199: Photochemotherapy and Photodynamic Therapy Flashcards
What is the definition of photochemotherapy with psoralens?
Photochemotherapy with psoralens combines the use of oral or topical psoralens (P) and ultraviolet A radiation (UVA).
What are the principles of photochemotherapy?
The principles of photochemotherapy include:
- Inducing remissions of skin diseases by repeated, controlled phototoxic reactions.
- Absorption of photons is confined to the skin.
- PUVA-induced phototoxic reactions are characterized by a delayed sunburn-like erythema and inflammation.
What are the mechanisms of action for psoralens in photochemotherapy?
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.
What are the indications for photochemotherapy?
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.
What are the acute side effects of photochemotherapy?
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.
What are the contraindications for photochemotherapy?
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).
What alternative psoralen could be considered to reduce side effects in a patient experiencing nausea and vomiting after taking 8-MOP?
5-methoxypsoralen (5-MOP) could be considered as it is associated with fewer gastrointestinal side effects compared to 8-MOP.
What could be the cause of severe erythema and blistering during photopheresis, and how should the treatment protocol be adjusted?
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.
How does PUVA induce apoptosis in malignant lymphocytes?
PUVA induces apoptosis in malignant lymphocytes by initiating phototoxic reactions with psoralens and UVA, leading to DNA damage and subsequent programmed cell death.
How does photopheresis induce immunologic tolerance in graft-versus-host disease (GVHD)?
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.
Why might PUVA therapy be contraindicated in a patient with a history of melanoma?
PUVA therapy is contraindicated in patients with a history of melanoma due to the increased risk of carcinogenesis associated with long-term PUVA exposure.
Why is erythropoietic protoporphyria an exception to the contraindication of porphyria in PUVA?
Erythropoietic protoporphyria is an exception because PUVA can induce light tolerance in this condition, unlike other forms of porphyria where light exposure exacerbates symptoms.
How does PUVA suppress immune effector cells in polymorphous light eruption?
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.
What could be the cause of pruritus during PUVA therapy, and how might it be managed?
Pruritus during PUVA therapy could be due to phototoxic reactions. It might be managed by using emollients, antihistamines, or adjusting the UVA dose.
How does PUVA stimulate melanogenesis in vitiligo?
PUVA stimulates melanogenesis by inducing phototoxic reactions that activate melanocytes and promote melanin production.
What role do regulatory T cells play in PUVA therapy for atopic dermatitis?
Regulatory T cells play a role in PUVA therapy by promoting immunologic tolerance and reducing inflammation in atopic dermatitis.
What is the underlying cause of photoaging during PUVA therapy for lichen planus?
Photoaging during PUVA therapy is caused by chronic actinic damage due to repeated UVA exposure.
How does PUVA therapy affect hair follicles in alopecia areata?
PUVA therapy may affect hair follicles by modulating immune responses and reducing inflammation around the follicles, potentially promoting hair regrowth.
What could be the cause of hypotension during PUVA therapy for graft-versus-host disease (GVHD), and how might it be managed?
Hypotension during PUVA therapy could be due to volume shifts during treatment. It might be managed by ensuring adequate hydration and monitoring blood pressure.
How does PUVA therapy reduce skin thickening in morphea?
PUVA therapy reduces skin thickening in morphea by suppressing fibroblast activity and modulating immune responses, leading to decreased collagen deposition.
How does PUVA therapy induce tolerance to sunlight in solar urticaria?
PUVA therapy induces tolerance to sunlight in solar urticaria by modulating immune responses and reducing hypersensitivity to UV radiation.
How does PUVA therapy affect lymphocytes in erythrodermic CTCL?
PUVA therapy affects lymphocytes by inducing apoptosis and suppressing their proliferation, thereby reducing the malignant cell population in erythrodermic CTCL.
Why are crystalline formulations of psoralens less effective in PUVA therapy for vitiligo?
Crystalline formulations of psoralens are less effective because they result in lower and later peak serum levels compared to liquid preparations.
Why are Langerhans cell numbers diminished during PUVA therapy for polymorphous light eruption?
