PFENNINGER & FOWLER’S
`
`Procedures
`for Primary
`Care
`
`THIRD EDITION
`
`Edited by
`
`John L. Pfenninger, MD
`President and Director, Medical Procedures Center, PC
`Private Practice
`Midland, Michigan
`Senior Consultant and Founder
`National Procedures Institute
`Austin, Texas
`Clinical Professor
`Michigan State University College of Human Medicine
`East Lansing, Michigan
`
`Grant C. Fowler, MD
`Professor and Vice Chair
`Department of Family and Community Medicine
`University of Texas Medical School at Houston
`Houston, Texas
`
`

`

`1600 John F. Kennedy Blvd
`Ste. 1800
`Philadelphia, PA 19103-2899
`
`PFENNINGER & FOWLER’S PROCEDURES FOR PRIMARY CARE
`THIRD EDITION
`© 2011, 2003, 1994 by Mosby, Inc, an affiliate of Elsevier Inc. All rights reserved.
`
`IBSN: 978-0-323-05267-2
`
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`
`Notices
`
`Knowledge and best practice in this field are constantly changing. As new research and experience
`broaden our understanding, changes in research methods, professional practices, or medical treatment may
`become necessary.
`Practitioners and researchers must always rely on their own experience and knowledge in evaluating and
`using any information, methods, compounds, or experiments described herein. In using such information
`or methods they should be mindful of their own safety and the safety of others, including parties for whom
`they have a professional responsibility.
`With respect to any drug or pharmaceutical products identified, readers are advised to check the most
`current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be
`administered, to verify the recommended dose or formula, the method and duration of administration, and
`contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge
`of their patients, to make diagnoses, to determine dosages and the best treatment for each individual
`patient, and to take all appropriate safety precautions.
`To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume
`any liability for any injury and/or damage to persons or property as a matter of products liability, negligence
`or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the
`material herein.
`
`Library of Congress Cataloging-in-Publication Data
`
`I. Pfenninger, John L.
`
`II. Fowler, Grant C.
`
`
`
`Pfenninger and Fowler’s procedures for primary care / edited by John L. Pfenninger, Grant C. Fowler.—3rd ed.
`
` p. ; cm.
` Other title: Procedures for primary care
`
`Includes bibliographical references and index.
`
`ISBN 978-0-323-05267-2
` 1. Primary care (Medicine) 2. Surgery, minor.
`III. Title: Procedures for primary care.
`
`[DNLM: 1. Primary Health Care—methods. 2. Diagnostic Techniques and Procedures. 3. Surgical
`Procedures, Operative—methods. W 84.61 P528 2010]
` RC48.P76 2010
` 616–dc22
`
`2010008159
`
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`Developmental Editor: Julie Mirra
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`

