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Guidelines of Care for Phototherapy and Photchemotherapy

Committee on Guidelines of Care: Lynn A. Drake, MD, Chairman, Roger I. Ceilley, MD, William Dorner, MD, Robert W. Goltz, MD, Gloria F. Graham, MD, Charles W. Lewis, MD, Stuart J. Salasche, MD, Maria L. Chanco Turner, MD, and Barbara J. Lowery, MPH

Task Force on Phototherapy and Photochemotherapy: Warwick Morison, MD, Chairman, Vincent A. DeLeo, MD, John Epstein, MD, Alan Menter, MD, and Robert S. Stern, MD

I. Introduction
The American Academy of Dermatology’s Committee on Guidelines of Care is developing guidelines of care for our profession. The development of guidelines will promote the continued delivery of quality care and assist those outside our profession in understanding the complexities and scope of care provided by dermatologists. For the benefit of members of the American Academy of Dermatology who practice in countries outside the jurisdiction of the United States, the listed treatments may include agents that are not currently approved by the U.S. Food and Drug Administration.

II. Definition
Phototherapy is exposure to nonionizing radiation for therapeutic benefit. It may involve exposure to UVB, UVA or various combination of UVB and UVA radiation. Photochemotherapy (PUVA) is the therapeutic use of radiation in combination with a photosensitizing chemical. It currently involves the use of psoralens and UVA radiation. Treatment with these modalities may involve partial or whole-body exposure.

III. Rationale
A. Scope
Phototherapy and psoralen photochemotherapy are administered in inpatient hospital settings, hospital clinics, day-care centers, and doctor’s offices under medical supervision. Certain forms of phototherapy and photochemotherapy are used at home. Diseases reported to respond to these treatments include, but are not limited to, the following:

1. Phototherapy
a) Psoriasis
b) Eczema
c) Photodermatoses
d) Pruritus
e) Pityriasis rosea
f) Lichen planus
g) Pityriasis lichenoides
h) Acne
i) Parapsoriasis
j) Pruritic eruptions of HIV infection
k) Other

2. Photochemotherapy
a) Psoriasis
b) Mycosis fungoides
c) Vitiligo
d) Eczema
e) Photodermatoses
f) Lichen planus
g) Pityriasis lichenoides
h) Parapsoriasis
i) Pruritic eruptions of HIV infection
j) Pruritus, other causes
k) Alopecia areata
l) Other

B. Issue
The safe and effective use of phototherapy and psoralen photochemotherapy requires the combination of the following:
1. A physician knowledgeable about these modalities
2. A trained staff to administer the treatments
3. Informed and reliable patients
4. Equipment that is safe, purpose-built, correctly maintained, and adequately monitored.

IV. Diagnostic criteria
A. Clinical
Several steps are involved in determining whether phototherapy and/or psoralen photochemotherapy are indicated and appropriate for the patient.
1. Evaluation of the disease
a) Severity of disease and/or disability
A patient should have a level of disease of disability that warrants use of these treatments. Such disability may be physical, psychologic, or both.
b) Site of disease
Disease on exposed and relatively hairless skin is most likely to respond to treatment. Certain sites require special consideration, such as the scalp, palm, soles, and genitalia. Disease of the palms and soles will favor psoralen photochemotherapy because of diminished penetration of UVB radiation at those sites.
c) Type of disease
Type of therapy varies with the disease, stage and degree of involvement, and general health. For instance, psoralen photochemotherapy may be especially helpful for treatment of psoriasis when plaques are thick but should be used with caution in the erythrodermic and pustular phases of the disease. Mild to moderate eczema may respond to phototherapy, but more severe disease to photochemotherapy.
d) Alternative therapies
There are other treatments for each indication for phototherapy and psoralen photochemotherapy. The risk/benefit ratio of these therapies must be considered.
e) Past response to treatment
A lack of response to phototherapy may be an indication for a trial of photochemotherapy and vice versa.
f) Other

2. Evaluation of the patient
a) History
1) General medical status
2) Age
Patients of any age may be treated with phototherapy and photochemotherapy. However, in children, photochemotherapy should only be used in special circumstances.
3) Sex
Phototherapy and photochemotherapy may be used in male and female patients. Photochemotherapy is contraindicated during breast-feeding and relatively contraindicated during pregnancy.
4) Compliance
Photochemotherapy is a complicated treatment and should only be used in patients who are able to comprehend and comply with all instructions.
5) Medications
Use of photosensitizing drugs should be recorded. Patients taking such medication require careful monitoring for phototoxic events.
6) History of photosensitivity and connective tissue disease
7) Skin type
8) Pregnancy
9) History of skin cancer
10) Prior history of exposure to ionizing radiation
11) Other

b) Physical examination
1) General physical examination as appropriate
2) Examination of the skin
The area to be treated should be examined to assess extent of disease, detect existing skin cancer, assess nevi, evaluate any photoaging, and detect other signs of cutaneous disease.
3) Ophthalmologic consultation
Required at the start of treatment with psoralen photochemotherapy and should be repeated yearly, or more often if there are abnormal findings.

