Continuing Medical Education
Photosensitivity Disorders
in Children
Dr. Haider A. Al-Sabak
From the Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol
University, Bangkok, Thailand,
and the Department of Dermatology, Henry Ford Hospital, Detroit, Michigan, USA.
Elecromagnetic Radiation Spectrum (EMR)
Waveband
Wavelength range (nm)
X-ray
0.1 – 1
Vaccum UV
10 – 200
UV C
200 – 290
UV B
290 – 320
UV A
320 – 400
UV A II
320 – 340
UV A I
340 – 400
Visible Light
400 – 760
Near IR
760 – 1000
Far IR
1000 - 100000
Microwaves and Radiowaves
> 1000000




The depth of penetration of UV to skin depends on WL
Longer WL UVA easily reaches the reticular dermis;
Shorter WL UVB absorbed in the epidermis
Only 2% - 3% of UV radiation from the sun reaches
earth’s surface
 UVB the major spectrum responsible for cutaneous
erythema or Sunburn response, While UVA elicits a
tanning response
 Recently, visible light induce a tanning response that is
more persistent
 Both UVA & UVB exposures generate metalloproteinases
& induce immunosuppression, & they therefore play a role
in photoaging and photocarcinogenesis.
Photodermatoses have their action spectrum in the UVA
&/or UVB &/or visible light range
Photosensitivity: defined as an abnormal or adverse reaction
of the skin to UV or visible radiation, & rarely artificial
light sources
Genetic or metabolic defects, or underlying systemic dis.
Child develops a sunburn reaction, swelling, or intense
pruritus after limited sun exposure or develops an eruption,
skin fragility, or scarring predominantly in sun-exposed
areas
The incidence of photodermatoses in the pediatric
population is much lower than in adults
Classification of pediatric photodermatoses
I. Immunologically mediated photodermatoses
 Polymorphous light eruption
 Juvenile spring eruption
 Actinic prurigo
 Hydroa vacciniforme
 Solar urticaria
II. Drug- and chemical-induced photosensitivity
 Exogenous
 Phototoxicity: systemic and topical
 Photoallergy: systemic and topical
 Endogenous
 cutaneous porphyrias
III. Hereditary photodermatoses
 Caused by defects in nucleotide excision repair
 Xeroderma pigmentosum
 Cockayne syndrome, including cerebro-oculo-facio-skeletal syndrome
 Trichothiodystrophy
 Ultraviolet light sensitive syndrome
 Caused by double strand break repair defects
 RothmundeThomson syndrome
 Bloom syndrome
 Caused by abnormal chemical stubstances
 Smith-Lemli-Opitz syndrome
 Hartnup disease
 Others
 Kindler syndrome
IV. Photoaggravated dermatoses
 Atopic dermatitis
 Darier - White disease
 Dermatitis herpetiformis
 Herpes simplex infection
 Lupus erythematosus and neonatal lupus erythematosus
 Juvenile dermatomyositis
 Pellagra
 Psoriasis
 Seborrheic dermatitis
Diagnosis:
• careful History taking and Physical examination
• Hx: Age of onset , season, timing after sun exposure, the nature,
duration, exposure to potential photosensitizers (both topical or
systemic), systemic, suggestive of autoimmune dis., family history &
consanguinity.
• Eruption after exposure to window glass-filtered sunlight indicate
action spectra in the UVA and/or visible light.
• Exam: distribution of lesions, areas of sparing, photoprotected sites
(upper eyelids, postauricular area (Wilkinson’s triangle), submental
area, nasolabial folds and neck folds, the volar aspect of the wrist, and
the antecubital fossae), & morphology.
• Invest: CBC, Autoimm. profile, Screening plasma porphyrin level,
Skin biopsy, Phototesting, Evaluation of growth parameters,
developmental milestones, systemic involvement, and neurologic
abnormalities, Chromosomal analysis and molecular genetic studies.
• Polymorphous Light Eruption (PMLE):
 Prevalence: most com. type in children
 affects both adults and children
 +ve family history is reported in 3% to 56% of patients
 inverse relation to latitude
 C/F: few hrs (20-30 mint. or 1-2 days)
 Hardening.
 Symp. Non-scarring pruritic eruption on a sun-exposed area (common
papular type to the relatively rare large papules, vesicular, plaque-like,
urticarial, hemorrhagic, insect bite like, and even EM like).
 In skin of color pt. pinhead pap.
 Resolve comp. in absence of sun exposure in days.
 Rare sympt. Chills, headache, fever & nausea
Polymorphous light
eruption.
A, A young white
boy with widespread
eruptions on the face.
Note the erythema on the
malar area and the bridge
of the nose and sparing of
the upper eyelid.
B, A 10-year-old boy of
Mexican and white
descent with
erythematous papules
and excoriation on
extensor forearms and
wrists after sun exposure.
