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.