Autosomal dominant condition. The disorder is latent in majority and usually precipitated after puberty by DRUGS, HORMONALFACTORS, ALCOHOL, FASTING, SURERY, MENSTRUAL CYCLE OR PREGNANCY.C/F: It is characterized by acute attacks of GI and neuropsychiatric symptoms. No cutaneous lesions. THE URINE IS PORTWINECOLORED.Investigations:
Urinary excretion of ALA and PBG are elevated during and between the attacks.
2 rapid screening tests are available to test freshly voided urine for increased PBG. The first is simply to expose the urine tobright sunlight for several hours ------- darkening to a deep red colour suggests that PBG is present. The second test knownas the HOESCH TEST is also a simple procedure to detect the urinary PBG. To 2 ml of Ehrlich’s reagent, 2 drops of freshlyvoided urine is added, a cherry red color of the sample gives a positive result.STEP 4:Hydroxymethybilane ------------- uroporphyrinogen IIIEnzyme = UROGEN III Synthase.Porphyria = CONGENITAL ERYHTROPOETIC PROPHYRIA (CEP).AUTOSOMAL RECESSIVEIt results in the accumulation of hydroxymethybilane which converts spontaneously to UROGEN I.Onset = in the first few months of life.C/F: There is moderate to severe photosensitivity. CEP CAUSES THE MOST MUTILATING SKIN LESIONS OUT OF ANY OF THEPORPHYRIAS. The photosensitivity is due to the excess URO I and COPRO I in the RBCs, plasma and skin which may cause photolysisof porphyrin rich cells. The skin manifestations include skin fragility and vesicles and bulla which may contain pink fluorescent fluid.Secondary infection, delayed healing and scar formation may occur. This may lead to loss of acral tissue such as tips of ears, nose,fingers and facial mutilation. Other features are ----
Hirsutism of the photoexposed skin
Irregular hypo and hyperpigmentation
Cicatricial alopecia
Eye changes ---- photophobia, keratoconjunctivitis, ectropion, symblepheron
Erythrodontia
Urine ---- fluoresce pink
Splenomegaly
hypersplenism
Hemolytic anemia
Porphyrin rich gallstone.INVESTIGATIONS:
Increased excretion of URO I and COPRO I in urine ------ appears burgundy red.
Increased COPRO I in the feces.
Marrow normoblasts exhibit relatively stable fluorescence and contain markedly elevated URO I, COPRO I and PROTO.STEP 5:UROGEN III -------------- COPROGEN IIIEnzyme = UROGEN decarboxylase.Porphyria = Porphyria cutanea tardaIt is the most common form of porphyria. The disease is classified into 2 forms --------
Type I ---- acquired/sporadic. The enzyme is deficient only in the liver. The disease manifests usually by 4
th
to 5
th
decade when the subject is exposed to some environmental agents like alcohol, estrogens, iron, viral infections(HCV, HIV), polychlorinated hydrocarbons particularly HCB, dioxin(environmental pollutant).
Type II ---- hereditary PCT. It is inherited as AD. The enzyme is reduced to 50% in all tissues including RBCs andcultured skin fibroblasts. Penetrance is very low. It may manifest in childhood.C/F:
The most common skin manifestation of PCT is SKIN FRAGILITY manifesting as erosions, vescicles and bulla in thephotoexposed and trauma prone areas --------- usually on the dorsa of hands and feet. They resolve with hypo andhyperpigmented scarring and milia.
In contrast to EPP, the subjective discomfort following sun exposure is distinctly uncommon in PCT. In fact many patients donot realize that their skin eruptions are causally related to sunlight.
Other cutaneous changes include facial hypertrichosis along the temples and cheeks, mottled pigmentation resemblingchloasma. There may be purplish red suffusion of the central part of the face particularly involving the periorbital areas.Sclerodermoid plaques can occur (both in PCT and HEP). They occur both in photoexposed and photo covered areas.Histopathology:In mild cases, homogenous Eosinophilic deposits are limited to the immediate vicinity of papillary dermal vessels best seen inPAS. In severe cases, these further extend and coalesce with each other. In addition the deeper vessels may show homogenousmaterial in the walls and around the eccrine glands.Drugs that are unsafe in acute porphyria:
1.
ANTICONVULSANTS---- barbiturates, valproate, trimethadione, ethosuximide, hydantoin, carbamazepine
2.
OTHER CNS DRUGS---- hydantoin, nitrazepam, diazepam, nortryptiline, clordiazepoxide, fentanyl.
3.
ANTIBIOTICS----- chloramphenicol, sulfonylurea, dapsone, Griseofulvin, chloroquin, erythromycin, nalidixic acid,rifampicin, INH, nitrofurantoin, pyrizinamide, cephalosporin
4.
HORMONES----- Estrogen, progesterone, chlorpropamide, tolbutamide, Danazol,
5.
PAIN KILLERS---- diclofenac, pentazocine, phenylbutazone,6.HEAVY METAL
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