phototherapy in dermatology, other than psorasis and vitiligo.

1. PHOTOTHERAPY BEYOND
PSORIASIS AND VITILIGO
DR. MIKHIN GEORGE THOMAS

2. • Definition
• History
• Types of phototherapy
• Mechanism of action
• Schedules and protocols
• Combination therapy

3. • Acute and long term effects of
phototherapy
• Indications of phototherapy
• Newer forms of phototherapy
• Extracorpreal photopheresis
• Targeted phototherapy

4. PHOTOTHERAPY
• Phototherapy is the use of ultraviolet
radiation or visible light for therapeutic
purposes
• UVB radiation (290–320 nm) is absorbed by
the epidermis and superficial dermis
• UVA radiation (320–400 nm) can reach the
mid- or lower dermis

5. • Heliotherapy
• Atharva veda- Psoralia Corylifolia
• 1896-Niels Ryberg Finsen
• 1923-Wiliam Henry Goeckerman
• 1953- John Ingram

6. • Revival of phototherapy- Ammi Majus and
Bergapten
• PUVA –Fitzpatrick
• 1992- UVA1 for atopic dermatitis
• 1980s- ECP introduced for CTCL

7. TYPES OF PHOTOTHERAPY
 Ultraviolet A
 Ultraviolet B
 Targeted phototherapy

9. NEWER FORMS OF PHOTOTHERAPY
• Excimer laser
• Intense pulse light therapy
• Light-based targeted phototherapy
• Photodynamic therapy
• Balneotherapy

10. MECHANISM OF ACTION

11. UV-B
 Interferes with the synthesis of proteins
and nucleic acids-decreased proliferation
of epidermal keratinocytes.
 Early changes
 Formation of pyrimidine dimers
 Membrane lipid peroxidation
 Induction of transcriptional factors.

12.  Delayed changes
 Alteration of antigen presenting cells and
cellular signaling mechanisms- Î IL10,PGE2
 Decrease the number of Langerhans cells
thus inhibiting the ability of dendritic cells to
present antigens.

13. PUVA
 Similar to UVB irradiation
 Penetrates into the dermis
 Effects on dermal dendritic cells,
fibroblasts, endothelial cells, and mast
cells as well as skin infiltrating
inflammatory cells including granulocytes
and T lymphocytes.

14.  Induces reactive oxygen species formation-
cell membrane and mitochondrial membrane
damage and eventual death of antigen-
presenting cells
 Stabilizes the mast cells
 Upregulates MMP

15. PSORALENS
Naturally occurring
compounds
8-methoxypsoralen (8-MOP)
5-methoxypsoralen (5-MOP)
4,5′,8-
trimethylpsoralen(TMP)

17. FACTORS
 INSOLUBLE IN WATER
 FOOD HINDERS ABSORPTION
 FIRST PASS METABOLISM
 ABSORPTION DEPENDS ON THE PHYSICAL
PROPERTIES
 LARGE INTERINDIVIDUAL VARIATION IN
ABSORPTION

20. JAAD 2010

22.  8-Methoxypsoralen, 0.4-0.6 mg/kg, taken 1-2
h before exposure to UVA
 UV protective eye wear should be worn when
outdoors for 12 h post ingestion
 Treatment -2-3/wk
 Initial improvement frequently seen within 1
mo of therapy

23. COMBINATION UVB WITH TOPICAL THERAPIES
 Emollients increase the transmission of UV
radiation by altering the optical properties of
psoriatic skin lesions and
improving therapeutic efficacy
 Sunscreens

24. No added benefit with concomitant topical steroid use
Calcipotriol use has shown equal efficacy with twice
weekly NBUVB when compared to thrice weekly
monotherapy
With topical retinoids, better efficacy but NBUVB
dosage to be reduced to avoid burning of skin

25.  Combination of methotrexate along with
phototherapy reduces the dose related
toxicity
 Combination with cyclosporine not tried
much as monotherapy itself has high chance
of non melanoma skin cancers
 Other combinations include retinoids and

26. UV- B

27.  Contraindications:
 Lupus erythematosus or Xeroderma
Pigmentosum
 Caution should be exercised in:
 Patients with skin types I and II
 History of arsenic intake or previous treatment
with ionizing radiation therapy,
 History of melanoma or multiple nonmelanoma
skin cancers
 Any medical condition that is severe enough
that patient cannot tolerate heat or prolonged

28.  Drug interactions: Cautious use with other
photosensitizing medications
 When used in conjunction with systemic
retinoids, dose of both retinoids and UVB
may need to be lowered
 Baseline monitoring: Full body skin check
before initiation of therapy

