199: Photochemotherapy and Photodynamic Therapy

Question 1

What is the definition of photochemotherapy with psoralens?

Answer 1

Photochemotherapy with psoralens combines the use of oral or topical psoralens (P) and ultraviolet A radiation (UVA).

Question 2

What are the principles of photochemotherapy?

Answer 2

The principles of photochemotherapy include:

1. Inducing remissions of skin diseases by repeated, controlled phototoxic reactions.
2. Absorption of photons is confined to the skin.
3. PUVA-induced phototoxic reactions are characterized by a delayed sunburn-like erythema and inflammation.

Question 3

What are the mechanisms of action for psoralens in photochemotherapy?

Answer 3

The mechanisms of action for psoralens include:

• Suppressing mitosis, DNA synthesis, and cell proliferation.
• Altering expression of cytokines and receptors, downregulating certain lymphocyte and antigen-presenting cell functions.
• Influencing adhesion molecule expression and diminishing Langerhans cell numbers within the epidermis.
• Affecting immune effector cells such as lymphocytes or PMN leukocytes.
• Stimulating melanogenesis.

Question 4

What are the indications for photochemotherapy?

Answer 4

Indications for photochemotherapy include:

• Psoriasis
• CTCL (Cutaneous T-cell Lymphoma)
• Atopic dermatitis
• Lichen Planus
• Cutaneous mastocytosis
• Acute and chronic pityriasis lichenoides
• Pityriasis rubra pilaris
• Alopecia areata
• Morphea
• Graft-versus-host disease
• Vitiligo
• Polymorphous light eruption
• Solar urticaria
• Erythropoietic protoporphyria.

Question 5

What are the acute side effects of photochemotherapy?

Answer 5

Acute side effects of photochemotherapy include:

• Drug intolerance: nausea and vomiting with oral MOP but not with 5-MOP.
• UVA overdosage, which can lead to increased delayed erythema reaction or severe burns with blistering.
• Systemic symptoms of excess phototoxicity, such as fever and general malaise.
• Pruritus.

Question 6

What are the contraindications for photochemotherapy?

Answer 6

Contraindications for photochemotherapy include:

• Pregnancy
• Severe hepatic/renal impairment
• Light-aggravated or light-induced diseases (e.g., LE, porphyria, except erythropoietic protoporphyria)
• Pemphigus vulgaris and bullous pemphigoid
• Chronic actinic damage
• History of skin cancer
• Previous arsenic intake
• Immunosuppressed individuals (except HIV, which can be safely used).

Question 7

What alternative psoralen could be considered to reduce side effects in a patient experiencing nausea and vomiting after taking 8-MOP?

Answer 7

5-methoxypsoralen (5-MOP) could be considered as it is associated with fewer gastrointestinal side effects compared to 8-MOP.

Question 8

What could be the cause of severe erythema and blistering during photopheresis, and how should the treatment protocol be adjusted?

Answer 8

The severe erythema and blistering could be due to UVA overdosage. The treatment protocol should be adjusted by reducing the UVA dose and ensuring proper calibration of the photopheresis device.

Question 9

How does PUVA induce apoptosis in malignant lymphocytes?

Answer 9

PUVA induces apoptosis in malignant lymphocytes by initiating phototoxic reactions with psoralens and UVA, leading to DNA damage and subsequent programmed cell death.

Question 10

How does photopheresis induce immunologic tolerance in graft-versus-host disease (GVHD)?

Answer 10

Photopheresis induces immunologic tolerance by infusing autologous haptenated cells in which apoptosis has been initiated by 8-MOP/UVA, leading to the induction of regulatory T cells.

Question 11

Why might PUVA therapy be contraindicated in a patient with a history of melanoma?

Answer 11

PUVA therapy is contraindicated in patients with a history of melanoma due to the increased risk of carcinogenesis associated with long-term PUVA exposure.

Question 12

Why is erythropoietic protoporphyria an exception to the contraindication of porphyria in PUVA?

Answer 12

Erythropoietic protoporphyria is an exception because PUVA can induce light tolerance in this condition, unlike other forms of porphyria where light exposure exacerbates symptoms.

Question 13

How does PUVA suppress immune effector cells in polymorphous light eruption?

Answer 13

PUVA suppresses immune effector cells by altering cytokine and receptor expression, downregulating lymphocyte and antigen-presenting cell functions, and diminishing Langerhans cell numbers in the epidermis.

Question 14

What could be the cause of pruritus during PUVA therapy, and how might it be managed?

