Manual of Dermatologic Therapeutics
7th Edition
© 2007 Lippincott Williams & Wilkins
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38
Diagnostic and Therapeutic Techniques
Jennifer Hunter-Yates
Cytologic Smears
I. Discussion
Cytologic techniques in dermatology are useful in the diagnosis of bullous diseases, vesicular viral eruptions, and molluscum contagiosum. Examination of the smear is not a substitute for a biopsy, but it does enable multiple lesions to be tested on repeated occasions and allows immediate confirmation of some disease processes.
II. Technique
  • Select an early lesion that shows no signs of trauma or infection.
  • Separate or remove the blister top with a scalpel or sharp scissors. Absorb excess fluid with a gauze pad.
  • Gently remove the blister contents and scrape the floor of the vesicle with a No. 10 or No. 15 scalpel blade or curette. Do not provoke bleeding.
  • Make a thin smear on a clean glass slide. With solid lesions such as molluscum, squeeze the material between two slides.
  • Air-dry. If the following reagents are available, fix tissue by dipping it four to five times in 95% ethanol or methanol or immerse the slide in these solutions for 1 to 2 minutes.
  • Stain with Wright, Giemsa (one-half dilution with tap water for 30 to 40 seconds), or hematoxylin and eosin stain.
  • Microscopic appearance. Examine first with a low-power objective to gain an impression of cell size and depth of stain relationships, then examine with 45 × or oil objective for the morphologic details.
    • The Tzanck smear can identify an infection as herpetic in origin but cannot distinguish between herpes simplex virus and varicella-zoster virus. Between 60% and 70% of Tzanck smears show the characteristic changes of herpesvirus infection, including large, bizarre, epidermal mononucleate and multinucleate giant cells, and “ballooning degeneration.” The giant cells contain eight to ten nuclei, which are often molded and may vary in size and shape. Occasionally, intranuclear inclusion bodies may be identified. For more specific identification of the causative virus, direct immunofluorescent antibody staining provides a rapid and useful laboratory aid.
    • Molluscum contagiosum bodies appear as multiple, large, oval to round, smooth-bordered masses up to 25 μm in diameter.
    • In most bullous eruptions, the smear will show only inflammatory cells. In pemphigus vulgaris, benign familial pemphigus, and staphylococcal scalded-skin syndrome, numerous rounded acantholytic epidermal cells with large nuclei and condensed cytoplasm are found.
Fungal Scraping and Culture
I. Discussion
Two techniques are available for diagnostic confirmation of a fungal infection: direct microscopy and fungal cultures. Immediate confirmation of the presence of a fungal infection may be accomplished easily by microscopic identification of organisms. Fungal culture will identify the causative organism specifically. This is therapeutically important because some nondermatophytic molds [Hendersonula toruloidea
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(Nattrassia mangiferae) and Scytalidium hyalinum], as well as Candida “species,” may mimic dermatophytes on potassium hydroxide (KOH) examination but are often resistant to conventional dermatophyte therapy. All scaling lesions from the scalp, angles of the mouth, axillae, groin, inframammary area, and feet, as well as blisters on the hands and feet, should be considered for both studies.
II. Technique
  • Scraping examination
    • Skin
      • If lesions are soiled or macerated, clean the skin well with alcohol and let dry.
      • Scrape with a scalpel or edge of a microscope slide at the active border of a lesion and collect scales on a glass slide. With blistering eruptions, the fungus is in the roof of the vesicle, which can be (i) gently dissected off with sharp scissors or scalpel or (ii) reflected back and the underside scraped with a No. 15 scalpel blade.
      • When obtaining culture specimens from anxious or uncooperative patients, vigorous rubbing of the lesion with a moistened sterile cotton swab provides an effective atraumatic alternative to actual scraping (1).
      • Small, thin fragments of tissue may be examined directly. Large pieces should be minced with a scalpel blade. Thick pieces should be discarded.
      • Gather scrapings together in the center of the slide.
