Plaque Psoriasis 

Psoriasis is a common, chronic, relapsing, inflammatory skin disorder with a strong genetic basis. The plaque type of psoriasis is the most common, although several other distinctive clinical variants of psoriasis are recognized (eg, Guttate Psoriasis; Psoriasis, Nails; Psoriasis, Pustular; Psoriatric Arthritis).

Plaque psoriasis is most typically characterized by circular-to-oval red plaques distributed over extensor body surfaces and the scalp. The plaques usually exhibit scaling as a result of epidermal hyperproliferation and dermal inflammation. The extent and duration of plaque psoriasis is highly variable from patient to patient. Acute flares or relapses of plaque psoriasis may also evolve into more severe disease, such as pustular or erythrodermic psoriasis.

Up to 10-20% of patients with plaque psoriasis also experience psoriatic arthritis. A population-based study by Wilson et al that spanned more than 30 years reported that less than 10% of psoriasis patients develop clinically recognized psoriatic arthritis. The clinical features that were associated with an increased chance of leading to psoriatic arthritis were reported as being scalp lesions, nail dystrophy, and intergluteal or perianal psoriasis.^[1]

For more information, see Psoriasis.

The pathophysiology of psoriasis must be understood in terms of the prominent pathologies occurring in both major components of the skin—the epidermis and the dermis.

Psoriasis is fundamentally an inflammatory skin condition with reactive abnormal epidermal differentiation and hyperproliferation. Current research suggests that the inflammatory mechanisms are immune based and most likely initiated and maintained primarily by T cells in the dermis.^[2]

In this model, antigen-presenting cells in the skin, such as Langerhans cells, are believed to migrate from the skin to regional lymph nodes, where they interact with T cells. Presentation of an as yet unidentified antigen to the T cells, as well as a number of co-stimulatory signals, triggers an immune response, leading to T-cell activation and the release of cytokines.

Co-stimulatory signals are initiated via the interaction of adhesion molecules on the antigen-presenting cells, such as lymphocyte function–associated antigen (LFA)–3 and intercellular adhesion molecule-1, with their respective receptors CD2 and LFA-1 on T cells. These T cells are released into the circulation and traffic back into the skin.

Reactivation of T cells in the dermis and epidermis and the local effects of cytokines such as tumor necrosis factor lead to the inflammation, cell-mediated immune responses, and epidermal hyperproliferation observed in persons with psoriasis.

An interleukin (IL)-12–related cytokine, IL-23, is involved in the establishment of chronic inflammation and in the development of a T helper (Th)–cell subset producing IL-17. These cells, which are designated Th17, are distinct from Th1 and Th2 populations. Th17 cells are now recognized as a third T-effector cell subset, and the IL-23/IL-17 pathway has been implicated in the induction and progression of a number of inflammatory diseases, including psoriasis.^[3]

Environmental factors

Infection and a number of physical agents (eg, HIV infection, alcoholism, smoking, UV light) all can affect the course, duration, and clinical appearance of plaque psoriasis. See Etiology of Plaque Psoriasis, below, for more details on the role of environmental factors.

Genetic factors

HLA-B13, -B17, and -Cw6 are all associated with plaque psoriasis. Multifactorial inheritance mechanisms and etiologies without any genetic component have not yet been excluded, although many families appear to exhibit autosomal dominant patterns of inheritance with decreased penetrance. Studies of twin siblings have shown concordant disease in 73% of monozygotic twins compared with 20% in dizygotic twins.

Several putative genetic susceptibility loci have also been identified, including psoriasis susceptibility 1 (PSOR1) on chromosome 6, which is associated with up to 50% of cases. Six other psoriasis susceptibility loci (PSOR2, PSOR3, PSOR4, PSOR5, PSOR6, PSOR7) have been discovered, as well as the transcription factor RUNX1. While this certainly points to genetic mechanisms, the absence of 100% concordance among monozygotes suggests that environmental factors must play a role in the pathophysiology of this disease.

