variegate porphyria (VP, mixed porphyria)
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Introduction
(See also porphyria)
Etiology
- deficiency in protoporphyrinogen oxidase
- inhibition of uroporphyrinogen I synthase by accumulated protoporphyrinogen
- pharmaceutical which may precipitate acute attacks
- anesthetics: barbiturates, halothane
- anticonvulsants:
- antimicrobials
- ergot alkaloids
- ethanol
- hormones: estrogens, progestins
- imipramine
- methyldopa
- sedatives/hypnotics
- pentazocine
- phenylbutazone
- sulfonylureas: chlorpropamide, tolbutamide
- theophylline * n) any drug that induces Cyt P450 will induce heme synthesis & potentially precipitate attack
Epidemiology
- all races
- especially prevalent in the white population of South Africa
- onset after puberty
- peak incidence: 2nd to 4th decades of life
Pathology
- decreased protoporphyrinogen oxidase & subsequent protoporphyrinogen inhibition of uroporphyrinogen I synthase have been implicated
- skin
- subepidermal bullae
- PAS-positive depositions in & around blood vessels in upper dermis
Genetics
- associated with defects in protoporphyrinogen oxidase (PPOX)
- associated with defects in HFE
Clinical manifestations
- somewhat variable in presentation
- skin lesions
- result from exposure to light, thus seasonal
- vesicles & bullae
- painful erosions from easily traumatized bullae
- atrophic scars at sites of erosions
- fragile skin
- milia
- periorbital heliotrope hue
- diffuse hyperpigmentation (melanoderma) on sun-exposed areas
- lesions localized to sun-exposed areas
- hypertrichosis
- GI manifestations
- acute attacks of abdominal pain
- nausea/vomiting
- constipation
- neuropsychiatric manifestations:
- systemic manifestations:
Laboratory
- fluorescent plasma with emission max at 626 nm
- increased urine porphobilinogen during acute attack
- elevated urine aminolevulinic acid (ALA) during acute attack
- high protoporphyrin in feces
- high coproporphyrin in feces
- complete blood count (CBC): leukocytosis
- serum iron, TIBC, serum ferritin
- evidence of iron overload
- HFE gene mutation
Management
- prognosis
- lifelong disease
- good prognosis if precipitating factors are avoided
- pharmaceutical agents
- oral beta carotene may or may not control skin manifestations, but has no effect on systemic manifestations
- narcotic analgesics for abdominal pain
- phenothiazines (Compazine) for nausea
- chloral hydrate for insomnia
- low doses of benzodiazepines for anxiety are probably safe
- parenteral nutrition if oral feeding is not possible
- intravenous glucose (300 g/day) had been recommended in the past
- intravenous heme:
- 3-4 mg IV QD for 4 days
- begin as soon as possible after attack
- preparations:
- hematin (Abbott)
- heme albumin
- heme arginate (Leiras Oy, Turka Finland)
- heme albumin & arginate chemically stable & less likely than hematin to produce phlebitis or anticoagulant effect
More general terms
Additional terms
- heme synthesis
- protoporphyrinogen IX
- protoporphyrinogen oxidase; PPO (PPOX)
- safe & unsafe drugs in acute intermittent porphyria (AIP), variegate porphyria (VP) & hereditary coproporphyria
References
- ↑ Textbook of Biochemistry with Clinical Correlations, 3rd ed., TM Devlin (ed), Wiley-Liss, NY 1992 pg 1012
- ↑ Clinical Diagnosis & Management by Laboratory Methods, 19th edition, J.B. Henry (ed), W.B. Saunders Co., Philadelphia, PA. 1996, pg 172
- ↑ Color Atlas and Synopsis of Clinical Dermatology, Common and Serious Diseases, 3rd ed, Fitzpatrick et al, McGraw Hill, NY, 1997, pg 260-62
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 2076, 2078
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 179