      • Cover with Swartz–Lamkins stain (SLS) or 10% to 20% KOH and a coverslip and heat gently, but not to boiling, for 15 to 30 seconds. Note that two types of KOH are available: one in water and the other in dimethyl sulfoxide (DMSO). The KOH in DMSO does not require heating.
      • SLS preparations can be examined immediately. Let KOH slides cool for 10 minutes (during which time the tissue is hydrolyzed and rendered clear), and then press the coverslip gently to flatten the tissue and push out air bubbles.
      • Examine under a scanning lens or high-dry magnification. It is very important to avoid getting KOH on the microscope objective, because it will etch the lens. The diaphragm should be closed down and the condenser lowered as far as possible. The ease of identification of hyphae varies inversely with the intensity of light passing through the slide.
      • With SLS, hyphae and spores appear blue against the unstained background of cells. The fungal stain consists of a dye, a surfactant to clear the tissues quickly, and less KOH (2%) than will etch glass and ruin microscope lenses. Because the hyphae stain selectively and are seen more easily with SLS, slides may be scanned more quickly at a lower power.
        In KOH preparations, hyphae and spores will stand out as refractile tubes and oval bodies against the background of cells and debris. It is not possible to make a species identification from tissue scrapings.
    • Hair and nails
      • Examine the scalp with a Wood’s lamp. If individual lesions fluoresce, pull out 10 to 15 hairs for examination. Otherwise, examine scales and 10 to 15 random hairs from the involved site. Fungus invades the hair in two ways: ectothrix involvement, where the hair shaft is surrounded by tiny spores, and endothrix infection, where the spores are found inside the hair shaft. Ectothrix fungi include Microsporum species as well as Trichophyton mentagrophytes and Trichophyton verrucosum. Endothrix infections are seen with Trichophyton tonsurans, Trichophyton violaceum, and Trichophyton schoenleinii. Altered, dystrophic, hypertrophic, or pigmented nails should be snipped off and minced on a slide. Subungual debris is less suitable for examination.
      • Heat the specimen on a slide or in a test tube with 10% to 40% KOH and let cool for 15 to 30 minutes. Tissue may then be stained with SLS or examined directly.
  • Culture. In addition to direct examination of scales, scrapings from a suspicious lesion should be cultured at room temperature on Sabouraud’s glucose agar,
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    Sabouraud’s agar with chloramphenicol and cyclohexamide (Mycobiotic, Mycosel), or dermatophyte test medium (DTM). Sabouraud’s agar with chloramphenicol and cyclohexamide is more selective for dermatophytes because the chloramphenicol inhibits bacteria and the cyclohexamide inhibits contaminants. DTM contains cyclohexamide, gentamicin, and chlortetracycline, preventing growth of bacteria and saprophytic fungi. DTM contains phenol red, which turns the agar from yellow to bright red when its pH becomes alkaline from dermatophyte growth. Contaminant growth does not alter the pH of the medium. Using DTM medium, the specimen should be inoculated onto the media and the cap loosely placed, thereby providing the fungi with the air they require for growth. If no color change takes place within 2 weeks, the culture may be discarded. If the color does change, it may be presumed that a pathogenic dermatophyte or yeast is present. Microscopic examination of the culture (culture mount) should then identify the exact species.
Wood’s Light Examination
I. Discussion
Wood’s glass, primarily barium silicate containing 9% nickel oxide, is opaque to all light except for a band extending from 320 to 400 nm. When light from a high-pressure mercury arc is passed through this filter, it is principally the 360-nm radiation that is transmitted as Wood’s light. Fluorescent bulbs (black lights) that emit a similar, although slightly broader, spectrum are also available. The Wood’s light was first found to have medical importance in detecting fungal infections, but it is useful for many other diagnostic tasks as well. Because ointments, exudates, tetracycline in sweat, makeup, deodorants, and soap may fluoresce, the skin should be well cleansed before examination, except if erythrasma is suspected. Wood’s lamp examination may be used in the following situations:
  • Detection and control of scalp ringworm. Hairs infected with Microsporum audouinii, Microsporum canis, or Microsporum distortum fluoresce a bright blue green. Fluorescent hairs may be selected for microscopic examination and culture. Pteridine compounds have been postulated as the cause of this fluorescence. As normal hair regrows, a band of nonfluorescent hair will emerge. The emergence of T. tonsurans, a nonfluorescent dermatophyte, as the most common cause of tinea capitis limits the usefulness of Wood’s lamp examination for screening purposes.
