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Cutaneous Photobiology

  • Jonathan Hale ZippinEmail author
  • Steven He
  • Jenny Z. Wang
  • Koji Ota
  • Anita Gade
  • Jonathan Galati
  • Emily Rachel Lebowitz
  • Stephanie Sutter
  • Bernice Y. Yan
  • Dalee Zhou
  • Olivia H. Wind
Living reference work entry
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Abstract

Photodermatology is a form of photobiology encompassing many interactions between light sources and the skin, from photo-induced or photo-exacerbated cutaneous diseases to light-based dermatologic therapies. This chapter aims to provide an overview of current photodermatologic topics. The first section reviews foundational principles upon which modern photodermatology is built, such as the electromagnetic spectrum, properties of light, and how it interacts with the skin. The majority of this chapter is dedicated to photodermatoses. Lastly, the chapter discusses several therapies such as phototherapy and lasers, which harness powerful light properties in clinical practice.

Keywords

Photobiology Photodermatology Photodermatosis Phototherapy Laser Electromagnetic spectrum X-ray Ultraviolet Visible light Infrared radiation Sunscreen Sun protection factor Chemical filter Physical filter Photodermatologic disorder Photoallergy Photoallergen Photo urticaria Solar urticaria Phytophotodermatitis Polymorphous light eruption Photodrug reaction Phototoxicity Porphyria Vitamin-dependent photobiology Vitamin deficiency Mineral deficiency Phototherapy Light therapy Light amplification by stimulated emission of radiation LASER Hair removal Vascular lesion removal Tattoo removal Skin rejuvenation 

1 Introduction to Photodermatology

Photodermatology is a form of photobiology encompassing many interactions between light sources and the skin. Photodermatology is concerned not only with common sunlight-skin interactions (such as sunburns and vitamin D synthesis) but also with less common photodermatoses. Photodermatoses are a group of conditions distinguished by atypical, adverse cutaneous reactions to light radiation. They may be idiopathic, acquired, genetic, metabolic, allergic, phototoxic, eczematous, acute, or chronic in nature. This chapter discusses these diverse photodermatoses, from clinical and histopathologic manifestations to therapeutic approaches, such that swift symptom relief and future prophylaxis can be provided.

Phototherapy and lasers are highly effective in treating various dermatologic conditions, including psoriasis, vitiligo, tattoo removal, and photoaging. The indications and considerations of these light-based therapies are explored in the final sections.

2 Electromagnetic Spectrum

It is important to acknowledge the diversity of properties that modulate the vast array of photodermatoses, from the biochemistry of the individual’s skin to the physical properties of the light itself. Photodermatology explores the optical interaction between light and the skin. As light interacts with the skin, it may be scattered, reflected, absorbed by chromophores, or dissipated as heat (Anderson and Parrish 1981).

The electromagnetic (EM) spectrum is characterized by waves of light that produce photons of varying energy (Table 1), which are inversely proportional to their wavelength (Fig. 1). The optical properties of the skin (Fig. 2) influence the penetration of each type of radiation.
Table 1

The electromagnetic spectrum

Electromagnetic spectrum

Wavelength (nm)

Characteristics

Clinical applications

Gamma ray

<0.01

Arises from radioactive decay of atomic nuclei

Gamma Knife surgery

X-ray

0.1–10

High-energy photons

Grenz rays are low-energy X-rays absorbed more superficially

Diagnostic X-ray

UVC

200–280

Strongly absorbed by DNA but blocked by ozone and does not reach the surface of the earth

N/A

UVB

280–315

Mostly absorbed in the epidermis. Leads to DNA damage and formation of photoproducts

Broadband and narrowband UVB for atopic dermatitis, psoriasis, and graft-versus-host disease

UVA

UVAII

UVA1

315–400

315–340

340–400

Makes up 95% of UV rays

Mostly absorbed in the dermis. Greater damage to the skin than UVA1

Makes up two-thirds of UVA rays. Mostly absorbed in the dermis

Psoralen plus UVA (PUVA) for atopic dermatitis, psoriasis, lichen planus, graft-versus-host disease, and cutaneous T-cell lymphoma (Tanew et al. 1986; Cislo and Maj 1988; Wiesmann et al. 1999; Shenoi and Prabhu 2014)

Long-wave UVA1 (e.g., for fibrotic skin diseases) (El-Mofty et al. 2004; Shenoi and Prabhu 2014)

Wood’s lamp (365 nm)

Visible

400–760

Waves visible to the human eye, ranging from violet to red

PDT (e.g., for widespread actinic keratoses)

IPL (e.g., for dyschromia)

Near infrared

760–1000

Infrared predominantly from the sun

Near-infrared lasers (e.g., diode)

Far infrared

1000–100,000

Significantly lower energy than near infrared

Far-infrared lasers (e.g., CO2)

Microwave/radio wave

>106,000

Longest wavelength, lowest energy

MRI

Fig. 1

The light equation. (Reproduced with permission)

Fig. 2

Optical properties of the skin. (Reproduced with permission)

2.1 X-Ray

X-rays generate high-energy photons and harm skin tissue via ionization. Grenz rays are low-energy (ultrasoft) X-rays with low penetration and lead to various immune reactions including reduction of Langerhans cells and decrease in inflammatory mediators (Cipollaro 1991, Lindelof et al. 1984, Anderson et al. 1954).

2.2 Ultraviolet

Ultraviolet (UV) rays cause acute and chronic inflammatory skin conditions, including photoaging and skin cancer (Pinnell 2003, Freeman et al. 1989) (Table 1).

UVA is capable of penetrating deeply into the dermis (Krutmann 2001). UVA1 is more common, but UVAII delivers more damage to the skin (Diffey et al. 1987) (Table 1). Chronic UVA1 radiation causes connective tissue degeneration and increases collagenase expression (Breuckmann et al. 2004).

UVB is mostly absorbed in the epidermis (Herrling et al. 2006), which leads to DNA damage, formation of photoproducts that catalyze prostaglandin formation (Kawada 1986), and sunburn/suntan (Gilchrest et al. 1981).

Fitzpatrick skin phototype is a classification of an individual’s tendency to burn or tan after sun exposure (Table 2). Sunburn occurs with immediate erythema in minutes and later desquamation (Willis and Cylus 1977), while suntan leads to biphasic stages of immediate pigment darkening and delayed tanning (Honigsmann et al. 1986) (Table 3).
Table 2

Fitzpatrick skin phototype and sunburn/suntan tendency

Fitzpatrick skin phototype

Sunburn tendency

Suntan tendency

I

Burns easily

Never tan

II

Burns easily

Tans slightly

III

Burns moderately

Tans moderately

IV

Burns minimally

Tans well

V

Rarely burns

Tans profusely

VI

Never burns

Tans profusely

Table 3

Effects of suntan: immediate pigment darkening and delayed tanning

Immediate pigment darkening

Delayed tanning

Due to UVA-induced oxidative damage, redistribution of melanin

Occurs over minutes to days after exposure

Due to newly synthesized melanin in response to UVB

Occurs 3–4 days after exposure, maximal at 7 days

2.3 Visible Light

“Visible light” describes wavelengths visible to the human eye and encompasses colors ranging from violet to red. The clinical applications of visible light include photodynamic therapy (PDT) (Charlesworth and Truscott 1993) and intense pulsed light (IPL) (Table 1).

2.4 Infrared Radiation

Infrared radiation (IR) is invisible to the human eye and commonly divided into the near- and far-infrared wavebands (Table 1). Clinical applications of IR include uses of infrared lasers for photorejuvenation (Omi and Numano 2014).