Diagnosis:
 Histopathology:
 Phototesting: Most PMLE pts have normal (MEDs) to UVA & UVB
However, reports showing decreased MED values to UVA or UVB.
Dx. can be confirmed by evaluating the patient after exposure to
sunlight or by performing provocative phototesting in the clinic, by
exposing the skin either to multiples of MEDs or to suberythemogenic
UV doses for 3 to 4 days followed by evaluation 1 to 2 days later for
the development of characteristic PMLE lesions.
 Pathogenesis: Delayed HR to endogenous, cut. UV induced Ag.
 PMLE pt. less likely to be photoimmunosuppressed, but repeated UV
exposure, photoimmunosuppression occurs; this explains why patients
tend to improve as the sunny season progresses.
D.Dx:
 AD, SLE, EPP, SU, HV & photosensitivity induced by exogenous
agents
Treatment:
 Proper photoprotection
 Symp. Rx topical steroid
 Pophylaxis 5-7 days prednisone, 0.6-1 mg/kg/day or if reccurant NBUVB or PUVA (3 times/wk for 5 wks) in early spring
 Other antimalarial agents, beta-carotene & nicotineamide.
• Juvenile Spring Eruption (JSE):
 C/F: localized form of PMLE
 Boys > girls, age 5-12 yrs, spring season
 Pruritic erythematous papules usually confined to the helix of the ears
& evolve into vesicles & crusts & heal with minimal or no scarring.
 Histopathology & Phototesting
 Pathogenesis: remain unknown, similar to PMLE
 Treatment: Proper photo protection & Symp. Rx
• Solar Urticaria (SU):
 Prevalence: uncommon form of physical urticaria and is also a rare
subtype of IMP, age (1st wk – 8th decade)
 C/F: urticaria, headache, nausea, wheeze….etc & anaphylaxis
 Diagnosis:
 Phototesting , caution……anaphylactic reaction
 Com. UVA & visible, less UVB, IR….heat urticaria
 Pathogenesis: immediate type HR.
 D.Dx: PMLE, EPP, drug induced photos.
 Treatment:
 Proper photo protection & Symp. Rx
 Hardening
 NB-UVB with caution
 Beta-carotene, antimalarial drugs, plasmapheresis (removal of a
circulating serum factor/photoallergen), systemic immunosuppressive
agents, & IVIG have been reported to be effective in adults.
• Hydroa Vacciniforme (HV):
 C/F:
 boy > girls, mean age 8 yrs, resole spont. in adulthood
 Recurrent crops of discrete 2-3mm erythematous macules evolve into
blisters hrs to a 1-2 days after sun exposure.
 Healing occurs within days, with umbilication followed by crusting &
pitted, varioliform scarring. Adverse effect on quality of life.
 Rare presentations ocular involvement (keratoconjunctivitis & uveitis)
& blistering of the lips.
 Histopathology:
 Phototesting: UVA in monochromatic phototesting…papulovesicular
 Pathophysiology: not clarified. (Latent EBV infection), some cases
reported in adult (fatal) different from that of children.
 D.Dx: EPP, vesicular PMLE, bullous SLE, & PCT.
 Treatment: Photoprotection, Chloroquine, beta-carotene & PUVA. In
severe cases, systemic corticosteroid.
Hydroa vacciniforme.
A, A 7-year-old boy
with
vesicles and crusts on
the malar area a few
days after sun
exposure.
B, A boy with pox-like
scars on the left
cheek.
• Actinic Prurigo (AP):
 Prevalence: Indian and Mestizo (mixed ancestry), Mexico & Central
& South America, living at high altitudes.
 strong association with HLA DRB1*0407
 C/F: age 2-43 yrs. (mean <10yr)
 intensely itchy papules, plaques, & nodules, excoriations and scars on
sun-exposed area, 2ndry eczematization & lichenification.
 Very shallow linear, flat, or punctate scars may occur on the face.
 Other: bach & buttock, cheilitis, conjunctivitis, pseudopterygium &
eyebrows alopecia.
 Diagnosis: Histopath., Phototesting, D.Dx
 Treatment: Photoprotection (sunglass, lip balms), topical steroid,
antihistamin, emollients, others (Chloroquine, beta-carotene, Vit.E,
pentoxyphillin), PUVA & NB-UVB effective.
 Thalidomide (50-100mg/day……50mg) most effective Rx
S/E teratogenic, peripheral neuropathy
Actinic prurigo:
Note the
erythematous papules
that have coalesced to
form a plaque on the
right cheek, V of the
neck, and extensor
surfaces of both distal
arms and forearms of
an 8-year-old girl
• Chronic Actinic Dermatitis (CAD):
 replaced the terms persistent light reactivity, actinic reticuloid,
photosensitive eczema, & chronic photosensitivity dermatitis.
 a persistent, chronic, eczematous eruption in the absence of exposure
to known photosensitizers
 usually broad-spectrum photosensitivity with decreased MED to UVA
&/or UVB, and at times visible light
 histology consistent with a chronic dermatitis, with or without features
of lymphoma
 C/F:
 middle-aged or elderly men, edematous, scaling, thickened patches &
plaques that tend to be confluent, involvement of unexposed sites,
progressing to erythroderma in the most severe cases.
