History

Fact Explanation
Classic triad of symptoms during acute exacerbations [1,4,6] A triad of symptoms, abdominal pain, psychiatric symptoms (hysteria, hallucinations, paranoia) and pheripheral neuropathy occurs. Abdominal pain is usually colicky and severe, mostly involves the epigastrium and lasts for several days. Nausea and vomiting may also be present.
Constipation or diarrhea [6] Due to autonomic disturbances.
Neuropathies [1] Peripheral, motor neuropathies are commoner than sensory neuropathy. Symptoms include constipation [6], colicky abdominal pain and vomiting. Hypertension restlessness, tremor and increased sweating occurs secondary to autonomic neuropathy. Painful neuropathies occur especially in the upper body.
Central nervous system disturbances [5] Cortical blindness, seizures, delirium, coma, insomnia and depression. [1,6] Seizures and coma may arise secondary to hyponatremia. [6]
Symptoms of bladder dysfunction [8] Patients may complain of urinary retention, incontinence, and dysuria. [1]
History of exposure to a precipitant Usually this autosomal dominant disease does not manifest until second or third decade of life, because some activity of the enzyme (porphobilinogen deaminase) remains. Some precipitants may cause exacerbations and also may cause early presentation. Common precipitants are fasting, dehydration, stress and infection. Physiological hormonal fluctuations (menstruation and pregnancy) may also act as a precipitant. [3] Barbiturates and steroids are common precipitant drugs. [5]
Symptoms of chronic kidney disease [2] Patients develop chronic kidney disease secondary to long standing hypertension.
Neuropsychiatric symptoms May be the only presenting complaint in some patients. Can cause psychosis, anxiety, depression, agitation and delirium. [8]
References
  1. HENRY T, VIKRAM P. K., PASHTOON M. K. Clinical Manifestations and Diagnostic Challenges in Acute Porphyrias. Case Reports in Hematology [online] 2013: 2013 [viewed 18 April 2014] Available from: http://dx.doi.org/10.1155/2013/628602
  2. UNZU C., SAMPEDRO A., SARDH E. et al., “Renal failure affects the enzymatic activities of the three first steps in hepatic heme biosynthesis in the acute intermittent porphyria mouse,” PLoS One [online] 2012: 7 (3). [viewed 18 April 2014] Available from: DOI: 10.1371/journal.pone.0032978
  3. DISLER PB, MOORE MR. Drug therapy in the acute porphyrias. Clin Dermatol [online] 1985; 3: 112–24 [viewed 18 April 2014] Available from: http://dx.doi.org/10.1016/0738-081X(85)90037-9
  4. ELDER GH, HIFT RJ, MEISSNER PN. The acute porphyrias. Lancet [online] 1997; 349: 1613–17 [viewed 18 April 2014] Available from: doi:10.1016/S0140-6736(96)09070-8
  5. JAMES M. F. M., HIFT R. J. Porphyrias. Br J Anaesth [online] 2000; 85: 143–53. [viewed 18 April 2014] Available from: http://bja.oxfordjournals.org/content/85/1/143.full
  6. MADHUR M., GIRIJA P. R., HARI H. D. Intensive care management of patients with acute intermittent porphyria: Clinical report of four cases and review of literature. Indian J Crit Care Med. [online] 2010 Apr-Jun; 14(2): 88–91. [viewed 18 April 2014] Available from: doi: 10.4103/0972-5229.68222
  7. LAIWAH AC, MACPHEE GJ, BOYLE P, MOORE MR, GOLDBERG A. Autonomic neuropathy in acute intermittent porphyria. J Neurol Neurosurg Psychiatry. [online] 1985;48:1025–30. [viewed 18 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/4056804
  8. ELLENCWEIG N, SCHOENFELD N, ZEMISHLANY Z. Acute intermittent porphyria: psychosis as the only clinical manifestation. Isr J Psychiatry Relat Sci.[Online] 2006;43(1):52-6. [Viewed 18 April 2014]. Available from: http://doctorsonly.co.il/wp-content/uploads/2011/12/2006_1_10.pdf