  • Detection of other fungal infections. Tinea versicolor may fluoresce a golden yellow. Although this is often imperceptible, Wood’s light examination nevertheless allows the accompanying pigmentary changes to be seen more vividly.
  • Detection of bacterial infections
    • Erythrasma, an intertriginous infection caused by Corynebacterium minutissimum, fluoresces a brilliant coral red or pink orange. The fluorescent substance is a water-soluble porphyrin and, therefore, may not be present if the area has been washed recently.
    • Pseudomonas aeruginosa infections give off a yellow-green fluorescence due to pyocyanin. Fluorescence due to fluorescein is detectable before obvious purulence appears, and it is useful in screening burn patients for infections.
  • Delineation of pigmentary disorders. Long-wave ultraviolet light (UVL) is transmitted into the dermis, where it gives a white to blue-white fluorescent color. Melanin present in the epidermis (but not dermis) acts to absorb long-wave UVL and thereby prevents this “white” color. Under Wood’s light, variations in epidermal pigmentations (freckles, melasma, vitiligo) are more apparent, and variations in dermal pigmentation (Mongolian spot, some instances of postinflammatory hyperpigmentation) are less apparent or unchanged compared with their appearance in ambient visible light. Wood’s light accentuates the contrast between pigmented and nonpigmented skin, but, more importantly, it separates hypopigmented from totally amelanotic areas (the latter have true white to blue-white fluorescence). It is used for examining patients with vitiligo, albinism, leprosy, and other disorders of hypopigmentation and is also useful as a screening procedure in nurseries to look for the small, ash-leaf-shaped, white macules, indicative of tuberous sclerosis.
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  • Detection of porphyrins. Acidified urine, feces, and, rarely, blister fluid from patients with porphyria cutanea tarda will fluoresce a brilliant pink orange.
  • Drug detection. Patients who ingested tetracycline in childhood during formation of their deciduous teeth may have teeth which fluoresce yellow. A pink fluorescence of the nail bed lunulae can be observed in patients on oral tetracycline therapy, whereas topical therapy will produce yellow fluorescence of the treated sites.
  • Miscellaneous. Fluorescent ingredients or markers in cosmetics, medications, or industrial compounds may be detected with Wood’s lamp examination.
Patch Testing
I. Discussion
Patch testing is used to document and validate a diagnosis of allergic contact sensitization and to identify the causative agent. It may also be of value as a screening procedure in some patients with chronic or unexplained eczematous eruptions (e.g., hand and foot dermatoses). It is a unique means of in vivo reproduction of disease in diminutive proportions, because sensitization affects the whole body and may therefore be elicited at any cutaneous site. The patch test is easier and safer than a “use test” because test items can be applied in low concentrations on small areas of skin for short periods of time.
II. Technique
  • Delay patch testing until any acute inflammation has subsided. Reexposure to the antigen may cause the eruption to flare. Neither low-dose systemic steroids nor antihistamines will influence the results.
  • Test only with potential allergens. There are no methods available for assaying primary irritants easily.
  • Be certain that the substances being tested will not irritate the skin. Cosmetics may be applied full strength, but items of unknown irritant potential should be diluted to 1% to 2% in petrolatum, mineral oil, or less preferably, water. Suitable dilution and vehicle data are available in Fisher’s Contact Dermatitis (2001), other references cited at the end of this chapter, and the textbooks mentioned previously (2).
  • The True Test is a prepackaged double adhesive strip with the 24 most common allergens in the United States. This is a general screen and tests <2% of the >3,700 known allergens. The True Test identifies the cause of the allergic contact dermatitis in <80% of patients. This testing is limited and can miss some other important allergens such as newer preservatives and corticosteroids. Supplemental allergens can be purchased and applied individually.