 Marked depigmentation (vitiligo). Patients may not realize their
condition is exacerbated by light. It may persist in all seasons.
 Pathogenesis: unknown. In some patients a preceding topical or oral
photosensitizer.
 Dx established by histologic evaluation and phototesting
 The finding of photosensitivity to UVA and UVB helps to differentiate
chronic actinic dermatitis from drug-induced photosensitivity
 D.Dx: PMLE, photoallergic CD, airborne CD, & MF or Sézary
syndrome
 Treatment: includes identifying & avoiding possible topical
photosensitizers by photopatch testing. Maximum sun avoidance &
broad-spectrum sunscreens.
• Topical tacrolimus is useful in some patients. Top. & sys. steroids.
• Azathioprine, 50–200 mg/day, is the most effective Rx & may be
required annually during periods of increased sun intensity.
• Low dose PUVA, but is often not tolerated, even with steroid
• Hydroxyurea, 500 mg twice a day. Cyclosporine A, thalidomide, &
mycophenolate mofetil may also be utilized. Immunosuppressive
agents may allow patients to tolerate PUVA therapy.
DRUG & CHEMICAL-INDUCED PHOTOSENS.
Photosensitivity by Exogenous Sensitizers:
 Rare in children, eiher phototoxic or photoallergic (next table)
 Almost all induced by UVA bec. Pentrate window glass, in lamp of
tanning booth, nail salon, dentist office, photocopy machine…etc
 NB-UVB safe
 Phytophotodermatitis: Plant-induced photosens. most common
phototoxic reaction of children, Citrus fruit (lemons & limes)…etc
 UV-induced eruption in day after exposure to the furocoumarin &
sunlight, severity from erythema to blistering & characteristic
hyperpigmentation.
 Linear streaks of hyperpigmentation, face, chest, hands, and lower
legs of children, over 1-2 wks & persist 6-12 months.
Differentiating features of phototoxic and photoallergic reactions
Feature
Phototoxic
 Clinical manifestations
Occurrence after first exposure
Yes
Onset of eruption after exposure
Minutes to hours
Dose of agents needed for reaction
Large
Cross reactivity with other agents
None
Clinical changes
Similar to sunburn reaction
Distribution



Histologic findings
Pathophysiology
Diagnosis
Topical agent
Systemic agent
Photoallergic
No
24-48 hrs
Small
Common
Varied morphology, usually
eczematous lesions
Exposed skin only
Exposed skin, may spread
to unexposed area
Necrotic keratinocytes, epidermal
Spongiotic dermatitis
degeneration, & dermal inflammation
Direct tissue injury
Cell-mediated immune response
Clinical
Clinical and phototest
Photopatch test
Clinical and phototest; possibly
photopatch test
Phytophotodermatitis:
A 9-year-old boy with a
linear hyperpigmented
streak on the right arm
a few days after
exposure to lime and
sunlight
 Most com. Drug Antibiotics (sulfonamides, quinolones, &
tetracyclines).
 Systemic phototoxic agents, Antibiotics (doxycycline, tetracyclines,
sulfonamides, nalidixic acid, and fluoroquinolones), Antifungal
(griseofulvin), sulfonylurea hypoglycemic agents, furosemide,
NSAID, amiodarone, quinine, isoniazid, & thiazide diuretics.
 Photoallergic agent: com. UV filter octocrylene, benzophenone-3, &
butyl methoxydibenzoylmethane.
 Treatment: The 1st line is removal of photosensitizer; restriction of
UV radiation exposure.
 Good broad spectrum sunscreens need to be used because the action
spectrum is in the UVA range.
Endogenous Chemical-induced Photosensitivity:
Cutaneous Porphyrias (CPs)
 They are a group of inherited & acquired disorders that are caused by
a specific enzymatic defect in the heme biosynthesis pathway.
 Heme is assembled from simple precursors in an 8-step pathway
 Each step is catalyzed by a different enzyme, represent partial def.,
bec. complete enzyme def. in the pathway is not compatible with life.
 Heme produced in RBC for Hb synthesis & in hepatocytes for
synthesis of cytochromes & hemoproteins. So (hepatic or cutaneous)
 Porphyrins, are potent photosensitizers in CPs, major action spectrum
(400-405 nm) (the Sorbet band), minor (600-650 nm) (visible red);
 Dihydroxyacetone, sunless tanning, blocking longer UVA & visible
light. It can provide excellent protection in cases of CPs.
 Differences in water solubility reflect the clinical features.
