Melanogenesis (including diseases) Flashcards
A = Tyrosine
B= L-DOPA
C= DOPAquinone
D= DOPAchrome
E- DHICA
F= DHI
G= DHICA-melanin
H= DHI-melanin
I= cysteinylDOPA
J= tyrosinase
K= also tyrosinase
L= no cysteine
M= cysteine
N= trp2
O= trp1
P= oxidation polymerization
What are melanoblasts?
Precursors to melanocytes
Unpigmented
Arise from neural crest cells
During embryogenesis, where do melanoblasts migrate to (may not develop into melanocytes in all of these locations)?
Skin
Peripheral nervous system
Bone
Cartilage of the head
Choroid of the eye
What are the primary signaling molecules in melanocyte migration and differentiation?
Wnt
endothelin-3 (ET3)
bone morphogenetic proteins (BMPs)
steel factor (stem cell factor)
hepatocyte growth factor
Where are epidermal melanocytes located?
Primarily basal layer
Where are follicular melanocytes located?
outer root sheath and the hair matrix
(in humans, there are also melanocyte stem cells in the hair follicle bulge)
What adhesion molecules to melanocytes express?
E and P-cadherins
What is thought to be the prime mediator of adhesion between melanocytes and keratinocytes?
E-cadherin
Other than the epidermis and hair follicle, where are mature melanocytes found?
sebaceous and sweat glands
the superficial dermis
the uvea of the eye
the cardiovascular system
the cochlea (stria vascularis)
the central nervous system and adipose tissue (leptomeninges)
Where in the ear are melanocytes found?
the cochlea (stria vascularis)
What is the function of melanocyte dendrites that weave intercellularly between keratinocytes?
transfer melanosomes to keratinocytes
What are melanosomes?
subcellular lysosome-like organelles in which melanin pigments are
synthesized and stored
What is the ratio of melanocyte to keratinocyte in the basal layer of the epidermis of dogs? Humans?
Dogs - 1:10 (up to 20)
Humans - 1:36
*same absolute number despite pigmentation, actual pigmentation is determined by melanogenic activity and melanosome number/size
What is an epidermal melanin unit?
The melanocyte and associated keratinocytes
How are melanosomes normally arranged in a keratinocyte?
“caps,” dorsal to nuclei
they are wearing little sun hats!
How do melanocytes look on normal H&E?
Clear
What special stains are best for looking for melanocytes on histopathology??
DOPA oxidase reaction
Fontana-Masson stain
Schmorl’s method
Which IHCs are best for looking at melanocytes on histopathology?
vimentin
S-100 protein
What are chromatophores?
Cells that contain pigment and reflect light in different ways that determine coloration
Found in amphibians, fish, reptiles, crustaceans, and cephalopods
Classified by appearance under white light:
- xanthophores (yellow)
- erythrophores (red)
- iridophores (reflective/iridescent)
- leukophores (white)
- melanophores (black/brown)
- cyanophores (blue)
What are the functions of melanocytes?
(1) cosmetic appearance
(2) protection against ionizing radiation (absorb UV and visible light)
(3) scavenger of cytotoxic free radicals and intermediates
*probably most against UV light, melanin is a stable free radical
4) secretion of IL-8, IL-1α, and TNFα (inflammatory)
5) inhibition of keratinocyte proliferation
6) calcium homeostasis
Melanin is the main determinant of skin and hair color. What other pigments influence coloration in mammals?
yellow carotenoids - epidermal cells
red - oxygenated hemoglobin
blue - unoxygenated hemoglobin in the dermal venules
What is constitutive pigment?
pigmentation that is genetically determined in the absence of external influences
What is facultative pigment?
pigmentation that occurs in response to stimuli (such as UV light)
What is the major differentiating factor between eumelanin, pheomelanin, and oxymelanin?
The amount of sulfur
Eumelanin = black/brown, lower sulfur
Pheomelanin = red/yellow, high sulfur
Oxymelanin = yellow/brown-red, no sulfur
What is oxymelanin?
yellow-red/brown non-dark pigments devoid of sulfur
found in humans, Argentinean goats, Addis sheep, and wild boar
What are the 4 main steps of melanin synthesis and distribution in the epidermis?
1) transcription of proteins required for melanogenesis
2) melanosome biogenesis
3) transport of the melanosome to the tips of dendrites
4) transfer of the melanosome to keratinocytes
What is the key intermediate in the synthesis of all forms of melanin?
dopaquinone
Which melanin is high in cysteine or glutathione?
