This document discusses various types of cutaneous porphyrias (porphyrias that affect the skin): 1. Porphyria cutanea tarda is the most common type, caused by a deficiency in the enzyme uroporphyrinogen decarboxylase. It causes fragile blistering skin in sun-exposed areas and is associated with liver disease. 2. Congenital erythropoietic porphyria is a very rare, severe disorder causing lifelong photosensitivity and scarring. It is caused by a deficiency in uroporphyrinogen cosynthase, leading to accumulation of porphyrins in red blood cells. 3. Acute

1. CUTANEOUS PORPHYRIAS

2. •Porphyrias - group of disorders caused by
defects in the biosynthesis of haem.
•Phototoxic properties of porphyrins, cause
photosensitivity.

4. The IRON in haem useful for
 electron transfer(respiratory cytochromes),
reversible oxygen binding (haemoglobin and myoglobin)
and
oxidation and reduction reactions (cytochrome P450,
catalase)

6. • 18 delocalised electrons- exited by long wavelength.
• Soret band – 408 nm – main absorption peak

7. Cutaneous disease
only
Cutaneous disease
and acute attacks
Acute attacks only
1. Porphyria cutanea
tarda(PCT)
Hereditary
coproporphyria(HC)
Acute intermittent
porphyria(AIP)
2. Congenital
erythropoietic
porphyria(CEP)
Variegate
porphyria(VP)
3. Erythropoietic
protoporphyria(EPP)

8. CONGENITAL ERYTHROPOIETIC PORPHYRIA
•Gunther disease
•severe ,rare childhood porphyria - lifelong
mutilating photosensitivity and haematological disease.
•AR
•inherited deficiency of uroporphyrinogen
ɪɪɪ cosynthase

9. • Uroporphyrinogen ɪɪɪ cosyntase
is required to form type ɪɪɪ
porphyrin isomers.
• Its absence- formation
of type ɪ isomers - cannot
participate in haem formation,
• Accumulates in erythroid
cells and leaks into plasma.

10. Clinical features
•hydrops fetalis to mild forms
•brown discoloration of amniotic fluid or pink/ brown
porphyrin staining of nappies (fluoresce red‐orange- Wood’s
light).
•Severe photosensitivity in neonatal period → blisters
developing
•Photomutilation- onycholysis, erosions
in terminal phalanges,
destructive changes in pinna and nose

11. •Repeated inflammation with vesicles and bullae, with
secondary infection → mutilating scarring - face and hands
•A diffuse pseudosclerodermatous thickening of exposed
skin with microstomia and sclerodactyly‐like changes.
•Hypertrichosis - upper arms, temples and malar region

12. •Eyes . Keratoconjunctivitis, blepharitis, cataracts, corneal
ulcers, scars
•Bones and teeth . When teeth emerge, stained brown(
fluoresce under Wood’s). Decreased bone density, osteopenia
and osteolytic lesions
•Haematology . Haemolytic anaemia, Hypersplenism
Under violet illumination most normoblasts- red
fluorescence localized to their nuclei

13. • Red cells and urine – large amounts of uro and
coproporphyrin.
• Faeces – coproporphyrin.
• Plasma spectrofluorimetry peak – 615 to 620nm.

14. TREATMENT
•Hypertransfusion - to maintain polycythaemia→ inhibits
Hb production and ↓ses porphyrin formation
•Allogeneic bone marrow transplantation from an
HLA‐compatible donor treatment of choice

15. Genetic counselling
• For parents of an affected child, the chance of future
offspring suffering - 25%.
•The diagnosis before birth by measuring the uroporphyrin
I concentration in amniotic fluid, increased as early as 16
weeks in utero

16. PORPHYRIA CUTANEA TARDA
•characterized by fragility and blistering of exposed skin.
• acquired and associated with liver disease.
•It does not cause acute attacks.
•deficiency of UROD uroporphyrinogen decarboxylase.

17. TYPES
Type 1 – sporadic
enzyme deficiency is acquired and restricted to
hepatocytes due to inhibition of normal UROD
Type 2 – familial
enzyme deficiency is hereditary, present in all
tissues with UROD gene mutation
Type 3 – hereditary enzyme deficiency localised to
liver.
Type 4 – toxic porphyria- halogenated hydrocarbons,
hexachlorobenzene.

