Psoriasis Australia

PUVA (Psoralen + UVA)

PUVA (Psoralen + UVA) therapy is a type of photochemotherapy used for treating moderate to severe psoriasis and other skin disorders. It involves the administration of a photosensitizing agent, psoralen, combined with exposure to ultraviolet A (UVA) light.

Overview

PUVA (Psoralen + UVA) therapy is a type of photochemotherapy used for treating moderate to severe psoriasis and other skin disorders. It involves the administration of a photosensitizing agent, psoralen, combined with exposure to ultraviolet A (UVA) light. PUVA is particularly effective for patients with psoriasis that has not responded to other therapies. However, its use is associated with both short-term and long-term side effects, necessitating careful patient selection and monitoring.

Mechanism of Action

PUVA therapy works by combining the effects of psoralen, a compound that sensitizes the skin to UVA light, and the UVA radiation itself, which penetrates deeper into the skin than UVB light. Here’s how it works in treating psoriasis:

  • Psoralen Sensitization: Psoralen is a naturally occurring compound that makes the skin more responsive to UVA radiation. Psoralen can be administered orally (most common), topically (as a bath or cream), or through soaking specific areas like hands or feet. After absorption, psoralen binds to the DNA of skin cells.

  • UVA Exposure: UVA light, with wavelengths ranging from 320-400 nm, penetrates the skin more deeply than UVB. When psoralen-treated skin is exposed to UVA, the radiation causes photochemical reactions that lead to cross-linking of DNA. This inhibits the rapid turnover of skin cells seen in psoriasis, reducing plaque formation and scaling.

  • Immunosuppressive Effects: In addition to slowing the overproduction of skin cells, PUVA has an immunosuppressive effect, reducing the activity of T-cells that are involved in the autoimmune component of psoriasis. This helps to reduce inflammation and scaling of the plaques.

Indications for Use in Psoriasis

PUVA therapy is often used in cases of moderate to severe psoriasis or when patients have not responded adequately to other treatments like topical corticosteroids, vitamin D analogues, or Narrowband UVB (NB-UVB) therapy. It is particularly effective for:

  • Chronic Plaque Psoriasis: PUVA is highly effective for treating chronic plaque psoriasis, especially when plaques are widespread and thick.

  • Palmoplantar Psoriasis: It is also used to treat psoriasis on the hands and feet (palmoplantar psoriasis), where other therapies may be less effective.

  • Resistant Psoriasis: PUVA is often employed when other therapies, including topical treatments, fail to control the symptoms of psoriasis.

Efficacy of PUVA in Psoriasis Treatment

PUVA therapy is one of the most effective treatments for moderate to severe psoriasis, with many patients achieving significant and long-lasting improvements.

  • High Success Rates: Studies have shown that 70-90% of patients experience substantial improvement in their psoriasis after completing a course of PUVA therapy. Many achieve PASI 75 or greater (meaning a 75% or greater reduction in disease severity).

  • Longer Remission: One of the advantages of PUVA therapy is the duration of remission. Patients treated with PUVA often remain in remission for several months after completing therapy, compared to shorter remission periods with NB-UVB.

  • Effective for Thick Plaques: PUVA is particularly beneficial for patients with thicker plaques that do not respond well to NB-UVB or topical treatments, as the deeper penetration of UVA light is more effective at treating these lesions.

Treatment Process

The typical PUVA treatment involves several key steps to ensure the safe and effective application of the therapy:

  1. Psoralen Administration: Psoralen is administered orally in tablet form about 2 hours before UVA exposure, allowing sufficient time for the drug to be absorbed and distributed to the skin. Alternatively, topical psoralen can be used for localized psoriasis or bath PUVA for extensive psoriasis on the hands and feet.

  2. UVA Exposure: After the psoralen has sensitized the skin, the patient is exposed to UVA light in a special phototherapy booth. UVA treatment is usually administered 2-3 times per week, with the dose of UVA light gradually increased over time to reduce the risk of burning or other side effects.

