Diagnosis

Acute intermittent porphyria

Etiology

Cause [9di]

• Deficiency or defect in a particular enzyme needed for a specific step of the heme synthesis pathway

• Inducers of acute attacks are alcohol, infections, low caloric intake, reproductive hormones change, and high-risk porphyrogenic drugs (ketamine, thiopental, chloramphenicol, erythromycin, nitrofurantoin, rifampicin, trimethoprim/sulfamethoxazole, spironolactone, methyldopa, valproic acid, carbamazepine, phenytoin, phenobarbital, primidone, and risperidone)

Pathophysiology

• Overproduction and accumulation of porphyrins and porphyrin precursors (toxic)

• Clinical manifestations depend on the step in which the enzymatic defect occurs.

1. Acute porphyrias: Acute intermittent porphyria, Hereditary coproporphyria, Variegate porphyria, Aminolevulinic acid dehydratase deficiency porphyria

   • Enzymatic defects in the initial steps of the metabolic cascade -> accumulation of early metabolic intermediates (aminolevulinic acid and porphobilinogen).

   • This causes attacks of (1) severe abdominal pain lasting days, (2) psychiatric symptoms, and (3) peripheral motor neuropathy.

2. Cutaneous porphyria: Porphyria cutanea tarda, Acute painful photosensitive porphyria, Congenital erythropoietic porphyria

   • Enzymatic defects in the final steps of the metabolic cascade -> porphyrin accumulation in the skin -> sunlight-induced cutaneous lesions (photosensitivity).

Epidemiology

Prevalence per 100.000 [9ak][0lj]

Incidence per 100.000 [9ak][0lj]

Approach

• Blood test

• Blood gas

• Urin analysis (ALA and PBG)

• CT abdomen

Treatment

The treatment goal for acute attacks of acute intermittent porphyria (AIP) is to decrease heme synthesis and reduce the production of porphyrin precursors [0lj]

1. Mild attacks: IV 5% glucose in 0.9% sodium chloride solution at a rate of 2 L/24 h.

2. Severe attacks: hematin (IV heme) 4 mg/kg/d for 4 days.

3. Pain: Narcotics + laxatives and stool softeners

4. Tachycardia/arrhythmia: beta-blockers

5. Hypertensive crisis: Clonidine and beta-blockers

6. Seizures: gabapentin

7. If intractable recurrent life-threatening attacks or severely affect quality of life: Liver transplantation cures AIP

Differential diagnoses

Abdominal abscess, Acute mesenteric ischemia, Acute pancreatitis, Adrenal cortical carcinoma, Adrenal crisis, Amebiasis, Aortic dissection, Appendicitis, Benign bile duct tumor, Bile duct stricture, Biliary obstruction, Cholangiocarcinoma, Cholecystitis, Choledocholithiasis, Cholelithiasis, Chronic mesenteric ischemia, Chronic pancreatitis, Constipation, Diverticulitis, Emphysema, Endometriosis, Esophagitis, Familial mediterranean fever, Femoral hernia, Gallbladder cancer, Gastric outlet obstruction, Gastritis, Gastrointestinal obstruction, Incisional hernia, Inguinal hernia, Intussusception, Irritable bowel syndrome, Lead toxicity, Liver abscess, Ogilvie syndrome, Pelvic inflammatory disease, Perforated ulcer, Portal vein obstruction, Primary biliary cirrhosis, Primary sclerosing cholangitis, Pyelonephritis, Ruptured aortic aneurysm, Ruptured ovarian cyst, Umbillical hernia, Urolithiasis