Pheomelanin
Which melanin is alkai-insoluble?
Eumelanin
Which melanin has elliptical melanosomes?
Eumelanin
Which melanin has an unorganized/microvessicle melanosome?
Pheomelanin
Which melanin is produced when there are high levels of tyrosinase?
Eumelanin
What is the rate limiting step in the synthesis of melanin?
Conversion of Tyrosine to LDOPA via tyrosinase (first step)
What is a critical cofactor for the enzyme tyrosinase?
Copper
What is a cofactor for the enzyme TYRP2?
Zinc
Which transcription factor is the primary regulator of melanogenesis?
MITF
(microphthalmia-associated transcription factor)
What does MITF induce the transcription of?
Tyrosinae,
TyRP1
DOPA
TyRP2
What upregulates MITF?
binding of c-kit with steel factor (stem cell factor)
–> activation of the cAMP pathway
binding of the MC1-R by α-MSH and ACTH (eumelanin)/ASP (pheomelanin)
How does Wnt play a role in melanogenesis?
Wnt signals play a role in neural crest cell –> melanoblast
Wnt3a turns melanoblasts –> melanocytes by maintain MITF expression
*if Wnt is bound to Frizzled it inhibits GSK3B so β-catenin can increase MITF
What are the main stimulators of melanogenesis?
α-MSH
ACTH
Endothelin1, steel (stem cell) factor
leukotrienes (LTB4, LTC4)
prostaglandins (PGE2, PGF2)
UV radiation
nitric oxide
histamine
neurotrophins
What does α-MSH do to melanogenesis?
Stimulates it (is one of the main drivers)
What are the precursors in the production of α-MSH?
pro-opiomelanocortin (POMC) and ACTH
Where is pro-opiomelanocortin (POMC) produced?
*pituitary gland
epidermal keratinocytes
What does UV light do to pro-opiomelanocortin (POMC)?
Stimulates it
Oxidative stress from UV light leads to POMC peptide production
What hormone(s) involved in melanin synthesis is pro-opiomelanocortin (POMC) the precursor to?
ACTH
α-MSH
How does c-kit affect melanogenesis?
Binds to steel factor/SCF
–> activates cAMP pathway
–> activates MITF
–> increases transcription of genes for melanogenesis
What are two important genes that play a role melanocyte differentiation and in MITF’s ability to produce tyrosinase?
SOX10
PAX3
What are the ligands of MC1R?
α-MSH, ACTH and ASP
How does MC1R affect melanogenesis?
Binds to α-MSH, ACTH or ASP
–> activates MITF (via two routes, one with cAMP and one without)
–> increases transcription of genes for melanogenesis
What are the two primary melanocyte cell membrane receptors involved in the synthesis of melanin?
c-Kit
MC1R
How does UV light stimulate melanogenesis?
Increases POMC –> increases α-MSH, ACTH (and MC1R) –> increase MITF
What do leukotrienes and prostaglandins do to melanin synthesis?
Stimulates it
What does histamine do to melanin synthesis?
Stimulates it
Which cytokines are inhibitors of melanin synthesis?
TNF-α
IL-1
IL-6
What does BMP-4 do in regards to melanin synthesis?
Inhibits neural crest cells becoming melanocytes
How is the endothelin (ET) family of peptides involved in melanin synthesis?
late steps of melanoblast migration from the dermis to the stratum basale
Where is endothelin-3 (ET3) produced?
ectodermal cells
What does endothelin-3 (ET3) interact with on the melanoblast?
endothelin receptor B (ednrB)
What is proper interaction of ET3 and ednrB important for?
survival, proliferation, and migration of melanoblasts
normal formation of enteric nerves
What do defects in ET3 or EdnrB result in?
prominent melanocytes loss
+/- problems with enteric nerves
What happens to foals with a mutation in EdnrB?
Lethal white foal syndrome
- White foal
- Dies in 1-5 days due to inability to defecate
Why can’t foals with lethal white foal syndrome defecate?
EdnrB mutation –> lack of the formation of myenteric plexuses –> colonic atresia
What is Type IV Waardenburg Syndrome?
Mutation in EdnrB
Deafness, facial bone defects, variation in hypopigmentation
What happens if you breed two Overo horses?
Lethal white foal syndrome
- autosomal recessive mutation in EdnrB
Which microtubule proteins are important for the transportation of melanosomes along the melanocyte dendrites?
dyneins (retrograde)
kinesins (anterograde)
In which fashion do dyneins move melanosomes along the melanosome dendrite?
