Continuing Education Activity

Phototherapy is an effective treatment modality for several diseases. It can be used to treat neonatal jaundice and mostly used to treat various common skin disorders. This activity outlines the different aspects of phototherapy and highlights the role of the interprofessional team in managing patients who undergo phototherapy for their various indications.

Objectives:

• Summarize the different aspects of phototherapy
• Describe the technique of phototherapy.
• Review the clinical significance of phototherapy.

Introduction

Phototherapy is a major effective therapeutic treatment modality in dermatology and has influenced the treatment of various skin diseases dramatically. It consists of a controlled administration of non-ionizing radiation to the skin in various dermatoses, which involves the ultraviolet part of the electromagnetic spectrum and commonly includes ultraviolet A (UVA) spectrum, ultraviolet A-1 (UVA-1) spectrum, UVA spectrum with a psoralene sensitizer (PUVA), and ultraviolet B (UVB) spectrum, i.e., broad-band (BB)-UVB, or narrow-band (NB)-UVB.[1]

The UVA spectrum is usually between 320 and 400nm, whereas UVA-1 (340-400nm) has longer wavelengths of UVA..[2]  The UVB spectrum is between 280-320nm, which may be delivered as full-spectrum (broad-band UVB lamps 270-350nm, along with the shorter wavelengths from UVA spectrum) or delivered as small-spectrum (narrow-band UVB lamps 311-313nm).[3]

Few specialized types of phototherapy exist, that include lasers, photodynamic therapy (PDT), bath-PUVA, and extracorporeal photochemotherapy. Phototherapy is still the most frequently used treatment modality for different skin diseases, including parapsoriasis, psoriasis, pityriasis lichenoides chronica, eczema, atopic dermatitis, vitiligo, photodermatitis, polymorphous light eruption, actinic prurigo, hydroa vacciniforme,  cutaneous porphyrias, Mycosis fungoides, and many others.[4][5]

UVB phototherapy has different properties like anti-inflammatory, immunosuppressive, and cytotoxic. The mechanisms of its action are unclear but include the induction of cis-urocanic acid, Langerhans cell depletion, altered antigen presentation, decreased activity of natural killer(NK) cells, and apoptosis of T lymphocytes and keratinocytes. The mechanisms of action of PUVA include the cross-linking of DNA through psoralen photoadducts, DNA replication inhibition, depletion of Langerhans cell, and immunosuppressive effects on T-lymphocyte function and migration.UVA-1 phototherapy penetrates deeper into the dermis, and it induces interstitial collagenase and cytokines, resulting in the softening of the sclerotic skin.[4] Photopheresis results in dendritic cells acquiring antigen from apoptotic lymphocytes, which elicit a specific immune response without causing systemic immunosuppression.[6]

Indications

Psoriasis

Narrow-band (TL-01) UVB (NB-UVB) can be used as monotherapy to treat all variants of adult psoriasis except generalized pustular and erythrodermic psoriasis, for which PUVA can, however, be considered.NB-UVB is more effective than broad-band UVB (BB-UVB). NB UVB is also recommended for pregnant patients and can be safely augmented with topical retinoids, vitamin D analogs, and steroids.PUVA needs to be considered in those patients who have failed to respond to UVB or whose duration of remission following UVB is consistent with a short duration.[4][7][8]

Chronic Eczema

Phototherapy is an effective treatment modality for nodular prurigo, severe generalized atopic eczema,  and can also be considered for localized palmoplantar eczema when other treatment modalities are inappropriate or unable to respond. NB-UVB is usually considered as first-line therapy for generalized body involvement while topical PUVA is the first-line therapy for localized palmoplantar eczema.[9]

Mycosis Fungoides

Narrow-band UVB and PUVA have been used effectively for the treatment of cutaneous T cell lymphoma.UVB is particularly useful for the patch stage and PUVA is preferable for the plaque stage. Increased inflammation may be seen in the early stages of treatment and it settles without stopping therapy. PUVA therapy is used in the tumor phase and can be combined with systemic therapies like PUVA and interferon.[10][5]

Vitiligo

In resistant cases of vitiligo where the disease is not responding to topical modalities, Phototherapy is a widely used second-line treatment option. Prolonged courses of  NBUVB therapy leads to complete remission in about 35% of patients, the relapse rates in the future is high in vitiligo.PUVA also has similar efficacy as in vitiligo. Phototherapy has been combined with fractional Carbon dioxide Laser for the treatment of vitiligo. A meta-analysis demonstrated no additional benefits for the fractional CO2 laser to UVB phototherapy for vitiligo patients.[11]

Polymorphic Light Eruption

Narrow-band UVB and PUVA are equally effective for desensitization of PLE but the former is used more frequently due to better side effect profile. The provocation of the rash, which occurs in about 50% of patients and it can be managed with topical steroid creams.

