Porphyria Notes

Contents

Osmosis High-Yield Notes

This Osmosis High-Yield Note provides an overview of Porphyria essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Porphyria by visiting the associated Learn Page.
NOTES NOTES PORPHYRIA GENERALLY, WHAT IS IT? PATHOLOGY & CAUSES ▪ Metabolic diseases; accumulation of heme precursors ▫ Porphyrin; neurologic/cutaneous disorders ▪ Mostly hereditary ▫ Porphyria cutanea tarda (most common) ▫ Acute intermittent porphyria ▫ Aminolevulinic acid dehydratase deficiency porphyria (AKA Doss porphyria) ▫ Hereditary coproporphyria ▫ Variegate porphyria ▫ Congenital erythropoietic porphyria CAUSES ▪ Sporadic/inherited enzyme mutations in heme production → porphyrin accumulates in tissues RISK FACTORS ▪ Smoke, alcohol, hormonal changes, fasting, stress, certain drugs, sunlight exposure, lead poisoning COMPLICATIONS ▪ Paralysis, seizures Chronic ▪ E.g. porphyria cutanea tarda, erythropoietic porphyria ▪ Skin manifestations ▪ Photosensitivity ▫ Pain, discomfort, burning of sunlightexposed areas ▪ Vesiculo-erosive manifestations (e.g. erosions, blistering) ▪ Increased skin fragility DIAGNOSIS LAB RESULTS ▪ Blood, urine tests ▫ Increased levels of porphobilinogen in urine ▪ Genetic testing TREATMENT MEDICATIONS ▪ Acute intermittent porphyria (AIP) ▫ Hospitalization during acute attack, intravenous hemin, etc. ▪ Porphyria cutanea tarda (PCT) ▫ Phlebotomy, chloroquine/ hydroxychloroquine sulfate, etc. SIGNS & SYMPTOMS Acute ▪ Resolve once attack passes (e.g. acute intermittent porphyria, doss porphyria) ▪ Abdominal pain, vomiting, hypertension, tachycardia, neurological/psychiatric symptoms (e.g. seizures, neuropathy, anxiety, confusion, hallucinations), red urine OSMOSIS.ORG 447
ACUTE INTERMITTENT PORPHYRIA (AIP) osms.it/acute-intermittent-porphyria PATHOLOGY & CAUSES ▪ Neurovisceral disease ▫ Acute, recurrent attacks of abdominal pain + other clinical manifestations (neuropsychiatric, gastrointestinal, urinary) CAUSES ▪ Autosomal dominant mutation of hydroxymethylbilane synthase (HBMS) gene → alterated codification of enzyme hydroxymethylbilane synthase (AKA porphobilinogen deaminase/ uroporphyrinogen I synthase) → impaired heme production → accumulation of metabolites: porphobilinogen (PBG), aminolevulinic acid (ALA) RISK FACTORS ▪ Drugs (e.g. barbiturates, antiepileptics, rifampin) ▪ Alcohol ▪ Exposure to tobacco smoke ▪ Hormonal fluctuations (e.g. menstruation) ▪ Dietary changes (e.g. reduced caloric intake) ▪ Stress (e.g. illness, psychological stress) COMPLICATIONS ▪ Hypertension, kidney failure, neuromuscular respiratory failure, hepatocellular carcinoma 448 OSMOSIS.ORG SIGNS & SYMPTOMS ▪ Acute episodes lasting several hours to few days ▫ Severe, diffuse abdominal pain ▫ Palpitations, sweating ▫ GI: nausea, vomiting, constipation ▫ Neurological: seizure, peripheral neuropathy (e.g. tingling sensations in limbs), muscle weakness ▫ Psychiatric: irritability, anxiety, hallucinations ▫ Urinary: dysuria, urinary retention, discolored (reddish, red-brown) urine MNEMONIC: 5Ps Features of Acute intermittent porphyria Pain in the abdomen Polyneuropathy Psychological abnormalities Pink urine Precipitated by drugs: including barbiturates, oral contraceptives, sulfa drugs DIAGNOSIS LAB RESULTS ▪ Elevation of heme precursor in urine (PBG) ▪ Genetic testing
Chapter 57 Porphyria TREATMENT MEDICATIONS ▪ Intravenous hemin ▪ Symptomatic treatment (e.g. antiemetics, pain medications) Figure 57.1 The urine of an individual with porphyria (right). PORPHYRIA CUTANEA TARDA (PCT) osms.it/porphyria-cutanea-tarda PATHOLOGY & CAUSES ▪ Blistering cutaneous lesions of sunlightexposed skin TYPES ▪ PCT Type I: acquired disease ▪ PCT Type II: autosomal dominant disease CAUSES ▪ Impaired function of uroporphyrinogen decarboxylase (UROD) enzyme → porphyrins overproduction, accumulation → photosensitizing porphyrins in skin damage proteins, lipids, basement membrane → cutaneous lesions RISK FACTORS ▪ ▪ ▪ ▪ ▪ Alcohol Exposure to tobacco smoke Hormonal imbalances Infectious disease (e.g. HIV, hepatitis C) Hemochromatosis, iron overloading COMPLICATIONS ▪ Cirrhosis, hepatocellular carcinoma SIGNS & SYMPTOMS ▪ Increased mechanical fragility after sunlight exposure → painful vesicles, blisters on hands/face (minor trauma) ▪ Increased facial hair growth (e.g. hypertrichosis) ▪ Hardened yellow skin lesions (e.g. scleroderma-like plaques) ▪ Hypermelanosis (brownish skin pigmentation) ▪ Abnormal urine color DIAGNOSIS LAB RESULTS ▪ Elevated porphyrins level (orange-red fluorescence on Wood lamp) ▪ Elevated porphyrins level in stool ▪ UROD activity in blood cells Skin biopsy of lesions ▪ Subepidermal bullae, inflammation ▪ Immunofluorescence ▫ Immunoglobulins at dermal-epidermal junctions OSMOSIS.ORG 449
TREATMENT MEDICATIONS ▪ Low doses of chloroquine/ hydroxychloroquine sulfate OTHER INTERVENTIONS ▪ Avoid sunlight exposure ▪ Discontinue aggravating substances (alcohol, estrogen) ▪ Blood removal (e.g. phlebotomy) ▫ Decrease body iron load ▪ Limit iron-rich food 450 OSMOSIS.ORG Figure 57.2 Skin lesions on the dorsum of both hands in a case of porphyria cutanea tarda.

Osmosis High-Yield Notes

This Osmosis High-Yield Note provides an overview of Porphyria essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Porphyria by visiting the associated Learn Page.