned radiation therapy which included the prostate gland with 1.5 cm margin and provided for the total dose of 72 Gy in 36 fractions. The irradiation was conducted with the four-field technique using a megavoltage linear accelerator. During radiotherapy we photo-documented skin lesions.
To our best knowledge hormone therapy (androgen deprivation) of prostate cancer patients has not been reported as an aggravating factor. Thus, the aim of our work is to present the case of a prostate cancer patient who experienced psoriasis exacerbation after implementation of hormonal blockade as a neoadjuvant oncological treatment.
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ReviewsPsoriasis: current perspectives with an emphasis on treatment

Abstract

Section snippets

Epidemiology

Quality of life and cost issues

Clinical presentation and pathophysiology

Complications

Treatment of psoriasis: mild-to-moderate disease

Treatment of psoriasis: severe disease

Treatment choice

Conclusions

Dermatol Clin

Dermatol Clin

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

Dermatol Clin

J Invest Dermatol

J Invest Dermatol

J Am Acad Dermatol

Dermatol Clin

Respir Med

Respir Med

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Derm

J Am Acad Dermatol

Dermatol Clin

Dermatol Clin

Dermatol Clin

J Invest Dermatol

Dermatol Clin

J Am Acad Dermatol

Dermatol Clin

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

Treatment of psoriasis

NEJM

Current estimates from the National Health Interview Survey, 1994. National Center for Health Statistics

Vital Health Stat

Ambulatory care visits to physician offices, hospital outpatient departments, and emergency departmentsUnited States, 1996. National Center for Health Statistics

Vital Health Stat

Effectiveness of topical therapy for psoriasisresults of a national survey

Cutis

Gene for familial psoriasis susceptibility mapped to the distal end of human chromosome 17q

Science

Reviews
Psoriasis: current perspectives with an emphasis on treatment