Abstract
The use of TNF-α inhibitors for the treatment of moderate to severe psoriasis and psoriatic arthritis is increasingly more frequent. The authors report a case of Guillain-Barré syndrome as a late manifestation of the treatment with adalimumab. Although unusual, this is relevant for professionals who prescribe biologic drugs. We also stress the importance of investigating the past and family medical history regarding demyelinating diseases before starting treatment.
Keywords:
Arthritis, psoriatic; Demyelinating diseases; Psoriasis; Guillain-Barre syndrome
INTRODUCTION
The treatment of moderate to severe psoriasis with biologics must be carried out in patients that are intolerant to traditional treatments or in whom these treatments failed.11 Naldi L. Epidemiology of psoriasis. Curr Drug Targets Inflamm Allergy. 2004;3:121-8.,22 Consenso Brasileiro de Psoríase 2012. Guias de avaliação e tratamento Sociedade Brasileira de Dermatologia. 2 ed. Rio de Janeiro: Sociedade Brasileira de Dermatologia, 2012. Two classes of biologic drugs are highlighted: anti-TNF-α (tumor necrosis factor alpha inhibitors), such as etanercept, adalimumab and infliximab; and interleukin 12 and 23 (ustekinumab) and 17A (secukinumab) inhibitors. Studies demonstrated that these drugs are effective to provide remission and control of symptoms in moderate to severe psoriasis.33 Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117:244-79. Among the main side effects related to them, infections, neoplasias and demyelinating diseases are of note.44 Manganelli S, Rossi M, Tuccori M, Galeazzi M. Guillain-Barré syndrome following adalimumab treatment. Clin Exp Rheumatol. 2012;30:592.
The objective of this article is to document a case of development of Guillain-Barré syndrome (GBS) during treatment with adalimumab for psoriasis and psoriatic arthritis and review the current literature.
CASE REPORT
A 45-year-old male patient had severe psoriasis for 10 years. We initially opted to treat with methotrexate (MTX), with improvement of skin lesions on the body but little improvement of lesions on the scalp. MTX was discontinued and we prescribed acitretin with phototherapy. Since there was no clinical improvement and the patient still complained of intense pruritus and axial and peripheral arthritis, adalimumab was started, with improvement of the joints and skin.
One year later, he presented to the emergency department complaining of acute pain in the lower limbs, difficulty walking and diarrhea, being treated with systemic steroids and opioids. He progressed to acute flaccid paralysis and respiratory insufficiency. Lumbar puncture and electroneuromyography were performed, and Guillain-Barré syndrome was diagnosed. Adalimumab was discontinued, and intravenous immunoglobulin and physical therapy were immediately started. The patient improved from the neurologic involvement but the flaccid paralysis in the lower limb remained.
DISCUSSION
GBS is an acute, autoimmune and demyelinating polyradiculoneuropathy, frequently severe and fulminant. It is characterized by areflexic motor paralysis of rapid onset, with or without sensory changes. The common pattern is ascending paralysis, that can be first noticed as heavy legs. Weakness appears within hours to days and, in the majority of cases, is accompanied by dysesthesia such as tingling sensation in the limbs. Motor sequelae persist in 5% to 10% of patients.55 Stübgen JP. Tumor necrosis factor-α antagonists and neuropathy. Muscle Nerve. 2008;37:281-92.
6 Viegas G V. Guillain-Barré syndrome. Review and presentation of a case with pedal manifestations. J Am Podiatr Med Assoc. 1997;87:209-18.-77 Lasky T, Terracciano GJ, Magder L, Koski CL, Ballesteros M, Nash D, et al. The Guillain-Barré syndrome and the 1992-1993 and 1993-1994 influenza vaccines. N Engl J Med. 1998;339:1797-802.
About two-thirds of GBS cases occur one to three weeks after an acute infectious process, being Campylobacter jejuni the microorganism most commonly involved.66 Viegas G V. Guillain-Barré syndrome. Review and presentation of a case with pedal manifestations. J Am Podiatr Med Assoc. 1997;87:209-18.,88 Alvarez-Lario B, Prieto-Tejedo R, Colazo-Burlato M, Macarrón-Vicente J. Severe Guillain-Barré syndrome in a patient receiving anti-TNF therapy. Consequence or coincidence. A case-based review. Clin Rheumatol. 2013;32:1407-12. GBS also occurs with higher frequency in immunosuppressed patients, such as those with lymphoma, acquired immunodeficiency syndrome, systemic lupus erythematosus and Sjögren syndrome.66 Viegas G V. Guillain-Barré syndrome. Review and presentation of a case with pedal manifestations. J Am Podiatr Med Assoc. 1997;87:209-18.
As stated by Alvarez-Lario et al., there are few reports of demyelinating diseases linked to TNF-α inhibitors use: less than 30 cases were published according to PubMed’s database. The search was conducted in December 2012, when 23 case reports of demyelinating diseases related to the use of anti-TNF-α were found. Eleven of those were related to infliximab; five to etanercept; and seven to adalimumab. The underlying disease was rheumatoid arthritis in 16 cases, Crohn’s disease in 3 cases, psoriatic arthritis in 3 cases and ulcerative colitis associated to spondyloarthropathy in only 1 case. There was no report in a patient undergoing treatment for psoriasis. Previous infection was seen in 56.5% of cases, including respiratory infection in 5 cases, fever in 3 and flu symptoms in 2; flu vaccination, gastroenteritis and C. jejuni infection were related to 1 case each (Table 1).88 Alvarez-Lario B, Prieto-Tejedo R, Colazo-Burlato M, Macarrón-Vicente J. Severe Guillain-Barré syndrome in a patient receiving anti-TNF therapy. Consequence or coincidence. A case-based review. Clin Rheumatol. 2013;32:1407-12.