Cutaneous Graft Versus Host Disease

It can respond to NBUVB, oral, and bath PUVA. These modalities can be used as an effective steroid-sparing agent. Prolonged PUVA therapy can lead to the development of squamous cell carcinoma. Although severe lichenoid GVHD can be treated with extracorporeal photopheresis.

Generalized Lichen Planus

The patients who do not respond to systemic immunosuppressive therapy, phototherapy is a good option. Current literature supports the use of both oral /bath PUVA and NB-UVB.

Other Indications

Pityriasis lichenoides chronica, generalized granuloma annulare, mastocytosis, chronic spontaneous urticaria, and generalized pruritus.[12][13]

Contraindications

Absolute Contraindications [14]

• Dysplastic naevus syndrome
• Systemic lupus erythematosus
• Dermatomyositis
• Genetic skin cancer syndromes (xeroderma pigmentosum, Gorlin syndrome)
• Bloom syndrome, Cockayne syndrome
• Patients unwilling or unable to comply with safety procedures
• Patients who are medically unfit and unable to stand, e.g. severe cardiovascular or respiratory disease

Relative Contraindications

• History of exposure to arsenic / ionizing radiation
• Previous melanoma
• Pregnancy
• Current pre-malignant skin condition
• Concomitant immunosuppressive therapy
• Photo-induced epilepsy
• Cataracts
• Bullous pemphigoid/pemphigus
• Non-melanoma skin cancer 
• Significant liver dysfunction
• Age <16 years

Equipment

Phototherapy is delivered by different types of equipment such as whole-body cabins, small panel radiators, whole body panels, and point sources for narrowband UVB. Whole-body cabins contain 1800 mm long fluorescent tubes that line the walls in front of reflective metal surfaces, which enable them to achieve greater dose uniformity and greater treatment efficiency. Small panel irradiators are used for the treatment of palmar and plantar skin.[15] 

Point source devices usually avoid unnecessary irradiation of unaffected skin, but care is needed to avoid under-or overdosing at overlap areas. Calibration and dosimetry are done by dose calculation and designated patient irradiance, and these values are important for the determination of irradiation by UV unit at regular intervals. The mean UV irradiance in whole body cabinet to which a patient is exposed is called designated patient irradiance(DPI), and the irradiance is measured at 12 sites of the body at posterior, anterior, and both lateral positions.

Preparation

The preparation of the patient for phototherapy needs regular monitoring of the equipment and some safety precautions.[15] Before entering the cabinet for treatment eye goggles, proper covering of genitalia and face shield is given for safety purposes. Accurate starting dose determination is done by minimal phototoxic dose/minimal erythema dose testing. Cabinet irradiance should be checked regularly by calibrated radiometer to determine accurate dosimetry. Lamp maintenance should be done by regular cleaning and inspecting the cabinet and lamps and change the lamps when it is needed. After the procedure, the patient should use UV protected glasses until sunset. The patient should also regularly use sunscreen on sun-exposed sites.

Technique or Treatment

The solar electromagnetic spectrum includes UVA(320-400nm), UVB(280 to 320nm), and UVC(<280nm) and is the part between X-rays and visible light.UVR is produced artificially by a technique in which fluorescent tubes containing mercury vapors and phosphorus coating which enable the electric current to pass, then excited electrons of mercury are absorbed by phosphorus coating and then by the process of fluorescence radiations of longer wavelengths reemit. UVA and UVB can be produced by changing of phosphorus.UVA rays penetrate deeper than UVB but UVB is more readily absorbed by DNA than UVA.[14]

Complications

Complications of UVB Therapy

Acute effects: The commonest side effects are erythema and burning. Erythema peaks at 12–24 hours and can be associated with pain, swelling, and blistering, more so in skin phenotype I or II, in obese or taking phototoxic drugs. Mild erythema can be managed with topical emollients and steroids. Another complication is Herpes simplex virus reactivation, which commonly affects the lip and occurs more frequently in those with a past history of such outbreaks. Blistering of psoriatic plaques is an uncommon side effect of phototherapy and is usually asymptomatic.[4]