3 Sunscreen

3.1 Sun Protection Factor

Exposure to UV radiation (UVR) is associated with photoaging, cutaneous malignancies, and immunosuppression (Bens 2014). Figure 3 provides an overview of UVA and UVB effects. The American Academy of Dermatology recommends daily use of water-resistant, broad-spectrum sunscreen with a sun protection factor (SPF) of 30 or higher.
Fig. 3

Summary of different effects of UV radiation. (Courtesy of Dr. Guido Bens, Dermatology Department, Orleans Regional Hospital, Orleans, France)

Fig. 4

Mechanism of UV filter excitation and relaxation after UV photon absorption. (Courtesy of Dr. Guido Bens, Dermatology Department, Orleans Regional Hospital, Orleans, France)

SPF is defined using the minimal erythemal dose (MED), the minimal dose of a single UVR exposure that produces erythema within 24 hours (Bens 2014). SPF is the ratio of the MED of the protected to unprotected skin when sunscreen is applied at a dose of 2 mg/cm2 of the skin (Sambandan and Ratner 2011). SPF does not address UVA protection, which is associated with tanning. There is currently no universal technique to measure UVA protection (Bens 2014). In the United States, a “broad-spectrum” sunscreen must have UVA protection with a minimum wavelength of 370 nm (Mancuso et al. 2017).

3.2 Chemical and Physical Filter

Table 4 provides an overview of chemical filters and physical filters. Most sunscreens are composed of both types, allowing for broader protection, greater photostability, and increased SPF. Table 5 highlights the FDA-approved chemically active sunscreen ingredients in the United States.
Table 4

Overview of chemical and physical filters

Type

Mechanism of action

Examples

Comments

Chemical (or organic) filters

Absorb high-energy photons and dissipate energy as heat or light at a longer wavelength (Cohen and Grant 2016) (Fig. 4)

Derivatives of anthranilates, benzophenones, camphors, cinnamates, dibenzoylmethanes, p-aminobenzoates, and salicylates (Gasparro et al. 1998)

Liquid or solid form (Mancuso et al. 2017)

Photodegradation can occur, leading to photoallergies, particularly to PABA derivatives, cinnamates, and benzophenones (Bens 2014)

Systemic absorption with topical application can occur (Bens 2014; Maier and Korting 2005)

Physical (or inorganic) filters

Minimal absorption of UV photons and reflect/scatter light (Sambandan and Ratner 2011)

Titanium dioxide and zinc oxide

Comedogenic

Iron oxide may be added to increase UVA coverage and to offset white pasty appearance (Bens 2014; Moloney et al. 2002)

Micronization for cosmesis leads to increased UVB and decreased UVA protection by titanium oxide, but does not impact zinc oxide efficacy (Mancuso et al. 2017)

Not approved in spray form given the concern for lung toxicity (Cohen and Grant 2016; Bens 2014)

Preferred in children and “sunscreen-allergic” individuals (Sambandan and Ratner 2011)

Table 5

FDA-approved organic active sunscreen ingredients in the United States

Group name

Ingredient name

Maximum approved concentration (%)

Comments

UVB only filters

PABA derivatives

Aminobenzoic acid (PABA)

15.0

Binds keratinocytes, conferring water resistance. Increased skin staining. Contact allergies reported (Sambandan and Ratner 2011)

Padimate O

8.0

Good safety profile, less skin staining (Sambandan and Ratner 2011). Often causes contact allergies and severe photodegradation with oxybenzone, thus rarely used (Mancuso et al. 2017)

Cinnamates

Octyl methoxycinnamate

7.5

Most popular group of UVB filters. No skin staining. Rare irritation. Some photodegradation and reduced water resistance, requiring frequent reapplication. Mixed with other filters to increase SPF (Sambandan and Ratner 2011). Cannot combine octyl methoxycinnamate with avobenzone due to destabilization (Mancuso et al. 2017)

Cinoxate

3.0

Salicylates

Homosalate

15.0

Good safety profile. Homosalate and octyl salicylate are photostable and prevent photodegradation of other ingredients (Sambandan and Ratner 2011)

Octyl salicylate

5.0

Trolamine salicylate

12.0

Trolamine salicylate has both analgesia and a good safety profile (Bens 2014)

 

Phenylbenzimidazole sulfonic acid

4.0

Hydrophilic, photostable, and prevents photodegradation of other filters (Mancuso et al. 2017, Bens 2014)

 

Octocrylene

10.0

Added to benzophenones, avobenzone, or cinnamates to increase photostability (Bens 2014, Sambandan and Ratner 2011) Combined with other ingredients to increase water resistance (Moloney et al. 2002)

UVA only filters

Dibenzoylmethane

Avobenzone

3.0

UVA1 (340–400 nm) filter. Poor photostability and thus must combine with other filters (Bens 2014). May cause other ingredients to photodegrade (Sambandan and Ratner 2011)

Anthranilates

Menthyl anthranilate

5.0

Used to enhance UVAII (315–345 nm) protection (Sambandan and Ratner 2011)

UVA–UVB filters

Benzophenones

Oxybenzone

6.0

Most common ingredient to cause photoallergy (Mancuso et al. 2017). Photolabile (Bens 2014, Sambandan and Ratner 2011); combined with other ingredients to improve SPF (Moloney et al. 2002).

 

Sulisobenzone

10.0

Photostable but photoallergic (Bens 2014)

4 Photodermatologic Disorder

4.1 Photoallergy

  • Definition: Photoallergy is a rare drug-induced photosensitivity disorder in which contact with a photoallergen and UVR results in a type IV hypersensitivity reaction, causing a pruritic eczematous eruption. A photoallergen is an exogenous agent that gains antigenicity by binding to a carrier protein when exposed to UVR, typically UVA (Kutlubay et al. 2014) (Table 6).

  • Clinical feature: Patients manifest with severely pruritic, poorly demarcated erythema with vesicles, blisters, scaling, oozing, weeping, and/or crusting in a photo-distributed manner (Onoue et al. 2017) (Figs. 5 and 6). Symptoms typically start within 24 hours to several days after exposure to photoallergen and UVR in a sensitized individual (Kutlubay et al. 2014).

  • Pathological manifestation: Epidermal histopathology includes spongiosis and vesiculation. The dermis has vascular dilatation, lymphohistiocytic infiltration, variable eosinophils (Glatz and Hofbauer 2012), and occasionally papillary edema (Wilm and Berneburg 2015). Dermal thickening and hyperkeratosis often characterize chronic lesions (Glatz and Hofbauer 2012, Lehmann and Schwarz 2011).

  • Prognosis and treatment: Most photoallergies eventually resolve with removal of the offending photoallergen. Rarely, persistent photosensitivity may develop (Wilm and Berneburg 2015, Gould et al. 1995). Photoallergens are identified with photopatch testing (Fig. 7, Table 7). Treatment consists of sun protection, topical corticosteroids, and antihistamines. In severe cases, oral corticosteroids can be used (Wilm and Berneburg 2015).

  • Differential diagnosis: Allergic contact dermatitis, phototoxicity, and polymorphous light eruptions (PMLE).

