Psoriasis

Definition, Etiology, PathogenesisTop

Psoriasis is a chronic immune-mediated inflammatory disease affecting 1% to 3% of the population worldwide. The pathogenesis of psoriasis is complex and polygenic; current evidence indicates that tumor necrosis factor (TNF)-alpha, interleukin (IL) 23/Th17, and Th1 pathways are crucial.

Psoriasis can also be induced by drugs. Several drugs have been linked to the induction of psoriasis, such as lithium, interferons, beta-blockers, and antimalarial drugs (eg, hydroxychloroquine and chloroquine). Despite being highly effective for psoriasis, TNF-alpha inhibitors can paradoxically induce psoriasis or psoriasiform dermatitis when used for treatment of inflammatory bowel disease, rheumatoid arthritis, or other chronic inflammatory conditions.

Clinical Features and Natural HistoryTop

Psoriasis has a wide spectrum of clinical manifestations. There are 5 major types of psoriasis:

1. Chronic plaque psoriasis: This is the most common type of psoriasis, characterized by well-defined erythematous plaques with overlying white-silvery scales. Areas of predilection include the elbows, knees, and lower back (Figure 1, Figure 2). Psoriasis can also involve areas such as the scalp, genitalia, and nails. Nail changes include pitting, subungual hyperkeratosis, onycholysis, leukonychia, and splinter hemorrhages.

2. Guttate psoriasis: Guttate psoriasis is characterized by an acute eruption of multiple fine-scaled, small papules (usually sized <1 cm), typically on the trunk and proximal extremities. It is often preceded by streptococcal pharyngitis, tonsillitis, or less commonly by perianal streptococcal disease.

3. Inverse psoriasis (also known as intertriginous or flexural psoriasis): This type of psoriasis affects intertriginous areas such as the groin and axillae and is characterized by well-defined erythematous plaques and patches that often lack the characteristic scaling due to the moisture in these areas.

4. Pustular psoriasis:

1) Generalized: Acute generalized pustular psoriasis, also known as the Von Zumbusch type, is a rare but severe variant. It is characterized by an acute onset of widespread pustules and systemic complications such as fever, malaise, arthralgia, and leukocytosis. Known triggers include hypocalcemia, withdrawal of systemic steroids, infections, and drugs. When it occurs in pregnancy, it is called pustular psoriasis of pregnancy or impetigo herpetiformis.

2) Localized: There are 2 well-known patterns of localized psoriasis: palmoplantar pustulosis (Figure 3) and acrodermatitis continua of Hallopeau.

5. Erythrodermic psoriasis: Erythroderma, also known as generalized exfoliative dermatitis, can be caused by psoriasis. It is characterized by diffuse, confluent erythema and scaling covering large areas of the skin. While some references use 75% body surface area (BSA) involvement as a cutoff point, others consider 90%.

Associated Comorbidities

1. Psoriatic arthritis: Approximately 10% to 30% of patients with psoriasis develop psoriatic arthritis. Psoriatic arthritis may precede, follow, or occur simultaneously with skin manifestations.

2. Cardiovascular disease and metabolic syndrome: Psoriasis is associated with an increased risk of metabolic syndrome (obesity, dyslipidemia, and impaired fasting blood glucose levels) and cardiovascular disease.

3. Depression: Psoriasis is associated with increased risk of depression and increased psychosocial burden. Quality of life is often highly impacted by psoriasis.

4. Inflammatory bowel disease: Patients with psoriasis are at increased risk of Crohn disease and ulcerative colitis.

5. Malignancy: Patients with psoriasis appear to be at increased risk of developing hematologic (eg, lymphomas), skin, and solid cancers.

DiagnosisTop

The diagnosis of psoriasis is primarily clinical and skin biopsy is rarely needed. Differential diagnosis includes pityriasis rubra pilaris, dermatitis, pityriasis rosea, subcorneal pustular dermatosis, and drug eruptions. When the clinical presentation is atypical, skin biopsy can be very helpful. Histopathologic findings include acanthosis, epidermal psoriasiform hyperplasia with elongation of the rete ridges and thinning of suprapapillary plates, and hypogranulosis. The papillary dermis shows mild edema, dilated capillaries, and lymphocytic infiltrate.

TreatmentTop

Patients should be educated about the natural chronic course of the disease and advised on frequent use of emollients. Treatment should be individualized taking into consideration its availability as well as the severity and extent of the disease, patient age, medical comorbidities, and possible contraindications to certain systemic or biologic therapies. Patients with severe psoriasis have poor quality of life and increased morbidity. However, with recent advances in treatment options and availability of biologic therapies, the prognosis of psoriasis has markedly improved. Phototherapy and systemic and biologic therapy should be provided by a dermatologist, rheumatologist, or internist experienced in the management of psoriasis.