18. UROD inactivated by Uroporphomethene, CI
(formed oxidation of uroporphyrinogen )
The inhibitor generated in liver by ROS
accumulated uroporphyrin diffuses into surrounding tissues→
phototoxic reaction in the upper dermis
This leads to lysis of cells in the superficial dermis with
formation of vacuoles which produce blister cavity under the
basal lamina

19. •Type 1 – adult ; type 2 – childhood
•Fragility and blistering in exposed sites
•Lesions resolve leaving atrophic scars, milia, mottled hyper
or hypo pigmentation
•Scarring alopecia, hypertrichosis,
melasma like hyperpigmentation, onycholysis, solar
elastosis,Morphoea‐like plaques, cicatricial conjunctivitis

20. HEPATOERYTHROPOIETIC PORPHYRIA(HEP)
•Homozygous form of familial PCT.
•90% reduction in UROD activity.
•Severe disease similar to CEP with phototoxicity during
infancy

21. RISK FACTORS FOR THE DEVELOPMENT OF PCT

22. INVESTIGATIONS
•PCT- urine – uroporphyrin
•A plasma spectrofluorimetry peak - 615–620 nm.
•Faeces - Isocoproporphyrin
few patients with VP have the PCT urine pattern (‘dual
porphyria’)
• HEP- additional finding → raised red cell
Zinc‐protoporphyrin, and lower red cell UROD activity

24. MANAGEMENT

25. •Photoprotection
sunscreens – titanium
dioxide or zinc oxide,
(with added iron oxide)
filter films for car and
home windows, gloves,
hats and clothes

26. Specific treatments
•Venesection
Around 500 mL of blood removed every week/2 weeks, ↓
transferrin saturation to 15%, Hb to 11–12 g/dL and plasma
ferritin to ˂ 25 μg/L
•Excision and grafting - ulcerated sclerodermoid lesions
•Desferrioxamine – rapidly chelates hepatic iron
•Low dose chloroquine- complexes with uroporphyrin and
excretes in bile.
•Dose-125mg or 250mg weekly twice

28. ERYTHROPOIETIC
PROTOPORPHYRIA
•Hereditary
•painful, lifelong photosensitivity
•Without blistering
•Deficient activity of
ferrochelatase enzyme.
•Gain‐of‐function mutations in
ALAS‐2 (the first enzyme in the
pathway)
•Common in 1st year of life

29. Mutation in ferrochelatase gene
Accumulation of protoporphyrin in RBC
Porphyrin laden cells pass dermal vessels and
are expose to soret wavelength
Acute injury to endothelium by singlet oxygen
and hydroxyl radical.

30. CLINICAL FEATURES
•Immediate pain on exposure to bright sunlight
•Pts describe discomfort, tingling or itching over dorsae of
hands and face
•partial relief with cold water and wet cloths
•Physical sign – erythema and oedema
•Patients experience a ‘priming phenomenon’ in which sunlight
tolerance is reduced on the day after significant sun
exposure

31. INVESTIGATIONS
•Plasma fluorimetry – peak at 633nm
•Red cell- free protoporphyrin
•Faeces – protoporphyrin
•Urine – normal
•Biopsy- deposition of PAS positive hyaline material in
walls of blood vessels.
•DIF- IgG deposition.

32. Management
•Photoprotection
sun protective clothing.
Dihydroxyacetone paint
window films
•Oral β‐carotene -
dose 180 mg daily in adults (90 mg daily in children)
•PUVA and NBUVB- photoprotection by inducing epidermal
thickening and pigmentation.
•Bone marrow transplantation

33. PORPHYRIAS
THAT
CAUSE
CUTANEOUS
DISEASE AND
ACUTE ATTACKS

34. HEREDITARY
COPROPORPHYRIA
• rare inherited disease
•characterized by acute attacks
•AD
•Inherited deficiency of
coproporphyrinogen oxidase
•puberty

35. CLINICAL FEATURES
•Skin - 10–20% - fragility and blistering in sun‐exposed
areas, Prominent hypertrichosis, pigmentation
•Harderoporphyria – jaundice, anemia, hepatosplenomegaly
in neonates