Table 6

List of common photoallergens (Onoue et al. 2017; Wilm and Berneburg 2015)

Topical agents

Systemic agents

Sunscreens

Antibiotics

Para-aminobenzoic acid (PABA)

Quinolones

Benzophenone-3

 

Benzoyl methane

Antiarrhythmics

Cinnamic acid ester

Quinidine

Fragrances

Antimalarials

6-Methylcoumarin

Quinine

Musk ambrette

 

Fragrance mix

Antifungals

 

Griseofulvin

Antimicrobial agents

 

Bithionol

Phenothiazines

Chlorhexidine

Chlorpromazine

Fenticlor

Promethazine

Hexachlorophene

 
 

Nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs

Ketoprofen

Diclofenac

Piroxicam

Ketoprofen

 
Fig. 5

Photoallergic dermatitis: eczematous eruption with signs of lichenification in sun-exposed areas. (Reproduced from Lehmann and Schwarz 2011; with permission)

Fig. 6

A patient with photoallergy to butyl methoxydibenzoylmethane: distribution of eczematous reaction showing relative sparing of non-sun-exposed areas, such as areas under the chin, nose, and lower lip. (Reproduced from Kerr and Ferguson 2010; with permission)

Fig. 7

Photopatch test with duplicate sets of photoallergen patches placed on the back: left side of the back showing covered patches that are not UV-exposed and right side showing patches that are UV-exposed. (Reproduced from Wilm and Berneburg 2015; with permission)

Table 7

Common allergens tested in photopatch tests (Wilm and Berneburg 2015; Goncalo et al. 2013; Bruynzeel et al. 2004)

Sunscreens

Concentration used

Petrolatum (control)

Benzophenone-3

10%

Benzophenone-4

2%

Butyl methoxydibenzoylmethane

10%

4-Methylbenzylidene camphor

10%

Ethylhexyl methoxycinnamate

10%

Isoamyl-p-methoxycinnamate

10%

Methylene bis-benzotriazolyl tetramethylbutylphenol

10%

PABA

10%

Nonsteroidal anti-inflammatory drugs

 

Ketoprofen

1%

Etofenamate

2%

Piroxicam

1%

Benzydamine

2%

4.2 Photo Urticaria (Solar Urticaria)

  • Definition: Solar urticaria, also known as photo urticaria, is a rare IgE-mediated photodermatosis against an endogenous photoallergen after sunlight exposure. The pathophysiology is not fully elucidated. In type I, IgE antibodies are produced against a photoallergen that arises after exposure to a patient-specific wavelength of light (Botto and Warshaw 2008) (Fig. 8). In type II, IgE autoantibodies are produced against normal chromophores (Lugovic Mihic et al. 2008). Medications including oral contraception, tetracycline, coal tar, repirinast, chlorpromazine, and benoxaprofen (Botto and Warshaw 2008, Horio 2003) and optical whiteners (Gardeazabal et al. 1998) are among the most offending cases.

  • Clinical feature: It is characterized by pruritic and burning erythematous wheals (Figs. 9 and 10), usually distributed over the upper chest, arms, and legs, and typically arises minutes after light exposure and subsides after a few hours (Goetze and Elsner 2015, Botto and Warshaw 2008). Systemic effects include wheezing, dyspnea, and anaphylaxis. Mucosal involvement with angioedema is rare (Botto and Warshaw 2008).

  • Pathological manifestation: Its pathological view is not specific.

  • Prognosis and treatment: Phototesting (Fig. 11) is used to determine the patient-specific action spectrum and the minimal urticarial dose. Sun protection (protective clothing, sunscreen) is recommended (Goetze and Elsner 2015). Treatment includes antihistamines, phototherapy, PUVA, plasmapheresis, IVIG, immunosuppressants, and leukotriene receptor antagonists (Goetze and Elsner 2015, Botto and Warshaw 2008). Approximately 25% of patients experience complete resolution within 10 years (Goetze and Elsner 2015), though most cases are chronic (Lugovic Mihic et al. 2008).

  • Differential diagnosis: PMLE, actinic prurigo, chronic actinic dermatitis, erythropoietic protoporphyria, hydroa vacciniforme, juvenile spring eruption, systemic lupus erythematosus, and porphyria cutanea tarda (Botto and Warshaw 2008).
    Fig. 8

    Pathophysiology of solar urticaria. (Courtesy of Dr. Steven Goetze, Dermatology Department, Jena University Hospital, Jena, Germany)

    Fig. 9

    Solar urticaria on the back. (Taken by Dr. Reagan Hunt, Department of Dermatology and Pediatrics, Texas Children’s Hospital, Texas, USA)

    Fig. 10

    Fixed solar urticaria occurring below the right back shoulder. (Taken by Dr. Steven Goetze, Dermatology Department, Jena University Hospital, Jena, Germany)

    Fig. 11

    Phototesting with visible light and UVB, respectively. (Taken by Dr. Hirsh Komarow, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, Maryland, USA)

4.3 Phytophotodermatitis

  • Definition: Phytophotodermatitis is a phototoxic reaction that occurs when the skin is exposed to furocoumarins and UVA (Bolognia et al. 2012, James et al. 2011). It is commonly affecting all ages and races (Wolff et al. 2013). It is exacerbated by heat and wet skin. Affected areas may be hypersensitive to UV radiation (Bolognia et al. 2012). Furocoumarins are in many plants notably limes (Anderson 2012, Bolognia et al. 2012; James et al. 2011). They enter the skin and become excited by UVA (320–400 nm), forming free radicals (Darby-Stewart et al. 2006), pyrimidine dimers, and DNA cross-links which cause erythema, edema, vesicles, and bullae (Anderson 2012; Bolognia et al. 2012; Darby-Stewart et al. 2006). Pyrimidine dimers and DNA cross-linking interrupt DNA synthesis (Anderson 2012), increase melanocyte mitosis, dendricity, hypertrophy, tyrosinase activity; and change melanosome size and distribution leading to hyperpigmentation (Bolognia et al. 2012).

  • Clinical feature: Linear erythema and edema develop acutely; vesicles and bullae are seen in severe cases (Figs. 11, 12, 13, 14, 15, and 16). Post-inflammatory hyperpigmentation develops later, takes years to resolve, and appears as linear, “dripping,” or hands/fingers (Raam et al. 2016; Bolognia et al. 2012; James et al. 2011) (Figs. 17 and 18).

  • Pathological manifestation: Acutely, “sunburn cells” appear in the epidermis (Fig. 19), and there are lymphocytic infiltrates and edema in the dermis (Patterson 2013; Anderson 2012; Bolognia et al. 2012; Elder et al. 2009; Maso et al. 1991) (Fig. 20). Later biopsies resemble post-inflammatory hyperpigmentation (Fig. 21).

  • Prognosis and treatment: Phytophotodermatitis resolves with cold compresses and NSAIDs (Raam et al. 2016, Marcos and Kahler 2015). Severe cases require burn unit admission (Raam et al. 2016).

  • Differential diagnosis: Chemical burns, child abuse, contact dermatitis, infectious lymphangitis, and type IV hypersensitivity reaction.
    Fig. 12

    Phytophotodermatitis: a 26-year-old female who developed an erythematous rash from squeezing limes. (Reproduced from Marcos and Kahler 2015; with permission)

    Fig. 13

    Phytophotodermatitis: linear bullae formation. (Reproduced from Bolognia et al. 2012; with permission)

    Fig. 14

    Phytophotodermatitis: erythematous lesions appeared after sunbathing in a meadow. (Reproduced from Wolff et al. 2013; with permission)

    Fig. 15

    Phytophotodermatitis: extreme bilateral bullous reaction after the patient had been gathering plants in bright sunlight. (Reproduced from Gawkrodger and Ardern-Jones 2017; with permission)

    Fig. 16

    Phytophotodermatitis: linear patterns of erythema and hyperpigmentation with blistering after using lime juice to rinse her hair and subsequent sun exposure. (Reproduced from Paller and Mancini 2016; with permission)

    Fig. 17

    Linear post-inflammatory hyperpigmentation due to phytophotodermatitis. (Reproduced from Bolognia et al. 2012; with permission)

    Fig. 18

    A child with hyperpigmentation in hand/finger patterns due to phytophotodermatitis. (Reproduced from Zitelli et al. 2012; with permission)

    Fig. 19

    Necrotic keratinocytes (“sunburn cells”) present in the epidermis consistent with phytophotodermatitis (H&E staining). (Reproduced from Patterson 2016; with permission)

    Fig. 20

    Presence of epidermal necrosis and intraepidermal bulla formation consistent with phytophotodermatitis (H&E staining). (Reproduced from Patterson 2013; with permission)

    Fig. 21

    Increased number of melanophages in the papillary dermis consistent with post-inflammatory hyperpigmentation (H&E staining). (Reproduced from Elder et al. 2009; with permission)

4.4 Polymorphous Light Eruption (PMLE)

  • Definition: PMLE is an intermittent, non-scarring, pruritic rash that appears minutes to days after exposure to UVR, typically from sunlight. It is the most common photodermatosis and usually resolves over several days (Honigsmann 2008). It shows genetic susceptibility and female predominance. It typically appears in the second and third decades of life. Phototesting can be used for diagnosis.