    Apply test substances to a disk of filter paper bound to plastic-coated aluminum (Al-Test) or in Finn chambers and attach to the skin with occlusive tape. The Al-Test is the standard utilized by the North American and International Contact Dermatitis groups. Alternatively, one can use a 1-in. square piece of soft cotton (Webril) and cover with occlusive tape (Scanpor) or cellophane and tape. A smaller patch, which may be slightly less effective, may be applied with a 1/4-in. piece of gauze, linen, cotton, or filter paper and covered with tape (or Dermicel for those who cannot tolerate tape). Liquids and ointments may be applied directly to the cotton or gauze. Volatile liquids should be applied directly to the skin and allowed to dry before being covered. Solids must be powdered before application. Moisten powders and fabrics with water before application. The site of application should be normal hairless skin on the back or inner arms. Pay careful attention to applying the appropriate concentration of the test substance. Too high a concentration may result in a false-positive reaction or may even sensitize the patient.
  • Leave the patches in place for 48 hours. If pain, pruritus, or irritation under a patch is noted, the patient should remove it at once. Readings should not be made until the patches have been off at least 20 to 30 minutes, because positive reactions may not be immediately apparent. Delayed reactions are not uncommon, and a final reading should be made at 4 days (96 hours).
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  • The results are interpreted and noted as follows:
    • ?+ = doubtful reaction
    • + = weak (nonvesicular) reaction—erythema and/or papules
    • + + = strong (edematous or vesicular) reaction—erythema, papules, and/or small vesicles
    • + + + = extreme reaction—all the foregoing plus large vesicles, bullae, and at times, ulceration
    • IR = irritant reaction
    A positive patch test only proves that the patient has a contact sensitivity but not necessarily that the eliciting substance is the cause of the clinical eruption.
  • False-negative tests may be caused by the following:
    • Low concentration or insufficient amount of antigen.
    • Improper testing, including inadequate occlusion, inappropriate vehicle, wrong site, incorrect reading times, or deteriorating substances.
    • Depressed reactivity owing to the administration of high amounts of systemic steroids or recent and aggressive topical steroid application.
    • Failure to reproduce the true conditions of exposure to antigen and lack of heat, friction, or trauma.
  • False-positive tests may be related to the following:
    • Primary irritant reactions.
    • Tape reactions and pressure effects.
    • Reactions to occlusion: maceration, miliaria, and folliculitis.
    • Contamination from another site.
    • Presence of impurities in the test material.
    • Multiple concomitant positive patch tests may result in a state of hyperreactivity (excited skin syndrome or angry back syndrome). Subsequent retesting with individual allergens will reveal those that were reactive spuriously (3).
  • Once developed, positive reactions may sometimes take several weeks to subside. A topical corticosteroid may be used on test sites with active or prolonged inflammation. Patch tests positive at 2 days and negative at 3 to 2 days are often irritant in origin.
Ultraviolet Light Therapy
I. Discussion
UVL, the part of the electromagnetic spectrum that begins next to the violet end of the color spectrum (400 nm) and extends to the beginning of the x-ray region (200 nm), may be used in the therapy of psoriasis, vitiligo, cutaneous T-cell lymphoma (mycosis fungoides), eosinophilic pustular folliculitis, pityriasis rosea, and chronic eczematous eruptions, as well as uremic or aquagenic pruritus. It has also been used in conjunction with psoralens administration for photochemotherapy of psoriasis, vitiligo, cutaneous T-cell lymphoma, alopecia areata, chronic graft-versus-host disease, and urticaria pigmentosa. In addition to these standard therapies, it may also be used as effective prophylactic therapy for polymorphous light eruption and other photodermatoses. UVL causes many profound biologic changes, including temporary suppression of epidermal basal cell division, followed by a later increase in cell turnover, and UVL-induced immunosuppression. The UVL spectrum is subdivided into three bands: ultraviolet C [UVC (200 to 290 nm)], UVB (290 to 320 nm), and UVA (320 to 400 nm). Each region has different photobiologic characteristics and will be discussed here separately.
