erythropoietic protoporphyria (EPP)
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Introduction
An inherited photosensitivity disorder unique among the porphyrias in that porphyrins & their precursors are not excreted in the urine. It is also the only porphyria in which biochemical defects manifest themselves in erythropoietic & hepatic cells.
Etiology
- deficiency in ferrochelatase
- accumulation of protoporphyrin
- overactivy of ALA synthetase appears to play a role
- precipitated by exposure to UV-A radiation
Epidemiology
- onset in childhood, rarely in early adulthood
- no sex preference
- all ethnic groups
- prevalence 1:100,000
Pathology
- liver
- periportal fibrosis & deposits of brown pigment
- birefringent granules within hepatocytes & Kupffer cells
- increased protoporphyrin in liver
- skin
- marked eosiniphilic homogenization & thickening of the blood vessels in the papillary dermis
- accumulation of an amorphous, hyaline-like eosinophilic substance in & around blood vessels
Genetics
- associated with defects in ferrochelatase (FECH)
Clinical manifestations
- skin manifestations
- stinging & itching within a few minutes of sunlight exposure
- delayed effects on skin 1-8 hours later
- no "rash", only exagerated & rapid "sunburn" response
- symptoms may occur when exposed to sunlight through windows
- chronic recurrent exposure
- shallow, often linear scars, especially on nose & dorsal aspect of hands
- diffuse wrinkling & waxy color of facial skin
- crusted erosive lesion may occur on nose & lips
- no sclerodermal-like changes, hirsuitism or hyperpigmentation
- systemic manifestations
- biliary colic (protoporphyrin cholelithiasis) may occur
- hemolytic anemia with hypersplenism (rare)
- hepatic cirrhosis & portal hypertension (20%)
Laboratory
- increased protoporphyrin in erythrocytes
- urine: no porphyrins or their precursors except in rare cases of fatal hepatic cirrhosis
- increased protoporphyrin in feces
- liver function tests
- peripheral blood smear: transient fluorescence at 400 nm
- liver biopsy if indicated
- skin biopsy
Radiology
gallstones may be present
Complications
fatal hepatic cirrhosis
Management
- prognosis
- lifelong condition, no curative therapy
- photosensitivity may become less prominent in older age
- symptomatic therapy
- beta carotene 180 mg PO daily, divided BID/TID provides amelioration of the photosensitivity
- PUVA photochemotherapy may enhance the dephotosensitizing effect of beta carotene
More general terms
Additional terms
- aminolevulinic acid [ALA] synthetase
- ferrochelatase, mitochondrial; heme synthase; protoheme ferro-lyase (FECH)
- heme synthesis
- protoporphyrin
References
- ↑ Williams Hematology, 5th edition, Beutler et al eds, McGraw-Hill, 1995 pg 740
- ↑ Color Atlas and Synopsis of Clinical Dermatology, Common and Serious Diseases, 3rd ed, Fitzpatrick et al, McGraw Hill, NY, 1997, pg 263-65
- ↑ Clinical Diagnosis & Management by Laboratory Methods, 19th edition, J.B. Henry (ed), W.B. Saunders Co., Philadelphia, PA. 1996, pg 172
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 178-79