B. Diagnostic tests
1. Biopsy and histologic examination of the skin may be indicated to establish the diagnosis.
2. Serum antinuclear antibody
Advisable if there is suggestion of associated connective tissue disease by history or clinical examination. A positive result should be investigated by further serologic testing to eliminate the possibility of clinical or subclinical lupus erythematosus.
3. Tests of liver and renal function
Before initiation of photochemotherapy if significant impairment of the function of these organs is suggested from the history and physical examination.

4. Other
C. Inappropriate diagnostic tests - Not applicable
D. Exceptions - Not applicable
E. Evolving diagnostic tests - Not applicable

V. Recommendations

A. Treatment
1. Medical
a) Treatments
1) UV phototherapy: exposure to UVB and/or UVA radiation using suberythemogenic or erythemogenic doses
The initial doses of radiation are determined by skin typing or phototesting to determine erythemal responses. Before using an erythemogenic protocol, the patient must be cautioned that the development of erythema is an integral component of the treatment.
2) Psoralen photochemotherapy: exposure to UVA radiation after medication with methoxsalen or trioxsalen given orally, topically, or in a bath. The doses of UVA radiation are intended to be suberythemogenic, but erythema is an inevitable consequence in a proportion of patients because of wide variation in individual absorption of methoxsalen. Patients should be warned of this risk.
3) Combination therapies: phototherapy and photochemotherapy may be used in combination with topical agents, such as tar, anthralin and corticosteroids, and systemic agents, such as retinoids and methotrexate.
4) Other

b) Equipment
1) An appropriately designed UVA and/or UVB treatment unit should be used. The equipment must have been established in clinical trials to be safe and effective for the therapy being given.
2) A total body treatment unit should include safety features such as the following:
(a) Proper electrical grounding
(b) An accurate timing or dosimetry device
(c) Protective shielding of lamps
(d) Handrails, handholds, or other support
(e) Viewing window or mirror
(f) Doors that can be opened by the patient
(g) Nonskid floor
(h) Adequate cooling of the chamber
(i) Other
3) The irradiance of the UVA equipment should be monitored by a photometer or radiometer.

c) Patient education
1) Provide an explanation of the nature of treatment, potential benefits, short-, and long-term risks and the precautions that are necessary. This explanation may be reinforced by a handout, video, or other educational material.
2) Provide periodic communication with patients verbally, or via a newsletter or handout emphasizing precautions that patients should take during treatments, ways to monitor for adverse effects such as possible skin cancer, and the need to bring such lesions to the attention of the physician.

d) Precautions
1) During treatment
(a) The eyes should be protected by wearing UV-blocking goggles. An occasional exception may be made in patients with recalcitrant disease of the eyelids or periorbital skin, and at the physician’s discretion.
(b) The face, genitalia, and radiation-damaged skin should be shielded unless involved with significant disease.

2) Before and after treatment with photochemotherapy
(a) Patients must wear UVA-blocking glasses, whenever using sunlight for illumination, from the time of exposure to psoralen until sunset that day. In addition, patients should be encouraged to wear UV-blocking glasses when exposed to sunlight on the following day.
(b) Patients should avoid unnecessary exposure to sunlight on days they receive treatment and should be discouraged from deliberate exposure to sunlight on nontreatment days.
(c) Patients should be encouraged to use sunscreen on exposed areas.

e) Monitoring of patients
1) During treatment
Trained personnel must be present throughout the treatment and be in a position to communicate with the patient (except for home therapy; see Section V.A.l.h.)
2) During a course of therapy
Regular evaluation of patients by the physician is essential to assess response to therapy and the development of adverse effects. A prime aim of these evaluations is to keep the exposure dose of radiation to a minimum compatible with adequate control of disease.
3) Periodic follow-up may be indicated for skin cancer screening.

f) Factors influencing choice of treatment
1) Absolute contraindications
(a) Xeroderma pigmentosum
(b) Other disorders with significant light sensitivity (e.g., albinism)
(c) Other