Retrograde
In which fashion do kinesins move melanosomes along the melanosome dendrite?
Anterograde
How many stages are there in melanosome maturation?
4
What happens in stage I of melanosome maturation?
Proteinaceous fibrils begin to form (no melanin yet)
What happens to MITF in the absence of SOX10?
MITF cannot induce the expression of tyrosinase
What happens in stage II of melanosome maturation?
Fibrous striations are fully formed (no melanin yet)
What happens in stage III of melanosome maturation?
Melanin synthesis begins and melanin-synthesizing enzymes are transported to the melanosomes
What happens in stage IV of melanosome maturation?
All internal structures are masked and the melanosome is fully melanized
What do melanocytes do in the stria vascularis?
Maintain endolymph via K transport regulation (high [K] in endolymph)
o Low K in endolymph without melanocytes = deafness
Why are individuals with albinism not deaf?
They still have melanocytes, it’s just that the melanocytes don’t make melanin
What stage melanosome is this?
Stage I
What stage melanosome is this?
Stage II (fibrils form)
What stage melanosome is this?
Stage III (melanin starts to be deposited on fibrils)
What stage melanosome is this?
Stage IV (mature)
How does the structure of follicular melanocytes differ from that of epidermal melanocytes?
Follicular melanocytes are larger and more dendritic than epidermal melanocytes and produce larger melanosomes
When in the hair cycle do follicular melanocytes undergo maturation?
Anagen
What do the proliferation and maturation of follicular melanocytes dependent on?
c-Kit expression by melanocytes
steel factor synthesis by follicular keratinocytes
When in the hair cycle does melanogenesis occurs and melanosomes are transferred?
Anagen
Where are follicular melanocytes located during anagen?
proximal hair bulb
What happens to follicular melanocytes during catagen?
They undergo apoptosis
Which genes/transcription factors are important in initiating melanoblast migration?
-Splotch
- Patch
- Piebald lethal
Which genes/transcription factors are important for having melanoblasts migrate to distant sites?
- dominant white spotting
- steel
- bc12
Which gene/transcription factor is most important for the survival and proliferation of melanocytes?
MITF
Which genes/transcription factors are important for initiating melanosome biogenesis?
- steel
-bc12
Which genes/transcription factors are important for initiating melanin biosynthesis?
- beige
- pallid
- pale-ear
- OA1
- mottled
- pink-eyed
Which genes/transcription factors are important for initiating melanin transfer?
- albino
- brown
- slaty
- silver
Which genes/transcription factors are important for initiating melanin degradation and processing?
dilute
What are the 10 steps in the development of melanin starting at neural crest cells?
1) melanoblast development from neutral crest cell
2) initiation of melanoblast migration
3) melanoblast migration to distant sites
4) melanoblast migration arrest
5) melanoblast differentiation into melanocytes
6) melanocyte survival and proliferation
7) melanosome biogenesis
8) melanin biosynthesis
9) melansome transfer
10) melansome degradation and processing
What does myosin-Va during melanosome transfer?
It is at the dendrite tip
Important for actin binding and melanosome transfer
What are the processes by which melanosomes are transferred from the melanocyte to the keratinocyte?
exocytosis
cytophagocytosis (keratinocyte eats dendrite tip)
fusion of plasma membranes
transfer by membrane vesicle
Where are melanosome proteins made in the melanocyte?
ribosomes bound to the ER
What does melanin synthesis produce that is damaging to melanocytes?
hydrogen peroxide
quinone intermediates
What happens to DOPA-quinone in presence of cysteine or glutathione?
becomes cysteine-DOPA –> pheomelanin
What happens to DOPA-quinone in absence of cysteine or glutathione?
DOPA-chrome tautomerase makes it into DOPA-chrome –> eumelanin
Is TYRP1 or 2 involved higher up (closer to tyrosine) in the melanin synthesis pathway?
TYRP2 is higher (DOPA-chrome –> DHICA)
Then TYRP1 (DHICA –> indole-5,6-quinone carboxylic acid)
Where is tyrosinase present in the melanogenesis pathway?
1st step: Tyrosine –> L-DOPA (rate limiting)
2nd step: L-DOPA –> DOPA-quinone
Lower down in eumelanin: DHI –> indole-5,6-quinone
In which condition are mutation in tyrosinase found?
oculocutaneous albinism
What mutations are found in Pmel17?