Heme biosysthetic pathway and sites of enzymatic defect in cutaneous porphyrias. ALA,Aminolevulinic acid; CEP,
congenital erythropoietic porphyria; CP III oxidase, coproporphyrinogen oxidase; EPP, erythropoietic protoporphyria; HC,
hereditary coproporphyria; HEP, hepatoerythropoietic porphyria; PBG, porphobilinogen; PCT, porphyria cutanea tarda; PP III
oxidase, protoporphyrinogen oxidase; URO decarboxylase, uroporphyrinogen decarboxylase; URO III synthetase,
uroporphyrinogen III synthase; VP, variegate porphyria
Congenital Erythropoietic Porphyria (CEP):
 Gunther dis., autosomal recessive dis.most disfiguring form caused by
def. of UROS III, results in a shift from production of III to I isomers
of uroporphyrinogen & coproporphyrinogen .
 C/F: dark colored urine during infancy, fluoresces red (Wood’s lamp),
severe photosensitivity in 1st 2 or 3 yrs of life, splenomegaly, &
hemolytic anemia. Patients show signs of discomfort after sun
exposure, although they cannot verbally communicate.
 Phototherapy during the neonatal period for hyperbilirubinemia may
lead to generalized blistering. When teeth erupt, they are dark colored,
& Wood’s lamp +ve bec. porphyrins bind to dental calcium phosphate.
 Hypertrichosis & hyperpigmentation of the face & extremities, Ocular
involvement, photophobia, corneal scarring, ulceration, ulcerative
keratoconjunctivitis, & cataracts.
 Hemolytic anemia with hypersplenism. Bony involvements include
osteodystrophia, combining osteolysis & osteoporosis; hypercellular
bone marrow is present. These changes may lead to bone fragility and
fracture
Congenital erythropoietic porphyria:
A, Teeth showing pink to brown color.
B, The teeth fluoresce pink under examination with a Wood’s
lamp because porphyrins bind to dental calcium phosphate
(erythrodontia).
Congenital
erythropoietic
porphyria:
A, Urine stained on
diaper from an infant
with congenital
erythropoietic
porphyria.
B, Urine fluoresced
pink under
examination
with a Wood’s lamp
Congenital
erythropoietic
porphyria:
A, A 10-month-old white
female with mutilating
ulceration and scarring
secondary to recurrent
eruption of vesicles and
bullae.
B, Hypertrichosis on the
face when the same
patient was 28 months
old (after bone marrow
transplantation)
 Diagnosis:
 Biochemical changes: uroporphyrin I & coproporphyrin I in RBC,
BM cell, plasma, urine & feces
 Wood’s lump: reddish orange porphyrin fluorescence in urine or
aqueous suspension of feces
 Hematological changes: normochromic anemia, reticulocyte count
 Skin biopsy
 Prenatal Dx.
 Treatment: rigorous sun avoidance, protective clothing, use of
opaque sunscreens containing nonmicronized titanium dioxide or zinc
oxide that block in the visible spectrum.
 Beta-carotene, Hypertransfusion and splenectomy, Bone marrow and
allogeneic stem cell transplantation
 The prognosis of the severe form is poor.
 Death---hemolytic anemia
Erythropoietic Protoporphyria (EPP):
 Most com. in childhood CPs, partial def. in FECH enz. when only
<50% of normal action.
 Mode of inheritance is complex, autosomal recessive EPP less com. &
ass. With severe liver disease.
 C/F: Accumulation of free protoporphyrin, in RBC & 2ndly in tissue
(skin & liver) or biologic specimens (serum, bile, &feces), leads to
painful photosensitivity & potential liver complications.
 EPP usually becomes symptomatic between 1 & 6 years of age
because of the photosensitivity. The average age is 4 years
 Immediate painful reaction within mint. of sun exposure. Severe
burning pain in hands & feet & the face---cold air & cold water.
Crying upon exposure to sunlight occurs in young children.
 Chronic lesions are common, thickening of skin on the knuckles &
subtle scarring on the bridge of the nose, increased rugosity of the
upper cutaneous lip.
Erytropoietic
protoporphyria:
A 12-year-old
boy with vesicles
and thickening
of the skin over
the knuckles.
 Hypochromic & microcytic anemia. Liver dysfunction in 10% to 20%
of EPP patients.
 Incidence of cholelithiasis in 2% ---irreversible cholestatic liver
failure develops
 Biochemical changes: free protoporphyrin in RBC, plasma, bone
marrow cells, and feces. It is highly lipophillic, urinary porphyrin
levels are normal, unless the patient is in hepatic failure.
 Examination under a fluorescence microscope--- +ve in RBC. Plasma
fluorescence emission spectroscopy shows a ccc peak at 634 nm
 Treatment: photoprotection, opaque sunscreen,
 beta-carotene (30-150 mg in children),
 cholestyramine (4g/day),
 chenodeoxycholic acid (15 mg/kg/day),
 Recently, subcutaneous implants of alfa MSH analog
 Liver transplantation
Porphyria Cutanea Tarda (PCT) &
Hepatoerythropoietic Porphyria (HEP):
 PCT most common form of porphyria in adults & the 2nd most
common form in children.