Trauma

All types of trauma have been associated with the development of plaque psoriasis (eg, physical, chemical, electrical, surgical, infective, and inflammatory injury). Even excessive scratching can aggravate or precipitate localized psoriasis. The development of psoriatic plaques at a site of injury is known as the Koebner reaction.

Sunlight

Most patients consider sunlight to be beneficial for their psoriasis; they report a decrease in illness severity during the summer months or periods of increased sun exposure. However, a small minority of patients find that their symptoms are aggravated by strong sunlight, and these individuals actually experience a worsening of their disease in the summer. A severe sunburn can lead to an exacerbation of plaque psoriasis via the Koebner reaction.

Infection

Pharyngeal streptococcal infections have been shown to produce a clinically distinctive disease flare known as guttate psoriasis. Some evidence suggests that subclinical streptococcal colonization or overgrowth could be responsible for refractory plaque psoriasis.

HIV infection

An increase in psoriasis activity has been observed in patients who are infected, or become infected, with HIV. The extent and severity of skin disease initially appears to parallel the disease stage. Psoriasis often becomes less active in advanced HIV infection.

Drugs

A number of medications have been shown to cause an exacerbation of psoriasis. Lithium and withdrawal from systemic corticosteroids are well known to cause flares of disease. Beta-blockers, antimalarials, and nonsteroidal anti-inflammatory drugs (NSAIDs) have also been implicated.

Psychogenic/emotional factors

Many patients report an increase in psoriasis severity with psychological stress. A clear cause-and-effect relationship between disease exacerbation and stress unfortunately has not been proven. Patients may show a decreased capacity to cope with their treatment regimen with higher levels of stress. Pruritus in the setting of increased anxiety or depression may promote scratching and a Koebner reaction.

Smoking

An increased risk of chronic plaque psoriasis exists in persons who smoke cigarettes.

Alcohol consumption

Alcohol consumption is considered a risk factor for psoriasis, particularly in young to middle-aged men.

Endocrinologic factors

Psoriasis severity has been noted to fluctuate with hormonal changes. Disease incidence peaks at puberty and during menopause. During pregnancy, symptoms are more likely to improve than worsen, if any changes occur at all. In contrast, the disease is more likely to flare in the postpartum period, again if any changes occur at all.

Plaque psoriasis occurs worldwide, although its prevalence varies with race, geography, and environmental factors (eg, sun exposure). In the United States, 1-2% of the population has plaque psoriasis.

Family history has been shown to predict disease occurrence. When both parents are affected by psoriasis, the rate in siblings of probands is as high as 50%. When one parent is affected, the rate is 16.4%. When neither parent has psoriasis, only 7.8% of siblings of probands are affected.

Of patients with psoriasis, 36-71% have one relative who is also affected by psoriasis. For siblings of patients whose psoriasis appeared before age 15 years, a 3-fold higher risk exists of developing disease compared with siblings of patients who first presented after age 30 years.

Psoriasis affects adult males and females equally. Among children and adolescents, plaque psoriasis has been found to affect females more than males, but this observation may be due to the earlier age of onset in females.

Plaque psoriasis first appears during 2 peak age ranges. The first peak occurs in persons aged 16-22 years, and the second occurs in persons aged 57-60 years. Females develop plaque psoriasis earlier than males, and patients with a positive family history for psoriasis also tend to have an earlier age of onset.

Mortality and morbidity

Disease-related mortality is exceedingly rare in psoriasis. Even then, mortality is related primarily to therapy: systemic corticosteroid therapy may provoke pustular flares of disease, which can be fatal; methotrexate therapy may result in hepatic fibrosis; and phototherapy (eg, psoralen plus UVA [PUVA]) may induce skin cancers, with subsequent metastasis.

Morbidity is a much greater problem in patients with psoriasis; it includes pruritus, dry and peeling skin, fissuring, self-consciousness and embarrassment about appearance, inconvenience, and the adverse effects and high cost of antipsoriatic treatment regimens. By far, reduced quality of life is the most significant morbidity. Studies have demonstrated that patients with psoriasis have deficiencies in quality of life similar to those for persons with congestive heart failure.