SILV (PMEL17) Merle
Harlequin (H)
SILV (PMEL17) Silver/Silver dapple horses
Rat Tail syndrome (cross bred hypotrichosis in cows)
What is Pmel17 important for?
Structural – fibrillar matrix within the melanosomes required for proper deposition of melanin
*melanosome cannot progress from stage I to stage II
A defect in which gene is associated with the SILV/merle pattern in dogs and what problems can arise from this?
PMEL17 (incomplete dominance)
May have ocular or skeletal abnormalities and potential deafness
*worse in double merles
A defect in which gene causes the Harlequin (H) pattern in great Danes?
PSMB7 (dominant)
Modifier of SILV (PMEL17) Merle
* must also have merle
Autosomal dominant, but homozygous is frequently embryonic lethal
* Increases cytotoxicity of altered Pmel
Patches of full color on a white background
A defect in which gene is associated with the SILV/silver dapple pattern in horses and what problems can arise from this?
PMEL17 (dominant)
Rocky mtn horse, icelandic horses, others
Heterozygous: ocular cysts
Homozygous: multiple ocular abnormalities
What condition happens when there is a defect in P protein?
oculocutaneous albinism type 2
What is the role of MART1/Melan A in melanin synthesis?
In Stage I and II melanosomes
Complexes with Pmel17
Affects expression, stability, trafficking, processing of Pmel17
What is the role of Heteroterameric Adaptor Protein Complexes in melanin synthesis?
Cargo sorting
Directs tyrosinase, TRP’s, Pmel17 to appropriate organelles
- affect hemostasis and lymphocytes
If absent: Hermansky-Pudlak syndrome
- albinism, platelet dysfunction, pulmonary
What is canine cyclic hematopoiesis/neutropenia?
Dog form of hermansky-pudlak type 2 aka “grey collie syndrome”
Lethal, autosomal recessive mutation in APB3 (adaptor protein complex 3)
Silver-grey collies with light nose
Poor-doers by 1 week, ill by 8-12 wk
- fever, diarrhea, infections, conjunctivitis, arthralgia
- alternate neutropenia and neutrophilia every 10-12 days
- don’t make neutrophil elastase
- die by 6 mo (can live to 2 with care)
Treatment: bone marrow transplant
What are the primary genes associated with Waardenburg syndrome?
EDNR-B
MITF
PAX3
SOX10
What species is prone to Waardenburg syndrome?
Ferrets
“blaze” coat color pattern (small white stripe on top of head)
What is piebaldism in dogs associated with?
Congenital hereditary sensorineural deafness
What causes deafness in congenital hereditary sensorineural deafness?
Mutations in melanocytes
Results in strial degeneration
What breed of dog is prone to congenital hereditary sensorineural deafness?
Dalmations
- normal until 3 weeks then rapid loss of hair cell function
What mutations are oculocutaneous albinism associated with?
Tyrosinase
TRYP1
MATP
What happens to the hearing of individuals with oculocutaneous albinism?
It is present (so melanocytes not essential for hearing)
More susceptible to loss from noise of toxins (melanocytes are protective)
What causes piebaldism?
Mutation in c-Kit/steel factor
Autosomal dominant
Failure of melanoblasts to migrate appropriately to the skin and/or survive
What is true about the eyes and ears of individuals with piebaldism?
rarely affects the melanocytes in the eyes or inner ear, so hearing usually remains intact
What is the locus that piebaldism is associated with?
Dominant white spotting locus (W)
*considered a normal color variant
What is lethal lavender foal syndrome?
Mutation in myosin-Va (MYO5A) gene
Egyptian Arabians
Foals are born a pale lavender, silver or pale-pinkish gray color
- are neurologic, unable to stand, and typically have an arched neck or back
- die shortly after birth
What is the locus that color dilution in dogs is associated with?
Dilute (D) locus
- esp mutation near MLPH (melanophilin)
What causes color dilution in dogs?
Mutations near MLPH
Enlarged melanosomes (macromelanosomes) in hairs
- has more pigment but because it is clumped it looks lighter
Melanocytes have abnormal dendrites so melanosome transfer is impaired
How do you diagnose color dilution?
Trichogram: macromelanosomes
Biopsy for confirmation:
- Atrophy, distortion and abnormal melanin in follicles
- Clumping of melanin in epidermis and around follicles
- Pigmentary incontinence at base of hair follicle
- Keratin plugged infundibula with dysplasia (irregular, misshapen)
Why is secondary bacterial folliculitis common in dogs with color dilution alopecia?
