To the Editor,
Porphyrias are metabolic bone diseases caused by deficiencies of enzymes involved in heme biosynthesis. Acute hepatic porphyrias (AHPs) can present as episodes of acute porphyria with abdominal pain, autonomic dysfunction (hypertension, tachycardia, and gastrointestinal disorders), and deep motor neuropathy. Variegate porphyria (VP) is a type of autosomal dominant hepatic porphyria secondary to protoporphyrinogen oxidase activity deficiency that can present acute neurological manifestations and/or cutaneous photosensitivity. Drugs are the factors most commonly implicated as triggers of acute attacks. We describe a patient with VP who received class Ic antiarrhythmic agents for paroxysmal atrial fibrillation (AF) and presented with an acute episode of porphyria, which consisted of acute abdomen and syndrome of inappropriate antidiuretic hormone secretion (SIADH).
Our patient was a 40-year-old male with a history of VP diagnosed by skin biopsy and elevation of blood aminolevulinic acid and porphobilinogen and fecal protoporphyrins who had a relative with the same condition but no activity to date. The patient experienced various episodes of paroxysmal AF. He was initially treated with flecainide but later switched to propafenone due to digestive intolerance. One week after initiating propafenone therapy, the patient began to have abdominal pain and bloody urine. He came to the emergency room and was referred to the internal medicine department for further study. During the examination, only the diffuse abdominal pain without accompanying signs of peritonism was relevant. The laboratory workup showed normal kidney function, GOT, 41 U/L; GPT, 43 U/L; alkaline phosphatase, 50 IU/L; GGT, 50 IU/L; LDH, 539 IU/L; sodium, 111 mEq/L; and plasma osmolarity, 231 mOsm/L. The urinary tests showed urinary sodium of 109 mEq/L and elevated osmolarity. The heart, thyroid, and adrenal panels were normal. An abdominal ultrasound showed no relevant findings; the Hoesch test was positive. Porphyrin and porphyrin precursor determination in urine showed an increase in porphobilinogen, as well as delta-aminolevulinic acid, coproporphyrin, and protoporphyrins in stools. Based on these findings and the normalization of biochemical and clinical parameters once propafenone was discontinued, an attack of propafenone-induced VP with SIADH as a form of expression was diagnosed. Hematin (5 mg/kg/day) was given for 4 consecutive days, and beta blocker therapy was started. The patient progressed favorably and the case was presented to the arrhythmia unit to consider AF ablation.
AHPs are characterized by episodes of acute porphyria (EAP) that, if not properly treated, can lead to death. Due to the low incidence of EAP in Spain, health care professionals caring for patients who present their first EAP are unlikely to recognize the condition and, therefore, patients are often not adequately treated and may even be given drugs capable of exacerbating the attack.
In the case of VP, drug exposure plays a significant role.1 According to the European Porphyria Initiative recommendations, class Ic antiarrhythmic agents are classified as possibly porphyrinogenic and amiodarone as probably porphyrinogenic.2, 3 Although the prevalence of AF in AHPs is low,4 there is a significant association in its appearance. The antiarrhythmic armamentarium in these patients is limited because most drugs are unsafe and can cause EAP (Table 1). All registers include beta blockers as antiarrhythmic agents to be used in AF, above all to control heart rate, whereas only sotalol appears to be safe for the prevention of recurrences. Both digoxin and adenosine have shown no toxicity and can be used in supraventricular arrhythmias in patients with AHPs. Conversely, Méndez et al.5 studied 17 patients with acute intermittent porphyria who used amiodarone between 2 and 20 years and concluded that amiodarone was safe. We found no literature reports of AHP associated with class Ic drugs. In patients with porphyrias and AF in whom cardiac rhythm needs to be controlled, percutaneous ablation could be proposed.6
Table 1. Antiarrhythmic Agents and Safety in Acute Porphyrias
| Antiarrhythmic drugs | Safety/porphyrinogenicity | Alternative |
| Class Ia | Unsafe | Beta blockers |
| Quinidine, procainamide | Porphyrinogenic | |
| Class Ib | Unsafe | Beta blockers |
| Lidocaine | Porphyrinogenic | |
| Mexiletine | Possibly porphyrinogenic | |
| Class Ic | Unsafe | Beta blockers |
| Flecainide, propafenone | Possibly porphyrinogenic | |
| Class II | Safe | |
| Beta blockers | Nonporphyrinogenic | |
| Class III | Unsafe | Sotalol |
| Amiodarone, ibutilide | Probably porphyrinogenic | |
| Class IV | Unsafe | Beta blockers |
| Verapamil, diltiazem | Probably porphyrinogenic | Digoxin |
| Others | Safe | |
| Digoxin, adenosine | Nonporphyrinogenic |
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Corresponding author: santisanti84@hotmail.com