II. Sources and Techniques
  • Sunlight is often the optimal source of UVL. It is the least expensive and most effective under most circumstances. Sun emits radiation with a continuous emission spectrum. The ozone layer in the upper atmosphere acts as a filter and absorbs virtually all UVL <290 nm. The erythema dose for a fair-skinned person is
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    20 minutes at latitude 41 degrees (Boston) at midday in June. The disadvantages of sunlight radiation are its variable absorption by clouds and the difficulty in controlling or monitoring its intensity.
  • UVC radiation from artificial sources is present in operating room germicidal lamps and in cold quartz lamps. These lamps (low-pressure, low-temperature mercury arcs) emit a band of radiation predominantly at 253.7 nm through a quartz envelope filter. The erythema dose is 30 seconds at 25 cm. The advantages are that (i) little or no pigmentation follows the erythema and (ii) severe burns cannot occur, because large increases in exposure time lead to only minimal increases in redness. Cold quartz radiation has been used to produce erythema and desquamation in acne patients, particularly in pigmented individuals who wish to avoid more intense melanin pigmentation. UVC radiation can cause a painful conjunctivitis after only seconds of exposure. You should not look directly into these lamps or spend much time around the lamp without adequate protection (protective clothing, glasses, and sunscreens).
  • UVB radiation is responsible for most of the therapeutic effects of sunlight and conventional artificial UVL therapy. Detailed protocols for aggressive UVB phototherapy of psoriasis have been developed and are very effective. They are administered best in hospital or office settings using UVB fluorescent bulb–lined phototherapy booths. UVB dose depends on skin type; skin type depends on constitutive color or inherent melanin content, as well as facultative color or genetic capacity to tan. Occasionally, patients may want to treat small areas of psoriasis at home. There are several sources of UVB for clinical use as follows:
    • UVB sources
      • Fluorescent sunlamp bulbs (FS40) (low-pressure, low-temperature mercury arc sources) emit a continuous spectrum with a peak at 313 nm. The radiation is filtered through calcium, zinc, and thallium phosphate phosphor in the glass envelope. The erythema dose is 90 to 120 seconds at 25 cm. These lamps are easily obtainable, relatively inexpensive, and good sources of sunburn radiation (290 to 320 nm). They are frequently used as a bank of four bulbs for home use or constructed into a light box lined by reflecting metal and many 2-, 4-, and/or 6-ft lamps for office or clinic use. Six units of 4- or 6-ft-long bulbs, which can be wall mounted or hung from door frames, are available for home phototherapy at a reasonable cost.
        Narrowband UVB (311 to 312 nm) therapy using a Philips bulb model TL-01 has greater selectivity for the treatment of psoriasis. Other reports document its usefulness in vitiligo, cutaneous T-cell lymphoma, and disseminated cutaneous lichen planus. A standard minimum erythema dose (MED) must be obtained at baseline for dosimetry; treatments are typically delivered three times a week starting at 50% of the MED and then increasing by 10% to 15% increments. Narrowband UVB phototherapy has also been combined with psoralens. Long-term studies are still required to further define the efficacy and safety parameters of narrowband UVB, but it appears to confer less risk than psoralens plus ultraviolet A (PUVA) in terms of carcinogenesis.
      • Sunlamp bulbs or units are low-pressure mercury lamps that emit UVL in the sunburn spectrum.
      • Hot quartz lamps (high-pressure, high-temperature mercury arc sources) emit a discontinuous UVL spectrum with bands at 254, 265, 297, 303, 313, and 365 nm but with particular effectiveness in the erythema-producing midrange. The erythema dose is 30 to 60 seconds at 46 cm. Overexposure can lead to severe burns. These large lamps (Hanovia) are expensive and have been used primarily for hospital and office patient care. Booths containing fluorescent bulbs emitting UVB or UVA have generally supplanted use of hot quartz lamps.