An association between psoriasis, obesity, and cardiovascular comorbidity was been recognized amongst patients with plaque psoriasis. This appears to be strongest in younger patients with severe disease. The association seems to be related to the metabolic syndrome, a state of chronic systemic inflammation characterized by at least 3 of the following:

• Abdominal obesity
• Impaired glucose regulation
• Hypertriglyceridemia
• Reduced high-density lipoprotein levels
• Hypertension

Psoriasis and obesity are now believed to share similar mediators (eg, cytokines tumor necrosis factor [TNF]–alpha and IL-6) that drive the inflammatory process in these conditions. This finding, as it becomes further elucidated, may have future implications on health screening and treatment of patients with psoriasis.^[4]

Racial disparity in psoriasis

Psoriasis can affect persons of any race; however, epidemiologic studies have shown a higher prevalence in western European and Scandinavian populations. In these groups, 1.5-3% of the population is affected by the disease.

The highest documented disease prevalence is in Arctic Kasach'ye, with 12% of the population affected, followed by Norway, where 4.8% of the population has psoriasis. Lower prevalence rates for psoriasis have been reported among Japanese and Inuit populations.

Psoriasis is thought to be rare in West Africans and African Americans and is nearly absent in North American Indians. Psoriasis was undetected in the Samoan population and in a study that examined 26,000 South American Indians.

Patient history

The typical history given by a patient with plaque psoriasis is relatively straightforward: patients report prominent itchy, red areas with increased skin scaling and peeling. Patients are particularly aware of lesions on the scalp and extensor surfaces. Patients typically are self-conscious about their lesions and commonly report using clothing to cover affected sites and avoiding potentially embarrassing social activities.

Patients commonly recognize that new lesions appear at sites of injury or trauma to the skin. This isomorphic phenomenon (Koebner reaction) typically occurs 7-14 days after the skin has been injured and has been found in 38-76% of patients with plaque psoriasis. In some patients, so-called reverse-Koebner reactions have also been noted in which preexisting psoriatic plaques actually clear after injury or trauma to the skin.

Patients may report that their disease worsens in the winter and improves in the summer.

Significant joint pain, stiffness, and deformity are reported in the 10-20% of patients with psoriasis who develop psoriatic arthritis.

Physical examination

Several cardinal features of plaque psoriasis can be readily observed during the physical examination.

Plaques

Psoriasis manifests as elevated lesions that vary in size from one to several centimeters (see image below). The thickened epidermis, expanded dermal vascular compartment, and infiltrate of neutrophils and lymphocytes account for the psoriatic lesions being raised and easily palpable. The number of lesions may range from few to many at any given time.

The plaques are irregular to oval and are most often located on the scalp, trunk, and limbs, with a predilection for extensor surfaces such as the elbows and knees. Smaller plaques may coalesce into larger lesions, especially on the legs and sacral regions (see image below). Fissuring within plaques can occur when lesions are present over joint lines or on the palms and soles.

Well-circumscribed margins

Psoriatic plaques are well defined and have sharply demarcated boundaries. Psoriatic plaques occasionally appear to be immediately encircled by a paler peripheral zone referred to as the halo or ring of Woronoff.

Red color

The color of psoriatic lesions is a very distinctive rich, full, red color. Lesions on the legs sometimes carry a blue or violaceous tint.

Scale

Psoriatic plaques typically have a dry, thin, silvery-white or micaceous scale; however, the amount and thickness of this scale is quite variable. Removing the scale reveals a smooth, red, glossy membrane with tiny punctate bleeding points. These points represent bleeding from enlarged dermal capillaries after removal of the overlying suprapapillary epithelium. This phenomenon is known as the Auspitz sign.

Symmetry

Psoriatic plaques tend to be symmetrically distributed over the body. Lesions typically have a high degree of uniformity with few morphologic differences between the 2 sides.