Examination

Fact Explanation
Pulse Tachycardia or bradycardia [4] and arrhythmias occur due to autonomic neuropathy. [1]
Blood pressure[2] Hypotension or hypertension can occur secondary to autonomic neuropathy. [4]
Motor neuropathy Mostly lower limb muscle groups are paralyzed. Patients can have quadriparesis as well. [3] Lower motor type paralysis is seen. (The muscle tone, power and reflexes are either absent or diminished, the extensor plantar response is absent)
Respiratory rate Bulbar paralysis may cause respiratory depression. [1,4]
Abdominal examination Often normal.
Mental status examination May show disturbances in mental status. [1]
References
  1. HENRY T, VIKRAM P. K., PASHTOON M. K. Clinical Manifestations and Diagnostic Challenges in Acute Porphyrias. Case Reports in Hematology [online] 2013: 2013 [viewed 18 April 2014] Available from: http://dx.doi.org/10.1155/2013/628602
  2. UNZU C., SAMPEDRO A., SARDH E. et al., “Renal failure affects the enzymatic activities of the three first steps in hepatic heme biosynthesis in the acute intermittent porphyria mouse,” PLoS One [online] 2012: 7 (3). [viewed 18 April 2014] Available from: DOI: 10.1371/journal.pone.0032978
  3. JAMES M. F. M., HIFT R. J. Porphyrias. Br J Anaesth [online] 2000; 85: 143–53. [viewed 18 April 2014] Available from: http://bja.oxfordjournals.org/content/85/1/143.full
  4. MADHUR M., GIRIJA P. R., HARI H. D. Intensive care management of patients with acute intermittent porphyria: Clinical report of four cases and review of literature. Indian J Crit Care Med. [online] 2010 Apr-Jun; 14(2): 88–91. [viewed 18 April 2014] Available from: doi: 10.4103/0972-5229.68222

Differential Diagnoses

Fact Explanation
Guillain-Barré syndrome [2] Peripheral motor neuropathy may mimic Guillain-Barré syndrome. Cerebro-spinal fluid analysis will reveal increased protein in Guillain-Barré syndrome. [3]
Acute abdomen [1] Severe abdominal pain in acute attacks may mimic an acute abdomen. Causes like appendicitis, pancreatitis, choledocholithiasis, cholelithiasis, gallbladder empyema, peptic ulcer disease, diverticulitis, pelvic Inflammatory disease and other causes should be considered.
Other acute hepatic porphyrias These include hereditary coproporphyria (HCP), variegate porphyria (VP) and ALA dehydratase deficient porphyria (ALAD). All these three porphyrias characteristically present with neurological symptoms. [1] HCP and VP are collectively known as neurocutaneous porphyrias and cause skin rashes in sun-exposed areas.
Lead Nephropathy Exposure to lead causes systemic hypertension and nephropathy which is worsened by the hypertension. [4]
Familial mediterranean fever hypertension. [4] Familial mediterranean fever usually present in the first decade of life. There is recurrent attacks of fever and painful polyserositis. The precipitants are more or less similar in both conditions. (stress, certain food, some drugs) [5]
Nephrolithiasis Patients complain of severe pain radiating from loin to the groin and often to the testicle or to the labia. Some may have hematuria. [6]
Nerve Entrapment Syndromes Cause sensory or motor neuropathies.
Constipation Other causes of constipation should also come in differential diagnosis.
References
  1. HENRY T, VIKRAM P. K., PASHTOON M. K. Clinical Manifestations and Diagnostic Challenges in Acute Porphyrias. Case Reports in Hematology [online] 2013: 2013 [viewed 18 April 2014] Available from: http://dx.doi.org/10.1155/2013/628602
  2. PERIASAMY V, AL SHUBAILI A, GIRSH Y. Diagnostic dilemmas in acute intermittent porphyria. A case report. Med Princ Pract. [online] 2002;11:108–11. [viewed 18 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12123102
  3. MADHUR M., GIRIJA P. R., HARI H. D. Intensive care management of patients with acute intermittent porphyria: Clinical report of four cases and review of literature. Indian J Crit Care Med. [online] 2010 Apr-Jun; 14(2): 88–91. [viewed 18 April 2014] Available from: doi: 10.4103/0972-5229.68222
  4. DATONYE D. A. Lead nephropathy: revisiting an overlooked cause of kidney disease. Nephrology Reviews [online] 2010; 2. [viewed 18 April 2014] Available from: doi:10.4081/nr.2010.e8
  5. Neda Z.,Terri G., Wayne W.G. Diagnosis and management of familial Mediterranean fever: Integrating medical genetics in a dedicated interdisciplinary clinic. Genetics in Medicine [online] 2011: 13, 263–269 [viewed 18 April 2014] Available from: . doi:10.1097/GIM.0b013e31820e27b1
  6. PHILLIP M. H. Nephrolithiasis: Treatment, causes, and prevention. Journal of Medicine. [online] October 2009: 76 (10) 583-591. [viewed 18 April 2014] Available from: doi: 10.3949/ccjm.76a.09043