  • UVA radiation from sunlight or fluorescent tubes will not, by itself, cause erythema or pigmentation except with extremely large doses. However, in the presence of a circulating photosensitizer such as psoralens, the long-wave UVL spectrum becomes an excellent therapeutic tool. This combination of light and drug is termed
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    photochemotherapy or PUVA therapy. In the doses used, neither the drug alone nor the light alone has any biologic activity. Absorption of electromagnetic energy in the UVA wave band in the presence of psoralens results in transient inhibition of deoxyribonucleic acid (DNA) synthesis as well as alterations of immune reactivity. PUVA treatment is useful in severe psoriasis and is also effective in some patients with vitiligo and mycosis fungoides. It is sometimes helpful in treating atopic dermatitis and other inflammatory dermatoses. PUVA therapy can be restricted to hand/foot exposure for limited disease. The treatment regimen is divided into a clearance phase, with more frequent therapy, and a maintenance phase after clinical response. Dosing of methoxsalen (Oxsoralen-Ultra) depends on weight (0.4 mg/kg); the pills should be taken 2 hours before light exposure. A fatty meal may enhance absorption. Topical PUVA requires application of 0.1% methoxsalen (Oxsoralen-Ultra) in Cetaphil 20 minutes before UVA.
    Short-term side effects of PUVA therapy include tanning, pruritus, nausea, headache, and dizziness. Long-term side effects include cataracts, lentigines, photoaging, squamous cell carcinoma, and melanoma. An ophthalmologic examination should be done before starting PUVA. Also, an antinuclear antibody (ANA) blood test should be confirmed negative. Contraindications to PUVA include lupus erythematosus, xeroderma pigmentosum, pregnancy, and severe liver or kidney disease. PUVA should also be avoided in children and in patients with pemphigus vulgaris, bullous pemphigoid, multiple skin cancers, or a family history of melanoma.
    For the treatment of psoriasis, PUVA may be combined with other modalities (methotrexate, retinoids), thereby reducing the number of PUVA treatments needed to attain remission, as well as reducing adverse effects from treatment and overall cost.
    • UVA sources
      • Fluorescent blacklight lamps (FS40BL) (low-pressure, low-temperature mercury arcs) emit a spectrum of 320 to 450 nm filtered through the barium disilicate phosphor in their glass envelopes. The peak emissions vary dramatically, depending on the bulb manufacturer; this variability and their overall low-intensity UVA emission limit their usefulness.
      • High-intensity UVA fluorescent bulbs were developed by GTE Sylvania, and it is these and similar bulbs that are best used in PUVA light boxes.
      • PUVA treatment boxes are used in hospital clinics and in some dermatologists’ offices. Two hours after ingestion of 8-methoxypsoralen, patients are exposed to incremental doses of UVA, starting at 1 to 5 J/cm2 (approximately 2 to 10 minutes), depending on the degree of melanization and skin type determination of a minimum phototoxic dose (MPD) (see Chap. 33). The treatment protocols are complicated, should be administered only under the direction of dermatologists experienced in their use, and will not be discussed here.
      • Sunlight-produced UVA can be used with psoralens for the treatment of vitiligo and psoriasis. This technique is potentially dangerous because it is nearly impossible to gauge UVL exposure accurately, and, hence, severe burns can result.
      • A topical psoralens solution can be painted on the skin of the hands and feet and then exposed to UVA radiation from a hand/foot unit. This method minimizes the total ultraviolet exposure, although care must be taken to protect the normal surrounding skin.
      • Some physicians advocate the delivery of psoralens through bath water immersion in a diluted solution of psoralens before the administration of the UVA. Studies have found equal efficacy and, more importantly, decreased total radiation requirement with this treatment option.
    • Biologic reaction to PUVA
      • The redness caused by PUVA may be absent or minimal at 12 to 24 hours after exposure (when UVB erythema is most intense) and may peak at 48 to 72 hours or later. Severe PUVA burns can continue to intensify for up to 1 week after exposure and can be treated with prednisone.
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      • PUVA pigmentation, which appears clinically and histologically similar to normal UVB-induced melanogenesis (tanning), maximizes approximately 5 to 7 days after exposure, may become very intense after repeated PUVA treatments, and lasts longer than a normal suntan, sometimes weeks to many months.
