Porphyria

Krista Fajman March 23, 2009

Overview

Involve a deficiency of an enzyme in the heme biosynthetic pathway which results in buildup of porphyrins and metabolites buildup in various tissues. Either genetic (autosomal dominant or autosomal recessive) or acquired. Heterozygotes are asymptomatic in between acute attacks. Classified depending on site of overproduction and accumulation of porphyrin, overlapping features common

Hepatic

Erythropoetic

Neurologic, mental disturbances Abdominal pain Extremity pain, paresthesias Motor neuropathy

Cutaneous photosensitivity long wave UV light excites porphyrins in skins causing cell damage
Hemolytic anemia

Heme Synthesis Pathway

Diagnosis

Overlapping, may be difficult to determine exactly Check plasma, urine, stool porphyrin excretion

Acute Intermittent Porphyria

Prevalence of 5-10 per 100,000 in the United states although thought to be higher in psychiatric populations More frequent in women than men. Heterozygotes are asymptomatic between acute attacks. Risk factors for exacerbation include medications, diet, weight loss, surgery, infection, menstrual hormones, smoking Common symptoms include:

Abdominal pain which is poorly localized, ileus, mild tenderness, N/V Neurologic, not an inflammatory etiology. Fever and leukocytosis rare Tachycardia, HTN, arrhythmia, orthostatic hypotension Psychiatric symptoms including anxiety, insomnia, depression, delirium, hallucinations, paranoia Peripheral neuropathy from axonal degeneration affecting motor neuron watch for respiratory muscle paralysis

Diagnosis with increased urinary porphobilinogen and delta aminolevulinic acid

Acute Intermittent Porphyria

Diagnosis:

Caused by a deficiency of PBG deaminase resulting in an accumulation of PBG and ALA

Treatment:

Discontinue all unnecessary or potentially harmful drugs. Fluid replacement, watch for SIADH Treat any infection or other comorbidities

Pain control with Morphine

Treat sympathetic hyperactivity with propranolol but caution because BP and HR are labile 300-400 grams of carbohydrates per day. IV heme at 3-5 mg/kg/day side effects include elevated PT, PTT, coagulopathy, renal insufficiency, IV phlebitis

Leuprolide vs. oral contraceptives if attacks during luteal phase of menstrual cycle.
Avoidance in the future of precipitating causes.

Multiple unsafe and potentially unsafe medications include: Sulfa drugs, Barbiturates, ACEI, CCB, Antiepileptics, Antifungals, Sulfonylureas, Benzodiazepines, Clonidine, Erythromycin, Tramadol, Spironolactone, Hydralazine.

Porphyria Cutanea Tarda

Most common porphyria which causes skin manifestations Deficiency of hepatic urodecarboxylase Cutaneous photosensitivity fluid filled vesicles on sun exposed areas, friable skin, wounds heal slowly, risk for infection, may see hypertrichosis and hyperpigmentation on face No neurologic manifestations Higher incidence of HCV and hepatocellular carcinoma Precipitants frequently include alcohol, estrogen and iron Treatment:

Avoid sunlight, use sunscreen Chloroquine or Hydroxychloroquine form complexes with porphyrins which enhance excretion Repeated phlebotomy goal Hct < 35% and ferritin < 10 ng/ml. Usually requires removal of 12-16 units of blood. Charcoal Cholestyramine Beta carotene may increase tolerance of sunlight through Vitamin A.

The Porphyrias and Vampires

Multiple references associating folklore about vampires and werewolves with patients who may have had porphyria

"On Porphyria and the tiology of Werewolves", was published in the Proceedings of the Royal Society of Medicine in 1964. Porphyria, Vampires and Werewolves: The Aetiology of European Metamorphosis Legends was published in the American Association for the Advancement of Science in 1985.

Some patients have reddish mouths and teeth Idea in the past that drinking blood may help disease Porphyric patients have multiple food restrictions including garlic which has high sulfur content

References

Chemmanur and Bonkovsky. Hepatic Porphyrias: Diagnosis and Management. Clinics in Liver Disease. Vol 8, Issue 4. 2004 Dombeck and Satonik. The Porphyrias Emergency Medicine Clinics of North America. Volume 23 Issue 3. August 2005. Harrisons Principals of Internal Medicine, 16th Edition, page 2303-2306 Sassa, S. Understanding the Porphyrias UpToDate Online. Last updated June 2008. Sassa, S. Acute Intermittent Porphyria UpToDate Online. Last updated March 2008. www.mayoclinic.com www.porphyriafoundation.com http://science.howstuffworks.com/vampire.htm http://en.wikipedia.org/wiki/Porphyria