Pregabalin to treat ciguatera fish poisoning

To the Editor:

Ciguatera fish poisoning is the commonest form of non-bacterial fish poisoning globally. Ciguatoxins (CTX) are a group of heat-stable lipophilic toxins produced by the dinoflagellate Gambierdiscus toxicus that occur in association with macroalgae in tropical and subtropical reefs.

Here we describe two cases of ciguatera poisoning from the South Pacific region that were effectively treated with pregabalin. While on holiday in Vanuatu two previously healthy women (aged 62 and 67 and taking no regular medications) ate a curry containing locally caught fish in a restaurant. They were uncertain of the type of fish it contained but within 3 h of the meal both had diarrhoea and vomiting. They were unaware of any other illnesses from the same restaurant. Around 6 h after the meal they had both developed paraesthesia of their hands and feet. One also had transient perioral paraesthesia and the other had significant pruritus, both lasting one week. Two days after the fish meal they attended the emergency department after returning to Australia and described neuropathic pain in a glove and stocking distribution, cold dysaesthesia and profound lethargy, which left them unable to walk more than around 100 metres without resting. A clinical diagnosis of ciguatera was made. No other neurological features were detected. Their initial laboratory tests were normal. Seven days after the fish meal they had persisting features of painful peripheral neuropathy and cold dysaesthesia.

At this time pregabalin was initiated at 75 mg daily and titrated to 150 mg twice daily over the following three weeks. They both experienced pain relief and improvement in dysaesthesia and lethargy within days of initiating pregabalin and their symptoms continued to improve during dose titration. Five weeks after the fish meal both patients reached a dose of 150 mg twice daily with almost complete resolution of their symptoms. In both patients the dose was dropped to 75 mg twice daily. Both experienced a recurrence of their painful peripheral neuropathy, dysaesthesia and lethargy and so the dose was increased to the maximum tolerated (150 mg twice daily for one, and 75 mg morning and 150 mg at night for the other). Fifteen weeks following the fish meal the dose for both patients was decreased to 75 mg daily and then weaned by 25 mg per week to zero. Following cessation of therapy (eighteen weeks following the fish meal) they were both left with mild distal paraesthesia in extreme cold but no pain.

CTX binds to subunit-5 of the alpha subunit of tetrodotoxin-sensitive sodium channels in autonomic and somatic neurones. The resulting increased Na+ permeability causes increased excitability and neurotoxicity.¹

Nerve injury can lead to an upregulation of the alpha-2-delta subunit of voltage-gated calcium channels on the central terminals of primary afferents. This is associated with increased calcium entry and augmented release of glutamate and other excitatory neurotransmitters that are associated with neuropathic pain.² CTX may also be an allosteric modulator at the transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor, causing increased receptor activation and neuropathic-type pain.

Gabapentinoids bind to and block the alpha-2-delta subunit and so reverse this neuroadaptation that may contribute to neuropathic pain. There is also evidence that activated TRPV1 receptors may enhance cytosolic access of gabapentinoids to facilitate their access to the alpha-2-delta subunits.³

The only randomised controlled trial of IV mannitol detected no differences between treatment and control groups but was underpowered.⁴ Mannitol was not used in this case because of uncertainty regarding the risk–benefit profile of this therapy. There are limited case reports of using amitriptyline, nifedipine and gabapentin to treat ciguatera.⁵ While awaiting more trials this report also supports the use of pregabalin to treat symptoms associated with ciguatera poisoning.

Acknowledgements

We thank GB and JF for consenting to be part of this case report.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.