The levels of evidence (I-IV) and strength of recommendation ratings (A-E) are defined at the end of the "Major Recommendations" field.
Photosensitizing Agents
Topical application of the prodrugs 5-aminolaevulinic acid (ALA) and methyl aminolaevulinate (MAL) is effective in cutaneous photodynamic therapy (PDT) (Strength of Recommendation A, Quality of Evidence I).
Light Sources and Dosimetry
Currently, a range of light sources, doses and irradiances continues to be used in ALA-PDT, whereas in MAL-PDT the standard procedure now typically involves a light-emitting diode (LED) source. A range of continuous wave light sources is effective in topical PDT (Strength of recommendation A, Quality of evidence II-iii).
Topical Photodynamic Therapy in Nonmelanoma Skin Cancer
Actinic Keratoses
Topical PDT is an effective therapy for thin and moderate thickness actinic keratoses (AK), with superiority to cryotherapy depending on protocol. Efficacy is relatively poorer for acral lesions, but PDT may still offer therapeutic benefit. Cosmetic outcome following PDT for AK is superior to cryotherapy (Strength of recommendation A, Quality of evidence I).
Bowen's Disease (BD)
Topical PDT is an effective therapy for BD, with equivalence to cryotherapy and equivalence or superiority to topical 5-fluorouracil (5-FU). Cosmetic outcome is superior to standard therapy. Topical PDT offers particular advantages for large/multiple patch disease and for lesions at poor healing sites (Strength of recommendation A, Quality of evidence I).
Squamous Cell Carcinoma (SCC)
The high efficacy of topical PDT for in situ SCC, and the efficacy figures reported particularly for superficial invasive lesions limited to papillary dermis, suggest that depth of therapeutic effect is the limiting factor for PDT in invasive SCC, with further study required. Current evidence supports the potential of topical PDT for superficial, microinvasive SCC, but in view of its metastatic potential, topical PDT cannot currently be recommended for the treatment of invasive SCC (Strength of recommendation D, Quality of evidence II-iii).
Basal Cell Carcinoma (BCC)
Topical MAL–PDT and ALA–PDT are effective treatments for superficial BCC (Strength of recommendation A, Quality of evidence I). Topical MAL–PDT is effective in nodular BCC, although with a lower efficacy than excision surgery, and may be considered in situations where surgery may be suboptimal (Strength of recommendation B, Quality of evidence I).
Cutaneous T-cell Lymphoma (CTCL)
Topical PDT can elicit a response and has a potential role in the treatment of localized CTCL. Further studies of PDT for CTCL are required to define optimal treatment parameters (Strength of recommendation C, Quality of evidence II-iii).
Intraepithelial Neoplasia of the Vulva and Anus
Topical PDT offers therapeutic benefit in vulval intraepithelial neoplasia (VIN), but refinement of practical aspects of delivery and optimization of protocol are required (Strength of recommendation C, Quality of evidence II-iii).
Extramammary Paget's Disease (EMPD)
Topical PDT, although potentially effective in EMPD, is currently associated with high recurrence rates in the limited cases reported (Strength of recommendation C, Quality of evidence III).
Photodynamic Therapy for Skin Cancer Prophylaxis
Hence, current evidence indicates that topical PDT has the potential to provide a preventive role although further evidence is required to clarify its mechanism of action (Strength of recommendation C, Quality of evidence IV).
Photodynamic Therapy in Organ Transplant Recipients (OTRs)
Current evidence suggests that topical PDT, although showing lower efficacy than in immunocompetent individuals, may provide a useful therapy for epidermal dysplasias in OTRs (Strength of recommendation B, Quality of evidence I).
Topical Photodynamic Therapy for Infectious and Inflammatory Dermatoses
Acne and Related Conditions
Although topical PDT can improve inflammatory acne on the face and back, optimization of protocols, to sustain response while minimizing adverse effects, is awaited (Strength of recommendation B, Quality of evidence I).
Viral Warts
Recent studies continue to support the potential of topical PDT in viral warts, particularly plantar warts, but it appears a relatively painful therapy option, with outcomes dependent on adequate paring and the use of a keratolytic agent pre-PDT (Strength of recommendation B, Quality of evidence I).
Genital Warts
Topical PDT may be considered as a treatment option for patients with genital warts (Strength of recommendation B, Quality of evidence I).
Cutaneous Leishmaniasis
Current evidence suggests that topical PDT is effective in clearing lesions of cutaneous leishmaniasis although further studies with culture confirmation of amastigote clearance are required (Strength of recommendation B, Quality of evidence I).
Psoriasis
Overall, current evidence, combined with studies reviewed in our previous guidelines, does not support the use of topical ALA-PDT as a practical therapy for psoriasis (Strength of recommendation D, Quality of evidence I).
Photodynamic Photorejuvenation
Interest is clearly gathering in this area, although at present there is a need for well-designed randomized, controlled, adequately powered studies with a longer follow up and ideally histological confirmation of clinical findings. The relative roles of PDT and intense pulsed light (IPL) as treatment/adjunctive treatment are anticipated to undergo further exploration. Standard topical PDT (continuous wave light source) and ALA-IPL appear effective in photorejuvenation (Strength of recommendation B, Quality of evidence II-iii).
Table: Clinical Indications for Topical Photodynamic Therapy in Dermatology: Recommendations and Evidence Assessment
Strength of Recommendation |
Quality of Evidence |
Indication |
A |
I |
- Thin and moderate thickness actinic keratoses
- Bowen's disease
- Superficial basal cell carcinoma
|
B |
I |
- Thin nodular basal cell carcinoma
- Epidermal dysplasias in organ transplant recipients
- Inflammatory acne on the face and back
- Viral warts, particularly plantar warts
- Genital warts
- Cutaneous leishmaniasis
|
B |
II-iii |
Photorejuvenation |
C |
II-iii |
- Localized cutaneous T-cell lymphoma
- Vaginal intraepithelial neoplasia
|
C |
III |
Extramammary Paget's disease |
C |
IV |
Skin cancer prevention |
D |
I |
Psoriasis |
D |
II-iii |
Invasive squamous cell carcinoma |
Adverse Effects
Acute
Pain is a common feature during light exposure in PDT, but topical PDT is overall a well-tolerated treatment modality with a low rate of serious acute adverse events (Strength of recommendation A, Quality of evidence I).
Application of topical anaesthetics is of limited use for pain relief during light exposure of AK (Strength of recommendation D, Quality of evidence II-i).
Carcinogenicity
Topical PDT has a low risk of carcinogenicity and reported cases of skin cancer occurring in relation to this therapy are rare (Strength of recommendation A, Quality of evidence II-iii).
Definitions:
Levels of Evidence
I: Evidence obtained from at least one properly designed, randomized controlled trial
IIi: Evidence obtained from well-designed controlled trials without randomization
IIii: Evidence obtained from well-designed cohort or case-control analytical studies, preferably from more than one centre or research group
IIiii: Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments could also be regarded as this type of evidence.
III: Opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees
IV: Evidence inadequate owing to problems of methodology (e.g., sample size, or length of comprehensiveness of follow-up or conflicts in evidence)
Recommendation Grades
- There is good evidence to support the use of the procedure.
- There is fair evidence to support the use of the procedure.
- There is poor evidence to support the use of the procedure.
- There is fair evidence to support the rejection of the use of the procedure.
- There is good evidence to support the rejection of the use of the procedure.