The Acute Porphyrias: a diagnostic and theraputic challenge in internal and emergency medicine

The porphyrias are a heterogeneous group ofmetabolic diseases resulting from a variable catalytic defectof one of the eight enzymes involved in the heme biosynthesispathway; they are mostly inherited diseases, but insome circumstances the metabolic disturbance may beacquired. The specific patterns of tissue overproduction (andhence accumulation and excretion) of toxic heme precursors,associated with each enzymatic deficiency, are responsiblefor the characteristic biochemical and clinical features ofeach of these diseases. Moreover, even in the presence of aspecific inherited enzymatic defect, many different environmentalfactors (such as drugs, calorie restriction, hormones,sunlight exposition, infections, etc.) often play a keyrole in triggering the clinical expression of the various formsof porphyrias. The porphyrias are often misdiagnosed diseases,due their multiform clinical manifestations, able tomimic many other more common diseases. For this reason,many different specialists, such as surgeons, psychiatrists,gastroenterologists, neurologists, emergency physicians anddermatologists may be variably involved in the diagnosticprocess, especially for the forms presenting with acute andlife-threatening clinical features. According to the clinicalfeatures, the porphyrias can be classified into neuropsychiatric(characterized by neurovisceral crises involving autonomicand central nervous system but also the liver and thekidney with possible consequences in terms of neurological,psychic, cardiac, respiratory, liver and kidney functions),dermatological (mostly presenting with cutaneous lesionsdue to photosensitivity), and mixed forms. From a strictlyclinical point of view, porphyrias presenting with neurovisceralattacks are also referred as acute porphyrias: they arethe object of the present review. An accurate diagnosis ofacute porphyria requires knowledge and the use of correctdiagnostic tools, and it is mandatory to provide a moreappropriate therapeutic approach and prevent the use ofpotentially unsafe drugs, able to severely precipitate thesediseases, especially in the presence of life-threateningsymptoms. To date, availability of a relatively stable haempreparation (haem arginate) has significantly improved thetreatment outcome of acute porphyric attacks, so theknowledge about the diagnosis and the management of thesediseases may be relevant for physicians working in internalmedicine, neurology and emergency units.