 Heterozygous deficiency in uroporphyrinogen decarboxylase causes
PCT, whereas homozygous deficiency in this enzyme results in HEP.
 PCT Age 3rd-4th decade
o Type I: sporadic PCT
o Type II: familial form
o Type III:
 C/F: Skin fragility most common, erosions, vesicles, or bullae on sunexposed cutaneous surfaces, esp. the dorsal aspects of the hands &
forearms, The blisters vary in size from 1 mm-3 cm., milia, infection.
 The lesions heal with hyperpigmentation; Periorbital hypertrichosis &
mottled hypo & hyperpigmentation are frequently present
 Rarely sclerodermoid changes only finding in sun-exposed &
protected sites, ocular pain, photophobia, scleral perforation.
 In adult PCT ass. with, iron overload, hepatitis C, alcoholic cirrhosis,
hemodialysis, administration of estrogens, hydantoins, or griseofulvin,
HIV infections, & hemochromatosis.
 Dx: levels of plasma, urinary & fecal porphyrins, with predominance
of uroporphyrin (8-carboxyl porphyrin) & 7 carboxyl porphyrin in
plasma & urine, & isocoproporphyrin in feces.
 Fluorescence emission spectroscopy of plasma shows a ccc peak at
620 nm.
 Treatment: like other porphyria……..
 low-dose hydroxychloroquine treatment (3 mg/kg twice a week)
Clinical improvement, which precedes biochemical improvement, is
observed in 4-6 months. Urinary & plasma concentration of porphyrin
monitored every 3 months.
 Phlebotomy is the treatment of choice in adult cases
 Prognosis: 5-16% of untreated pt.------hepatocellular CA
HEREDITARY PHOTODERMATOSES
 Caused by defects in nucleotide excision repair (NER):
 The NER pathway serves to repair DNA damaged by UV radiation,
chemical carcinogens, & other non UV-induced oxidative damage.
 28 proteins in the NER pathway.
 NER-------normal development, (the nervous system).
 Complex relationship between clinical phenotypes and the molecular
defects in NER.
 Different defects in 1 gene may lead to different C/F.
Xeroderma Pigmentosum (XP):
 autosomal recessive dis. ccc by marked photosensitivity, ocular, &
increased risk of cutaneous malignancy. Patients with XP have defects
in NER causing decreased ability to repair DNA damage induced by
UV radiation
 Prevalence is increased in communities of common consanguinity.
 The disease is categorized into 7 complementation groups, A through
G, & a variant subtype
 Each group has a specific genomic deficit.
 C/F:
 Onset, 1 & 2 years of age. The most common is photosensitivity.
50% of affected pts have a history of acute sunburn reaction with
blistering or persistent erythema after minimal UV exposure.
 more severe photosensitivity later develop neurologic abnormalities.
 The other 50% of the pts tan normally without excessive erythema.
Marked freckling of sun-exposed areas presents in most pts before 2
yrs of age, continued sun exposure causes actinic damage, such as dry
& parchment like skin with hyperpig., poikiloderma, & AK.
 XP is an example of accelerated photoaging, with pts developing
non-melanoma skin cancers at a mean age of 10 years. Patients who
are <20 years of age have a greater than 1000 fold increased risk of
cutaneous BCC, SCC, or melanoma. Multiple primary cutaneous
neoplasms are common.
Fig 1. XP. A 10 month-old boy presenting with developmental delay and marked
freckling on the face and sun-exposed area.
Fig 2. XP. An 8 year-old girl presenting with dry and parchment-like skin with
hyperpigmentation, and multiple pigmented BCC on the face. Both eyes showed
corneal opacification.
o Eye features in XP is almost as common as the cut. C/F, onset median
age of 4 years, anterior portion of the eye (exposed to sunlight).
o Chronic UV-induced conjunctivitis and keratitis leading to corneal
opacification and vascularization…inflammatory lesions (pingueculae
and ptergyia).
o Atrophy of the skin of the eyelids (ectropion, entropion &, in severe
cases, complete loss of the lids).
o Epithelioma, SCC, & melanoma of UV-exposed portions of the eye
o About 30% of XP patients have a progressive neurologic deg.,
especially, pts with XP/CS complex, onset may be early in infancy or
delayed until the 2nd decade of life. The earliest C/F are diminished or
absent deep tendon reflexes & high frequency hearing loss.
o Others, microcephaly, progressive intellectual deterioration, spasticity,
ataxia, or seizure. Swallowing difficulties, leading to aspiration of
food.
o 10-20 fold increase in internal CA, (brain, lungs, hematopoietic
system, kidney,& gastrointestinal tract). -----die 20 years of age.
o A small no. of XP pts have C/F of XP & other dis. with NER defects,
Patients with the XP/CS complex have skin and eye disease of XP and
the somatic and neurologic abnormalities of CS.
o In XP/TTD syndrome, previously known as photosensitivity,
ichthyosis, brittle hair, intellectual impairment, decreased fertility, and
short stature (PIBIDS) syndrome, they do not show an increased risk
of developing skin cancer.
o XP variant have skin & eye C/F identical to other forms of XP (high
rate of skin cancer) but don’t have a defect in NER. Most XP variant
pts don’t have XP neurologic abnormalities.