PUVA therapy diminishes Langerhans cell numbers by inducing phototoxic reactions that alter immune cell functions, reducing hypersensitivity to UV radiation.
How does PUVA therapy modulate cytokine expression in acute GVHD?
PUVA therapy modulates cytokine expression by altering the expression of cytokines and receptors, which helps reduce inflammation in acute GVHD.
What is the primary aim of photodynamic therapy?
To destroy the desired target selectively, thereby minimizing damage to normal tissue.
What are the five criteria that photosensitizers should ideally meet?
- Chemical purity
- High singlet-oxygen quantum yield
- Significant light absorption at wavelengths that penetrate the skin sufficiently deeply
- High tissue selectivity
- Efficacy after topical application.
What is the role of reactive oxygen species (ROS) in photodynamic therapy?
ROS cause damage to subcellular structures, such as mitochondria, lysosomes, or endoplasmic reticulum, leading to tumor ischemia and subsequent necrosis.
List some oncologic indications for photodynamic therapy.
- Actinic keratosis
- Bowen disease
- Actinic cheilitis
- Superficial BCC
- Nevoid BCC syndrome
- Keratoacanthoma
- Superficial SCC
- Kaposi sarcoma
- Cutaneous metastases
- Cutaneous T-cell lymphoma.
What are some non-oncologic indications for photodynamic therapy?
- Localized scleroderma
- HPV-associated dermatoses (Epidermodysplasia verruciformis, Verruca vulgaris, Condyloma acuminata)
- Leishmaniasis
- Acne vulgaris
- Rosacea
- Photochemorejuvenation of sun-damaged skin.
Why are porphyrins used as photosensitizers in photodynamic therapy?
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.
What is the underlying mechanism for localized necrosis of tumor vessels during PDT?
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.
What photosensitizer and light wavelength are likely being used for a patient with acne vulgaris treated with PDT?
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.
Why is DNA not a primary target of photodynamic therapy for superficial basal cell carcinoma (BCC)?
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.
What is the principle behind using PDT for non-oncologic conditions like localized scleroderma?
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.
How does PDT selectively target tumor cells in Kaposi sarcoma?
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.
What are the expected benefits of PDT for rosacea?
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.
What is the role of singlet oxygen in PDT for actinic cheilitis?
Singlet oxygen, generated during PDT, plays a crucial role by causing oxidative damage to subcellular structures, leading to the destruction of the target tissue.
What is the mechanism of action of PDT in HPV-associated verruca vulgaris?
In HPV-associated verruca vulgaris, PDT works by generating reactive oxygen species that selectively destroy infected cells while sparing normal tissue.
What wavelength of light is likely being used for superficial squamous cell carcinoma (SCC) during off-label PDT?
Wavelengths around 630 nm are likely being used to increase depth of penetration while matching the absorption maxima of porphyrin photosensitizers.
Why are vascular effects important in PDT for Kaposi sarcoma?
Vascular effects, such as vasoconstriction, blood stasis, and thrombosis, are important in PDT for Kaposi sarcoma as they lead to tumor ischemia and necrosis.
Why is 5-aminolevulinic acid (ALA) used as a photosensitizer for acne vulgaris?
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.
Why is blue light used in PDT for actinic keratosis?
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.
How does PDT minimize damage to normal tissue?
PDT minimizes damage to normal tissue by using photosensitizers with high tissue selectivity and activating them with specific wavelengths of light.
Why is thrombosis of tumor vessels beneficial during PDT?
Thrombosis of tumor vessels during PDT is beneficial because it leads to tumor ischemia and subsequent necrosis, effectively reducing tumor size.
Why are wavelengths around 630 nm used in PDT for acne vulgaris?
Wavelengths around 630 nm are used in PDT for acne vulgaris to increase depth of penetration while matching the absorption maxima of porphyrin photosensitizers.
What is the importance of reactive oxygen species (ROS) in PDT for actinic cheilitis?
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.
Why are porphyrins effective photosensitizers in PDT?
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.
Why are wavelengths around 630 nm preferred in PDT for Kaposi sarcoma?
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.