  3. Eye Protection: During and after the treatment, patients must wear UV-blocking glasses for up to 24 hours to protect their eyes from potential damage, as psoralen also sensitizes the eyes to UVA radiation.

  4. Treatment Duration: A typical course of PUVA therapy involves 20-30 sessions, but the exact number varies depending on the patient’s response to treatment and the severity of their psoriasis.

Advantages of PUVA Therapy

Despite the risks associated with PUVA, it has several advantages over other treatments:

  • Effective for Severe and Recalcitrant Psoriasis: PUVA is one of the most effective treatments for severe psoriasis that is resistant to other therapies, including NB-UVB.

  • Longer Remission Periods: Compared to other therapies, PUVA can induce longer periods of remission, reducing the need for continuous treatment.

  • Beneficial for Palmoplantar Psoriasis: PUVA is especially helpful for treating palmoplantar psoriasis, a form of psoriasis affecting the hands and feet that often responds poorly to other treatments.

Side Effects and Risks

While PUVA therapy is highly effective, it is associated with several potential side effects, ranging from mild short-term reactions to serious long-term risks.

a. Short-Term Side Effects

  • Nausea: One of the most common side effects of oral psoralen is nausea, which occurs in up to 20-30% of patients. It usually subsides after the treatment session or can be mitigated by taking psoralen with food.

  • Sunburn-Like Reactions: Excessive UVA exposure can cause erythema (skin redness) or even blistering, similar to a sunburn. Patients with fair skin are particularly at risk, so doses are carefully titrated to avoid this.

  • Itching and Dryness: Like other forms of phototherapy, PUVA can cause dryness and itching of the skin, especially in the early stages of treatment.

b. Long-Term Side Effects and Risks

  • Skin Cancer Risk: One of the most significant long-term risks of PUVA therapy is the increased risk of skin cancer, particularly squamous cell carcinoma (SCC) and, to a lesser extent, basal cell carcinoma (BCC). The risk increases with the cumulative number of treatments, and PUVA is generally avoided after 200-300 sessions due to this heightened risk.

  • Melanoma Risk: There is also an increased risk of malignant melanoma, a more dangerous form of skin cancer, particularly in patients who have received numerous PUVA treatments.

  • Photoaging (Premature Skin Aging): PUVA therapy accelerates photoaging, leading to skin wrinkling, hyperpigmentation, and increased skin fragility. Patients often experience these effects after long-term use.

  • Cataracts: Psoralen sensitizes the eyes to UVA light, increasing the risk of developing cataracts. This risk can be mitigated by wearing protective UV-blocking glasses during and after treatment.

Comparison to Other Phototherapy Options

  • Compared to Narrowband UVB (NB-UVB): PUVA is generally more effective than NB-UVB for thicker plaques and palmoplantar psoriasis, but it carries greater risks, including a higher likelihood of skin cancer and long-term side effects. NB-UVB is safer for long-term use, making it a preferred option for many patients.

  • Compared to Systemic Treatments: PUVA is less invasive than systemic therapies like methotrexate, cyclosporine, or biologics, but it requires frequent clinic visits and comes with higher risks of skin damage and cancer than biologic therapies.

Alternatives and Combination Therapies

PUVA is sometimes combined with other treatments to enhance its effectiveness or reduce the number of sessions required:

  • PUVA with Topicals: Combining PUVA with topical therapies such as corticosteroids or vitamin D analogues can improve results and help reduce the number of phototherapy sessions.

  • Combination with Systemics: PUVA can also be used in conjunction with systemic medications like methotrexate or retinoids for more severe cases. However, this increases the risk of side effects and is reserved for specific patients.

Summary

PUVA therapy remains a valuable option for patients with moderate to severe psoriasis, particularly for those with thick plaques, palmoplantar psoriasis, or cases resistant to other therapies. However, due to its risks—especially the increased likelihood of skin cancer—it is often reserved for patients who have not responded to safer alternatives like NB-UVB. Careful monitoring and appropriate patient selection are essential to balance the benefits of PUVA therapy with its potential risks.