29.  Ongoing monitoring: Regular full skin
examination to monitor signs of photoaging,
pigmentation, and cutaneous malignancies
 Pregnancy: Generally considered safe
(expert opinion)

30.  Nursing: Generally considered safe (expert
opinion)
 Pediatric use: No adequate study; may be
used with caution in individuals aged18 y
 Psoriatic arthritis: No studies

31. TOXICITY: PUVA
 Acute:
 Nausea and vomiting are common
 Dizziness and headache are rare
 Erythema: peaks at 48-96 h
 Pruritus
 Tanning: starts 1 wk after PUVA
 Blisters
 Photo-onycholysis
 Melanonychia

32.  Chronic:
 Photocarcinogenesis (SCC, BCC, and
possible melanoma)
 Increased risk of photocarcinogenesis in
Caucasians with skin types I-III after 200
treatments; this risk not present for non-
Caucasians
 Photoaging and lentigines are common,
especially in patients of skin types I-III and
are cumulative UVA dose dependent

33.  Contraindications: Known Lupus
Erythematosus, Porphyria, or Xeroderma
Pigmentosum
 Caution should be exercised: In patients with
skin types I and II who tend to burn easily
 History of arsenic intake or previous treatment
with ionizing radiation therapy
 History of melanoma or multiple non melanoma

34.  Any medical condition that is severe enough
that patient cannot tolerate heat or prolonged
standing in light box
 Severe liver disease that could lead to toxic
levels of psoralens, possibly those who have
been treated with cyclosporine or
Methotrexate

35.  Caution when patient is taking other
photosensitizing medication
 Should decrease UVA dose by one-third if oral
retinoids are started while patient is receiving PUVA
 Skin cancer screening
 Eye examination
 ANA panels (anti-Ro/La antibodies)
 Liver enzymes

36.  Regular full skin examination because of potential increased
risk of photocarcinogenesis in Caucasians
 In patients who are noncompliant with eye protection, yearly
eye examination
 Pregnancy: Category C
 Nursing: Contraindicated for period of 24 h after ingesting
psoralen
 Pediatric use: No studies; may be used with caution in
individuals aged18 y
 Psoriatic arthritis: No studies

37. FDA APPROVED INDICATIONS
 PSORIASIS
 VITILIGO

38. OFF LABEL INDICATIONS
 Malignancy
• Mycosis fungoides
 Inflammatory
• Seborrheic dermatitis
 Photodermatoses
• Actinic reticuloid
• PMLE
• Solar urticaria
 Clonal disorders
• Parapsoriasis
• Pityriasis lichenoides
 Immune dysfunction
• Atopic dermatitis
• Alopecia areata
• Lichen planus
 Others
• Granuloma annulare
• Urticaria pigmentosa
• Lichen myxedematous
• Morphoea

39. MYCOSIS FUNGOIDES (MF):
 Non-Hodgkin Lymphomas (NHL), which are
characterized by their initial presentation in
the skin
 MF (together with other types of CTCL) is the
only malignant disease that is treated with
ultraviolet (UV) radiation, the major
environmental skin carcinogen
 UVB decreases the allo-activating and
antigen presenting capacity of Langerhan
cells

40.  Treatment schedule consists of clearance,
maintenance and follow up
 Histological evaluation of clearing of lesions
 Maintenance therapy includes two therapies
a week for 1month and then one exposure
for a month for 3-6months.

41.  PUVA has been tried in all stages of mycosis
fungoides
 Most successful in early-stage disease, i.e. less
than stage IIa.
 Rate of complete remission after an initial
course of PUVA- 90% for stage IA, 76% for
stage IB, 78% for stage IIA, 59% for stage IIB,
and 61% for stage III disease

42.  Once a patient achieves complete remission, a
confirmatory biopsy of a previously exposed site is
often recommended
 Bath PUVA has been utilized as a therapeutic
modality in patients in whom oral psoralens cannot be
given
 There were no differences in time to relapse between
patients treated with PUVA and those treated with
narrow-band UVB

43. REASONABLE APPROACH
 Start with NB-UVB and in case of lack of
response switch to PUVA
 Patches and thin plaques-NB-UVB
 In late stage disease-PUVA may be
combined with methotrexate, bexarotene or
interferon as first-line therapy

44.  Complete clearing may be induced when the
cells are confined to the epidermis and the
superficial dermis and do not exceed the
depth of UVA penetration into the skin.
 PUVA is not sufficient as monotherapy
 Reduce the tumor burden in the skin
 Improve the quality of life for patients

