Physical Treatments

John S. Barbieri, MD, MBA

Sherry H. Yu, MD

Phototherapy

Basic Concepts

In phototherapy, UVR is used to induce a therapeutic effect. Methods include:
- bbUVB: 290 to 320 nm.
- nbUVB: 311 to 313 nm.
- Excimer laser: 308 nm.
- UVA: 320 to 400 nm.
- UVA1: 340 to 400 nm.
- PUVA: Psoralens such as 8-methoxsalen (8-MOP) (peak erythema action spectrum 330-335 nm) are applied topically or taken orally and then the patient is exposed to UVA radiation (peak 352 nm).
- ECP: WBCs are extracted from the body and treated with UVA irradiation after exposure to 8-MOP.
To review the electromagnetic spectrum, see Figure 1.19.
The most important chromophore for nbUVB is nuclear DNA, causing cyclobutane-pyrimidine dimers. In PUVA, psoralens cross-link with pyrimidine bases in nuclear DNA. nbUVB and PUVA each reduce cellular proliferation and suppress the immune system (adaptive > innate) through release of anti-inflammatory cytokines, which is helpful in the treatment of inflammatory dermatoses.

Clinical Applications

nbUVB is commonly used for the management of psoriasis, parapsoriasis, pityriasis lichenoides, PR, AD, vitiligo, LP, pigmented purpura, pruritus, GA, CTCL, and LyP.
UVA1 and PUVA are commonly used for the management of psoriasis, GVHD, morphea, SSc, scleredema, and CTCL.
- Calcipotriene should not be applied prior to phototherapy, since it will both block UVR and be broken down by UVR.
ECP is commonly used for the management of GVHD and CTCL.

Safety Considerations

Short-term complications from phototherapy include sunburn and increased risk of HSV reactivation. PUVA can be complicated by phototoxic eruption/photoonycholysis and transient pruritus. UVB erythema appears after 4 to 6 hours and peaks 12 to 24 hours after exposure, whereas PUVA erythema appears after 24 to 36 hours and peaks 72 to 96 hours after exposure.
Long-term complications from nbUVB include photoaging and skin cancer, although the increased risk of skin cancer with nbUVB is minimal to nonexistent.
Long-term complications from PUVA include hyperpigmentation and lentigines, photoaging, skin cancer, cataracts, and hepatotoxicity. It is important for patients being treated with oral PUVA to wear eye protection following treatment.
Phototherapy dosing can be determined by skin type or by checking the MED/minimal phototoxic dose (MPD), which is the lowest dose resulting in erythema 48 hours after exposure to UVR.
- While the solar simulator is used for MED/MPD testing, the spot size is too small for use in phototherapy.
ECP is contraindicated in severe cardiac disease due to fluid shifts from the apheresis procedure.

Photodynamic Therapy

Basic Concepts

In PDT, a photosensitizer, commonly ALA or methyl aminolevulinate (MAL), is activated by light to induce a therapeutic effect.
The penetration of these photosensitizers is limited by the thickness of the stratum corneum. Thus, acetone scrubs and superficial chemical peels can reduce incubation times. In addition, the methyl group in MAL makes it more lipophilic, allowing for deeper penetration.
ALA and MAL are metabolized along the heme pathway into porphyrins, notably protoporphyrin IX.
- PDT generates protoporphyrin IX.
Protoporphyrin IX has excitation peaks at the Soret band (400-410 nm), which can be activated by blue light, and ˜625 nm, which can be activated by red light. Following excitation, porphyrins generate ROS resulting in cellular damage.
ALA is typically used with blue light and MAL is typically used with red light. Since red light has deeper penetration, it may be more appropriate for dermal processes, whereas blue light may be more appropriate for epidermal processes.

Clinical Applications

PDT is primarily used for field treatment of AKs and treatment of some superficial keratinocyte skin cancers. The abnormal epidermis of these lesions is thought to facilitate increased penetration by ALA and MAL, leading to selective destruction.
Cutibacterium acnes naturally accumulates porphyrins. Blue or red light alone can act as a potential treatment for acne; however, the evidence is limited.

Figure 7.1. MUCOCUTANEOUS ADVERSE EVENTS OF RADIATION THERAPY. A, Acute radiation dermatitis. B, Chronic radiation dermatitis (fluoroscopy-induced). C, Lymphedema of the right upper extremity secondary to modified radical mastectomy, lymph node dissection, and radiation therapy for breast cancer. D, Radiation therapy-induced angiosarcoma.

(A, Reprinted with permission from Elder DE, Elenitsas R, Rosenbach M, et al. Lever’s Histopathology of the Skin. 11th ed. Wolters Kluwer; 2015. C, Reprinted with permission from Strauch B, Vasconez LO, Herman CK, et al. Grabb’s Encyclopedia of Flaps: Head and Neck. 4th ed. Wolters Kluwer; 2015. D, Reprinted with permission from Mulholland MW, Lillemoe KD, Doherty GM, et al. Greenfield’s Surgery: Scientific Principles and Practice. 6th ed. Wolters Kluwer; 2016.)

Safety Considerations

After PDT, patients should not expose themselves to sunlight or other intense light for at least 48 hours. Since the porphyrins are excited by light in the visible spectrum, sunscreen will not be effective in preventing complications such as phototoxic eruption.
Daylight PDT, in which ALA or MAL is applied and then sunlight is used for photoexcitation, may have similar effectiveness to conventional blue light or red light PDT with fewer complications.

Radiation Therapy

Basic Concepts

In radiation therapy, ionizing radiation is used to induce a therapeutic effect. Methods include:
- Low-energy photons.
- Electrons.
- Brachytherapy: direct application of a radioactive source to involved tissues (eg, radioactive molds and implants).
- Office-based radiation therapy.
X-rays produce double-stranded deoxyribonucleic acid (dsDNA) breaks that cause cell death in more rapidly dividing malignant cells out of proportion to normal adjacent tissues.