 Dx: by C/F,
• Functional tests on living cell, to screen for abnormalities in DNA
repair. Cells from individuals with XP with defective NER are
hypersensitive to killing by UV in comparison to normal cells; cells
from individuals with the XP variant may have normal or near normal
post-UV cell survival.
 Management:
• All patients with XP require strict life-long sun protection with UVblocking protective clothing, high SPF broad spectrum sunscreens,
UV-absorbing glasses with side shields, & hats.
• Vitamin D (age 0-1 year, 400 IU/day; age>1 year, 600 IU/day) is
recommended to prevent deficiency from sun avoidance.
• Methylcellulose eye drops should be applied to keep the corneas
moist, & soft contact lenses should be worn to protect against
mechanical trauma in individuals whose eyelids are severely
deformed.
• Corneal transplantation may be required for patients with severe
keratitis & corneal opacity.
• Premalignant & malignant skin dis. should be treated. Oral
isotretinoin, 0.25 to 2 mg/kg has been used for prevention of non
melanoma skin CA. In order to reduce the occurrence of side effects
that are dose dependent, initiating low doses of retinoids & gradually
increasing according to the patient’s response.
• Cockayne syndrome (CS):
 a rare autosomal recessive disorder with ccc facies, extremely short
stature, immature sexual development, & multisystemic degeneration.
It results in a reduced lifespan but NO increased incidence of CA.
 CS is caused by defects in the repair of actively transcribed DNA;
2 genes responsible for CS (ERCC8 & ERCC6). Mutations in ERCC8
cause CS type A (CSA, 25%) & mutations in ERCC6 cause CS type B
(CSB, 75%); both CSA and CSB have identical phenotypes.
 CS spans a wide spectrum of diseases, & classified into 3 groups:
They are type I (classic CS), type II (early-onset CS), & type III (mild
or atypical CS). Recently, a fourth newly documented group, UV
sensitivity only/adult onset.
 Pts with CS are normal at birth but experience postnatal failure of
brain growth. They have a ccc facies with deep set eyes, prominent
ears, & a wizened facial appearance.
 The major C/F of CS are postnatal growth failure, neurologic deg.,
photosensitivity, pigmentary ‘‘salt and pepper’’ retinopathy, cataracts,
sensorineural hearing loss, cachectic dwarfism, & immature sexual
development.
 photosensitive but without pigmentary changes or increased skin CA
frequencies as seen in XP, premature aging & results in early death.
 Others: dental (absent or hypoplastic teeth & delayed teeth eruption);
renal (abnormal renal function & pathologic abnormalities); endocrine
(undescended testes); cutaneous (anhidrosis and malar rash); & GI
abnormalities (abnormal liver function & hepatosplenomegaly).
The average lifespan in CS is 12 years.
 Dx: C/F & Sequence analysis for both genes is clinically available.
 Treatment: no effective Rx, most patients die by the 3rd decade of life
as a result of arteriosclerotic vascular disease, profound neurologic
deterioration, or both.
 Physical therapy prevents contractures & maintains ambulation, while
gastrostomy tube placement prevents malnutrition. Spasticity may be
alleviated by medication. Hearing loss, cataracts, other eye dis. &
dental caries are treated as in the general population.
 The use of sunscreens & sunglasses & avoidance of excessive sun
exposure are helpful. Surveillance includes yearly assessment for
complications, including HTN, renal or hepatic dysfunction, &
declining vision & hearing.
Trichothiodystrophy (TTD):
 Heterogeneous group of autosomal recessive disorders ccc by sulfurdeficient brittle hair with neuroectodermal manifestations.
 To date, 4 genes responsible for TTD: XPD, XPB, p8/TTDA, &
TTDN1 (TTD nonphotosensitive 1).
 Approx. 110 patients have been reported to date.
 C/F: remarkably varied, ranging from only hair involvement to severe
neurologic & somatic developmental abnormalities.
 The hairs sparse, short, dry, & brittle (Next fig); break easily with
trauma. Light microscopy reveals hairs with a wavy, irregular outline
& a flattened shaft that twists like a folded ribbon. Polarizing
microscopy shows ccc alternating light and dark bands,‘‘tiger-tail’’
appearance.