Cases under treatment with anti-TNF-α that developed Guillain-Barré syndrome* * Alvarez-Lario et al.8
Anti-TNF-α agents can cross the blood-brain barrier, increasing its concentration in the compartment of the peripheral nervous system, reducing TNF-α concentration and prolonging the response of myelin-specific T-cells, triggering or worsening the demyelinating process.99 Fernández-Espartero MC, Pérez-Zafrilla B, Naranjo A, Esteban C, Ortiz AM, Gómez-Reino JJ, et al. Demyelinating disease in patients treated with TNF antagonists in rheumatology: data from BIOBADASER, a pharmacovigilance database, and a systematic review. Semin Arthritis Rheum. 2011;40:330-7.,1010 Shin IS, Baer AN, Kwon HJ, Papadopoulos EJ, Siegel JN. Guillain-Barré and Miller Fisher syndromes occurring with tumor necrosis factor a antagonist therapy. Arthritis Rheum. 2006;54:1429-34.
It is believed that anti-TNF-α could activate a latent infection, which could trigger an autoimmune process. This could deregulate TNF-α intrinsic balance and its receptors in the peripheral nervous system, creating a different gradient on each side of the blood-brain barrier, leading to an upregulation and resulting in inflammation and demyelination.55 Stübgen JP. Tumor necrosis factor-α antagonists and neuropathy. Muscle Nerve. 2008;37:281-92.,1010 Shin IS, Baer AN, Kwon HJ, Papadopoulos EJ, Siegel JN. Guillain-Barré and Miller Fisher syndromes occurring with tumor necrosis factor a antagonist therapy. Arthritis Rheum. 2006;54:1429-34.
Even though the patient was being treated with a TNF-α inhibitor, the development of GBS only occurred 12 months after the beginning of therapy. It is possible to state that the action of anti-TNF-α biologics in the onset of GBS is indirect. For example, the use of biologics increases the incidence and severity of infections and reduces the production of defense complexes; an infection in a patient with an altered immune system, producing less defense cytokines is the optimal environment for the development of GBS. The lack of complete improvement after discontinuing the medication makes the assessment of the relationship between adalimumab and the neurologic involvement difficult.
The occurrence of GBS and other demyelinating diseases during treatment with anti-TNF-α drugs is known. The causal relationship in this case cannot be established, but it is crucial to inquire about personal or family history of demyelinating diseases prior to biologic therapy. In this case, the patient had no previous infectious process, neither had improvement after cessation of therapy. Therefore, it was not possible to evaluate if the occurrence of GBS was only casual or a consequence of anti-TNF-α use.
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*
Study conducted at Hospital Naval Marcílio Dias (HNMD) - Rio de Janeiro (RJ), Brazil.
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Financial Support: None
REFERENCES
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1Naldi L. Epidemiology of psoriasis. Curr Drug Targets Inflamm Allergy. 2004;3:121-8.
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2Consenso Brasileiro de Psoríase 2012. Guias de avaliação e tratamento Sociedade Brasileira de Dermatologia. 2 ed. Rio de Janeiro: Sociedade Brasileira de Dermatologia, 2012.
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3Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117:244-79.
-
4Manganelli S, Rossi M, Tuccori M, Galeazzi M. Guillain-Barré syndrome following adalimumab treatment. Clin Exp Rheumatol. 2012;30:592.
-
5Stübgen JP. Tumor necrosis factor-α antagonists and neuropathy. Muscle Nerve. 2008;37:281-92.
-
6Viegas G V. Guillain-Barré syndrome. Review and presentation of a case with pedal manifestations. J Am Podiatr Med Assoc. 1997;87:209-18.
-
7Lasky T, Terracciano GJ, Magder L, Koski CL, Ballesteros M, Nash D, et al. The Guillain-Barré syndrome and the 1992-1993 and 1993-1994 influenza vaccines. N Engl J Med. 1998;339:1797-802.
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8Alvarez-Lario B, Prieto-Tejedo R, Colazo-Burlato M, Macarrón-Vicente J. Severe Guillain-Barré syndrome in a patient receiving anti-TNF therapy. Consequence or coincidence. A case-based review. Clin Rheumatol. 2013;32:1407-12.
-
9Fernández-Espartero MC, Pérez-Zafrilla B, Naranjo A, Esteban C, Ortiz AM, Gómez-Reino JJ, et al. Demyelinating disease in patients treated with TNF antagonists in rheumatology: data from BIOBADASER, a pharmacovigilance database, and a systematic review. Semin Arthritis Rheum. 2011;40:330-7.
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10Shin IS, Baer AN, Kwon HJ, Papadopoulos EJ, Siegel JN. Guillain-Barré and Miller Fisher syndromes occurring with tumor necrosis factor a antagonist therapy. Arthritis Rheum. 2006;54:1429-34.
Publication Dates
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Publication in this collection
2017
History
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Received
04 Apr 2015 -
Accepted
03 Oct 2016