  • Clinical feature: Most commonly, PMLE manifest pruritic, grouped, erythematous papules which may coalesce into plaques (Fig. 22). Papulovesicles, bullae, (facial) edema, insect bite-like (strophulus), and erythema multiforme-like are other features. Pinpoint papular subtype is most common in African and Asian descent. “Juvenile spring eruption” variant appears as vesicles on ear helices, predominantly in young boys. Rare variant is localized to elbows. Rarely, the only symptom is erythema or pruritus. Systemic symptoms are rare. The lesions are symmetric and limited to only sun-exposed skin. Within an individual, lesions are monomorphic and recur in same sites (Honigsmann 2008).

  • Pathological manifestation: It shows nonspecific, variable histology and often resembles delayed hypersensitivity reactions. Papular PMLE (most common variant) shows focal spongiosis of the epidermis and lymphohistiocytic dermal infiltrate (Honigsmann 2008) (Fig. 23).

  • Prognosis and treatment: Eruptions are usually most severe at the start of summer, often becoming milder with repeated sun exposure. This sort of light tolerance (a.k.a. “hardening”) is due to UV-induced immunosuppression. Lesions persist days to weeks after UV exposure and typically resolve without scarring. For mild cases, only avoidance from sun exposure is suggested. For moderate and severe cases, topical and systemic corticosteroids are prescribed. Phototherapy with narrowband UVB or psoralen photochemotherapy (PUVA), azathioprine, and cyclosporine are other treatments (Honigsmann 2008).

  • Differential diagnosis: Lupus erythematosus, photoallergy, photo-aggravated dermatoses (atopic or seborrheic dermatitis), solar urticarial, pruritus simplex, photosensitive erythema multiforme, erythropoietic protoporphyria, and acute eczema.
    Fig. 22

    Papular PMLE on the V-shaped area of the chest. (Taken by Dr. Jonathan Hale Zippin, Department of Dermatology, Weill Cornell Medical College, New York, NY, USA)

    Fig. 23

    Histopathology of PMLE displaying typical perivascular lymphocytic inflammation and marked papillary dermal edema (H&E staining). (Courtesy of Dr. Cynthia Magro)

    Fig. 24

    Acute phototoxic reaction from doxycycline, sparing the sunshade areas. (Reproduced from Monteiro et al. 2016; with permission)

4.5 Photodrug Reaction

  • Definition: Phototoxicity occurs when a medication (oral or topical) causes an adverse reaction in the UV-exposed skin (Tables 8 and 9). Prior sensitization to the offending agent is not required, and reactions can occur within minutes of initial sun exposure.

  • Clinical feature: Sun-exposed areas are affected (e.g., face, anterior chest, dorsal arms), while the clothing-protected skin is spared. Most phototoxic eruptions manifest as a severe sunburn. Different types of photodrug reactions have been summarized in Table 10.

  • Pathological manifestation: Epidermal necrosis, dermal edema, and neutrophilic infiltrates are consistent with severe sunburn (Drucker and Rosen 2011) (Fig. 26). In hyperpigmentation, there may be dermal deposits of amiodarone, lipofuscin, reduced silver, etc. (Jaworski et al. 2014). In pseudoporphyria, there is subepidermal separation at the lamina lucida, similar to porphyria cutanea tarda (PCT) (Kutlubay et al. 2014).

  • Prognosis and treatment: Usually symptoms resolve once the drug is discontinued, but drug remnants/metabolites can remain in the skin up to months after drug cessation. Hyperpigmentation or lichenoid photodermatitis may take months to resolve (Gould et al. 1995). Drug cessation, sun protection, topical corticosteroids, and antihistamines are the therapeutic options.

  • Differential diagnosis: Allergic contact dermatitis, irritant contact dermatitis, solar urticaria, and photoallergy.
    Table 8

    Topical agents offending phototoxicity

    Sunscreens

    Benzophenones

    Para-aminobenzoic acid (PABA)

    Cinnamates

    Salicylates

    Fragrances

    Musk

    6-Methylcoumarin

    Photodynamic therapy (PDT)

    Photofrin

    Porphyrins

    Miscellaneous

    5-Fluorouracil (oral and topical)

    Psoralens

    Benzoyl peroxide

    Coal tar

    Tretinoin

    Table 9

    Oral agents offending phototoxicity

    Antibiotics

    Fluoroquinolones (e.g., ciprofloxacin)

    Tetracyclines (e.g., doxycycline)

    Antimalarials

    Quinine

    Quinidine

    Hydroxychloroquine

    Neuroleptics (anticonvulsants)

    Phenothiazines (e.g., chlorpromazine, fluphenazine)

    Thioxanthenes (e.g., chlorprothixene)

    Nonsteroidal anti-inflammatory drugs (NSAIDs)

    Ibuprofen

    Naproxen

    Ketoprofen

    Celecoxib

    Targeted therapies

    Vemurafenib

    Dabrafenib

    Imatinib

    Vandetanib

    Sulfur-containing medications

    Bumetanide

    Furosemide

    Hydrochlorothiazide

    Sulfonamides

    Sulfonylureas (glipizide, glyburide)

    Miscellaneous

    Amiodarone

    Diltiazem

    Retinoids

    Psoralens

    Fig. 25

    A 53-year-old patient on 2 weeks of voriconazole treatment developing tense bullae containing clear fluid on the dorsa of the hands. (Reproduced from Sharp and Horn 2005; with permission)

    Table 10

    Different types of photodrug reactions

    Types of photodrug reactions

    Clinical manifestation

    Most common offending agents

    Exaggerated sunburn

    Mild pricking sensation, pruritus, or severe sunburn with blisters, vesicles, and edema (Zuba et al. 2016)

    Tetracyclines and fluoroquinolones (de Guidi et al. 2011)

    Hyperpigmentation

    Blue-gray pigmentation (Eichenfield and Cohen 2016) and golden-brown pigmentation (Jaworski et al. 2014)

    Amiodarone, chlorpromazine, desipramine, and silver

    Pseudoporphyria

    Fragile, blistered, easily bruised skin of porphyria cutanea tarda (PCT) (Beer et al. 2014)

    Naproxen (Maerker et al. 2001) (Figs. 24 and 25)

    Photo-onycholysis

    Painful separation of the distal nail plate from the nail bed

    Tetracyclines (Badri et al. 2004; Lasser and Steiner 1978), fluoroquinolone, psoralen (Baran and Juhlin 1987), and atypical antipsychotic use (Gregoriou et al. 2008)

    Telangiectatic reactions

    Red, thread-like skin patterns due to vascular dilations

    Nifedipine, amlodipine (Bakkour et al. 2013), and cefotaxime (Borgia et al. 2000)

    Fig. 26

    Photodrug reaction: pauci-inflammatory subepidermal separation with festooning of dermal papillae (H&E staining, X100). (Reproduced from Sharp and Horn 2005; with permission)

4.6 Photosensitive Porphyria

  • Definition: Porphyrias result from enzymatic defects in the heme biosynthesis pathway, leading to the accumulation of porphyrins or other heme precursors (Bickers and Frank 2012). Disease may be inherited or acquired (Wolff et al. 2013), with inherited forms presenting more often in childhood (Ramanujam and Anderson 2015). Porphyria cutanea tarda (PCT), the most common porphyria, is linked to alcohol abuse, exogenous estrogen use, and hepatitis C (Horner et al. 2013). The subtypes of porphyrias with cutaneous manifestations are summarized in Table 11.