      • Repeated high-dose UVA or PUVA exposure to laboratory animals causes cataracts and skin cancer, just as UVB or sun exposure does. An increased number of basal cell carcinomas, squamous cell carcinomas, and melanoma have been found in patients with long-term PUVA psoriasis. Men being treated with PUVA therapy should always wear some form of protection for their genital skin. Patients must be observed carefully for evidence of accelerated actinic damage and melanoma and nonmelanoma skin cancers. Sunglasses with UVA-blocking properties must be worn on PUVA treatment days to decrease UVA exposure to the lens of the eye.
Photodynamic Therapy
I. Discussion
Photodynamic therapy (PDT) is used to treat numerous skin diseases, most commonly actinic keratoses and superficial nonmelanoma skin cancers. PDT involves exposure to a photosensitizer followed by light activation and resultant cell death through the formation of singlet oxygen and other free radicals. Because the photosensitizer concentrates in epidermal cells with higher metabolic activity (i.e., rapidly growing cells found in malignancies, hair follicles, and sebaceous glands), more singlet oxygen and other free radicals accumulate in, and more damage is done to, the desired target as compared with normal skin. The light source used must emit a wavelength which falls within the absorption spectrum of the photosensitizing agent for activation to occur.
PDT has been reported in the medical literature since the early 1900s, and its use by dermatologists to treat actinic keratoses and superficial nonmelanoma skin cancers has increased recently, particularly when large body surface areas require treatment. PDT has also been reported to be effective in the treatment of actinic cheilitis, acne vulgaris, sebaceous hyperplasia, localized scleroderma, cutaneous T-cell lymphoma, Hailey-Hailey disease, psoriasis, human papillomavirus, molluscum contagiosum, and other cutaneous infections. In addition, PDT is currently being used for photorejuvenation in sun-damaged skin.
II. Technique
Patients undergoing PDT must first be exposed to a photosensitizer. Photosensitizing agents may be either systemic [e.g., porphimer sodium (Photofrin)] or topical [e.g., 5-aminolevulinic acid (ALA)]. Topical ALA is converted to protoporphyrin IX, a potent photosensitizer. The absorption spectrum for porphyrins, including porphimer sodium and protoporphyrin IX, exhibits a maximum peak in the Soret band ranging from 360 to 400 nm and smaller peaks between 500 and 635 nm. Topical use of ALA has become more widespread because of ease of application and accumulation in desired target lesions. Typically, 20% ALA solution (with 48% ethanol) is applied to the area to be treated and left in place for several hours (14 to 18 hours per initial protocols). Newer studies suggest that shorter incubation time (15 to 60 minutes) does not decrease the effectiveness of treatment but may help minimize side effects and increase treatment convenience.
After an appropriate incubation time, the patient is exposed to a light source. Many different light sources have been used, such as incoherent sources (slide projectors, halogen lamps, xenon lamps, and fluorescent lamps), blue light (405 to 420 nm), red light (635 nm), pulsed dye lasers (585 nm), and intense pulsed light sources (500 to 1,200 nm). Depth of penetration is proportional to the wavelength of the light source. Hence, longer wavelengths may be more effective in the treatment of thicker skin lesions, whereas shorter wavelengths may be used for superficial lesions. Recommended times of exposure and light dosing vary considerably, depending on the disease and the light source used. PDT may be repeated at various intervals if needed.
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Stinging, burning, itching, and localized erythema and edema at the treatment site have been reported from PDT. Pain and hyperpigmentation of the treatment site are less common side effects but have been reported, especially with the treatment of acne vulgaris. Treated lesions, which respond to PDT, often exhibit scaling and crusting followed by healing in 2 to 8 weeks. Severe reactions such as blistering and ulceration are rare and may signify overexposure to light or increased sensitivity to light (as seen in diseases such as porphyria cutanea tarda and systemic lupus erythematosus). Prolonged cutaneous photosensitivity is the major side effect encountered in patients treated with PDT. Patients receiving PDT should be counseled to avoid sunlight and excessive indoor light and to use appropriate protective measures (sunscreen and tightly woven clothing) for approximately 1 to 2 weeks after treatment.
References
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3. Bruynzeel DP, Maibach HI. Excited skin syndrome (angry back). Arch Dermatol 1986;122:323–328.
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