2) Contraindications
(a) Lupus erythematosus
(b) Breast-feeding
Contraindicated for photochemotherapy but phototherapy may be used.
(c) Other
3) Treatment may be used with caution in the following circumstances:
(a) History or family history of melanoma
(b) Past history of nonmelanoma skin cancer, extensive solar damage, and previous treatment with ionizing radiation or arsenic
(c) Pemphigus and pemphigoid
(d) Immunosuppression
(e) Uremia and hepatic failure
May be contraindicated for photochemotherapy because of disturbed drug metabolism.
(f) Severe myocardial disease or other infirmity likely to make standing for a prolonged period in the treatment unit hazardous of difficult
(g) Cataracts and aphakia
Careful attention to eye protection is required if such patients are treated with psoralen photochemotherapy.
(h) Pregnancy
Usually contraindicated for photochemotherapy but phototherapy may be used.
(i) Photosensitivity, with or without photosensitizing drugs
(j) Other

g) Records
A record should be kept documenting each patient’s treatment, including exposure dose/time and area treated.

h) Home therapy
Therapeutic use of UV radiation outside a physician’s office or clinic should be restricted mainly to patients who have difficulty in attending on-site therapy. It requires special consideration of the ability of the physician to adequately monitor the treatment. The patient should be judged to be intelligent, motivated, and reliable so that he or she is likely to sue the treatment correctly, keep records of exposure, and attend for regular evaluations. The treatments are as follows:
1) UV phototherapy using devices emitting predominantly UVB radiation for the treatment of psoriasis
2) Phototherapy with UV or visible radiation for the treatment of solar urticaria
3) Photochemotherapy with trioxsalen and sunlight in the treatment of vitiligo and photodermatoses. More photoactive psoralens such as methoxsalen should not be used except with extreme caution. Exposure to UV light in tanning booths or natural sunlight can result in severe burns.
4) Other

i) Other
1) Anticipated side effect of phototherapy
(a) Erythema, blistering, and pruritus
(b) Photoaging of skin
(c) Skin cancer
(d) Other
2) Anticipated side effects of photochemotherapy
(a) Gastrointestinal and neurologic disturbances with oral methoxsalen
(b) Erythema, blistering, and pruritus
(c) Photoaging of skin
(d) Skin cancer
(e) Other
3) Idiosyncratic side effect of phototherapy
(a) Photosensitivity
(b) Herpes simplex
(c) Other
4) Idiosyncratic side effects of photochemotherapy
(a) Photosensitivity
(b) Herpes simplex
(c) Toxic reactions including bronchoconstriction, hepatitis, and exanthem
(d) Ankle edema
(e) Other

2. Surgical - Not applicable

B. Miscellaneous - Not applicable

VI. Supporting evidence
See Bibliography (Appendix)

VI. Disclaimer

Adherence to these guidelines will not ensure successful treatment in every situation. Further, these guidelines should not be deemed inclusive of all proper methods of care or exclusive of other methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all the circumstances presented by the individual patient. For the benefit of members of the American Academy of Dermatology who practice in countries outside the jurisdiction of the United States, the listed treatments may include agents that are not currently approved by the U. S. Food and Drug Administration.