 50% of pts (XP/TTD syndrome), also known as PIBIDS syndrome.
 Pts may born premature or small for their gestational age, & they have
a high frequency of cong. cataracts & of multiple infections.
 Skeletal abnormalities, peripheral osteopenia & central osteosclerosis
 Neurologic manifestations, (developmental defects, microcephaly,
intellectual impairment, & ataxia).
 Nail abnormalities, such as onychodystrophy, splitting, ridging or
thickening, decreased fertility, & features of premature aging may be
observed; no specific treatment is available.
Ultraviolet-sensitive syndrome UV(S)S:
• was first described by Itoh et al in 1994. They reported 2 DNA repairdefective siblings with mild C/F similar those of XP;
• defective transcription-coupled repair (TC-NER), the subpathway of
NER. & it is genetically heterogeneous, with mutations in (ERCC6).
• C/F: photosensitivity, dryness with freckling and pigmentation
anomalies of sun-exposed areas, & telangiectasia.
• Unlike other photosensitive dis., no neuro. Or developmental signs, &
no tendency to skin CA.
Trichothiodystrophy.
Note the
sparse, short,
dry, brittle
hairs.
Trichothiodystrophy.
A, Light microscopy
shows hairs with
irregular outline and
a flattened shaft.
B, Under polarizing
microscopy, the
characteristic
alternating light
and dark bands, the
‘‘tiger-tail’’
appearance, is
evident
Hereditary photodermatoses caused by double strand
break repair defects (DSBR):
 This pathway is implicated in maintaining genomic stability.
 DNA double-strand breaks (DSBs) can promote genomic instability
resulting in chromosomal abnormalities.
 There are 2 dis. RTS & BS.
Rothmund-Thomson syndrome (RTS):
 also known as poikiloderma congenitale, is a rare autosomal recessive
disorder ccc by poikiloderma, sparse hair, sparse eyebrows/ lashes,
small stature, skeletal abnormalities, cataracts, and an increased risk
for cancer, especially osteosarcoma.
 Gene mutations is RECQL4 gene in 66%, with risk of osteosarcoma.
 C/F:
 Erythema, swelling, & blistering of the face that develops in infancy,
generally at 3 to 6 months of age, with sparing of the trunk & flexural
areas, then evolves into reticulated hyper- & hypopigmented patches,
telangiectases, & areas of punctate atrophy.
 The eruption extends to extensor surface of the extremities, trunk,
abdomen, & buttocks.
 Keratotic lesions in 1/3 of cases on the elbows, knees, hands, & feet.
 Palmoplantar keratoderma.
 Sparse hair, eyelashes, &/or eyebrows.
 Nail abnormalities, and gastrointestinal disturbances.
 Juvenile cataract, prevalence of<10%.
 Many individuals tend to be small for gestational age at birth, & have
small stature throughout life.
 The majority of individuals (75%) have radiographic finding of the
bone (dysplasias, absent or malformed bones, or delayed bone
formation) & dental abnormalities (rudimentary or hypoplastic teeth
& increase incidence of caries).
 Osteosarcoma is the most common malignancy in RTS, (prevalence
30% & median age of onset at 11 years of age).
 Othere, BCC, SCC & melanoma, prevalence 5%.
Rothmund-Thomson
syndrome.
A, Widespread
poikiloderma, sparse
hair, some keratotic
papules on the trunk
& extremities.
B, Plantar
hyperkeratosis.
C, Sparse hair &
scarring alopecia on
the crown area.
D, Absence of radii &
thumbs on both
hands.
Bloom syndrome (BS):
 also called congenital telangiectatic erythema, is a rare autosomal
recessive disorder that is associated with a predisposition to cancer.
 80% of affected children are male.
 Higher prevalence within the Ashkenazi Jewish population
 Mutations in the gene Bloom helicase (BLM helicase or BLM )
 lack of BLM protein may lead to tumor formation
 C/F: ccc of severe pre & postnatal growth retardation, sun-induced
chronic erythema, type II diabetes in 17.7%, & frequent infections.
 The most striking C/F is proportionate dwarfism with highly ccc
sparseness of subcutaneous fat tissue. BS patients are usually small
for gestational age. Lack of interest in feeding.
 Cutanuous features in the first few years of life inform of
Erythematous patches & telangiectasia arise on sun-exposed areas,
Loss of the lower eyelashes & blister & fissure of the lower lip.
Multiple cafe-au-lait spots with neighboring hypopigmentation




Gastroesophageal reflux--------repeated otitis media & pneumonia
BS pts are prone to CA., mean age 24 years, & death before 30 years
Lymphomas & leukemia occur 150 to 300 times than normal,
CA of GIT, (colorectal CA), respiratory tract, skin, breast, & liver;
hematologic malignancy, acute leukemia & lymphoma; connective
tissue sarcoma; retinoblastoma; & brain tumor.