Investigations - for Diagnosis

Fact Explanation
Urinary porphobilinogen (PBG) and δ‐aminolaevulinic acid Levels are increased especially during acute attacks. [1]
Serum porphobilinogen Increased levels are observed during acute attacks. [1]
Stool porphyrins May be normal or increased.
Genetic testing Diagnose the genetic defects responsible for enzyme deficiency. [2]
References
  1. HENRY T, VIKRAM P. K., PASHTOON M. K. Clinical Manifestations and Diagnostic Challenges in Acute Porphyrias. Case Reports in Hematology [online] 2013: 2013 [viewed 18 April 2014] Available from: http://dx.doi.org/10.1155/2013/628602
  2. SCHUURMANS M.M., SCHNEIDER-YIN X., RÜFENACHT U.B., SCHNYDER C., MINDER C.E. Influence of Age and Gender on the Clinical Expression of Acute Intermittent Porphyria Based on Molecular Study of Porphobilinogen Deaminase Gene among Swiss Patients. Molecular Medicine [online] 2001: 7 (8) 535-542. [viewed 18 April 2014] Available from: http://www.scopus.com/record/display.url?eid=2-s2.0-0035434324&origin=inward&txGid=DC43BEC7F96195A75BC33A70F5FBBBA2.y7ESLndDIsN8cE7qwvy6w%3a2

Investigations - Followup

Fact Explanation
Serum electrolytes Hyponatremia can present as a result of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). It is non-specific and not diagnostic. [1]
Electrocardiogram Evaluates arrhythmia. [1]
Arterial blood gas analysis Detects acid base disturbances secondary to respiratory depression. [2]
References
  1. HENRY T, VIKRAM P. K., PASHTOON M. K. Clinical Manifestations and Diagnostic Challenges in Acute Porphyrias. Case Reports in Hematology [online] 2013: 2013 [viewed 18 April 2014] Available from: http://dx.doi.org/10.1155/2013/628602
  2. JAMES M. F. M., HIFT R. J. Porphyrias. Br J Anaesth [online] 2000; 85: 143–53. [viewed 18 April 2014] Available from: http://bja.oxfordjournals.org/content/85/1/143.full

Investigations - Screening/Staging

Fact Explanation
Urinary Porphobilinogen [1] Using Watson and Schwartz test this enables screening of patients to diagnose an acute attack.
References
  1. SOUMITRA G., PRANIT K.R.C., HIRANYA K. G. An analysis of six cases of acute intermittent porphyria (AIP). Indian J Psychiatry [online] 2006 Jul-Sep; 48(3): 189–192. [viewed 18 April 2014] Available from: doi: 10.4103/0019-5545.31584

Management - General Measures

Fact Explanation
Analgesics [3] Pain control usually requires narcotics.
Laxatives and stool softeners Treat constipation which results secondary to narcotic analgesics and autonomic neuropathy.
Anti- epileptics [3] Controls seizures.
Sedatives Propofol and anti-epileptics are widely used. This will reduce the anxiety. [3]
Fluid management Patients often have dehydration. [1]
Electrolyte Electrolyte disturbances should be corrected. [1]
Antihypertensive Some patients remain hypertensive. Antihypertensive medication should be started to control blood pressure.
Treatment of chronic kidney disease Chronic kidney disease and the hypertensive complications are the most common cause of death. [2]
Intubation and mechanical ventilation [1] Patients with respiratory failure should be ventilated.
Health education Patients should be advised to avoid precipitants. [3]
References
  1. JAMES M. F. M., HIFT R. J. Porphyrias. Br J Anaesth [online] 2000; 85: 143–53. [viewed 18 April 2014] Available from: http://bja.oxfordjournals.org/content/85/1/143.full
  2. CHURCH SE, MCCOLL KE, MOORE MR, YOUNGS GR. Hypertension and renal impairment as complications of acute porphyria. Nephrol Dialysis Transplant [online] 1992; 7: 986–90. [viewed 18 April 2014] Available from: http://ndt.oxfordjournals.org/content/7/10/986.abstract?ijkey=4a3208b1b2c20d6e621b71a216b615a7c028a6a9&keytype2=tf_ipsecsha
  3. MADHUR M., GIRIJA P. R., HARI H. D. Intensive care management of patients with acute intermittent porphyria: Clinical report of four cases and review of literature. Indian J Crit Care Med. [online] 2010 Apr-Jun; 14(2): 88–91. [viewed 18 April 2014] Available from: doi: 10.4103/0972-5229.68222

Management - Specific Treatments

Fact Explanation
High doses of glucose (300-500 gm/day) [1] In mild disease this can inhibit heme synthesis which in turn reduces the synthesis of porphyrin precursors.
Hematin (4 mg/kg/d for 4 days) This is the preferred mode of treatment in severe attacks with neurological symptoms. [1]
References
  1. MADHUR M., GIRIJA P. R., HARI H. D. Intensive care management of patients with acute intermittent porphyria: Clinical report of four cases and review of literature. Indian J Crit Care Med. [online] 2010 Apr-Jun; 14(2): 88–91. [viewed 18 April 2014] Available from: doi: 10.4103/0972-5229.68222