Transient paresis of the right recurrent laryngeal nerve after treatment with etanercept for plaque-type psoriasis

ARTICLE

Auteur(s) : Katharina Fiala¹, Michael Schierl², Friedrich Breier², Robert Feldmann², Paul G Sator²

¹Dermatologist's practice H. Weltler, Hauptstrasse 4, 7000 Eisenstadt, Austria
²Department of Dermatology and Venerology, Hospital Hietzing, Wolkersbergenstrasse 1, 1130 Vienna, Austria

Psoriasis vulgaris (PV) is a chronic inflammatory, T-cell-mediated autoimmune disease with a genetic background, in which TNFα plays a key role. Etanercept, a recombined human fusion protein, shows competitive inhibitory effects by direct binding onto the TNFα-receptor. It is approved for the treatment of moderate-to-severe PV if the administration of other systemic therapeutic agents remains unsuccessful or contraindicated.

We report a 53-year-old male patient with a history of psoriasis vulgaris since early adolescence. Due to an acute exacerbation of his skin condition he was started on etanercept (25 mg s.c. twice a week) in January 2005.

Initially etanercept was well tolerated, but in week 15 he presented hoarseness without any further clinically distinctive features and paresis of the right recurrent laryngeal nerve (RLN) was diagnosed. Subsequently, etanercept was discontinued and our patient underwent a thorough investigation which showed no pathological findings. Serological screening for viral infections merely revealed a stable titer of 1:320 for cytomegalovirus (CMV). After administration of corticosteroids, rheologic infusions and speech therapy, the patient achieved complete remission within 6 months.

Most frequently pareses of the RLN are observed after operations or disorders of the thyroid gland, endotracheal intubation, malignancies of the upper airways or lung cancer and for neurologic, traumatic and finally idiopathic reasons. These idiopathic pareses occur almost exclusively in the left RLN in up to 20% of cases.

Since extensive thorough investigations had ruled out all common causes, we focused on the viral hypothesis. The literature numbers two cases in which cytomegalovirus caused a paresis of the left RLN in patients with concomitant HIV-infection [1, 2]. Seropositivity for cytomegalovirus is common within the Austrian population, therefore the stable CMV-titer remained only of marginal interest within this context. Moreover the patient showed no further clinical signs of a questionable CMV- infection.

There is evidence that biologic agents with anti-TNFα-activity are able to induce a range of autoimmune disorders that also attack the central and peripheral nervous systems by both T-cell-mediated and humoral immune mechanisms. Recently, a review article reported that this attack targets the peripheral nerve myelin sheath, leads to vasculitis-induced nerve ischemia or even inhibits axonal signaling transport [3]. Most of these neuropathies improve after withdrawal of the biological, as was the case in our patient. Another review on medication-induced peripheral neuropathy also reported the neurotoxic effects of certain drugs, including tumor necrosis factor-alpha blockers, infliximab and etanercept [4].

But we would also like to mention a case report that describes the successful treatment with etanercept of trigeminal neuralgia related to auricular chondritis in a patient with rheumatoid arthritis. It is presumed that the trigeminal neuralgia was caused by compression of the trigeminal nerve from inflammation or ischemia secondary to vasculitis [5].

Finally it remains unclear if direct viral damage of the recurrent laryngeal nerve was responsible for the paresis or if the inhibition of TNFα by etanercept therapy had induced autoimmune mechanisms affecting the neuronal micro-environment. The authors suggest the reported case probably related to the latter.

In regard of current discussions about fatal outcomes after the administration of efalizumab, a CD11a-receptor antagonist, which possibly leads to progressive multifocal encephalopathy, further epidemiological studies on the safety of anti-TNFα-agents are needed, although there is not a single confirmed PML case so far in the large number of patients treated with TNFα-antagonists. In this context it is important to point out that the effect of efalizumab is not attributed to blocking the TNFα-receptor but to inhibiting the activation of T-cells by binding onto the CD11a-receptor of leucocytes and blocking them. [6]

Disclosure

References

2 Small PM, McPhaul LW, Sooy CD, Wofsy CB, Jacobson MA. Cytomegalovirus infection of the laryngeal nerve presenting as hoarseness in patients with acquired immunodeficiency syndrome. Am J Med 1989; 86: 108-10.

3 Stuebgen JP. Tumor necrosis factor-alpha antagonists and neuropathy. Muscle Nerve 2008; 37: 281-92.

4 Weimer LH, Sachdev N. Update on medication-induced peripheral neuropathy. Curr Neurol Neurosci Rep 2009; 9: 69-75.

5 Pamuk ON, Harmandar F, Cakir N. The development of trigeminal neuralgia related to auricular chondritis in a patient with rheumatoid arthritis-relapsing polychondritis and its treatment with etanercept. Description of the first case. Clin Exp Rheumatol 2009; 27: 128-9.

6 Livio F, Ivanyuk A, Biollaz J. Pharmacovigilance and teratovigilance 2008. Rev Med Suisse 2009; 5: 130-4.