Answer 14

Pruritus during PUVA therapy could be due to phototoxic reactions. It might be managed by using emollients, antihistamines, or adjusting the UVA dose.

Question 15

How does PUVA stimulate melanogenesis in vitiligo?

Answer 15

PUVA stimulates melanogenesis by inducing phototoxic reactions that activate melanocytes and promote melanin production.

Question 16

What role do regulatory T cells play in PUVA therapy for atopic dermatitis?

Answer 16

Regulatory T cells play a role in PUVA therapy by promoting immunologic tolerance and reducing inflammation in atopic dermatitis.

Question 17

What is the underlying cause of photoaging during PUVA therapy for lichen planus?

Answer 17

Photoaging during PUVA therapy is caused by chronic actinic damage due to repeated UVA exposure.

Question 18

How does PUVA therapy affect hair follicles in alopecia areata?

Answer 18

PUVA therapy may affect hair follicles by modulating immune responses and reducing inflammation around the follicles, potentially promoting hair regrowth.

Question 19

What could be the cause of hypotension during PUVA therapy for graft-versus-host disease (GVHD), and how might it be managed?

Answer 19

Hypotension during PUVA therapy could be due to volume shifts during treatment. It might be managed by ensuring adequate hydration and monitoring blood pressure.

Question 20

How does PUVA therapy reduce skin thickening in morphea?

Answer 20

PUVA therapy reduces skin thickening in morphea by suppressing fibroblast activity and modulating immune responses, leading to decreased collagen deposition.

Question 21

How does PUVA therapy induce tolerance to sunlight in solar urticaria?

Answer 21

PUVA therapy induces tolerance to sunlight in solar urticaria by modulating immune responses and reducing hypersensitivity to UV radiation.

Question 22

How does PUVA therapy affect lymphocytes in erythrodermic CTCL?

Answer 22

PUVA therapy affects lymphocytes by inducing apoptosis and suppressing their proliferation, thereby reducing the malignant cell population in erythrodermic CTCL.

Question 23

Why are crystalline formulations of psoralens less effective in PUVA therapy for vitiligo?

Answer 23

Crystalline formulations of psoralens are less effective because they result in lower and later peak serum levels compared to liquid preparations.

Question 24

Why are Langerhans cell numbers diminished during PUVA therapy for polymorphous light eruption?

Answer 24

PUVA therapy diminishes Langerhans cell numbers by inducing phototoxic reactions that alter immune cell functions, reducing hypersensitivity to UV radiation.

Question 25

How does PUVA therapy modulate cytokine expression in acute GVHD?

Answer 25

PUVA therapy modulates cytokine expression by altering the expression of cytokines and receptors, which helps reduce inflammation in acute GVHD.

Question 26

What is the primary aim of photodynamic therapy?

Answer 26

To destroy the desired target selectively, thereby minimizing damage to normal tissue.

Question 27

What are the five criteria that photosensitizers should ideally meet?

Answer 27

1. Chemical purity 2. High singlet-oxygen quantum yield 3. Significant light absorption at wavelengths that penetrate the skin sufficiently deeply 4. High tissue selectivity 5. Efficacy after topical application.

Question 28

What is the role of reactive oxygen species (ROS) in photodynamic therapy?

Answer 28

ROS cause damage to subcellular structures, such as mitochondria, lysosomes, or endoplasmic reticulum, leading to tumor ischemia and subsequent necrosis.

Question 29

List some oncologic indications for photodynamic therapy.

Answer 29

- Actinic keratosis - Bowen disease - Actinic cheilitis - Superficial BCC - Nevoid BCC syndrome - Keratoacanthoma - Superficial SCC - Kaposi sarcoma - Cutaneous metastases - Cutaneous T-cell lymphoma.

Question 30

What are some non-oncologic indications for photodynamic therapy?

Answer 30

- Localized scleroderma - HPV-associated dermatoses (Epidermodysplasia verruciformis, Verruca vulgaris, Condyloma acuminata) - Leishmaniasis - Acne vulgaris - Rosacea - Photochemorejuvenation of sun-damaged skin.

Question 31

Why are porphyrins used as photosensitizers in photodynamic therapy?

Answer 31

Porphyrins are used as photosensitizers in PDT because they absorb maximally in the Soret band (400-410 nm, blue light) and can generate reactive oxygen species, particularly singlet oxygen, upon excitation.

Question 32

What is the underlying mechanism for localized necrosis of tumor vessels during PDT?

