Phototherapy JURAJ HEGYI FNUSA & MU Definitions ● ● ● ● ● PHOTOTHERAPY: It is a form of treatment for skin conditions involving the administration of non ionizing radiation (most commonly within the ultraviolet part of the electromagnetic spectrum) in a controlled manner to the skin PHOTOBIOLOGY: It is the study of the effects of UV and VL on living matter PHOTODERMATOLOGY: It is the study of normal as well as abnormal effects of UV and VL on skin PHOTOSENSITIVITY: Abnormal response to “ordinary “ light exposure PHOTOMEDICINE: Study of skin diseases caused by radiation in UV and visible spectra Terrestrial radiation ● It is the infrared radiation emitted from the atmosphere 1. Ultraviolet- 100 to 400nm 2. Visible - 400 to 700 mm 3. Infrared- > 700nm Meet ultraviolet ● ● ● Radiation with wavelength shorter than light but longer than X ray It has both benign and malignant impact on the health of a living being UVA: 400 to 315nm – relatively long wavelength – represents close to 95% of the UV Rays – skin aging, wrinkles – damages keratinocytes in basal layer of epidermis = skin cancers – dominant tanning ray Meet ultraviolet ● ● UVB: 315-250 nm – Medium wavelength – Only part passes through the atmosphere – Damages skin cells directly – Main ray that causes sunburn UVC: 280-100nm – Most harmful – Does not reach the earth surface – Completely filtered by ozone layer Fitzpatrick skin types Clinical effects of UV radiation ● ● Acute – Erythema – Tanning – Immunomodulation Chronic – Skin cancer – Photoaging Erythema ● ● ● ● ● UV radiation induced inflammation Sunburn - common, visible, acute inflammatory response to excessive exposure to UV radiation Associated with redness Wavelength around 300nm is most erythmogenic 307.5 causes max burning Tanning ● ● Immediate pigment darkening – Due to immediate photo-oxidation of existing colourless melanin precursors to UVA and visible radiation – Fades within 15 minutes – Almost undetectable in fair skinned individuals – Easily observed in skin type 4 or darker Persistent pigment darkening – response to higher UV dose >10 J\cm2 – Peaks 2 hours post radiation – Lasts for 1-5 days – Due to persistent oxidation of melanin precursors – End point used to assess UVA protection of sunscreens Tanning ● Melanogenesis or delayed tanning – Facultative pigmentation or neomelanogenesis – Stimulation of new melanin synthesis by basal epidermal melanocytes – Transported via dendrites to adjacent keratinocytes – Redistributed towards skin surface Immunomodulation ● Effect on antigen presenting cells: – ● depletes the epidermis of Langerhans cells Effect on T cells: – Stimulates the circulating suppressor T cells - alters the ability of lymphocytes to respond to mitogens and antigens – Suppression of delayed hypersensitivity and contact hypersensitivity- reduction of tumour rejection – increased incidence of malignancies. – Alters the proportion of circulating T cell sub types. – Release of inflammatory mediaters-IL-1 and IL-6 which are immunosuppressive and alter cell trafficking. – Other effects-impairment of immunological responses of the epidermal keratinocytes and lymphocytes Skin cancer ● Malignant melanoma ● Non melanoma skin cancers Photoaging ● Process of skin aging which has been accelerated by chronic solar exposure. ● Also known as DERMATOHELIOSIS. ● Clinically distinct from chronological aging Photoaging Phototherapy ● ● ● ● ● ● Form of treatment of a skin condition involving the administration of non ionizing radiation in a controlled manner to skin. 1400 BC: India- vitiligo patients were given certain plant extracts and exposed to sun. 1903: Neils Finsen received Nobel prize for therapeutic results with UV radiation in Lupus vulgaris 1974: Parish et al reported useful role of high intensity UVA tubes in combination with psoralens for psoriasis. 1978: Wiskemann introduced irradiation cabins with broad band UVB tubes for treatment of psoriasis and uremic pruritus. 1988: NBUVB phototherapy was introduced by van Weelden et al and Green et al. Therapeutic modalities ● UVB ● LONG WAVE UVA ● PUVA (BALNEOTHERAPY) ● EXTRACORPOREAL PHOTOPHERESIS ● PHOYODYNAMIC THERAPY ● TARGETED PHOTOTHERAPY UVB ● UVB- 280-320 nm ● Full spectrum(BBUVB)- 270-350nm ● Narrow band(NBUVB)- 311-313nm ● NBUVB is now the gold standard ● ● Advantage - decrease in the erythmogenic wavelength with a 5 fold increase in longer wavelengths resulting in increased therapeutic effect Mechanism of action in Psoriasis- anti-inflammatory, immunosuppressive and cytotoxic. UVB ● ● ● ● Minimal erythema dose (MED): the dose of radiation that produces minimal, just perceptible erythema at 24hrs post radiation