  • Clinical feature: Photosensitive porphyrias are characterized by blistering, bullae, and fragility of the sun-exposed skin (Figs. 27, 28, 29, 30, 31, and 32) (Grossman et al. 1979). Erosions (Fig. 33) and petechiae (Fig. 34) may also be seen (Holme et al. 2006). In severe cases, “sclerodermoid” scarring (Bickers and Frank 2012) and tissue necrosis may occur (Fritsch et al. 1997).

  • Pathological manifestation: Biopsy of a blister (Fig. 35) reveals subepidermal vesiculation, dermal papillae projecting into the blister cavity, and minimal inflammatory cells (Horner et al. 2013). Elongated eosinophilic bodies known as “caterpillar bodies” can be found in the epidermis (Elder 2003).

  • Prognosis and treatment: Porphyrias are not easily cured, but most cases can be well managed (Table 11). Sun protection is of paramount importance, and vitamin D supplementation may be required (Bickers and Frank 2012).

  • Differential diagnosis: Phototoxic drug eruption, PMLE, pseudoporphyria, and epidermolysis bullosa.
    Table 11

    Photosensitive porphyrias

    Type of porphyria

    Enzymatic mutation

    Clinical presentation

    Management

    Porphyria cutanea tarda

    Uroporphyrinogen decarboxylasea

    Blistering of sun-exposed skin, scarring, erosions, facial hypertrichosis, and hepatomegaly

    Phlebotomy and low-dose hydroxychloroquine

    Congenital erythropoietic porphyria

    Uroporphyrinogen III synthase

    Bullae of sun-exposed skin, severe scarring, skin infection, erythrodontia, scleritis, and bone resorption

    Vitamin D supplementation, sun protection, and allogeneic bone marrow transplantation

    Hepatoerythropoietic porphyria

    Uroporphyrinogen decarboxylaseb

    Bullae, severe photosensitivity, hypertrichosis, and sclerodermoid scarring

    Vitamin D supplementation and sun protection

    Variegate porphyria

    Protoporphyrinogen oxidase

    Bullae and erosive lesions on sun-exposed skin ± neurovisceral attacks

    Sun protection and glucose and intravenous hemin for acute attacks

    Erythropoietic protoporphyria

    Ferrochelatase

    Pruritus and burning pain following sun exposure, erosions, petechiae, linear scarring of sun-exposed skin, and cholelithiasis

    Oral beta-carotene and afamelanotide

    X-linked protoporphyria

    Delta-aminolevulinic acid synthasec

    Pruritus, swelling, and pain upon sun exposure and cholelithiasis

    Oral beta-carotene and afamelanotide

    Hereditary coproporphyria

    Mitochondrial enzyme coproporphyrinogen oxidase

    Neurovisceral attacks ± blistering of sun-exposed skin

    Glucose and intravenous hemin for acute attacks

    aPartial enzymatic deficiency

    bComplete enzymatic deficiency

    cGain of function mutation

    Fig. 27

    Porphyria cutanea tarda in a patient with a history of alcohol use and hepatitis C. (Courtesy of Dr. Richard P. Usatine, Department of Family and Community Medicine, University of Texas Health Science Center, San Antonio, Texas)

    Fig. 28

    Erosions, plaques, and a bulla on the hands of a patient with porphyria cutanea tarda. (Reproduced from Horner et al. 2013, Copyright John Wiley and Sons; with permission)

    Fig. 29

    Erythrodontia in a child with congenital erythropoietic porphyria. (Reproduced from Paller and Mancini 2016; with permission)

    Fig. 30

    Vesicles and crusting on the face of a child with congenital erythropoietic porphyria. (Reproduced from Paller and Mancini 2016; with permission)

    Fig. 31

    Blisters on the hand of a patient with variegate porphyria. (Reproduced from Hift et al. 2012, Copyright BMJ Publishing Group Ltd.; with permission)

    Fig. 32

    Variegate porphyria: cutaneous photodamage on the dorsa of the feet. (Reproduced from Holland et al. 2017; with permission)

    Fig. 33

    Erosive lesion on the ear of a child with erythropoietic protoporphyria. (Reproduced from Horner et al. 2013, Copyright John Wiley and Sons; with permission)

    Fig. 34

    Petechiae in a child with erythropoietic protoporphyria. (Reproduced from Burgin et al. 2017; with permission)

    Fig. 35

    Porphyria cutanea tarda: a subepidermal bulla (H&E stain). (Reproduced from Handler et al. 2017, Copyright John Wiley and Sons; with permission)

    Fig. 36

    Vitamin A deficiency: hyperkeratotic papules with central keratinous plug on the elbow. (Reproduced from Bleasel et al. 1999; with permission)

    Fig. 37

    Vitamin B3 deficiency: “Casal’s necklace” and dorsal hand involvement. (Reproduced from Oldham and Ivkovic 2012; courtesy of Dr. Richard Johnson, Department of Dermatology, Massachusetts General Hospital, Boston, MA, USA)

5 Vitamin- and Mineral-Dependent Photobiology

5.1 Vitamin and Mineral Deficiency and Cutaneous Disease

  • Definition: Vitamin and mineral deficiencies are a prominent global health issue in regions with malnutrition and limited food access (Bailey et al. 2015). While rare in industrialized countries due to improved nutritional access and vitamin-enriched foods, these deficiencies remain relevant in certain populations, such as those with disordered absorption (Moynahan 1974), bowel surgery (Wechsler 1979), anorexia (Karthikeyan and Thappa 2002), reclusiveness (Hirschmann and Raugi 1999), alcoholism (Powers 2003), or certain medication use (Ghavanini and Kimpinski 2014).

  • Clinical feature: Clinical presentation depends on the vitamin deficiency in question (Table 12). Multiple deficiencies may be present concurrently depending on the etiology (Ragunatha et al. 2011). Non-cutaneous manifestations are associated with specific vitamin deficiencies. Vitamin deficiency can lead to photosensitivity.

  • Pathological manifestation: Pathologic samples are often nonspecific and unnecessary for diagnosis, and skin biopsy results depend on cutaneous presentation.

  • Prognosis and treatment: Prompt replenishment of any vitamin deficiency often leads to rapid symptom resolution, with no sequelae. While diet-based deficiency may be addressed with supplements and improved nutrition, those with medical conditions susceptible to vitamin deficiency may require parenteral or extended supplementation (Perafán-Riveros et al. 2002). Acute cutaneous symptoms usually resolve within weeks (Karthikeyan and Thappa 2002), but hyperpigmentation may persist (Hirschmann and Raugi 1999).