45. ATOPIC DERMATITIS
 Second-line treatment in the
management of atopic dermatitis
 Moderate, severe and erythrodermic
cases respond to PUVA
 More difficult to treat
 Alteration of lymphocyte function in the
dermal infiltrate.
 Airconditioned treatment cabinets
improve patients tolerance to
phototherapy

46.  The action of UVA-1 is mediated through T
lymphocyte apoptosis and decreased
expression of interferon γ (IFN-γ) by
activated T cells.
 Medium dose UVA1 and NB-UVB
phototherapy are most effective as observed
in various randomized controlled trials and
half-body paired comparison studies
 RELAPSE IS FREQUENT
 NEED PROLONGED TREATMENT

47. LICHEN PLANUS
 Effective alternative to steroids in disseminated
lesions, recalcitrant oral lesions
 Response rate – 50 to 90%
 More sessions
 Post inflammatory hyperpigmentation
 More cumulative doses required
 Re-PUVA a better option

48. GRAFT VS HOST DISEASE

49. URTICARIA PIGMENTOSA

50.  Histamine induced migraines and flushing
also subsides with continued treatment
 Gradually increasing doses to be
administered to avoid degranulation of
mast cells

51. PITYRIASIS LICHENOIDES
 PUVA found to be beneficial
 NB UVB widely used though the condition
tends to remain persistent in some cases.
 Conflicting reports

52. PARAPSORIASIS
 Phototherapy is indicated for all types of
parapsoriasis and its clinical variants.
 Clearing of recalcitrant lesions as well as
preventing evolution in to MF

53. PITYRIASIS RUBRA PILARIS
 Some respond, others flare
 Some require combination with retinoids
or methotrexate

54. GRANULOMA ANNULARE
• Lesions found to resolve completely
• Relapse frequent
• Long term maintenance required

55. LICHEN MYXOEDEMATOSUS
 Papular lichenoid eruption and mucin deposition
in the dermis
 Paraproteinemia
 Histologically, the proliferation of fibroblasts is
enhanced in the dermis, and collagen bundles
are split by mucinous infiltration
 PUVA treatment has a suppressive effect on
DNA synthesis and cell proliferation

56. ALOPECIA AREATA
• Found to respond after a number of sessions
• Cirscumscribed lesions respond better
compared to total alopcia
• Follow up studies showed phototherapy not
very effective
• Relapse is high

57. MORPHEA
 Low dose ultraviolet A-1 phototherapy (UVA
1, 340–400 nm) has been shown to improve
symptoms of morphea
 Induce a marked softening of the skin
 Complete resolution of the thickened and
hyalinized collagen bundles
 Return to histologic features of normal skin

58. MECHANISM
 Induction of interstitial collagenase (matrix
metalloproteinase 1)
 Release of singlet oxygen
 Release of signaling peptides such a
interleukin- 1a (IL-a), IL-1b, and IL-6
 Release of hydrogen peroxide, which
increases mRNA levels of interstitial

59.  Different types of phototherapy have been
used
 UV-A 1 found to be most effective
 Longer the wavelength greater the
penetration

60. PRURITUS
 Renal
 Hepatic
 Aquagenic pruritus
 Aquagenic urticaria
 Chronic urticaria
 Hiv and eosinophilic folliculitis

61. PHOTODERMATOSES
 Preventive treatment by producing hardening
 3-4 weeks of PUVA sufficient to suppress the
disease
 PUVA induces pigmentation rapidly
 10% report new lesions- no need to reduce
dosing
 5- MOP preferred

62.  REGULAR SUN EXPOSURES REQUIRED
FOR MAINTENANCE
 REMISSION FOR 2-3 MONTHS

63. EXTRACORPOREAL PHOTOCHEMOTHERAPY
 Introduced in early 1980s for palliative
treatment of CTCL
 Immunomodulatory therapy that combines
leukapheresis with phototherapy
 Treat autoreactive or neoplastic disorders
caused by aberrant clones of T lymphocytes

64.  Patient’s blood is extracted and
centrifuged to obtain the leukocyte
concentrate
 8-MOP is administered directly into the
bag containing the leukocyte concentrate
 The 8-MOP molecule enters the cell and
its nucleus quickly

65.  T-Cell Apoptosis
 Dendritic cells- blood monocytes adhere
to the plastic surface of the device, get
converted to immature dendritic cells
 Anti tumor response –CD 8 cells
 stimulate the TH1 response

66. PREDICTORS OF GOOD RESPONSE
 Erythroderma
 Less than 2 years since diagnosis
 Leukocyte count lower than 20,000/μL
 Presence of 10% to 20% circulating Sézary
cells
 Absence of palpable lymph nodes
 Absence of visceral involvement
 Absence of previous intensive chemotherapy
 High peripheral blood CD8 lymphocyte count

67. ADVERSE EFFECTS
 Headache
 Nausea
 Fever
 Muscle pain
 Hypotension
 Exacerbation of skin lesions after treatment
 Vasovagal syncope
 Septicemia
 Injection site infection.