Starting dose: 70% or 50% of MED Increments: As the skin acclimatizes to UV, by epidermal thickening and pigmentation, it is necessary to increase the dose – low increment- 20% – high increment- 40% Frequency: 2 or 3 times per week UVA-1 ● Long wavelength – 320 - 400 nm while filtering the erythmogenic UVA and UVB wavelengths ● Penetrates deeper in the dermis ● Induces interstitial collagenase and cytokines ● Softening of sclerotic skin ● Doses – High: >60 J\cm2 – Medium: 30-60 J\cm2 – Low: 10-20 J\cm2 PUVA ● Psoralen + UVA ● Inhibits DNA replication ● Langerhans cell depletion ● ● Immunosuppressive effect on T lymphocyte functions Migration and restoration of Th17/regulatory T cells imbalance in Psoriasis PUVA ● ● The drug psoralen has no therapeutic effect of its own. Only produces effect when patient is exposed to UV radiation Drugs used: – Methoxsalen (8-methoxypsoralen) – Bergapten (5-methoxypsoralen) PUVA FDA APPROVED INDICATIONS Psoriasis Vitiligo OTHER DERMATOLOGIC USES Neoplastic Seborrheic dermatitis Chronic hand dermatitis Atopic dermatitis Palmoplantar pustulosis Papulosquamous/dermatitis Lichen planus Histiocytosis X Parapsoriasis Mycosis fungoides/Sézary sy. Pityriasis lichenoides Lymphomatoid papulosis Balneotherapy ● ● ● Process of delivery of 8 methoxy psoralen or different salt solutions through bath with a subsequent UVA or UVB irradiation Delivery of psoralens by bath prevents systemic side effects associated with oral PUVA Advantage of shorter and selective photosensitization leading to significantly lower cumulative UVA exposure – Bath PUVA – Bathing suit PUVA – Soak PUVA – Turban PUVA Extracorporeal photophoresis ● ● ● ● ● ● A discontinuous leukapheresis procedure that combines the administration of 8-MOP with extracorporeal UVA irradiation to a fraction of peripheral blood leukocytes It targets the effects of photochemotherapy directly to circulating pathogenic leukocytes Photo testing not necessary as irradiation occurs outside the body in a machine. Frequency: 2-3 successive days once a month During 1 treatment session 5%-10% of the circulating T cell pool is treated Duration about 6 months PUVA ● Minimal phototoxic dose (MPD): measured 2 hours ( or 2.5 hours for 5 MOP) after patient has ingested standard dose of psoralen. Test site read after 72-96 hours ● Starting dose: 40% of MPD for topical PUVA ● 70% of MPD for oral PUVA ● Increments: 20% to 40% ● Frequency: twice daily as erythema is delayed ● Eye protection: following ingestion of psoralen, patients are required to wear UVA absorbing glasses before therapy and for at least 12 hours post therapy( children 24 hours) Puva contraindications ● Dysplastic nevus syndrome ● SLE ● Dermatomyositis ● Xeroderma pigmentosum ● Bloom syndrome ● Unreliable patients ● Medically unfit Photodynamic therapy (PDT) • Photodynamic reaction, also known as the photodynamic phenomenon has been known since the end of the 19th century • At the beginning of the 20th century, Tappeiner and Jesionek published a report on his experiments with the treatment of spinalioma, basal cell carcinoma and lupus vulgaris by topically applied eosin and subsequent irradiation • Tappeiner was also the first to treat the reactions with a photoactive substance, followed by irradiation in the presence of oxygen, the term "photodynamic effect" however, the results of his work were forgotten • Since the 1980s, there has been a resurgence of interest in this treatment method Photodynamic therapy (PDT) • In recent years, in addition to dermatology, PDT has also been used in other medical fields, such as ENT, gastroenterology, pneumology, gynecology and urology Photodynamic therapy (PDT) • Is a modern, non-invasive, therapeutic and diagnostic method used in the treatment of mainly skin tumors • Consists in the local application of a photosensitizer to the treated lesion (especially a tumor) followed by irradiation with visible light • PDT principle - based on the photodynamic effect • Photodynamic effect: photosensitizer molecules activated by visible light excite oxygen to a reactive state, with the formation of free oxygen radicals "ROS" (reactive oxygen species), which then damage both tumor cells and endothelium of blood vessels that supply the tumor with oxygen and nutrients PDT - mechanism of action Statistics od PDT Treatment success rate - 91% (the remaining 9% are patients who relapsed within 6 months of the last PDT course and patients who did not respond to the therapy) Before PDT PDT After III. courses of PDT Before PDT After IV. courses of PDT Before PDT After II. courses of PDT Before PDT After II. courses of PDT Before PDT After IV. courses of PDT