`

`CHAPTER 60
`
`PHOTODYNAMIC THERAPY
`
`Greta McLaren
`
`The history of photodynamic therapy (PDT) dates back to the early
`1900s. Various chemicals, acting as photosensitizers, were found to
`have cytotoxic effects on specific types of cells after absorption into
`the cell when followed by activation with light in the presence of
`oxygen. The principle of PDT is currently used medically to treat
`various dermatologic conditions, connective tissue disorders, and
`malignancies. This chapter reviews the various dermatologic condi-
`tions, both medical and cosmetic, that can be treated in the office
`setting using topical PDT. Both U.S. Food and Drug Administration
`(FDA)–approved applications as well as “off-label” applications are
`discussed.
`PDT using the topical photosensitizer 5-aminolevulinic acid
`(ALA-PDT) as a procedure to treat various dermatologic condi-
`tions has been gaining popularity over the past decade among
`dermatologists and primary care physicians alike. The procedure
`received FDA approval in 1999 for the treatment of minimally to
`moderately thick actinic keratoses of the face and scalp. However,
`multiple off-label uses have been investigated and found to be safe
`and effective. Some of the more common off-label treatment proto-
`cols that can be performed in the office setting include the treatment
`of acne, photodamage, sebaceous gland hyperplasia, and hidradeni-
`tis suppurativa. Extensive research regarding the “off-label” use of
`ALA-PDT in the treatment of nonmelanoma skin cancers, includ-
`ing basal cell carcinoma and Bowen’s disease, has been published.
`However, these topics are not covered in this chapter. Please refer
`to the Bibliography for more information on these subjects (e.g.,
`Gilbert, 2007).
`The most common form of ALA used by physicians in the
`United States is 20% 5-ALA (Levulan Kerastick; Dusa Pharmaceu-
`ticals, Inc., Wilmington, Mass). This photosensitizing chemical has
`the unique property of being absorbed by the outer layer of the skin
`and being taken up selectively by cells undergoing rapid turnover.
`As a result, this procedure allows for the targeting of rapidly repro-
`ducing, unhealthy, sun-damaged, precancerous, and cancerous
`skin cells.
`The mechanism by which ALA-PDT works is as follows: once
`applied to the skin and allowed to incubate and be absorbed, ALA
`is converted to a potent photosensitizer (PS), protoporphyrin IX
`(PpIX). When exposed to oxygen and light of various wavelengths,
`PpIX reacts to produce a cytotoxic effect (singlet oxygen) on the
`targeted cells. The absorption peaks for PpIX show a maximum peak
`at 409 nm, with lesser peaks at 509, 544, 584, and 635 nm (Fig.
`60-1). Higher fluencies (light energy) are needed for the lesser peaks,
`although the deeper penetration at the longer wavelengths may
`have an added benefit.
`)
`(
`+
`→
`2 +
`O PS light
`singlet oxygen which destroys the target
`ALA-PDT used off label in the treatment of acne vulgaris works
`in two ways: (1) destruction of Propionibacterium acnes, the bacte-
`rium associated with the disorder; and (2) shrinkage of the oil glands
`with less production of oil as a result. The procedure is considered
`an alternative to isotretinoin (Accutane), with results in some
`studies lasting for up to 2 years.
`
`In the presence of ALA, P. acnes makes a large amount of
`photosensitive porphyrins, increasing its photosensitivity. The pilo-
`sebaceous unit itself selectively accumulates the photosensitizer,
`PpIX. Light application again produces a chemical reaction that in
`turn kills the bacteria and also causes involution of the sebaceous
`gland.
`A second PDT photosensitizer, methyl aminolevulinate (Metvix,
`Galderma Laboratories, Paris; and PhotoCure AS, Oslo), has been
`FDA approved as second-line therapy for the treatment of nonhy-
`perkeratotic actinic keratoses of the face and scalp not amenable to
`conventional therapy. Despite FDA approval, however, Metvix has
`not yet been launched in the U.S. market.
`Lasers and light sources capable of emitting wavelengths of light
`that correspond to the absorption peaks for PpIX (see Fig. 60-1) are
`possible sources for activation of ALA. The activating light source
`for ALA approved in the FDA protocol for the ALA-PDT procedure
`is the BLU-U, a 417-nm wavelength light manufactured by Dusa
`Pharmaceuticals. Multiple other light and laser sources noted under
`the “Equipment” section of this chapter have been found to be
`effective in activating ALA. Devices such as intense pulsed light
`(IPL) or pulsed-dye laser (PDL) can be synergistic in that not only
`are they capable of activating ALA, they are able to target other
`chromophores such as hemoglobin or melanin. As a result, these
`devices can simultaneously activate ALA and treat telangiectases
`and solar lentigines, thereby enhancing the cosmetic result for pho-
`todamaged skin. This procedure using a PDL or IPL source is often
`referred to as photorejuvenation with ALA.
`
`INDICATIONS
`FDA Approved
`Actinic keratoses, mild to moderate thickness.
`
`Off-Label Use
`• Acne vulgaris
`• Acne rosacea
`• Cosmetic photorejuvenation
`• Sebaceous hyperplasia
`• Hidradenitis suppurativa
`• Nonmelanoma skin cancers
`• Actinic cheilitis
`• Warts
`
`CONTRAINDICATIONS
`Absolute
`• Pregnancy
`• Breast-feeding (not studied)
`• Planned sun exposure within 48 hours
`• Isotretinoin (Accutane) use within the previous 6 months
`
`397
`
`