Answer 32

The localized necrosis of tumor vessels during PDT is due to vascular effects such as vasoconstriction, blood stasis, and thrombosis, leading to tumor ischemia and subsequent necrosis.

Question 33

What photosensitizer and light wavelength are likely being used for a patient with acne vulgaris treated with PDT?

Answer 33

5-aminolevulinic acid (ALA) is likely being used as the photosensitizer, and wavelengths around 630 nm are used to increase depth of penetration while matching the absorption maxima of porphyrin photosensitizers.

Question 34

Why is DNA not a primary target of photodynamic therapy for superficial basal cell carcinoma (BCC)?

Answer 34

In PDT, DNA is not a primary target because the reactive oxygen species generated, such as singlet oxygen, primarily damage subcellular structures like mitochondria, lysosomes, or the endoplasmic reticulum.

Question 35

What is the principle behind using PDT for non-oncologic conditions like localized scleroderma?

Answer 35

The principle behind using PDT for non-oncologic conditions like localized scleroderma is the selective destruction of the target tissue while minimizing damage to normal tissue through the generation of reactive oxygen species.

Question 36

How does PDT selectively target tumor cells in Kaposi sarcoma?

Answer 36

PDT selectively targets tumor cells by using photosensitizers that have high tissue selectivity and are activated by specific wavelengths of light, leading to the generation of reactive oxygen species that damage tumor cells.

Question 37

What are the expected benefits of PDT for rosacea?

Answer 37

The expected benefits of PDT for rosacea include the reduction of inflammation and vascular abnormalities through the generation of reactive oxygen species and vascular effects.

Question 38

What is the role of singlet oxygen in PDT for actinic cheilitis?

Answer 38

Singlet oxygen, generated during PDT, plays a crucial role by causing oxidative damage to subcellular structures, leading to the destruction of the target tissue.

Question 39

What is the mechanism of action of PDT in HPV-associated verruca vulgaris?

Answer 39

In HPV-associated verruca vulgaris, PDT works by generating reactive oxygen species that selectively destroy infected cells while sparing normal tissue.

Question 40

What wavelength of light is likely being used for superficial squamous cell carcinoma (SCC) during off-label PDT?

Answer 40

Wavelengths around 630 nm are likely being used to increase depth of penetration while matching the absorption maxima of porphyrin photosensitizers.

Question 41

Why are vascular effects important in PDT for Kaposi sarcoma?

Answer 41

Vascular effects, such as vasoconstriction, blood stasis, and thrombosis, are important in PDT for Kaposi sarcoma as they lead to tumor ischemia and necrosis.

Question 42

Why is 5-aminolevulinic acid (ALA) used as a photosensitizer for acne vulgaris?

Answer 42

5-aminolevulinic acid (ALA) is used as a photosensitizer in PDT for acne vulgaris because it is effective after topical application and has high tissue selectivity.

Question 43

Why is blue light used in PDT for actinic keratosis?

Answer 43

Blue light (400-410 nm) is used in PDT for actinic keratosis because porphyrins absorb maximally in this wavelength range, enhancing the generation of reactive oxygen species.

Question 44

How does PDT minimize damage to normal tissue?

Answer 44

PDT minimizes damage to normal tissue by using photosensitizers with high tissue selectivity and activating them with specific wavelengths of light.

Question 45

Why is thrombosis of tumor vessels beneficial during PDT?

Answer 45

Thrombosis of tumor vessels during PDT is beneficial because it leads to tumor ischemia and subsequent necrosis, effectively reducing tumor size.

Question 46

Why are wavelengths around 630 nm used in PDT for acne vulgaris?

Answer 46

Wavelengths around 630 nm are used in PDT for acne vulgaris to increase depth of penetration while matching the absorption maxima of porphyrin photosensitizers.

Question 47

What is the importance of reactive oxygen species (ROS) in PDT for actinic cheilitis?

Answer 47

Reactive oxygen species (ROS) are important in PDT for actinic cheilitis because they cause oxidative damage to subcellular structures, leading to the destruction of abnormal cells.

Question 48

Why are porphyrins effective photosensitizers in PDT?

Answer 48

Porphyrins are effective photosensitizers in PDT because they have high singlet-oxygen quantum yield and significant light absorption at wavelengths that penetrate the skin deeply.

Question 49

Why are wavelengths around 630 nm preferred in PDT for Kaposi sarcoma?

Answer 49

Wavelengths around 630 nm are preferred in PDT for Kaposi sarcoma because they increase depth of penetration while matching the absorption maxima of porphyrin photosensitizers.