Porphyrias Flashcards
In what range of light do porphyrias tend to absorb light?
401-410 nm (making it the short end of the visible spectrum)
What is the difference in clinical findings of water vs lipid-soluble porphyrins?
Water-soluble: Causes blisters
Lipid-soluble: Acute burning and erythema
What is the most common porphyria?
Porphyria cutanea tarda
What causes porphyria cutanea tarda?
Decreased hepatic uroporphyrinogen decarboxylase (UROD) activity
What are the 3 types of porphyria cutanea tarda?
I: familial
II: Sporadic/acquired
III: Normal UROD gene, but multiple affected family members
What type of porphyria cutanea tarda is most common?
Type II sporadic/acquired
What are the skin findings of porphyria cutanea tarda?
Skin fragility, vesicles, bullae, erosions, milia, scarring, hyperpigmentation, hypertrichosis in photo distributed areas (especially dorsal hands/forearms
What should be screened for if a patient has porphyria cutanea tarda?
Hemochromatosis
What is the plasma peak fluorescence pattern for porphyria cutanea tarda?
620nm
What is the definition of an acute vs non-acute porphyria?
Acute suggests the presence or potential for potentially life-threatening acute neurologic attacks as part of the dz
Which of the porphyrias are acute?
Acute intermittent porphyria, Variegate porphyria, Hereditary coproporphyria, ALA-D deficiency porphyria
Which porphyrias are autosomal recessive?
Most of the porphyrias are autosomal dominant. Exceptions include one XLD dz (X-linked dominant protoporphyria), and 3 autosomal recessive ones
AR ones: ALA-D deficiency porphyria, Congenital erythropoietic porphyria, Hepatoerythropoietic porphyria, and rarely erythropoietic porphyria
What porphyrias are not associated with skin findings?
ALA dehydratase deficiency porphyria and acute intermittent pophyria
What porphyria results from a homozygous mutation in uropophyrinogen decarboxylase (UROD)?
Hepatoerythropoietic porphyria
- This is opposed to porphyria cutanea tarda which is a diminished action of this same enzyme. This is why you see very exaggerated findings of PCT occurring early (starts in childhood, extreme photosensitivity, hypertrichosis, milia, vesicles/bullae/erosions/ulcers and the same plasma fluorescence emission peak (620nm)
What is the preferred lab testing to confirm the diagnosis for suspected porphyria cutanea tarda?
Serum/plasma porphyrins
What is the most common form of porphyria cutanea tarda?
Type 1 (absence of UROD mutation, 80% of cases)
What is the pathogenesis of skin lesions in porphyria cutanea tarda?
When the porphyrins accumulate that are seen in PCT, are exposed to a wavelength near 400nm the porphyrins enter an excited state and release photons that activate oxygen in the tissues to singlet oxygen which damages tissues leading to blister formation
What are some triggers for porphyria cutanea tarda?
Alcohol abuse, estrogen, iron and hemochromatosis, hepatitis C, and HIV
What is the histology of porphyria cutanea tarda?
cell-poor subepidermal bulla w/ “festooning” of dermal papillae, “caterpillar bodies” (pink BMZ material in blister cavity and epidermis)
- Festooning is from papillary fibrosis which makes that area keep its shape when you loose the epidermis
What are the DIF findings in porphyria cutanea tarda?
IgG, IgM, fibrinogen, and C3 linearly along BMZ and in superficial dermal vessels (see thickened deposits around vessels)
What is the treatment for porphyria cutanea tarda?
Avoid precipitating factors (alcohol and estrogen), photoprotection/sun avoidance, treat the underlying conditions (if any), phlebotomy, low dose hydroxychloroquine, and deferasirox