`

`398
`
`AESTHETIC MEDICINE
`
`PpIX absorption in vivo
`(mouse skin)
`
`2.5
`
`2.0
`
`1.5
`
`1.0
`
`0.5
`
`Absorption (arb.u.)
`
`0 3
`
`00
`
`350
`
`650
`
`700
`
`600
`550
`500
`450
`400
`Wavelength (nm)
`Figure 60-1 The absorption peaks for protoporphyrin IX (PpIX).
`(Courtesy of Dusa Pharmaceuticals, Inc., Wilmington, Mass.)
`
`as hydroquinone 4% gel or cream 2 weeks before and up to 4
`weeks after the procedure when treating skin types IV and above.
`• The side effects and potential downtime with this procedure vary
`significantly from patient to patient. Some of the more common
`side effects are erythema, swelling, peeling, crusting, dryness, and
`discomfort. As a general rule, the amount of target tissue present,
`such as the prevalence of actinic keratoses or severity of acne,
`along with the length of the incubation period will determine the
`amount of downtime and side effects.
`• Retinoid use before the procedure may enhance the results but will
`also increase the downtime. For better predictability of downtime
`and side effects, retinoids can be discontinued 1 to 2 weeks before
`the procedure, unless the enhanced effect, with its potential
`increased severity of downtime, is desired and discussed with the
`patient during the consultation.
`• ALA-PDT should not be performed on patients who have used
`isotretinoin (Accutane) within the previous 6 months.
`• The use of photosensitizing drugs, including tetracyclines, must be
`taken into consideration when performing this procedure. It is
`acceptable to continue the medication during the treatments;
`however, the incubation time of ALA is decreased by 15 minutes
`on the initial treatment to determine if increased side effects due
`to photosensitivity are likely to occur.
`• The discomfort and nerve irritation that may occur with
`ALA-PDT may stimulate a herpes simplex virus recurrence in
`patients with a history of cold sores. Antivirals should be used
`prophylactically to prevent this potential side effect in such
`patients.
`
`PATIENT EDUCATION AND POST-TREATMENT
`GUIDELINES
`Because of the potential severity of side effects and reactions to this
`procedure, an initial consultation with the patient by a physician
`with a full explanation of the potential risks, downtime, and side
`effects is recommended. Once ALA is applied and absorbed in the
`skin, it may remain reactive to sunlight for the next 24 to 48 hours,
`regardless of cleansing after the application. It is therefore impera-
`tive that patients understand the need to avoid sunlight, both direct
`and indirect, for a minimum of 48 hours after the procedure. An
`educational handout and informed consent should be reviewed with
`the patient during the initial consultation.
`
`PROCEDURE
`1. Baseline photographs are always helpful.
`2. Review consent form and post-treatment guidelines with the
`patient.
`3. Review the history to note any contraindications or use of
`photosensitizing drugs.
`4. Note any cold sore risk and prescribe antivirals if indicated.
`
`Relative
`• Seizure disorder
`• Diabetes
`• Photosensitizing drug use
`• Tobacco use
`
`EQUIPMENT
`• Acetone and 4 × 4 gauze for skin preparation
`• Microdermabrasion machine (optional)
`• 20% 5-ALA (Levulan Kerastick)
`• BLU-U (417 nm), ClearLight (405 to 420 nm; Lumenis, Ltd.,
`Yokneam, Israel), Omnilux Blue Light (415 nm; Photo Thera-
`peutics, Inc., Carlsbad, Calif), PDL (585 or 595 nm), broad-band
`light source or IPL (410 to 1200 nm)
`• Zimmer chiller (optional)
`
`PATIENT SELECTION AND PRECAUTIONS
`• Photodynamic therapy with ALA can be used on all skin types,
`Fitzpatrick I through VI, if indicated, using one of the previously
`noted light devices. Photorejuvenation using an IPL or PDL
`should be reserved for patients with skin types I through IV only.
`Patients with darker skin types (Fitzpatrick IV and above) are more
`susceptible to postinflammatory hyperpigmentation (PIH) after this
`procedure. These patients should be well informed of the poten-
`tial risk of PIH before undergoing the procedure. For the first PDT
`treatment in skin types IV and above, a shorter incubation time
`should be considered. The incubation time for subsequent treat-
`ments may be gradually increased in 15-minute increments if
`tolerated (Table 60-1). It is prudent in these patients to take
`prophylactic measures by prescribing a skin-lightening agent such
`
`TABLE 60-1 Levulan Incubation Time for ALA-PDT Treatment
`Area
`Treatment Number
`Fitzpatrick Skin Type
`
`Disease Severity
`
`Occlusion
`
`Time (in minutes)
`
`Face/scalp
`
`Chest, back, arms or legs
`
`Chest, back
`
`First
`Second–Fifth
`First
`Second–Fifth
`First–Fifth
`First–Fifth
`First–Fifth
`First–Fifth
`First–Fifth
`
`I–III
`I–III
`I–III
`I–III
`IV–VII
`I–III
`I–III
`IV–V
`VI
`
`Mild to moderate
`Same as above
`Moderate to severe
`Same as above
`All
`Mild to moderate
`Moderate to severe
`All
`All
`
`No
`No
`No
`No
`No
`Yes
`Yes
`Yes
`Yes
`
`60
`60–90*
`30
`45–60*
`30–45
`120
`90–120
`60–90
`60
`
`*Incubation time may be gradually increased with subsequent treatments if the patient’s reaction is well tolerated.
`
`