Pruritus

Pruritus, one of the main symptoms of plaque psoriasis, is quite variable in intensity but should not be ignored. Emotional instability (eg, high levels of anxiety, depression) that might be induced by the disease often manifests as an increased tendency to scratch.

Nail psoriasis

Nail changes are commonly observed in patients with plaque psoriasis. Nails may exhibit pitting, onycholysis, subungual hyperkeratosis, or the oil-drop sign. A proper assessment of any patient suspected of having psoriasis should include careful examination of the nails.

Psoriasis in children

Plaque psoriasis manifests slightly differently in children. Plaques are not as thick, and the lesions are less scaly. Psoriasis may often appear in the diaper region in infancy and in flexural areas in children. The disease more commonly affects the face in children compared with adults.

Inverse psoriasis

This is a variant of psoriasis that spares the typical extensor surfaces and affects intertriginous (ie, axillae, inguinal folds, inframammary creases) areas with minimal scale.

Psoriatic arthritis

Approximately 10-20% of all cases of plaque psoriasis are associated with psoriatic arthritis. Signs of psoriatic arthritis include the following:

• Red, warm, tender, and inflamed joints
• Joint deformity
• Dactylitis
• Sausage digits

Obesity

Patients with obesity and psoriasis may have an increased risk of cardiovascular disease. This association appears to be strongest in younger patients with severe disease and may be related to the metabolic syndrome.^[4]

Alcoholism

Alcoholism can be considered a complication of psoriasis. Male patients with severe disease are particularly at risk for this type of substance abuse.

The differential diagnosis of plaque psoriasis includes the following:

• Bowen Disease
• Drug Eruptions
• Erythema Annulare Centrifugum
• Lichen Planus
• Lichen Simplex Chronicus
• Lupus Erythematosus, Discoid
• Nummular Dermatitis
• Parapsoriasis
• Pityriasis Rosea
• Seborrheic Dermatitis

The diagnosis of psoriasis is almost always made on the basis of clinical findings. Laboratory investigations are rarely indicated. In severe cases, patients may have mild hyperuricemia and low folate levels, presumably because of enhanced epidermopoiesis.

Skin biopsies can confirm the diagnosis of plaque psoriasis; however, this is usually reserved for the evaluation of atypical cases or for excluding other conditions in cases of diagnostic uncertainty. See Histologic Findings, below, for more details on plaque histology.

Mitotic activity of basal keratinocytes is increased almost 50-fold, with keratinocytes migrating from the basal to the cornified layers in only 3-5 days rather than the normal 28-30 days. With hyperproliferation of skin cells, the epidermis becomes thickened or acanthotic in appearance and the rete ridges increase in size.

Abnormal keratinocyte differentiation is noted throughout the psoriatic plaques, as manifested by the loss of the granular layer. The stratum corneum is also thickened, and the retention of cell nuclei in this layer is referred to as parakeratosis.

Neutrophils and lymphocytes can be observed migrating upwards from the dermis into the acanthotic epidermis. Neutrophils may form localized collections known as Munro microabscesses. The presence of alternating collections of neutrophils sandwiched between layers of parakeratotic stratum corneum is virtually pathognomonic for psoriasis. (See image below.)

Signs of inflammation can be observed throughout the dermis in persons with plaque psoriasis. Marked hypervascularity and an increase in the size of the dermal papillae occur. An activated CD3⁺ lymphocytic infiltrate is noted around blood vessels, with T cells expressing cutaneous lymphocyte–associated antigen, co-stimulatory molecules such as CD2, and lymphocyte function-associated antigen–1 (LFA-1) adhesion molecules. An aggregation of neutrophils in the dermis occurs that extends up into the epidermis.

Plaque psoriasis is a chronic skin condition. Any approach to the treatment of this disease must be considered for the long term. Treatment regimens must be individualized according to age, sex, occupation, personal motivation, other health conditions, and available resources.