  • Differential diagnosis: Malnutrition, malabsorption, hereditary disorders, bleeding disorders, and vasculitis.
    Table 12

    Vitamin and mineral deficiencies and cutaneous presentations

    Vitamin

    Availability

    Metabolic role

    Cutaneous manifestations

    Other clinical features

    Vitamin A (retinol)

    Liver, cod liver oil, eggs, and dark leafy vegetables

    Vision, immunity, epidermal thickness, glycosaminoglycan synthesis, and collagen production (Kafi et al. 2007; Schiltz et al. 1986; Semba 1994; Wolf 1978; Lassen 1930)

    Dryness, pruritus, hyperkeratotic papules, and plaques with a keratin plug (phrynoderma) most commonly on extensor surfaces of arms (Fig. 36), knees, thighs, and buttocks (Ragunatha et al. 2011; Bleasel et al. 1999; Loewenthal 1933)

    Night blindness and xerophthalmia (Ragunatha et al. 2011)

    Vitamin B2 (riboflavin)

    Diary and meat

    Fatty acid oxidation, red blood cell production, skeletal and gastrointestinal development, and neuroprotection (Powers 2003)

    Dermatitis (scrotum, labia, nasolabial, or intertriginous folds), angular stomatitis, cheilosis, or glossitis (Roe 1991)

    Anemia and peripheral neuropathy (Galimberti and Mesinkovska 2016)

    Vitamin B3 (niacin)

    Meat, eggs, milk, beans, enriched flour, cereals, and rice

    Precursor to coenzymes NAD and NADP; essential to carbohydrate, fatty acid, and protein synthesis and metabolism (Karthikeyan and Thappa 2002)

    Symmetric, photosensitive, hyperpigmented, hyperkeratotic, sharply demarcated dermatitis predominantly on sun-exposed areas, such as the neck and dorsal hands (Fig. 37) (Oldham and Ivkovic 2012; Ashourian and Mousdicas 2006; Heath and Sidbury 2006). May develop into edema, vesicles, and bullae (Karthikeyan and Thappa 2002)

    “Pellagra” triad: dermatitis, diarrhea, and dementia. Fatal if untreated (Oldham and Ivkovic 2012)

    Vitamin B6 (pyridoxine)

    Fish, potatoes, fruits, and fortified cereals

    Enzymatic cofactor in tryptophan metabolism and niacin synthesis (Barthelemy et al. 1986)

    Perioral seborrheic dermatitis, generalized xerosis, eczema, glossitis, and intertriginous erosions (Barthelemy et al. 1986)

    Hypochromic and microcytic anemia, peripheral neuropathy, immune suppression (Galimberti and Mesinkovska 2016)

    Vitamin C

    Citrus, green vegetables, and tomatoes

    Amino acid synthesis, metallic enzymatic reactions, and collagen formation (Chambial et al. 2013)

    Follicular hyperkeratosis, fragmented “corkscrew” (coiled) or “swan-neck” (bent) hair and perifollicular hemorrhages (Fig. 38) mostly on the thighs, forearms, and abdomen (Fossitt and Kowalski 2014). Bleeding into skin, gums (may become necrotic) and nails

    Petechiae and ecchymoses (Fig. 39); “woody edema” (purplish discoloration, pain, limited motion in legs) (Reuler et al. 1985)

    Poor wound healing, dehiscence of previous wounds, ulcer formation (Crandon et al. 1940), fatigue, irritability, and joint pain (Smith et al. 2011)

    Zinc

    Meat, seafood, egg yolk, and legumes

    Wound repair, growth, immunity, and reproduction (Shankar and Prasad 1998; Prasad and Oberleas 1973)

    Erythematous ulcerations and scaly plaques in perioral, acral, and perianal regions (Figs. 40 and 41) (Nistor et al. 2016;Perafán-Riveros et al. 2002; Kay and Tasman-Jones 1975)

    Alopecia and diarrhea (Galimberti and Mesinkovska 2016)

    Fig. 38

    Perifollicular hemorrhages in vitamin C deficiency. (Taken from Hirschmann and Raugi 1999; with permission)

6 Phototherapy (Light Therapy)

Phototherapy, or light therapy, denotes the use of UV radiation to treat diseases. It is safe, effective, and commonly used to treat dermatoses, including psoriasis, atopic dermatitis, vitiligo, actinic keratosis, and cutaneous T cell lymphoma (Jarrett and Scragg 2017).

Phototherapy encompasses broadband UVB (BB-UVB), narrowband UVB (NB-UVB), excimer laser, UVA1, UVA2, psoralen plus UVA (PUVA), extracorporeal photochemotherapy, UVA and UVB (UVAB), blue and red light, and photodynamic therapy. Table 13 outlines the distinct features and clinical applications for each modality. Dosing and frequency are tailored to each patient based on age, Fitzpatrick skin type, and disease severity. Prior to treatment, patients are assessed for minimal erythema dose (MED); initial dosing is generally 50–70% of the MED and increased as tolerated on subsequent visits (Honigsmann and Schwarz 2012).
Table 13

Phototherapy use in dermatology

Modality (nm)

Mechanism

Dermatologic indications

Adverse effects

Comments

UVA

UVA1 (340–400)

UVA2 (320–340)

Anti-fibroblastic and anti-T-lymphocytic activity.

Long wavelengths enable deep dermal penetration to reach fibroblasts, endothelial cells, and dendritic cells (Abeck et al. 2000). UVA1 irradiation promotes T-cell apoptosis (Weichenthal and Schwarz 2005) and may decrease dermal Langerhans and mast cells. UVA1 decreases fibroblast proliferation and downregulates collagen gene expression (Hayashi et al. 2012)

Fibrotic disorders (Morison et al. 1978) and acute flares (Patrizi et al. 2015) of atopic dermatitis (Rodenbeck et al. 2016), localized scleroderma (Lim et al. 2015), systemic lupus erythematosus, cutaneous T-cell lymphoma, cutaneous mastocytosis, and pruritus

Erythema

UVA1 decreases erythemogenic and carcinogenic effects of UVA2

Psoralen plus UVA (PUVA)

Photochemical reaction between psoralen plus UVA (Fig. 42).

Phototoxic psoralens (e.g., 8-methoxypsoralen (8-MOP) or 5-methoxypsoralen (5-MOP)) are administered topically or orally 30 minutes to 2 hours before UVA exposure (Morison et al. 1993). Psoralens sensitize cells to UVA by intercalating between DNA base pairs, absorbing photons, forming cross-links, and preventing DNA synthesis (Honigsmann and Schwarz 2012). Photochemotherapy promotes reactive oxygen species formation, which damage cell membranes and antigen-presenting cells

Induces re-pigmentation: Stimulates melanin production, melanocyte proliferation, and migration

Psoriasis (Fig. 43): requires fewer treatments to achieve psoriasis clearance and leads to longer remission as compared to UVB and other phototherapies (Yones et al. 2007)

Vitiligo: PUVA has been largely replaced by NB-UVB due to skin cancer risk

Others: cutaneous T-cell lymphoma, dermatitis, and lichen planus

Erythema, pruritus

Skin cancer:

high cumulative exposure to PUVA (Stern and Lunder 1998) increases the risk of non-melanoma (particularly SCC) (Habif 2016) and melanoma skin cancers (Lindelöf et al. 1991)

Gastrointestinal:

8-MOP ingestion is associated with nausea and vomiting; 5-MOP can be offered as an alternative

Ocular:

photokeratitis and cataracts can be prevented with eye protection during and after treatment (Backman 1982)

Contraindicated during lactation and for individuals with xeroderma pigmentosum, albinism, porphyria, blistering disease, and systemic lupus erythematosus

With the advent of biologics, PUVA use has significantly diminished

Extracorporeal photochemotherapy (photopheresis)

Mechanism of action is not fully elucidated. It induces immunologic tolerance via regulatory T cells, and promotes apoptosis of activated T lymphocytes (Heshmati 2003).