Macromelanosomes cause hair to fracture
What is black hair follicular dysplasia?
Similar to color dilution alopecia but causes hair loss in black areas
Autosomal recessive
What is Chediak-Higashi Syndrome?
Autosomal recessive mutation in LYST
Results in defective lysosome and vesicular transport
–> large lysosomes in neutrophils/macrophages, macromelanosomes
Albinism, photophobia, increased susceptibility to disease
Persian cats, GSD, Hereford cattle, Australian blue rats, mice, mink, foxes, and an albino orca
What is vitiligo?
Acquired disease that causes melanocyte destruction = leukoderma
Pathogenesis is unclear
- in some cases cytotoxic T-cells are triggered to attack melanocytes
- Belgian Tervuren have anti-melanocyte antibodies
Does not cause loss of architecture or crusts/erosions
May progress or repigment
In what breeds of dogs and cats has a hereditary component of vitiligo been proposed?
Belgian Tervuren dogs, rottweilers, Old English sheepdogs, Siamese cats
What does histopathology of vitiligo look like?
early lesions: some melanocytes and inflammatory infiltrate
late lesions: complete lack of melanocytes and inflammatory infiltrate
What causes graying in animals?
Reduction in melanocyte replication via senescence
Age and genetically related
What is Dudley nose?
Dogs with no nasal pigment and present from birth
Histopathology: no melanocytes in epidermis, some in dermis
Mutation in TYRP1
What is seasonal nasal hypopigmentation?
Sometimes also called Dudley nose but is hypo- not de-pigmentation
Usually darker in the summer, lighter in winder
Siberian Huskies, golden retrievers, labs, bernese mountain dogs
What breed of dogs is prone to a tyrosinase deficiency?
Chow-Chows
Rare
Occurs in puppies
Frequently resolved in 2-4 months
What happens to the hair of black cats fed a tyrosinase deficient diet?
It became reddish-brown
Can be reversed by feeding a normal diet
*May occur with poorly made canned fish-based foods
What is lentigo/lentigo simplex?
Asymptomatic macular melanosis
Orange cats are prone to this around lip, nose, gingiva, and eye lid
Pugs have an autosomal dominant form (lentiginosis profusa)
histopath can have increased production of type 4 melanosomes
What are epidermal nevi?
Benign patches, plaques, or nodules
May be hereditary, may follow Blaschko lines or nerves, can be linear
Epidermal and melanocytic nevi have increased pigment
What is feline acromelanism?
Form of albinism
Siamese, Himalayans, etc
Tyrosinase in the hair bulb is temperature sensitive (only works <~36C)
- normally pigment production is limited to extremities
- shaving will temporarily cool skin enough to have hair temporarily be darker
What is the most common form of acquired hyperpigmentation in dogs and cats?
Post-inflammatory hyperpigmentation
What breeds of dogs are prone to post-inflammatory menalotrichia?
Poodles, Yorkshire terrier, Bedlington terrier, poodle, old English sheepdog
- usually due to deep inflammatory disease (ex. folliculitis)
Why is post-inflammatory hyperpigmentation thought to occur?
keratinocytes releasing melanocyte-stimulating factors
Which drugs can induce hyperpigmenation?
Mitotane
Doxycycline
Cabergoline (Argentinian boar hounds)
Ketoconazole (single brussels griffon
What is the theory behind why hyperadrenocorticism, hypothyroidism, and sex hormone dermatosis are associated with hyperpigmentation?
1) direct effect of hormone on melanocytes
- Corticotropin and pituitary lipotrophic hormones stimulate melanogenesis
2) they increase alopecia which increases UV effect on melanocytes
Which nutrient deficiencies cause leukotrichia?
Copper
zinc
pyridoxine
pantothenic acid
lysine
What are some precipitating factors for periocular leukotrichia in Siamese cats?
pregnancy
dietary deficiencies
systemic illness
What is Aguirre’s syndrome?
Reported in cats (Siamese)
Unilateral periocular depigmentation Siamese cats associated with Horner’s syndrome, corneal necrosis with uveitis, and URI
What is Vogt-Koyanagi-Harada (VKH) Syndrome in humans?
rare, T cell-mediated autoimmune disease
- Attack against melanocyte or tyrosinase and gp100
- results in leukoderma, uveitis, aseptic meningitis, hearing impairment, poliosis, and alopecia
What are the 3 phases of Vogt-Koyanagi-Harada (VKH) Syndrome described in humans?
