Psoriasis

Mark Lebwohl, M.D.

Psoriasis is an inflammatory disorder of the skin in which activation of T lymphocytes results in release of cytokines that leads to proliferation of keratinocytes. In normal skin, the cells of the epidermis are regenerated every 28 days, while in psoriatic skin epidermis is regenerated every two to four days.

There are four clinical types of psoriasis. The most common type, plaque psoriasis, is characterized by sharply demarcated erythematous scaling plaques (Figure 1) that most commonly occur on the elbows and knees, and in the scalp and groin. More extensive involvement can occur, with psoriasis affecting most of the cutaneous surface. Nail involvement is common, e.g., yellow discoloration, thickening, surface pitting, and lifting of the nail plate off of the distal nail bed (onycholysis). Guttate psoriasis commonly occurs after streptococcal pharyngitis. It is characterized by multiple scaling red papules on the trunk and extremities.

In erythrodermic psoriasis, the entire skin surface becomes red, inflamed and scaly (Figure 2). Patients lose many of the protective functions of the skin in this form of psoriasis. They may lose fluids through the skin, resulting in hypotension or electrolyte imbalance. They may lose nutrients, resulting in anemia, or they may lose control of body temperature, resulting in fever or hypothermia. Ultimately, some patients succumb to infection. In pustular psoriasis, patients can develop sterile pustules that are either localized to the palms and soles, or are generalized. As in erythrodermic psoriasis, this latter form of psoriasis can be life-threatening. Approximately one out of ten patients with psoriasis develops psoriatic arthritis, most commonly of the small joints of the hands and feet.

Mild or limited psoriasis can be treated with topical therapy, including topical corticosteroids, tars, anthralin, calcipotriene (a vitamin D3 analog), or tazarotene (a retinoid). In more generalized cases phototherapy with ultraviolet B iseffective.

Sun exposure can also be helpful. Treatment with oral psoralens plus ultraviolet A exposure, called PUVA, is effective in most patients, but has been associated with an increased risk of skin cancers after many treatments over several years. Recently, narrowband UVB has been introduced for the treatment of psoriasis. It uses a narrow portion of the spectrum of ultraviolet B around 311nm, the spectrum which is optimal for the treatment of psoriasis. Narrowband UVB is more effective than traditional broadband UVB, but may be somewhat less effective than PUVA. In the few years since it has been available, it has not been associated with the skin cancer risks seen in patients treated with PUVA.

Oral retinoids, cyclosporine, and methotrexate have also been used for treatment of severe generalized psoriasis, erythrodermic psoriasis, and pustular psoriasis. Most recently, biologic agents have been introduced for the treatment of psoriasis.

Alefacept, which was approved by the USFDA in 2003, works by interfering with T-cell activation and reducing circulating CD45RO+ T-cells. It is a fusion protein consisting of the Fc receptor of human IgG1 and LFA3, a costimulatory ligand, which interacts with CD2 on the surface of T-cells. When it is effective, it offers long remissions. Patients treated with alefacept must have weekly monitoring of CD4 cells during the period of therapy to make sure that CD4 counts don't fall too low.

Efalizumab has been recommended for approval for psoriasis. This humanized antibody to CD11a interferes with T-cell trafficking into inflamed tissues and prevents T-cell activation. It is rapidly effective, but upon discontinuation, some patients experience rebound of their psoriasis.

Three agents that block TNFa have also been used to treat psoriasis. Etanercept, a fusion protein directed against soluble TNFa , has been approved for the treatment of psoriatic arthritis and is also effective for psoriasis of the skin. Infliximab, a chimeric monoclonal antibody against soluble and cell bound TNFa , is dramatically effective against psoriasis. Adlimumab, a human monoclonal antibody to TNFa , has begun trials for psoriasis and initial results are promising.

References

  1. Lebwohl M. Psoriasis. Lancet. 2003; 361 (9364) : 1197-204.
  2. Lebwohl M, Ali S. Treatment of psoriasis. Part 2. Systemic therapies. J Am AcadDermatol. 2001 45(5) : 649-61; quiz 662-4.
  3. Lebwohl M, Ali S. Treatment of psoriasis. Part 1. Topical therapy and phototherapy.J Am Acad Dermatol. 2001 Oct; 45(4) : 487-98; quiz 499-502.
  4. Krueger JG. The immunologic basis for the treatment of psoriasis with new biologics. J Am Acad Dermatol.2002; 46(1):1-23; quiz 23-6.

Figure Legends

Figure 1 - Plaque psoriasis is characterized by sharply demarcated erythematous scaling plaques.

Figure 2 - Erythrodermic psoriasis is characterized by generalized erythema and scaling.

Questions - Psoriasis

1. The most common type of psoriasis is:

A) Guttate psoriasis
B) Plaque psoriasis
C) Erythrodermic psoriasis
D) Pustular psoriasis
E) Nail psoriasis

2. Guttate psoriasis frequently follows:

A) Streptococcal pharyngitis
B) Staphylococcus infection
C) Candida infection
D) Tinea infection
E) Haemophilus ear infection

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