Guillain-Barre syndrome following immune reconstitution after antiretroviral therapy for primary HIV infection.
Article Type: Case study
Subject: Antiviral agents (Dosage and administration)
Guillain-Barre syndrome (Risk factors)
Guillain-Barre syndrome (Diagnosis)
Guillain-Barre syndrome (Drug therapy)
Guillain-Barre syndrome (Case studies)
HIV infection (Diagnosis)
HIV infection (Drug therapy)
HIV infection (Complications and side effects)
HIV infection (Case studies)
Authors: Teo, Ecy
Azwra, A.
Jones, R.
Gazzard, Brian G.
Nelson, Mark
Pub Date: 09/01/2007
Publication: Name: Journal of HIV Therapy Publisher: Mediscript Ltd. Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2007 Mediscript Ltd. ISSN: 1462-0308
Issue: Date: Sept, 2007 Source Volume: 12 Source Issue: 3
Geographic: Geographic Scope: United Kingdom Geographic Code: 4EUUK United Kingdom
Accession Number: 181992009
Full Text: INTRODUCTION

Guillain-Barre syndrome (GBS) was first described in 1916 as an acute inflammatory neuropathy with ascending muscle weakness, areflexia and mild paraesthesia. It is likely to be a post-infectious immune-mediated disease, the most common pathogens implicated in its onset being Campylobacter jejuni, cytomegalovirus (CMV) and Mycoplasma pneumoniae. It has also been proposed that reconstitution of the immune system may trigger an autoimmune attack on the neurones. Two other GBS cases have been described associated with highly active antiretroviral therapy (HAART) [1,2]. These cases had complicated past medical histories, which may have influenced the course of neurological disease. We describe a case of GBS with a strong temporal association with the initiation of HAART.

CASE REPORT

A 26-year-old homosexual male presented with a 2-week history of numbness in his fingers and feet and difficulty walking. Six months earlier, he had presented with generalised lymphadenopathy and was diagnosed as having primary HIV infection. Four months into that diagnosis, therapy with efavirenz and Truvada was commenced, together with Septrin as prophylaxis. Two months later, he experienced diarrhoeal symptoms. Figure 1 summarises the changes in CD4 cell count and HIV viral load measurements.

[FIGURE 1 OMITTED]

Ten days after presentation, he experienced ascending muscle weakness to the extent that he became wheelchair-bound, and experienced difficulty in breathing, palpitations, slurred speech, dysphagia, impaired facial movement, decreased bowel movements and urination. The numbness remained mild and confined to a glove and stocking distribution. There was areflexia with grade 4 power in all limbs, and bilateral paraesthesia with profound loss of proprioception.

Blood tests revealed the level of serum creatinine kinase as 430 units/l, alanine transaminase 251 IU/l, and gammaglutamyl transpeptidase 52 IU/l. Vitamin B12 and folate levels were normal. Cerebrospinal fluid contained protein at 2.98 mg/dl and 3 white blood cells per [mm.sup.3]. Serology revealed IgM and IgG positivity to C. jejuni and IgG positivity to CMV. He had negative results for rheumatoid factor, Lyme disease and HBa1C glucose levels were normal--ruling out any other causes of neuropathy. Immunological tests revealed there were no GM1 ganglioside antibodies or MAG antibodies in the blood. Magnetic resonance imaging studies revealed no spinal cord lesions, and chest radiography was normal. His lung vital capacity ranged from 3.7 l to 5.35 l. Electromyography showed evidence of motor conduction consistent with demyelination.

The patient was treated with Vigan at 1mg/kg, and given physiotherapy, occupational therapy and prophylaxis against deep-vein thrombosis. He did not require ventilation support, and recovered sufficiently to be discharged 1 month after admission.

DISCUSSION

The pathogenesis of GBS is based largely on the action of T cells, macrophages and cytokines. Following the presentation of bacterial or viral epitopes by macrophages, T cells become activated and penetrate the endoneurium, where they engage epitopes on abaxonal Schwann cells, thereby triggering a cytokine cascade [3]. In a 10-year retrospective study of GBS-affected patients in Africa, a higher incidence was observed in patients infected with HIV than those not infected [4], suggesting an association between GBS and HIV. It has also been reported that GBS usually occurs early in HIV infection, such that HIV-GBS can precede overt AIDS in the course of immunosuppression [5].

Immune reconstitution inflammatory syndrome (IRIS) is characterised by paradoxical, transient clinical deterioration following initial improvement upon commencement of antiretroviral therapy [6]. A diagnosis of IRIS may be made if an HIV-positive person, upon receiving HAART, experiences a decrease in HIV viraemia, an increase in CD4 cell count, symptoms of an inflammatory nature, and has a clinical course not consistent with drug toxicity or opportunistic infections [7].

A case series of GBS in HIV-infected patients given azathioprine and cyclosporine suggested the role of T cell suppression in the triggering of GBS [8]. This suppression, in addition to the actual HIV infection, may make the immune system prone to autoimmune attacks. Other reports suggest, however, an association between GBS and antiretroviral therapy. Piliero et al. documented an exacerbation of GBS-like neuropathic symptoms following initiation of a regimen consisting of abacavir, lamivudine, efavirenz, lopinavir, amprenavir and enfuvirtide [1]. Makela et al. described a recurrence of GBS in a patient, once possibly at seroconversion, and then following a dramatic increase in CD4 cell count on commencement of combivir and nevirapine [2]. However, both cases reported past medical histories of neurological disorders, which may have influenced the course of the neurological disease.

This patient presented with symptoms consistent with GBS 2 months after the commencement of antiretroviral therapy. This case is unique in that GBS occurred during a period that corresponded with a sharp decrease in viral load and a stabilisation of the CD4 cell count following HAART, and that there was no prior history of neurological disease. While GBS could have been due to HIV infection per se, given the chronology of events peculiar to this patient, the disease may be considered a manifestation of IRIS. The trigger was probably an aberrant proliferation of T cells mediating demyelination following C. jejuni infection.

REFERENCES

[1.] Piliero PJ, Fish DG, Preston S et al. Guillain-Barre syndrome associated with immune reconstitution. Clin Infect Dis, 2003, 36, e111-114.

[2.] Makela P, Howe L, Glover S et al. Recurrent Guillain-Barre syndrome as a complication of immune reconstitution in HIV. J Infect, 2002, 44, 47-49.

[3.] Hughes RA, Cornblath DR. Guillain-Barre syndrome. Lancet, 2005, 366, 1653-1666.

[4.] Melaku Z, Zenebe G, Bekele A. Guillain-Barre syndrome in Ethiopian patients. Ethiop Med J, 2005, 43, 21-26.

[5.] Brannagan TH 3rd, Zhou Y. HIV-associated Guillain-Barre syndrome. J Neurol Sci, 2003, 208, 39-42.

[6.] Lipman M, Breen R. Immune reconstitution inflammatory syndrome in HIV. Curr Opin Infect Dis, 2006, 19, 20-25.

[7.] Shelburne SA, Montes M, Hamill RJ. Immune reconstitution inflammatory syndrome: more answers, more questions. J Antimicrob Chemother, 2006, 57, 167-170.

[8.] Qureshi AI, Cook AA, Mishu HP et al. Guillain-Barre syndrome in immunocompromised patients: a report of three patients and review of the literature. Muscle Nerve, 1997, 20, 1002-1007.

Correspondence to: Dr Esmeralda Teo, Imperial College School of Medicine, London SW7 2AZ, UK Email: ecyteo@yahoo.co.uk
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