68. TARGETED THERAPY

69. ADVANTAGES
 Exposure of involved areas only and sparing
of uninvolved areas
 Quick delivery of energy and thereby
shortened duration of treatment
 Delivery of higher doses (super-
erythemogenic doses) of energy because
uninvolved areas are not exposed

70.  This has been claimed to shorten duration of
treatment, leading to less frequent visits to clinic, and
thereby lessen the inconvenience for the patient
 The maneuverable hand piece allows treatment of
difficult areas such as scalp, nose, genitals, oral
mucosa, ear, etc.
 Easy administration for children as delivery is hand-
held
 Targeted phototherapy machines occupy less space

71. EXCIMER LASER
 Mixture of noble gas and a halogen
 “Excited dimmers.”
 Depth of penetration is shallow-very
precise action
 Ablative photodecomposition
 Pulsed wave lasers-they deliver a high
energy in a short time, rapidly breaking

72.  Overall treatment time is usually shorter
 Mean number of treatments and the
cumulative UV dose are significantly lower
 Lower therapeutic cumulative dose of the
XeCl laser involves a lower risk of
carcinogenesis.
 This treatment option makes it possible to
selectively treat skin lesions and spares

73. BALNEOTHERAPY
 Bath water delivery of 8-methoxypsoralen (bath
PUVA) or different salt solutions with a
subsequent UVB- or UVA-irradiation
 Bath PUVA has the advantage of selective and
shorter photosensitization
 no serious side effects
 Found to be efficacious compared to NBUVB
monotherapy

74. PHOTODYNAMIC THERAPY
 Kennedy, et al. in 1990
 Destroy the desired target selectively
 5-aminolaevulinic acid is the main agent
used
 Actinic keratoses of the face and scalp
 Bowens disease
 Superficial basal cell carcinomas

75. ULTRAVIOLET A1 THERAPY
o 340-400nm
o Used as a tool for provocative testing for
PMLE
o Photopatch testing
o Treatment of several ultraviolet responsive
conditions

76. MECHANISM
 Induce T-cell apoptosis- atopic dermatitis and
MF
 Reduction in mast cells and Langerhan cells
 Increase collagenase expression- morphoea,
keloid
 Tanninng- prophlaxis of PLE.

77. INDICATIONS
 Atopic dermatitis
 PLE
 Morphoea

78.  CTCL
 Follicular mucinosis
 Hand eczema
 Hypereosinophilic syndrome
 GVHD
 POEMS
 Keloids

79. HAND ECZEMA
 Both local NB-UVB phototherapy and PUVA
irradiation show similar beneficial responses.
 Thick lesions UV-A preferred
 Studies show UV-A is better, more
penetration
 NB UV-B preferred in dry and dyshidrotic
types

80. SEBORRHEIC DERMATITIS
 Many patients improve upon exposure to
natural sunlight
 Abnormal immunological response to the
yeast or its degradation products may play
an important pathogenetic role

81.  Modulatory effect on inflammatory and
immunological processes in the skin
 A direct effect of UV irradiation on P. Ovale
leading to ultrastructural changes and growth
inhibition
 Long standing cases and widespread
involvement responded better
 Relapse is common

83. ACNE VULGARIS
 Porphyrins accumulated in the bacteria
Propionibacterium acnes one of the etiologic
factors involved in the pathogenesis, allows
phototherapy to be a successful modality
 Although blue light is best for the activation
of porphyrins, red light is best for deeper
penetration and an anti-inflammatory effect

84. RATIONALE
 Porphyrins produced by P. acne
 Photothermal damage to the sebaceous
glands
 Anti-inflammatory effect

85. PHOTODYNAMIC THERAPY IN ACNE
 Aminolevulinic acid (ALA)- taken up by the
pilosebaceous units
 Destruction of pilosebaceous units and killing
of P.acne

86. ADVERSE EFFECTS
 Discomfort
 Transient hyperpigmentation
 Exfoliative erythema
 Crust formation
 Photosensitivity

87. TO SUM UP…….
 Good modality of treatment
 Alternative mode of management
 Relapse is common
 Carcinogen
 Cost of treatments