`

`
`
`60 —— PHOTODYNAMIC THERAPY
`
`399
`
`5. Cleanse and prepare the skin with either a vigorous acetone
`scrub or microdermabrasion.
`6. Crush the Levulan Kerastick according to directions and shake
`the solution for 3 minutes.
`7. Protect the patient’s eyes and mouth with petrolatum ointment
`or gauze and apply the Levulan solution to the treatment area
`(face, neck, chest, back, arms, hands, or legs). Areas with more
`severe disease may be treated with a second coat of Levulan.
`8. Incubate to allow for sufficient absorption of the Levulan
`depending on area, disease severity, and skin type (see Table
`60-1).
`9. Areas other than the face and neck, such as chest, back, hands,
`arms, and legs, require longer incubation times for sufficient
`absorption of the Levulan. If treating these areas, occluding the
`area with cellophane (kitchen plastic wrap) and tape will
`enhance the absorption and decrease the incubation time
`required (see Table 60-1).
`10. When significant acne and or photodamage is present or if the
`patient has a darker skin type and is at risk for PIH, consider a
`shorter initial incubation time. Gradually increase incubation
`times with subsequent treatments, depending on tolerance. Do
`not exceed a 30-minute incubation time in Fitzpatrick skin type
`VI because of the increased risk of PIH in these patients (see
`Table 60-1).
`11. Wash the treated area with a gentle cleanser and water after
`incubation, before starting the light treatment.
`12. Activate the Levulan by exposing the treated area to a light
`source. Narrow-band blue light, IPL, PDL, and light-emitting
`diode light that falls within the required wavelength absorption
`spectrum for PpIX (see Fig. 60-1) are all possible sources for
`activation of Levulan. The operator should use the chosen
`device in accordance with the individual device’s operating
`protocol. If using the BLU-U light alone, the exposure time is
`approximately 15 minutes. The recommended energy for the
`Omnilux 415-nm light, according to the manufacturer, is 48
`J/cm2 for 20 minutes. However, this energy setting can cause
`significant discomfort, so start with a setting of 24 J/cm2 for 20
`minutes. Energy settings can always be increased. For significant
`photodamage, actinic keratoses, or deep cystic acne, use IPL at
`25 to 45 J/cm2, depending on the skin type and cooling mecha-
`nism, followed by additional exposure using blue light (410 to
`417 nm) at 10 to 48 J/cm2 for 3 to 8 minutes, depending on the
`energy settings used.
`13. Apply a gentle moisturizer or Aquaphor.
`14. Inform the patient that the redness and swelling will likely
`intensify over the next 48 hours. The patient should use a hat
`or umbrella and sunscreen to guard against any sun exposure for
`the next 48 hours.
`15. Patients appreciate a follow-up by phone or office visit in 24 to
`72 hours.
`16. To help prevent PIH, prescribe a lightening agent such as
`hydroquinone 4% cream for darker skin types (IV to VI) once
`the skin is fully recovered.
`17. When IPL with ALA is used for sebaceous gland hyperplasia,
`at a 7- to 10-day follow-up, hyfrecate the majority of the lesions
`still present. After two to three treatments with ALA-PDT,
`there is a significant reduction in the number of newly occurring
`lesions.
`
`COMPLICATIONS
`• PIH is a potential complication of this procedure. If this occurs,
`prescribe a combination cream of hydroquinone 4%, tretinoin
`0.05%, and fluocinolone acetonide 0.01% to be used once or
`twice daily for up to 8 weeks. Microdermabrasion every 2 weeks
`may also be added.
`• Sun exposure in the first 48 hours may result in blistering, severe
`discomfort, and peeling. Cold compresses, pain medication, Aqua-
`
`A
`
`B
`
`Figure 60-2 A, Photodamage before treatment. B, Photodamage
`after three photodynamic therapy treatments with intense pulsed light and
`BLU-U.
`
`phor, and frequent follow-up visits to monitor for infection are
`recommended.
`• Infection is rare but can occur. If impetigo occurs, mupirocin
`(Bactroban) topical ointment or cephalexin 500 mg twice daily
`may be prescribed for 7 to 10 days. If herpes simplex virus infec-
`tion occurs, antivirals such as acyclovir should be prescribed.
`• Also see some of the common after-effects noted previously.
`
`POSTPROCEDURE MANAGEMENT
`Avoiding sun exposure and keeping the treated area moist are essen-
`tial. Aquaphor is a preferred healing ointment. To soften any sig-
`nificant crusting, apply wet gauze soaked in a solution of one
`teaspoon of vinegar to one cup of water. This may be applied for 10
`minutes three times daily.
`
`RESULTS
`With three to five photorejuvenation treatments with ALA-PDT
`(60-minute incubation time) in combination with IPL followed by
`BLU-U for 3 minutes (Fig. 60-2A and B); or with three to five acne
`treatments with ALA-PDT (60-minute incubation time) and
`BLU-U exposure alone for 15 minutes (Figs. 60-3 and 60-4), the
`patient satisfaction rate is very good.
`
`Figure 60-3 Acne before treatment.
`
`