Chronic effects: Chronic complications of UVB therapy include photoaging that clinically appears as leathery appearance, xerosis, wrinkling, pigmentary changes, loss of elasticity, and increased fragility. Broad-band UVB has a carcinogenic risk that is not well defined. The carcinogenic risk of NB-UVB, which is being increasingly used for delivering phototherapy, is not fully defined in humans but is less than that of PUVA. Extrapolation from animal studies suggested that NB-UVB is 2–3 times per MED more carcinogenic than BB-UVB. Genital protection during phototherapy is highly recommended.[13]

Complications of PUVA Therapy

Acute effects: Acute PUVA phototoxicity can range from mild erythema to severe pain with edema, blistering, and systemic upset, including malaise and fever.PUVA erythema also lasts longer. A rarer form of phototoxic reaction to PUVA is nail damage with photo-onycholysis or subungual hemorrhage. Nausea is a common side effect in patients treated with oral 8-MOP PUVA. This can be decreased by taking antiemetics or taking the psoralen. Like UVB, PUVA  can also cause the reactivation of Herpes Simplex.

Chronic effects: PUVA lentigines and PUVA keratoses manifest as multiple hyperkeratotic papules on non-sun-exposed sites, for example, the legs, trunk, and sides of the hands, feet, and digits. There is now substantial evidence for the carcinogenic risk of PUVA therapy in large cohorts of patients followed up for prolonged periods of time. There is a marked and dose-dependent increase in Squamous Cell Carcinoma. PUVA can stimulate the growth of melanoma cells and induce melanocytic tumors in animal experiments. As PUVA alters immune function and surveillance, there is a concern that the risk of internal malignancy, particularly of lymphoproliferative neoplasms, may be increased. Psoralens can penetrate the ocular lens, where 8-MOP has been detected in humans. Cataract development following PUVA has been reported in some animal experiments. It is recommended that protective eyewear be worn in individuals with pre-existing cataracts or who may be at increased risk of cataract (e.g., children and patients with atopic eczema.[16][15]

Clinical Significance

Phototherapy is a safe, easy, and effective treatment modality in a number of dermatoses with lower cost and lower side effects. As the disease burden of dermatological diseases is high, phototherapy has a superior efficacy as compared to topical or systemic therapy in treating the patients of psoriasis, mycosis fungicides, atopic dermatitis, pityriasis Versicolor, chronic urticaria, palmoplantar pustulosis, and vitiligo. Phototherapy prevents patients from the side effects of systemic therapy because it is a safe alternative.[2]

Enhancing Healthcare Team Outcomes

Patient education has a sole implication in this context, proper explanation of the procedure with special importance to factors that can lead to burning should be adequately explained. Patients must wear UV-blocking goggles for 12 hours following the ingestion of psoralen. Patients should be provided with approved UV protective eyewear. Factors that can lead to inadvertent burning should be discussed with each patient. Obese patients may require a modified treatment protocol, i.e. a lower starting dose, as areas such as the breasts, buttocks, and abdomen are closer to the lamps.[5]

Nursing, Allied Health, and Interprofessional Team Interventions

All patient information leaflets should be provided to patients before treatment. Consent should be taken before the procedure and give time to the patient if they change their decision. Long term treatment options, side effects, and other alternative options need to be discussed. Practicalities of treatment should be discussed. Records of patients should be available at each clinic at the start of treatment for review by the consultant and nurse.

To retain the competence of physicians and nursing staff, continued training and education is essential.

Nursing, Allied Health, and Interprofessional Team Monitoring

The most important risk to staff is exposure to UVB. Staff who conduct dosimetry should wear goggles, face shields, appropriate clothing, and sunscreen (SPF>30) if they have to enter the cabinet with the lamps on. A formal physiotherapist or nurse is undertaken before the start of phototherapy. It must be recorded and includes cumulative doses of phototherapy. There is also a need to do blood tests in a few cases, allergies testing and also keep a record of current medication and special needs assessment.

In cabinets that have combined UVB and UVA lamps, it is essential that the correct tubes are selected for treatment. Male patients should wear appropriate clothing to protect the genitalia. The face (if not involved by the dermatosis being treated) should be shielded with a visor to avoid unnecessary UV exposure. For some indications, whole-body treatment may not be required (e.g., for polymorphic light eruption desensitization, treatment limited to the photo exposed skin may be sufficient.