Chemical- and Drug-Induced Photosensitivity
Photosensitivity induced by exogenous agents
Introduction
Exogenous agents induce photodermatitis by two mechanisms:
Phototoxicity
Direct tissue damage caused by phototoxic agent and light
In all individuals ( adequate doses of agent and light)
Photoallergy
Type 4 hypersensitivity
In sensitized individuals with minimal concentration of photoallergen
In photodermatology referral centers
5 to 15% phototoxicity
4% to 8% photoallergy
Pathogenesis
Phototoxicity
Generation of oxygen free radicals, superoxide anions, hydroxyl radicals and singlet oxygen, leads to a cytotoxic tissue effects
Other mechanisms include:
Formation of photoadducts reported with psoralens
Generation of inflammatory mediators reported with porphyrins and demeclocyclines
Apoptosis, PDT is a potent iducer of apoptosis in adition to generating reactive oxygen products
Photoallergy
UV energy convert a photoallergen to an excited state molecule or a stable photoproduct which could conjugate with a carrier protein to form a complete Ag .
Once the NeoAg is formed the mechanism of photoallergy is identical to that of allergic contact dermatitis:
APC T cells Type 4 hypersensitivity
Clinical features
Phototoxicity
Sun burn reaction is the prototype
Develops within hours; for the vast majority of agents
Erythema and edema as well as burning and stinging sensations
vesicles and bullae seen in severely affected patients
These reactions then resolve spontaneously with desquamation and hyperpigmentation once the photosensitizer or UVR is avoided.
Other less common manifestations of phototoxicity
Pseudoporphyria
NSAIDs, especially naproxen
photo-onycholysis
Tetracyclines and psoralens, fluoroquinolones
slate-gray hyperpigmentation
amiodarone, chlorpromazine, tricyclic antidepressants and diltiazem
lichenoid eruptions
quinine and quinidine
Burning or painful sensation
Amiodarone
Evolution to CAD
thiazides, quinidine, quinine or simvastatin
A woman taking naproxen while using tanning booths
Pseudoporphyria in a haemodialysis patient
Other less common manifestations of phototoxicity
Pseudoporphyria
NSAIDs, especially naproxen
photo-onycholysis
Tetracyclines and psoralens, fluoroquinolones
slate-gray hyperpigmentation
amiodarone, chlorpromazine, tricyclic antidepressants and diltiazem
lichenoid eruptions
quinine and quinidine
Burning or painful sensation
Amiodarone
Evolution to CAD
thiazides, quinidine, quinine or simvastatin
Photo-onycholysis induced by doxycycline
Other less common manifestations of phototoxicity
Pseudoporphyria
NSAIDs, especially naproxen
photo-onycholysis
Tetracyclines and psoralens, fluoroquinolones
slate-gray hyperpigmentation
amiodarone, chlorpromazine, tricyclic antidepressants and diltiazem
Other phototoxicity related features 
Exacerbation of 5-FU-induced inflammation in sites with actinic keratoses
Methotrexate occasionally causes a recurrence ('recall') of previous UVR-induced erythema
UVR-induced erythema is most likely due to retinoid-induced thinning of the stratum corneum
Phytophotodermatitis
Linear streaks of erythema occurring a day or so after skin contact with plants containing furocoumarins + exposure to sunlight
Yarrowبومادران , parsley (جعفری), celery (کرفس), lime and fig (انجیر), parsnip (هویج وحشی), carrots, fennel (رازیانه), dill(شوید), hogweed (نوعی هویچ وحشی)
In Roofers and road workers tar and concomitant UVA induce phototoxicity
Phytophotocontact dermatitis
Cow parsnip rash
Common phototoxic agents
Antiarrhythmics
Amiodarone, Quinidine
Triazole antifungals
- Voriconazole
Diuretics
Furosemide, Thiazides 
Nonsteroidal anti-inflammatory Drugs
Nabumetone, Naproxen, Piroxicam
Phenothiazines
Chlorpromazine,Prochlorperazine
Psoralens
Methoxypsoralen,8-Methoxypsoralen, 4,5',8-Trimethylpsoralen
Quinolones
Ciprofloxacin
Lomefloxacin
Nalidixic acid
Sparfloxacin
St. John's wort
Hypericin
Sulfonamides
Sulfonylureas
Tar (topical)
Tetracyclines
Doxycycline, Demeclocycline
Hypericin is one of the active compounds that were identified in the plant called St. John’s Wort that is nowadays used on a large scale in treating depression
Clinical features
Photoallergy
A pruritic eczematous eruption in sun exposed area very similar to allergic CD
Vesicles and bullae in more severely affected patients and less commonly than in phototoxic reactions
PIH is rare ( unlike phototoxic reactions )
lichenoid eruptions
HCTZ, quinine and quinidine
Evolution to CAD
thiazides, quinidine, quinine or simvastatin
Common photoallergic agents
Topical agents:
Sunscreens
Fragrances
6-Methylcoumarin, Musk ambrette, Sandalwood oil .
Antimicrobial agents
Bithionol, Chlorhexidine, Fenticlor, Hexachlorophene
Nonsteroidal anti-inflammatory drugs
Diclofenac, Ketoprofen
Phenothiazines
Chlorpromazine, Promethazine
Systemic agents ( also toxic):
Antiarrhythmics
Quinidine
Antimalarials
Quinine
Antifungals
Griseofulvin
Antimicrobials
Quinolones (e.g. enoxacin,lomefloxacin),Sulfonamides
Nonsteroidal anti-inflammatory drugs
Ketoprofen, Piroxicam*
* Often have positive patch test to thimerosal
Photoallergic reaction to HCTZ
Pathology
Phototoxicity
scattered necrotic keratinocytes ('sunburn cells') and a dermal infiltrate of primarily lymphocytes and neutrophils
Photoallergy
Epidermal spongiosis plus a dermal lymphohistiocytic infiltrate, indistinguishable from other spongiotic dermatitis
Pathology
Phototoxicity
scattered necrotic keratinocytes ('sunburn cells') and a dermal infiltrate of primarily lymphocytes and neutrophils
Photoallergy
Epidermal spongiosis plus a dermal lymphohistiocytic infiltrate, indistinguishable from other spongiotic dermatitis
hototoxicity
DDx
Phototoxicity
Sunburn
LE
Irritant CD
SU
PLE
Photoallergy
airborne contact dermatitis
Seborrheic dermatitis
Atopic dermatitis
Allergic CD
PLE
CAD
Treatment
Identification and avoidance of the offending agent
If not possible; strict photoprotection (UVB and UVA)
With evening dosing of a phototoxic drug peak systemic levels occur during the night
Symptomatic treatment with analgesics, steroids (topical or systemic)