`

`400
`
`AESTHETIC MEDICINE
`
`Figure 60-4 Acne after three photodynamic therapy treatments with
`BLU-U.
`
`PATIENT EDUCATION GUIDES
`See the patient education and patient consent forms available
`online at www.expertconsult.com.
`
`BILLING AND CODING
`Limited reimbursement for the FDA-approved treatment of actinic
`keratoses is available through some insurance companies. The
`majority of the off-label uses of ALA-PDT are considered cosmetic
`and are unlikely to be covered by insurance.
`
`• For treatment of actinic keratoses, use the CPT code 17004
`(destruction premalignant lesions, 15 or more).
`• For acne, the ICD-9 code is 706.1 (photodynamic therapy by
`external application of light to destroy premalignant and/or
`malignant lesions of the skin and adjacent mucosa, each photo-
`therapy exposure session).
`• Use J code 7308 for amino-levulinic acid.
`
`For support in documentation and billing and current CPT codes,
`Dusa Pharmaceuticals has a reimbursement and coding support
`center:
`
`Dusa Customer Service and Support: (822) 533-3872 (United
`States/Canada)
`Pinnacle Health Group, Inc. (866) 369-9290 (United States/
`Canada)
`Dusa@thepinnaclehealthgroup.com
`
`SUPPLIERS
`(See contact information online at www.expertconsult.com.)
`20% 5-ALA (Levulan Kerastick) and light sources for activation
`of ALA
`Dusa Pharmaceuticals, Inc.
`Broad-band light (BBL)
`Sciton
`ClearLight and Omnilux Blue
`Lumenis
`Photo Therapeutics, Inc.
`Intense pulsed light
`(See Chapters 48 through 55 for other units)
`Cutera
`Palomar
`Pulsed-dye laser
`Candela
`
`ONLINE RESOURCE
`American Society for Laser Medicine & Surgery. Available at www.aslms.
`org.
`
`BIBLIOGRAPHY
`Alexiades-Armenakas M: Aminolevulinic acid photodynamic therapy for
`actinic keratoses/actinic cheilitis/acne: Vascular lasers. Dermatol Clin
`25:25–37, 2007.
`Blume JE, Oseroff AR: Aminolevulinic acid photodynamic therapy for skin
`cancers. Dermatol Clin 25:5–14, 2007.
`Gilbert DJ: Incorporating photodynamic therapy into a medical and cos-
`metic dermatology practice. Dermatol Clin 25:111–120, 2007.
`Gold MH: Introduction to photodynamic therapy: Early experience. Der-
`matol Clin 25:1–4, 2007.
`Gold MH: Photodynamic therapy in dermatology: The next five years. Der-
`matol Clin 25:119–120, 2007.
`Gold MH, Bradshaw VL, Boring NM, et al: The use of novel intense pulsed
`light and heat source and ALA-PDT in the treatment of moderate to
`severe inflammatory acne vulgaris. J Drugs Dermatol 3(6 Suppl):S15–S19,
`2005.
`Goldman MP: Procedures in Cosmetic Dermatology Series: Photodynamic
`Therapy, 2nd ed. Philadelphia, Saunders, 2007.
`Nestor MS: Evolving use of 5-aminolevulinic acid (ALA) topical photo-
`dynamic therapy clinically and cosmetically: A clinician’s perspective.
`Cosmetic Dermatol 18:2–5, 2005.
`Nestor MS: The use of photodynamic therapy for the treatment of acne
`vulgaris. Dermatol Clin 25:47–57, 2007.
`Nootheti PK, Goldman MP: Aminolevulinic acid-photodynamic therapy for
`photorejuvenation. Dermatol Clin 25:35–45, 2007.
`Richey DF: Aminolevulinic acid photodynamic therapy for sebaceous gland
`hyperplasia. Dermatol Clin 25:59–65, 2007.
`Taub AF: Photodynamic therapy: Other uses. Dermatol Clin 25:101–109,
`2007.
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`