 Chronic bronchitis & bronchiectasis are also common.
 Most pts have normal intelligence.
 Women fertile, but menopause occurs early, whereas men are infertile.
 Dx: confirmed by molecular genetic analysis of BLM.
 The cutaneous findings in BS have a tendency to improve with age.
 Rx: Avoidance of sun exposure & protection by clothing &
sunscreens can prevent some of the cutaneous eruptions associated
with photosensitivity.
 Appropriate antibiotics for infections & control of gastroesophageal
reflux.
 Patients should be followed closely for early signs of neoplasm.
Hereditary photodermatoses caused by abnormal
biochemical substances
Smith-Lemli-Opitz syndrome (SLOS):
• Autosomal recessively inherited syndrome caused by an abnormality
in cholesterol metabolism resulting from deficiency of the enzyme 7dehydrocholestrol (7-DHC) reductase.
• Growth and mental retardation & hypospadias are common.
• Photosensitivity in the UVA light range 73% of patients.
• Dx is made based on C/F & detection of elevated serum concentration
of 7-DHC. Although serum concentration of cholesterol is usually
low, it may be in the normal range in about 10% of patients.
• Sequence analysis of DHCR7 detects 96% of known mutations.
• Objective improvement in clinical symptoms including
photosensitivity shown after supplementation with cholesterol.
• Photoprotection, including sun avoidance, is recommended.
• Early intervention & physical/occupational/speech therapies for
identified disability should be encouraged
Hartnup disease (HD):
 Rare autosomal recessive metabolic disorder caused by impaired
gastrointestinal & renal transport of neutral amino acids, including
tryptophan.
 Clinical presentations are attributed to defective transport of
tryptophan & a consequent decrease in nicotinic synthesis; its clinical
symptoms are similar to niacin deficiency (pellagra).
 Patients present with pellagra-like skin eruptions, cerebellar ataxia,
and gross aminoaciduria.
 Mutations in SLC6A19 encoding the neutral A.A. transporter B0AT1.
 The onset of disease in children is 3 to 9 years of age.
 Dx: elevation of neutral amino acids in urine. Plasma amino acid
concentrations are usually normal.
 Rx: avoidance of sunlight exposure & high protein diet intake. In
patients with niacin deficiency & symptomatic disease, prolong oral
administration of high doses (100-250 mg daily) of nicotinic acid or
nicotinamide is recommended.
Other hereditary photodermatoses
Kindler syndrome (KS):
 Kindler syndrome is an autosomal recessive genodermatosis
associated with mutations in FERMT1
 Kindler syndrome is ccc by poikiloderma, skin and mucosal fragility,
trauma induced skin blistering, photosensitivity, & an increased risk of
cancer.
PHOTOAGGRAVATED DERMATOSES
• Photoaggravation is well documented in this group of diseases, but the
pathophysiology is poorly understood
Atopic dermatitis
• 3% of patients with AD; the majority are female
• 2 clinical reaction patterns; photosensitive AD & AD with coexisting
PMLE.
Darier disease
• DD can be exacerbated by UVB irradiation, heat, friction, & infection.
Juvenile dermatomyositis
• Photosensitivity clearly is a part of dermatomyositis, but the
pathogenesis remains unknown.
Lupus erythematosus and neonatal lupus erythematosus
 There is a clear relationship between UVR & the C/F of LE.
 UVR may induce or exacerbate the cutaneous lesions & systemic
manifestations associated with the diseases of LE.
 The American College of Rheumatology defines photosensitivity in
their criteria for diagnosis of SLE as ‘‘unusual skin reaction from
exposure to sunlight by patient’s history or physician’s observation”.
 This college also define photosensitivity,
• 57% - 73% of patients with SLE,
• 50% - 90% with SCLE,
• 50% with DLE,
• & nearly all with tumid LE (LET)
 It is difficult for patients with LE to link sun exposure with their skin
lesions, because of a delayed time interval between UV exposure &
the exacerbation of skin lesions.
Neonatal lupus
erythematosus.
A, A 2-month-old
infant presenting with
scaling annular
erythema on the face.
B, Characteristic ‘‘owleye’’ appearance in a
patient with neonatal
lupus erythematosus.
Pellagra
 Pellagra is a systemic disturbance caused by a cellular deficiency of
niacin; it is clinically manifested by the 4 D’s: photosensitive
dermatitis, diarrhea, dementia, & death. Pellagra is the late stage of
severe niacin (vitaminB3) deficiency.
 4 theories in photosensitivity have been proposed:
(1) cutaneous deficiency in urocanic acid;
(2) accumulation of kynurenic acid;
(3) deficiency of nicotinamide adenine dinucleotide/nicotinamide
adenine dinucleotide phosphate;
(4) altered porphyrin metabolism.
 Exposure to UVA, UVB, & visible light has been reported to induce
photosensitivity in pellagra.
Thank you