What are the diagnostic tests and treatment options for a patient presenting with symptoms of porphyria, including skin itching and sensitivity to light?

From the Guidelines

Diagnostic testing for porphyria should begin with a random urine sample to measure aminolevulinic acid (ALA), porphobilinogen (PBG), and creatinine, as this is the most sensitive and specific test for acute hepatic porphyrias 1.

Key Diagnostic Tests

• Urine tests: ALA, PBG, and creatinine
• Blood tests: plasma porphyrin measurements
• Stool tests: fecal porphyrin measurements
• Genetic testing: to confirm specific types of porphyria

Treatment Options

• Avoiding triggers: alcohol, certain medications, fasting, and sun exposure
• Acute attacks: intravenous hemin (Panhematin) at 3-4 mg/kg daily for 3-4 days, often with glucose loading (300-500g daily) and pain management
• Cutaneous symptoms: beta-carotene (120-180 mg daily) may reduce photosensitivity, while hydroxychloroquine (100-200 mg 2-3 times weekly) can help with skin manifestations in some types
• Phlebotomy: may be recommended for erythropoietic protoporphyria
• Supportive care: adequate hydration, carbohydrate intake (300g daily), and pain control with safe medications like acetaminophen or opioids

Importance of Prompt Diagnosis

Prompt diagnosis is crucial as porphyria can cause severe neurological damage if left untreated, and treatments are most effective when started early in an attack 1. Patients should maintain a high-carbohydrate diet and carry a medical alert card listing safe and unsafe medications. The most recent and highest quality study recommends a random urine sample for initial diagnosis, which is sufficient and does not require a 24-hour urine collection 1. Genetic testing can confirm specific types of porphyria and is essential for appropriate care 1. Considering the symptoms of skin itching and sensitivity to light, it is essential to consider porphyria as a potential cause and perform the necessary diagnostic tests to confirm the diagnosis 1.

From the FDA Drug Label

2 DOSAGE AND ADMINISTRATION For intravenous infusion only. 2. 1 Dosing

• Before PANHEMATIN therapy is begun, the presence of acute porphyria must be diagnosed using the following criteria:

1. Presence of clinical symptoms suggestive of acute porphyric attack.
2. Quantitative measurement of porphobilinogen (PBG) in urine The single-void urine sample should be refrigerated or frozen without additives and shielded from light for subsequent quantitative δ-aminolevulinic acid (ALA), PBG, and total porphyrin determinations.

The diagnostic tests for porphyria include:

• Presence of clinical symptoms suggestive of acute porphyric attack, such as skin itching and sensitivity to light
• Quantitative measurement of porphobilinogen (PBG) in urine
• Quantitative measurement of δ-aminolevulinic acid (ALA) in urine
• Quantitative measurement of total porphyrin in urine Treatment options for porphyria include:
• Hemin therapy, such as PANHEMATIN, which is administered intravenously
• Glucose therapy for mild porphyric attacks
• Elimination of triggering factors 2

From the Research

Diagnostic Tests for Porphyria

• The diagnosis of porphyria relies on the measurement of increased urinary 5-aminolevulinic acid (in patients with aminolevulinic acid dehydratase deficient porphyria) or increased 5-aminolevulinic acid and porphobilinogen (in patients with other acute porphyrias) 3
• Examinations of urine and plasma are first-line tests for detecting excess of porphyrins or heme precursors in suspected patients 4
• Mutation screening of family members is recommended to identify presymptomatic carriers and to prevent acute attacks 4

Treatment Options for Porphyria

• Treatment is directed to reduce aminolevulinic acid (ALA) production by reducing the activity of the enzyme aminolevulinate synthase (ALAS)-most effectively by heme therapy 5
• Management of attacks requires intensive care, strict avoidance of porphyrinogenic drugs and other precipitating factors, caloric support, and often heme therapy 3
• Patients with porphyria cutanea tarda benefit from iron depletion, hydroxychloroquine therapy, and, if applicable, elimination of the hepatitis C virus 3
• An α-melanocyte-stimulating hormone analogue can reduce sunlight sensitivity in patients with erythropoietic protoporphyria or X-linked protoporphyria 3
• Teetotalism is a therapeutically and prophylactically important measure in all types of hepatic porphyrias 6

Symptoms and Classification of Porphyria

• Porphyrias are a group of rare metabolic disorders, inherited or acquired, along the heme biosynthetic pathway, which could manifest with neurovisceral and/or cutaneous symptoms, depending on the defective enzyme 5
• Cutaneous symptoms are a consequence of elevated porphyrins in the blood stream, which react to light, affecting sun-exposed areas and producing fragile erosive skin lesions or non-scarring stinging and burning symptoms 5
• Porphyrias can be divided into categories of acute vs non-acute or hepatic vs erythropoietic porphyrias, with acute hepatic porphyrias manifesting in attacks and non-acute porphyrias leading to the accumulation of porphyrins that cause skin photosensitivity and occasionally severe liver damage 3