Disease severity is defined not only by the number and extent of plaques present but also by the patient's perception and acceptance of the disease. Treatment, therefore, must be designed with the patient's specific expectations in mind rather than the extent of the body surface area involved.^[5]

Many treatments exist for psoriasis; however, the construction of an effective therapeutic regimen is not necessarily complicated. Three basic treatment modalities are available for the overall management of psoriasis: topical agents; phototherapy; and systemic agents, including biologic therapies. All of these treatments may be used alone or in combination.

The American Academy of Dermatology has published guidelines of care for the management of psoriasis and psoriatic arthritis. See the following sections:

• Section 1. overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics^[6]
• Section 2. psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics^[7]

Outpatient topical therapy is the first-line treatment of plaque psoriasis. A number of topical treatments are available (eg, corticosteroids, coal tar, anthralin, calcipotriene, tazarotene).

No single topical agent is ideal for plaque psoriasis, and many are often used concurrently in a combined approach. With the different adverse effect profiles for the various agents, using a rotational therapeutic approach in which different topical agents are used sequentially over time in the same patient is common.

In general, the effects of topical therapy should become evident within the first 2-3 weeks of use. Clearing of scale is usually observed first, followed by flattening of the treated plaques. Resolution of erythema may take 6-8 weeks.

Auxiliary agents such as keratolytics can often be added to these preparations. However, some auxiliary agents are incompatible with the active ingredients of these preparations. For example, salicylic acid inactivates calcipotriene. On the other hand, agents such as anthralin require the auxiliary agent salicylic acid for chemical stability.

Initiate phototherapy only in the presence of extensive and widespread disease (generally practically defined as more lesions than can be easily counted). Resistance to topical treatment is another indication for phototherapy.

The 2 main forms of phototherapy are ultraviolet B (UVB) irradiation psoralen plus ultraviolet A irradiation (PUVA). Proper facilities are required for both UVB irradiation and PUVA photochemotherapy.

UVB irradiation uses light with wavelengths of 290-320 nm (in comparison, the visible light range is 400-700 nm). Narrow-band UVB phototherapy uses a fluorescent bulb with a narrow emission spectrum that peaks at 311 nm. This selective and relatively longer wavelength is more effective than broadband UVB for the treatment of plaque-type psoriasis, and poses less risk of burning.^[8] Excimer laser UVB therapy can deliver high-dose light to limited plaques.

UVB therapy is usually combined with one or more topical treatments. The Goeckerman regimen uses coal tar followed by UVB exposure and has been shown to induce disease remission in more than 80% of patients. The Ingram method comprises anthralin application following a tar bath and UVB treatment. At present, UVB is more commonly combined with topical corticosteroids, calcipotriene, tazarotene, or simply bland emollients.

UVB phototherapy is extremely effective for treating moderate-to-severe plaque psoriasis. The major drawback of this therapy is the time commitment required for treatments and the accessibility of the UVB equipment. Patients may dislike the unpleasant odor when coal tar is added.

Home ultraviolet therapy can overcome some of the logistical problems associated with phototherapy. Because of the expense of the home units, it is most suitable for patients who require long-term maintenance therapy.

PUVA photochemotherapy, also known as PUVA, uses the photosensitizing drug methoxsalen (8-methoxypsoralens) in combination with UVA irradiation to treat patients with more extensive disease. UVA irradiation uses light with wavelengths of 320-400 nm. PUVA interferes with DNA synthesis, decreases cellular proliferation, and induces apoptosis of cutaneous lymphocytes, leading to a localized immunosuppression.

More than 85% of patients report relief of disease symptoms with 20-30 treatments. Therapy is usually administered 2-3 times per week in an outpatient setting, with maintenance treatments every 2-4 weeks until remission.

Adverse effects of PUVA therapy include nausea, pruritus, and a burning sensation. Long-term complications include increased risks of photo damage to the skin and (more importantly) skin cancer. PUVA has been combined with oral retinoid derivatives to decrease the cumulative dose of UVA radiation to the skin.