Involves passage of blood from the arm vein through an ECP unit (Honigsmann and Schwarz 2012). Blood is separated, and the red blood cell fraction is returned to the patient. In the ECP device, 8-MOP is added to the leukocyte-rich buffy coat, followed by UVA irradiation, and reinfused into the patient

Cutaneous T-cell lymphoma and chronic cutaneous graft-versus-host disease

Nausea, hypotension, tachycardia, and gain of fluid volume

Contraindicated in congestive heart failure

UVB

BB-UVB (280–320)

NB-UVB (311–313)

Endogenous chromophores, such as nuclear DNA, absorb UVB and form pyrimidine dimers (Honigsmann and Schwarz 2012) (Fig. 44). This results in decreased DNA synthesis, increased p53, and keratinocyte apoptosis.

Immunosuppressive:

Inhibits epidermal hyperplasia via Th1/Th17 (Tintle et al. 2011) and Th2/T22 polarization (Zanolli 2003). Inhibits epidermal angiogenesis and causes T-cell apoptosis (Krueger et al. 1995). UVB also inhibits proinflammatory markers (IL-12, IFN-gamma, IL-8).

Induces re-pigmentation:

Stimulates perifollicular pigmentation and promotes stabilization in vitiligo lesions (Dogra and Kanwar 2004). May induce melanocyte differentiation (Dong et al. 2012), proliferation, and migration via endothelin 1 (Esmat et al. 2016).

Inhibits pruritus:

Target epidermal opioid systems, cytokines, mast cells, and nerve fibers involved in “itch” pathogenesis (Rivard and Lim 2005)

Autoimmune and inflammatory cutaneous diseases: atopic dermatitis (Sidbury et al. 2014), psoriasis, vitiligo (Bethea et al. 1999) (Fig. 45), cutaneous T-cell lymphoma (Hodak and Pavlovsky 2015), and uremic pruritus (Ada et al. 2005)

Goeckerman therapy: topical application of coal tar with UVB radiation for psoriasis

Erythema, xerosis, pruritus, and pain Exacerbation of blistering disorders and systemic lupus erythematosus

Safe and well-tolerated

BB-NVB has largely been replaced by NB-UVB;

NB-UVB is more effective, safer, and less erythemogenic and carcinogenic than BB-UVB as it excludes shortwave UVB and reduces total UV exposure NB-UVB is used in children and pregnant females (Walters et al. 1999) Maintenance therapy may be recommended to prevent disease recurrence

Excimer laser

(308)

Induces T lymphocyte (Novák et al. 2002) and keratinocyte apoptosis (Bianchi et al. 2003). Decreases Langerhans cells in the skin.

“Excited dimer” consists of a noble gas and halide, which repel each other (Mehraban and Feily 2014), such as XeCl laser. Delivers focused, high-intensity, monochromatic UVB radiation to cutaneous lesions, with minimized exposure to the healthy, unaffected skin. Excimer light may also be administered via a lamp with similar efficacy (Le Duff et al. 2010). Excimer may be combined with topical therapies (e.g., calcipotriene) to enhance response (Mouzakis et al. 2011)

Psoriasis (Menter et al. 2010), vitiligo (Rodrigues et al. 2017), atopic dermatitis, alopecia areata, folliculitis, cutaneous T-cell lymphoma, pityriasis alba, prurigo nodularis, and scleroderma

Erythema, hyperpigmentation, and blistering (Feldman et al. 2002)

Safe and well-tolerated

Patients achieve rapid clearance with fewer and shorter treatments compared to NB-UVB or BB-UVB

Visible light

Photodynamic therapy (PDT)

Topical photosensitizer is activated by light.

5-Aminolaevulinic acid (ALA) is activated by blue light.

Methyl aminolevulinate (MAL) is activated by red light; occlusion is recommended.

Photosensitizing agents are converted to protoporphyrin IX within mitochondria and activated to a higher-energy state (Fai et al. 2016) This results in generation of reactive oxygen species that destroy cell membranes and organelles, causing cell necrosis and apoptosis (Henderson and Dougherty 1992)

Actinic keratosis and SCC

Prevents actinic keratosis progression to SCC (Grinblat et al. 2015) Effective as field therapy to treat numerous lesions over large areas of skin, especially in immunosuppressed or solid organ transplant recipients (Ericson et al. 2008)

Pain is the most common complaint (Cohen and Lee 2016)

Erythema, inflammation (edema, blistering), hypersensitivity to photosensitizer, hypopigmentation, and hyperpigmentation

Safe and well-tolerated

Red light (620–750)

Blue light

(450–495)

Combination of red and blue light decreases inflammation and kills Propionibacterium acnes (P. acnes) (Das and Reynolds 2014).

Red light: anti-inflammatory.

Decreases inflammatory cytokines in the skin (Lee et al. 2016). Penetrates deeper than blue light, reduces sebocyte lipid production, and stimulates collagen (Jung et al. 2015)

Blue light: bactericidal.

P. acnes produce porphyrins, which on exposure to blue light generate reactive oxygen species; this leads to bacterial cell death (Ashkenazi et al. 2003)

Acne vulgaris

Mild xerosis and erythema

Safe and well-tolerated

Visible light lacks carcinogenic features of UV radiation

Fig. 39

Petechiae and ecchymoses on the lower limb in vitamin C deficiency. (Reproduced from Hirschmann and Raugi 1999; with permission)

Phototherapy is well-tolerated and often used for patients with refractory diseases. It is a suitable alternative to pharmacological agents, especially for patients with comorbidities or prior drug toxicity (Lim et al. 2015). It has few side effects, including transient photodamage, erythema, pain, xerosis, and bullae. Safety measures during treatment include protective eyewear (UV-opaque goggles) and genital shields. Except for long-term PUVA, there is no evidence of increased skin cancer risk with conventional phototherapy (Valejo Coelho and Apetato 2016).

7 Light Amplification by Stimulated Emission of Radiation (LASER)

Light amplification by stimulated emission of radiation (LASER) harnesses the power of selective photothermolysis to target specific structures, leading to thermal coagulation (Anderson and Parrish 1983, Anderson and Parrish 1981). Lasers have several properties unique from other light sources, including monochromaticity, coherence, and collimation (Table 14). All lasers need a medium (gas, liquid, or solid), source of energy, optical cavity for excitation, and delivery system (Herd et al. 1997). Clinical applications of lasers are widespread and often combine cooling the skin to achieve selective photothermolysis to minimize unwanted skin reactions (Table 15).
Table 14

Unique properties of lasers

Monochromaticity

The emission of a uniform wavelength

Coherence

A single-phase emission as it passes through the media

Collimation

The unidirectionality of the wave

Radiance

The power emitted per unit surface area

Fig. 40

Zinc deficiency: perioral region in acrodermatitis enteropathica. (Reproduced from Nistor et al. 2016; with permission)

Table 15

Key parameters of lasers

Wavelength (nm)

Determined by the type of laser

Fluence (J/cm2)

Describes the amount of energy delivered per unit area

Pulse duration or width (ms or s)

Describes the exposure time to a set amount of laser energy; shorter pulse duration delivers the predetermined amount of energy over a shorter period of time

Spot size (mm)

Describes the laser beam diameter on the skin surface; larger spot size has deeper penetration and less scatter compared to smaller spot size

