Porphyria: A Comprehensive Guide for Junior Doctors

Introduction

Porphyria is a group of rare metabolic disorders that result from defects in the heme biosynthesis pathway. The clinical presentation can vary significantly depending on the type, but two broad categories are generally recognized: acute porphyrias and cutaneous porphyrias. This blog post focuses on the acute form, as it presents more commonly in the emergency department. The goal is to guide you, a junior doctor, through the process of history-taking, examination, investigations, and management of patients suspected of having acute porphyria.

History Taking: Key Questions

When assessing a patient with suspected porphyria, the history is crucial for identifying triggers and characteristic symptoms.

·     Chief complaint and onset:

·      Ask about acute abdominal pain, which is often severe, poorly localized, and out of proportion to clinical findings.

·      Inquire about neurological symptoms like weakness, numbness, or tingling (especially in the limbs).

·      Ask about psychiatric symptoms such as anxiety, depression, confusion, or hallucinations.

·      Associated symptoms:

·      Nausea, vomiting, and constipation: Gastrointestinal symptoms are common due to autonomic dysfunction.

·      Urinary changes: Dark, reddish-brown urine is a hallmark of acute porphyria due to increased porphyrin levels.

·      Photosensitivity or skin lesions: If there is a cutaneous component, ask about blistering, particularly on sun-exposed areas.

·      Precipitating factors:

·      Medications: Ask about the use of porphyrinogenic drugs, such as barbiturates, sulfonamides, and certain anticonvulsants.

·      Alcohol: A known trigger for acute attacks.

·      Menstruation: In women, ask about any relationship between symptoms and the menstrual cycle, as hormonal fluctuations can trigger episodes.

·      Infections or fasting: Both can precipitate an acute attack.

·     Family history:

·      Porphyrias are often hereditary (autosomal dominant in most cases), so it’s important to ask about any family history of similar episodes or diagnoses.

Examination Findings

While the examination can be non-specific, several key signs should raise your suspicion of porphyria:

·      General appearance:

·      The patient may appear acutely ill, often distressed due to pain.

·      Look for signs of mental status changes, including confusion, agitation, or delirium.

·     Abdominal examination:

·      Although pain is a common complaint, physical examination findings may be minimal. The abdomen might be soft with no signs of peritonism, despite the severe pain reported by the patient.

·     Neurological findings:

·      Motor weakness: Check for proximal muscle weakness, which may progress to paralysis in severe cases.

·      Cranial nerve involvement: Rare but possible, especially in advanced cases.

·      Hyporeflexia: Reflexes may be diminished in affected limbs.

·     Dermatological examination (if relevant):

·      In cases with cutaneous manifestations, examine the skin for blistering, scarring, or hyperpigmentation, particularly on sun-exposed areas.

Investigations

The diagnosis of porphyria can be challenging and often requires specific tests.

·     Urine tests:

·      Urine porphobilinogen (PBG): This is the most important initial test for diagnosing acute porphyria during an attack. Elevated PBG levels confirm the diagnosis.

·      Urine color: The classic dark, reddish-brown color of urine may be noted, particularly after exposure to sunlight.

·     Blood tests:

·      Serum electrolytes: Hyponatremia is common due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

·      Liver function tests: As porphyria affects the liver, LFTs may be abnormal, although not diagnostic.

·      Genetic testing: If available, genetic testing can confirm the type of porphyria, but this is not typically done acutely.

·     Imaging:

·      Abdominal imaging (e.g., ultrasound, CT): This is often done to rule out other causes of acute abdominal pain, as imaging findings in porphyria are generally normal.

·     Neurological tests:

·      In severe cases with significant neurological involvement, nerve conduction studies may show axonal neuropathy, but these are typically performed later in the disease course.

Management Plan

Managing acute porphyria involves a combination of symptomatic treatment, addressing precipitating factors, and specific therapies aimed at correcting the underlying metabolic disturbance.

·     Symptomatic management:

·      Pain control: Narcotics like morphine or fentanyl are often required due to the severity of pain.

·      Antiemetics: Medications like ondansetron or metoclopramide can help manage nausea and vomiting.

·      Hydration: Ensure adequate fluid resuscitation, especially if there are signs of dehydration or hyponatremia.

·     Specific treatment:

·      Hematin or heme arginate: This is the treatment of choice in acute attacks, as it helps to downregulate ALA synthase, reducing porphyrin precursor production. It is often administered in specialized centers.

·      Glucose infusion: High carbohydrate intake, either orally or intravenously, can help reduce heme precursor synthesis, particularly in milder attacks.

·      Addressing precipitating factors:

·      Medication review: Stop any porphyrinogenic drugs and replace them with safer alternatives.

·      Hormonal treatment: In women with menstrual-related attacks, GnRH analogs can be considered to suppress cyclical hormonal fluctuations.

·     Monitoring:

·      Regularly monitor electrolytes (especially sodium) and ensure there is no worsening of neurological deficits.

·      For patients with motor weakness or respiratory involvement, close monitoring of respiratory function is essential, as respiratory muscle paralysis is a life-threatening complication.

Disposition and Follow-up

·       Most patients with acute porphyria will require admission, particularly if they have neurological symptoms or need specific treatments like heme arginate.

·       Involve a multidisciplinary team, including neurology, hepatology, and genetics, for long-term follow-up and genetic counseling.

·       Patients should be educated on avoiding triggers and given detailed instructions on which medications to avoid in the future.