(1) Meningoencephalic phase
(2) Acute ophthalmic phase
(3) Dermatologic phase
*also can be classified into 4 stages (prodromal, acute, chronic convalescent and chronic recurrent stages)
How does the presentation of uveodermatologic syndrome (VKH-like) differ in dogs from humans?
Dogs have granulomatous uveitis and depigmenting dermatitis but no meningitis
What typically happens first with canine uveodermatologic syndrome, ocular changes or dermatologic changes?
Ocular (Uveitis –> glaucoma –> retinal detachement)
Which dog breeds are predisposed to uveodermatologic syndrome?
Akita
A predisposition in Siberian Huskies and Samoyeds is also suspected
What breed of horse is vitiligo common in?
Arabian fading syndrome aka juvenile Arabian leukoderma
- happens at a young age (1-2 yr)
*Early vitiligo
Lymphocytes infiltrate the basal layer of the epidermis (arrow heads) in
very low numbers at the junction of depigmented and non-depigmented epidermis
Pigmentary incontinence (arrow) accompanied by a very mild, mononuclear, perivascular, inflammatory cell infiltrate.
What are the most common cutaneous signs associated with dogs with uveodermatologic syndrome?
Symmetrical leukoderma and/or leukotrichia, followed by erosions-ulcerations, alopecia, crust and erythema
- mostly on face/head (nose, lips, periorbital, potentially oral cavity)
Canine uveodermatologic syndrome
What are the histopathologic findings associated with canine uveodermatologic syndrome?
Perivascular to lichenoid inflammation (but not interface)
* Macrophages (dust melanin / “peppered”)»_space; neuts, lymphs, plasma cells
* Inflammation can be periadnexal and nodular
Partial to complete loss of basal cell melanin / melanocytes
* Depigmentation
Exocytosis of lymphocytes and/or neutrophils
*but basal keratinocyte damage (interface dermatitis) is limited or absent
What is the treatment of canine uveodermatologic syndrome?
*Aggressive therapy to try to save eyes!
Glucocorticoids are mainstay in people
Immunosuppression with glucocorticoids, azathioprine, and cyclosporine
Usually lifelong therapy
canine uveodermatologic syndrome
lymphocyte satellitosis around melanocytes
“peppered”/dust-like melanosomes
What is leukoderma in horses?
A common inflammatory reaction pattern associated with:
- infections
- wounds
- phenols and rubber (contain ingredients that inhibit melanogenesis)
What animal gets reticulated/”tiger stripe” leukotrichia?
Quarter horses predisposed (hereditary?)
Usually yearlings
Dorsal midline from withers to base of tail
Linear crusts in characteristic cross-hatched pattern -> white hair
Underlying skin is normal pigmented
Histopath: form of EM (lichenoid interface dermatitis with apoptotic keratinocytes and satellitosis in basal layer) and may have vesicles
o May be related to vaccines, possibly rhinopneumonitis, herpes
What is hyperesthetic leukotrichia in horses?
Rare skin condition that causes painful crusts and hair loss on the back
Persist for 1-3 months, hair comes back as patchy leukotrichia
Some associated with herpesvirus vaccine, recurs with later vax
May be a form of EM based on histopathology
May be related to reticulated leukotrichia but affects older horses
What causes Congenital Stationary Night Blindness in horses?
The leopard complex or appaloosa spotting
Patterning genotype is incomplete dominance (need LP/LP to be blind)
- LP/LP does not have many spots
Mutation in TRPM1
Small cornea, night blindness, increased risk for equine recurrent uveitis
- if they do not have equine recurrent uveitis, it does not get worse with age
What is Type I photosensitivity?
Primary
Injection, ingestion or contact with a photosensitizing agent
- St. John’s wort
- Perennial rye
- tetracyclines
- sulfonamides
What is Type II photosensitivity?
Hepatic involvement
- hepatic insufficiency
–> inadequate clearance of chlorophyll breakdown product phylloerythrin
- Pyrrolizidine alkaloids
–> fire weed, rape/kale, heliotrope, ragworts
- Bluegreen algae, liver abscesses, lymphosarcoma, hepatic neoplasia, copper toxicity, etc
What is Type III photosensitivity?
Due to aberrant pigment synthesis (porphyria)
What is a potential treatment for vitiligo?
oral L-phenylalanine