Appendix. Bibliography

Abel EA, ed. Photochemotherapy in dermatology. New York: Igaku-Shoin Medical Publishers, 1992.
Anderson TF, Waldinger TP, Voorhees JJ. UVB phototherapy: an overview. Arch Dermatol 1984;120:1502-7.
Bickers DR. Position paper—PUVA therapy. J AM ACAD DERMATOL 1983;8:265-70.
Bickfore ED, Berger DS, Corth R, et al. Risks associated with use of UVA irradiators being used in treating psoriasis and other conditions. Photochem Photobiol 1979;30:199-202.
Buchness MR, Lim HW, Hatcher VA, et al. Eosinophilic pustular folliculitis in the acquired immunodeficiency syndrome: treatment with ultraviolet B phototherapy. N Engl J Med 1988;318:1183-6.
Carabott FM, Hawk JL. A modified dosage schedule for increased efficiency in PUVA treatment of psoriasis. Clin Exp Dermatol 1989;14:337-40.
Chue B, Borok M, Lowe NJ. Phototherapy units: comparison of fluorescent ultraviolet B and ultraviolet A units with a high-pressure mercury system. J AM ACAD DERMATOL 1988;18:641-5.
Cram DL, Winkelmann RK. Ultraviolet-induced acantholysis in pemphigus. Arch Dermatol 1965;92:7-13.
Current status of oral PUVA therapy for psoriasis. J AM ACAD DERMATOL 1979;1:106-17.
Current status of oral PUVA therapy for psoriasis: eye protection revisions. J AM ACAD DERMATOL 1982;6:851-5.
Diffey BL, Roelandts R. Status of ultraviolet A dosimetry in methoxsalen plus ultraviolet A therapy. J AM ACAD DERMATOL 1986;15:1209-13.
Epstein JH, Tuffanelli DL, Dubois E. Light sensitivity and lupus erythematosus. Arch Dermatol 1965;91:483-5.
Fanselow D, Crone M, Dahl MV. Dosimetry in phototherapy cabinets. J AM ACAD DERMATOL 1987;17:74-7.
Gilchrest BA, Parrish JA, Tanenbaum L, et al. Oral methoxsalen photochemotherapy of mycosis fungoides. Cancer 1976;38:683-9.
Gilchrest BA, Rowe JW, Brown RS, et al. Relief of uremic pruritus with ultraviolet phototherapy. N Engl J Med 1977;297:136-8.
Gschnait F, Hönigsmann H, Brenner W, et al. Induction of UV light tolerance by PUVA in patients with polymorphous light eruption. Br J Dermatol 1978;99:293-5.
Harber LC, Bickers DR. Photosensitivity diseases: principle of diagnosis and treatment. 2nd ed. Philadelphia: BC Decker, 1989.
Harber LC, Bickers DR, Epstein JH, et al. Report on ultraviolet light sources: report by the task force on photobiology of the national program for dermatology. Arch Dermatol 1974;109:833-9.
Jekler J, Larko O. UVB phototherapy of atopic dermatitis. Br J Dermatol 1988;119:697-705.
Jordan WP Jr, Clark AM, Hale Rk. Long-term modified Goeckerman regimen for psoriasis using an ultraviolet B light source in the home. J AM ACAD DERMATOL 1981;4:584-91.
Lehmann P, Hölzle E, Kind P, et al. Experimental reproduction of skin lesions in lupus erythematosus by UVA and UVB radiation. J AM ACAD DERMATOL 1990;22:181-7.
Lowe NJ, Urback F, Bailin P, et al. Comparative efficacy of two dosage forms of oral methoxsalen in psoralens plus ultraviolet A therapy of psoriasis. J AM ACAD DERMATOL 1987;16:994-8.
Morison WL. Phototherapy and photochemotherapy of skin disease. New York: Raven Press, 1991.
Morison WL, Momtaz K, Mosher DB, et al. UVB phototherapy in the prophylaxis of polymorphous light eruption. Br J Dermatol 1982;106:231-3.
Morison WL, Parrish J, Fitzpatrick TB. Oral psoralen photochemotherapy of atopic eczema. Br J Dermatol 1978;98:25-30.
Nyfors A, Dahl-Nyfors B, Hopwood D. Liver biopsies from patients with psoriasis related to photochemotherapy (PUVA): findings before and after 1 year of therapy in twelve patients. J AM ACAD DERMATOL 1986;14:43-8.
Ortonne JP, Mosher DB, Fitzpatrick TB. Vitiligo and other hypomelanoses of hair and skin. New York: Plenum Medical, 1983:260-86.
Parrish JA, Chylack LT, Woehler ME, et al. Dermatological and ocular examinations in rabbits chronically photosensitized with methoxsalen. J Invest Dermatol 1979;73:250-5.
Parrish JA, Fitzpatrick TB, Tanenbaum L, et al. Photochemotherapy of psoriasis with oral methoxsalen and longwave ultraviolet light. N Engl J Med 1974;291:1207-11.
Picascia DD, Rothe M, Goldberg NS, et al. Antinuclear antibodies during psoralens plus ultraviolet A (PUVA) therapy—Are they worthwhile? J AM ACAD DERMATOL 1987;16:574-7.
Prystowsky JH, Keen MS, DeLeo VA. Measurement of the transmittance of ultraviolet and visible radiation through human eyelids.
Photochem Photobiol 1990;51:3S.
Ramsay CA. Solar urticaria treatment by inducing tolerance to artificial radiation and natural light. Arch Dermatol 1977;113:1222-5.
Ros AM. PUVA therapy for erythropoietic protoporphyria. Photodermatology 1988;5:148-9.
Saltzer EI. Relief from uremic pruritus: a therapeutic approach. Cutis 1975;16:298-9.
Stern RS, Kleinerman RA, Parrish JA, et al. Phototoxic reactions to photoactive drugs in patients treated with PUVA. Arch Dermatol 1980;116:1269-71.
Stern RS, Morison WL, Thibodeau LA, et al. Antinuclear antibodies and oral methoxsalen photochemotherapy (PUVA) for psoriasis. Arch Dermatol 1979;115:1320-4.
Stern RS, Parrish JA, Fitzpatrick TB. Ocular findings in patients treated with PUVA. J Invest Dermatol 1985;85:269-73.
Tuffanelli DL. Antinuclear antibodies and photosensitivity in lupus erythematosus—Relevant in PUVA therapy? [Editorial] J AM ACAD DERMATOL 1987;16:614-6.
Zachariae H, Kragballe K, Sogaard H. Liver biopsy in PUVA-treated patients. Acta Derm Venereol (Stockh) 1979;59:268-70.

American Academy of Dermatology Association

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