36. INVESTIGATIONS
•615–620 nm peak - plasma spectrofluorimetry
•increased uro‐ and coproporphyrin – urine
•increased coproporphyrin - faeces

37. VARIEGATE PORPHYRIA
•rare inherited disease
•AD
•Deficiency of protoporphyrinogen oxidase.
•Accumulation of CPP and PPP inhibits
PBG deaminase.
•Local accumulation – secondary
photoinactivation of UROD

38. CLINICAL FEATURES
•Begins in adolescence
•Mild skin fragility with painful bullae in exposed areas
•Lesions heal with scarring and pigmentary abnormalities-
pseudoscleromatous changes.
•Intercurrent biliary obstruction exacerbates cutaneous
disease

39. Acute attacks
•17%
•severity varies from mild abdominal pain, vomiting and
constipation, to very severe attacks with bulbar palsy and
respiratory paralysis.

40. INVESTIGATIONS
•Plasma spectroflurimetry – peaks around 626nm.
•Urine – coproporphyrin and uroporphyrin similar to PCT.
•Faeces – copro and protoporphyrin

41. TREATMENT
•Photoprotection
•β carotene
•UVB phototherapy

42. ACUTE INTERMITTENT PORPHYRIA
•AD
•Deficiency of porphobilinogen
deaminase
•Primary or secondary
•Triggered by drugs- CYP 450
•Gunter triad – abdominal pain,
vomiting , constipation

43. Pathogenesis
Liver- heme is incorporated into CYP450 proteins
Drug or hormone induces P450
Acutely increases hepatic requirement
Inability of pathway to respond adequately
Secondary accumulation of ALA

44. CLINICAL FEATURES
•Acute autonomic neuropathy – pain, tachycardia,
hypertension, partial ileus.
•Confusion, agitation, hallucination- abnormal behaviour
•Motor neuropathy - Respiratory muscle paralysis - death

45. MANAGEMENT
•Urine – PBG excretion
•Treatment – safe drugs
•Analgesia, sedatives, antiemetics and hydration
•IV hematin or haem arginate – suppress hepatic ALA
synthase activity

47. PSEUDOPORPHYRIA
•non‐porphyric dermatosis
•clinically and histologically indistinguishable from PCT
•Porphyrin concentrations - normal
•clinical presentations of drug‐induced photosensitivity:
Also, non‐drug‐related causes.

48. Causes
•Photosensitizing drugs
•Hemodialysis
•Sunbeds – UVA tanning beds

49. Photosensitizing drugs
•NSAIDs- naproxen, ketoprofen, mefanamic acid.
•Nalidixic acid
•Tetracyclines- minocycline
•Furosemide
•Isotretinoin
•Dapsone

50. Clinical features
•vesicles, bullae, fragility, milia and scarring on
exposed skin - dorsal hands, face, chest
•Diagnosis – Normal porphyrin conc in plasma, urine and
faeces.
•Treatment – stop offending drug, sunbed usage.

53. CASE #1
45y male alcoholic house painter with c/o blisters on
hands and tight skin.

54. Urine:
Elevated Uroporphyrin > Coproporphyrins
Feces: elevated Isocopro
RBC: nl
CBC: wbc=8,
Hg=16, Hct=50, Plt=250
LFT: elevated
PORPHYRIA CUTANEA
TARDA

55. Case #3
Mother comes in with 3yr old child. She says used to cry
after going out in the sun.He would often turn red and
blister afterwards.
you notice sclerodermoid changes of the face along with
excessive hair growth along the temples.
Mother states that both she and the father have
problems with Blistering of their hands with extensive sun
exposure.

56. Hepatoerythropoietic
Porphyria

57. Case scenario #4
40y woman from S.Africa. C/o blisters and scarring of
the hands Since age of 20.
Recently admitted to the GI service for N/V/D with
abdominal pain. Urine: Copro > Uro (opposite of PCT)
Variegate
Porphyria

58. Case #5
3yo female who cries when she Goes outside, and
Then runs inside to stand in front of AC vent.
She now presents to you with elliptical scars on the face
and pebbling of the nose and hands
Erythropoietic protoporphyria