Initiate systemic treatment only after both topical treatments and phototherapy have proved unsuccessful. Consider systemic therapy for patients with very active psoriatic arthritis. Patients who have disease that is physically, psychologically, socially, or economically disabling are also considered candidates for systemic treatment. All patients must be informed of the risks and adverse effects of systemic therapy before treatment is initiated.^{[9, 10, 11]}

These relatively new systemic therapies provide selective, immunologically directed intervention at key steps in the pathogenesis of the disease.^[12] These steps include the following:

• Inhibiting the initial cytokine release and Langerhans cell migration
• Targeting activated T cells, preventing further T-cell activation, and eliminating pathologic T cells
• Blocking the interactions that lead to T-cell activation or migration into tissue
• Altering the balance of T-cell types
• Inhibiting proinflammatory cytokines such as tumor necrosis factor (TNF),^[13] IL-12, and IL-23^[14]

As with the systemic agents, biologic therapies are typically reserved for more severe and recalcitrant cases.^{[15, 16, 17, 18, 19, 20, 21, 22, 23]} Patients with active psoriatic arthritis in addition to their skin disease should also be considered.

In a study completed by the Psoriatic Arthritis Study Group, beneficial effects were observed for patients with psoriasis and psoriatic arthritis on stable doses of methotrexate when one or more courses of intramuscular alefacept were added. Further benefit in psoriatic arthritis was apparent after a second course of alefacept, and no additional toxicity was observed.^[24]

Psoriasis of the palms and soles is more difficult to treat than psoriasis on other body sites. Adalimumab is effective, but only 31% of patients treated with adalimumab for hand or foot psoriasis in a placebo-controlled trial achieved clear or almost clear.^[25]

Consider consultation with a rheumatologist for patients who have evidence of psoriatic arthritis. Patients with cardiovascular comorbidities should be considered for referral to a cardiologist. Evidence-based guidelines have been published on the management of cardiovascular morbidities.^[26]

Alcohol is considered a risk factor for psoriasis in young to middle-aged males. All patients with psoriasis should avoid or minimize alcohol use; patients with dependency states should be appropriately treated. Otherwise, specific dietary restrictions or supplements other than a well-balanced and adequate diet are unimportant in the management of plaque psoriasis.

Avoiding specific exacerbating factors (see Etiology of Plaque Psoriasis for details) may help prevent or minimize flare-ups of psoriasis in some patients, although the cause of disease exacerbation in many patients often is unknown.

Overly aggressive use of topical steroids could produce progression from plaque psoriasis to generalized pustular or erythrodermic forms. Topical steroids used with occlusion increase the risk of developing cutaneous atrophy. Potential adverse effects of systemic agents and phototherapy should be monitored on a regular basis and treated as soon as possible.

Patient education is one of the foundations for managing this chronic and typically relapsing disorder. Not only is psoriasis associated with morbidity, its treatment can also cause significant adverse effects (even death in rare instances). Patients should be familiar with these details in order to make proper and informed decisions about therapy.

The National Psoriasis Foundation is an excellent organization that provides support to patients with psoriasis.

For patient education information, see the Psoriasis Center, as well as What Is Psoriasis?, Plaque Psoriasis, Types of Psoriasis, Understanding Psoriasis Medications, and Nail Psoriasis.

The course of plaque psoriasis is unpredictable. Predicting the duration of active disease, the time or the frequency of relapses, or the duration of a remission is impossible. The disease rarely is life threatening but often is intractable to treatment, with relapses occurring in most patients.

Both early onset and a family history of disease are considered poor prognostic indicators. Some suggest that stress is also associated with an unfavorable prognosis.

Environmental factors (particularly sunlight and warm weather) help alleviate the disease and are considered advantageous. Methotrexate, PUVA, cyclosporine, oral retinoids, and biologic therapies all have helped induce and maintain remission in severe cases of plaque psoriasis.