Fig. 41

Zinc deficiency: perianal region in acrodermatitis enteropathica. (Reproduced from Nistor et al. 2016; with permission)

The primary skin chromophores are water, hemoglobin, and melanin; each absorbs energy at different wavelengths known as their absorption spectrum (Fig. 46). The targeted chromophores absorb energy and dissipate heat to nearby molecules, leading to destruction (Herd et al. 1997).
Fig. 42

Psoralen photochemistry. (Reproduced from Honigsmann and Schwarz 2012; with permission)

Several parameters are considered in laser calibration, including wavelength, fluence, pulse duration, and spot size (Table 15). Thermal relaxation time is the time needed for a chromophore to diffuse 50% of its heat (Yadav 2009). The optimal pulse duration should equal the thermal relaxation time of the chromophore.
Fig. 43

PUVA for the treatment of psoriasis: (A) before therapy and (B) after 6 weeks of therapy. (Reproduced from Honigsmann and Schwarz 2012; with permission)

7.1 Application of Laser

7.1.1 Hair Removal

Photoepilation is driven by selective photothermolysis of melanin within the hair shaft and follicular stem cells in the bulge (Lepselter and Elman 2004, Hobbs et al. 2000) (Fig. 47). This decreases the frequency of hair regrowth so that with multiple treatments, hair follicles are reduced to 40–80% (Lepselter and Elman 2004). While numerous lasers are used for photoepilation (Table 16), alexandrite is the most commonly used.
Fig. 44

Emission spectra of BB-UVB and NB-UVB bulbs. (Reproduced with permission)

Table 16

Common dermatologic lasers and clinical applications (AccessMedicine, the McGraw-Hills Company)

Commonly used dermatologic lasers(nm)

Target

Effect in target

Mode

(pulse duration)

Applications

Excimer (XeCl)

(308)

DNA and proteins

Photochemical reactions

Pulsed

(μs)

Comparable to NB-UVB (311 nm)

Argon

(488/514)

Vascular lesion Tissue

Semiselective coagulation

Pulsed

(ms)

Telangiectasias, spider nevi, venous lakes

Syringoma, xanthelasma, and epidermal nevi

Frequency-doubled Nd:YAG(532)

Vascular lesions

Selective coagulation

(“KTP” laser)

Pulsed

(ms)

Telangiectasias, spider nevi, and venous lakes

Frequency-doubled Nd:YAG

(532)

Pigmented lesions

Selective and fast heating

(explosion)

Pulsed

(ns)

Benign melanin-containing lesions and tattoos (red)

Flashlamp pulsed dye

(585–600)

Vascular lesion

Tissue

Selective coagulation

Pulsed

(ms)

Port-wine stain, telangiectasias, rosacea, spider nevi

Scars, keloids, warts, and photoaging

Ruby

(694)

Pigmented lesions

Selective and fast heating

(explosion)

Pulsed

(ns)

Benign melanin-containing lesions and tattoos (black, blue, and green)

Alexandrite

(755)

Vascular lesions

Tissue

Pigmented lesions

Selective coagulation

Selective and fast heating

(explosion)

Pulsed

(ms)

Pulsed

(ns)

Large vessels (leg veins and hypertrophic port-wine stain), hair removal, and benign melanin-containing lesions, tattoos (black, blue, and green)

Diode

(810)

Vascular lesions

Tissue

Selective coagulation

Pulsed

(ms)

Large vessels (leg veins, hypertrophic port-wine stain) and hair removal

Nd:YAG

(1064)

Vascular lesions

Vascular lesions

Tissue

Pigmented lesions

Unspecific

coagulation

Selective coagulation

Selective and fast heating

(explosion)

Continuous wave (cw)

Pulsed

(ms)

Pulsed

(ns)

Vascular malformations, tumors, large vessels (leg veins, hypertrophic port-wine stain), hair removal, benign melanin-containing lesions, and tattoos (black, blue, and green)

Diode

(1450)

Tissue

Selective coagulation

(nonablative)

Pulsed

(ms)

Skin remodeling, photoaging

Er:YAG

(2960)

Tissue

Selective and fast heating (ablation)

Pulsed

(ms)

Skin resurfacing and epidermal ablation

CO2

(10,600)

Tissue

Unspecific coagulation (vaporization) and selective and fast heating (ablation)

cw

Pulsed

(ms)

Vaporization of tissue, skin resurfacing, and epidermal ablation

Fig. 45

Narrowband UVB for the treatment of vitiligo: (A) before therapy and (B) after 10 months of therapy. (Reproduced from Honigsmann and Schwarz 2012; with permission)

Fig. 46

Absorption spectrum of chromophores in the skin. (Reproduced with permission)

Fig. 47

Q-switched alexandrite photoepilation. (Reproduced from Bologna et al. 2012; with permission)

Fig. 48

Treatment of port-wine stain using PDL. (Reproduced from Bologna et al. 2012; with permission)

Fig. 49

Ablative CO2 laser resurfacing for skin rejuvenation. (Reproduced from Bologna et al. 2012; with permission)

7.1.2 Vascular Lesion Removal

Laser treatment of vascular lesions aims to target the chromophore oxyhemoglobin, which absorbs at wavelengths of 418, 542, and 577 nm. Pulsed dye laser (PDL) is the most common laser used to treat port-wine stains (Gange et al. 1988), superficial hemangiomas, telangiectasias, rosacea, angiofibromas, acquired lymphangioma circumscriptum, and cherry angiomas. The KTP is an alternative laser commonly preferred in lighter skin (Fitzpatrick I–III). Port-wine stains are highly responsive to PDL (Fig. 48) with response rates up to 70% in children and young adults (Reyes and Geronemus 1990). Treatment is well-tolerated, with bruising as the most common complaint.

7.1.3 Tattoo Removal

The exact mechanism of laser tattoo removal is poorly understood, with the current hypothesis proposing fragmentation of ink particles by high-energy photons that are subsequently phagocytized. Q-switched ruby and alexandrite are effective options for lighter skin (Alster 1995), while Q-switched Nd: YAG laser is preferred in darker skin due to the lower risk of dyspigmentation (Levine and Geronemus 1995). Multiple treatments are often necessary, and complete clearance is not always attained (Alster 1995). Treatments are well-tolerated, and adverse reactions can include dyspigmentation, scarring, and paradoxical darkening with treatment resistance (Ross et al. 2001; Anderson et al. 1993).

7.1.4 Skin Rejuvenation

Intense pulsed light (IPL) lasers target melanin and hemoglobin via polychromatic light to treat disorders such as poikiloderma of Civatte, rosacea, telangiectasias, and solar lentigines (Bjerring et al. 2004). Ablative lasers with carbon dioxide (CO2) and Er:YAG lasers are also used for skin rejuvenation (Fig. 49) and stimulate skin tightening through collagen formation (Walsh et al. 1988).

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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Jonathan Hale Zippin
    • 1
    Email author
  • Steven He
    • 1
  • Jenny Z. Wang
    • 2
  • Koji Ota
    • 3
  • Anita Gade
    • 4
  • Jonathan Galati
    • 1
  • Emily Rachel Lebowitz
    • 1
  • Stephanie Sutter
    • 1
  • Bernice Y. Yan
    • 1
  • Dalee Zhou
    • 1
  • Olivia H. Wind
    • 2
  1. 1.Department of DermatologyWeill Cornell Medical CollegeNew YorkUSA
  2. 2.Albert Einstein College of MedicineNew YorkUSA
  3. 3.SUNY Downstate College of MedicineBrooklynUSA
  4. 4.New York Institute of Technology College of Osteopathic Medicine (NYITCOM)Old WestburyUSA

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