The treatment of psoriasis depends mostly on the severity and extent of the disease. Assessment of the severity of psoriasis is crucial. In the clinic, BSA is the most widely used tool for the measurement of skin involvement and can be easily estimated. The National Psoriasis Foundation defines mild psoriasis as <3% BSA; moderate psoriasis as 3% to 10% BSA; and severe psoriasis as >10% BSA. Many other scoring systems are available to assess disease severity or its effect on patients’ quality of life. The most widely used scores are the Physician Global Assessment (PGA), the Psoriasis Area and Severity Index (PASI), and the Dermatology Life Quality Index (DLQI) (www.bad.org.uk). PGA and PASI scores are assigned by physicians, while the DLQI is reported by patients.

Mild disease is typically treated with topical therapy. Topical treatments can be prescribed by primary care providers. Indications for ultraviolet and systemic or biologic therapy, usually delivered by a clinician specializing in this condition, include failure to respond to topical therapy, facial, genital, or palmoplantar involvement, and moderate to severe disease, especially if >10% BSA and PASI of ≥10 are reported. It is important to remember that psoriasis can be severe irrespective of BSA involvement when it affects selected areas such as the hands or genitals, when it causes exceptional pruritus, or when it has a serious emotional impact for the patient.

Rebound psoriasis and worsening of psoriasis after withdrawal of systemic glucocorticoids is a well-established phenomenon. Therefore, these drugs should be avoided.

Topical Therapy

1. Moisturizers: This category includes occlusive moisturizers, emollients, and humectants. Occlusive moisturizers create a physical barrier helping to trap moisture and seal water in the skin. Emollients have mild sealing properties to keep water inside the skin and soften it. Humectants attract water to the skin making it soft and moist.

2. Topical glucocorticoid creams and ointments (betamethasone valerate 0.1%, betamethasone dipropionate, clobetasol propionate 0.05%).

3. Topical vitamin D analogues such as calcipotriene (calcipotriol) available in Canada as an ointment and cream (50 microg/g; Dovonex).

4. Combination of topical glucocorticoids and vitamin D analogues: A combination of calcipotriene (calcipotriol; 50 microg/g) and betamethasone dipropionate (0.5 mg/g) is available in Canada as a gel (Dovobet) and foam (Enstilar).

5. Topical retinoids: Tazarotene cream is available in Canada at concentrations of 0.05% and 0.1% (Tazorac).

6. Calcineurin inhibitors: Tacrolimus ointment (Protopic 0.03% or 0.1%) and pimecrolimus (available in Canada as 1% cream) are steroid-free agents and are very useful for facial and genital psoriasis where potent topical steroids should absolutely be avoided.

Phototherapy and Photochemotherapy

These therapies are mostly available in academic institutions and should be operated only under supervision of a dermatologist. Different types of phototherapy are available for psoriasis:

1) Narrowband ultraviolet B (UVB) phototherapy.

2) Broadband UVB phototherapy.

3) Oral or bath psoralen plus ultraviolet light in the A range (PUVA) photochemotherapy: Psoralens are photosensitive drugs that absorb ultraviolet and cause cell apoptosis.

Conventional Oral Agents

Conventional drugs include acitretin, methotrexate, and oral cyclosporine (Table 1).

Small-Molecule Drugs

Apremilast is an oral phosphodiesterase-4 inhibitor approved for the treatment of moderate to severe psoriasis and psoriatic arthritis. The recommended dose is 30 mg bid. Adverse effects are mostly related to the gastrointestinal tract and include nausea, diarrhea, and weight loss. Advantages of apremilast include its lack of immunosuppression and good safety profile. Also, no prescreening tests or ongoing laboratory monitoring are required.

Biologic Agents

Biologic agents such as TNF-alpha inhibitors, IL-12/23 inhibitors, IL-17 inhibitors, and IL-23 inhibitors can be used. The choice depends on the presence or absence of psoriatic arthritis, other medical comorbidities, patient age, and drug availability (Table 2).

Tables AND FIGURESTop

Figure 4.5-1. Plaque-type psoriasis with well-defined erythematous plaques with whitish-silvery scales. Photograph courtesy of Dr Mohannad Abu-Hilal.

Figure 4.5-2. Diffuse plaque-type psoriasis. Photograph courtesy of Dr Mohannad Abu-Hilal.

Figure 4.5-3. Palmoplantar pustulosis. A, palmar pustulosis. B, plantar pustulosis. Photograph courtesy of Dr Mohannad Abu-Hilal.