EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Key words : Autoimmune hepatitis, Posttransplant infection, Varicella-zoster virus

Solid-organ transplant recipients face various complications in the postoperative period; neurological complications are common early after transplant, and usually the central nervous system is involved. Peripheral nervous system involvement is rare. Few cases of Guillain-Barre syndrome in liver transplant recipients have been described in the literature. Here, we report a case of Guillain-Barre syndrome in an orthotopic liver transplant recipient who presented with reactivation of varicella-zoster virus (VZV) infection, leading to the iatrogenic condition of immunosuppression known as immune reconstitution inflammatory syndrome (IRIS).

A 34-year-old female patient underwent deceased donor liver transplant for end-stage liver disease secondary to autoimmune hepatitis with primary sclerosing cholangitis. The posttransplant course was complicated, as she had a low urine output of less than 10 mL/h; in addition, analysis of her arterial blood gas showed persistent metabolic acidosis. On posttransplant day 4, we performed sustained low-efficiency dialysis and renal replacement therapy, and the patient’s urine output gradually improved. She was started on tacrolimus 0.5 mg twice daily. On posttransplant day 10, she had multiple spikes of fever along with respiratory difficulties, generalized weakness, and irritability. Her respiratory discomfort increased further, resulting in maintenance on ventilator support. Furthermore, she had progressive lower limb weakness, which then gradually progressed to the trunk and upper limb. We were encountering an unexpected posttransplant course. Clinical examinations revealed acute symmetric weakness in the bilateral lower limb along with quadriparesis, which were rapidly progressing in the lower limbs. Weakness mainly involved proximal muscles. Decreased reflex was present on all limbs on serial examination.

She underwent electrodiagnostic tests and cerebrospinal fluid analysis. The cerebrospinal fluid analysis showed elevated protein concentration and albuminocytologic dissociation. Electrodiagnostic tests revealed temporal dispersion, conduction block, and nonuniform slowing of conduction velocities. A prolonged distal compound muscle action potential was also shown.

We performed a contrast-enhanced magnetic resonance imaging scan of the patient’s spine and brain, and transverse myelitis or any compressive causes of polyradiculopathy were ruled out. Serum polymerase chain reaction tests for Epstein-Barr virus, parvovirus, and cytomegalovirus were negative. A test for Campylobacter jejuni was also negative.

After clinical and radiological examinations, we diagnosed the patient with Guillain-Barre syndrome causing acute symmetric flaccid tetraparesis. Later, the patient developed bilateral knee joint swelling along with skin blisters over the abdomen and flank region. In view of the above clinical features, we performed a polymerase chain reaction test for VZV, which was positive. Acyclovir was started (5 mg/kg every 8 hours) for the infection.

The patient fulfilled the Brighton criteria for Guillain-Barre syndrome, and she was treated with intravenous immunoglobulin (2 g/kg/d for 5 days) and a high dose of methylprednisolone (200 mg for 5 days). Active physiotherapy was started with serial monitoring of limb power. The patient gradually improved clinically, and, at the time of discharge, she remained on a rehabilitation program. At follow-up, she continued doing well and has almost complete functional recovery.

Guillain-Barre syndrome is an acute-onset, immune-mediated polyneuropathy that usually follows an antecedent infection. Guillain-Barre syndrome was described by Landry in 1859, and the term is often considered to be synonymous with acute inflammatory demyelinating polyradiculopathy. The most frequent mechanism proposed for Guillain-Barre syndrome physiology is the molecular-mimicry process, which is triggered by infections or other immunogenic triggers, such as surgery, malignancy, pregnancy, or trauma. Guillain-Barre syndrome is a part of disimmune neuropathies and is unexpected to be shown in immunocompromised patients. However, various cases have been identified in patients with HIV but rarely in transplant recipients.¹

A few cases of Guillain-Barre syndrome in liver, kidney, heart, lung, and bone marrow transplant have been reported due to cytomegalovirus infection, allograft rejection, Campylobacter jejuni infection, autoimmune disease, and influenza vaccination posttransplant.^2-4 Our patient was negative for cytomegalovirus; therefore, its association with Guillain-Barre syndrome was ruled out. Tacrolimus-related peripheral neuropathy was unlikely as we had maintained low serum tacrolimus levels; despite this precaution, Guillain-Barre syndrome can occur with normal and even with lower levels of tacrolimus.

Our patient had autoimmune hepatitis as an underlying cause of liver failure. An association between autoimmune hepatitis and Guillain-Barre syndrome is rare, and only a single case has been reported.⁵

Another underlying cause for Guillain-Barre syndrome in our patient could be due to VZV. The pathophysiology by which Guillain-Barre syndrome develops following a herpes zoster attack is poorly understood. Because Guillain-Barre syndrome results from autoimmune-mediated insults to the peripheral nervous system, which is triggered by a preceding infectious event, a suggestion of Guillain-Barre syndrome developing after herpes zoster attack is related to autoimmune-mediated responses initiated by the VZV reactivation in an immune-compromised patient.⁶

However, whether this condition could make such patients prone to developing VZV is still unknown, and a prior pathogen triggered by a second pathogen, as well as the cross-reactivity of immunological response, may play a role. However, there are no data on possible structural mimicry between VZV and the molecules of human peripheral nerves. The aberrant immunological status of the host is generally considered to play an important role.

We conclude that Guillain-Barre syndrome in our patient happened in the context of potent immunosuppressive therapy in a clinical case of disimmune disease of autoimmune hepatitis with VZV reactivation. The patient was treated with methylprednisolone along with immunoglobulin therapy.⁷ Immune reconstitution inflammatory syndrome in transplant recipients, although rare, has been reported in kidney and liver transplant recipients. Immune reconstitution inflammatory syndrome is an imbalance between protective immunity and inflammatory pathology that is likely mediated by anti-inflammatory responses and proinflammatory responses.⁸ Management of IRIS in immunocompromised individuals without HIV infection is unknown, and treatment modalitieshave included use of corticosteroids, intravenous immunoglobulins, and nonsteroidal anti-inflammatory drugs.^9,10

Guillain-Barre syndrome in a liver transplant recipient is rare, and early and precise diagnosis of Guillain-Barre syndrome may be challenging. In our case of a patient with autoimmune hepatitis and liver transplant, Guillain-Barre syndrome can be explained by reactivation of VZV in the posttransplant period. Guillain-Barre syndrome has been described in immunocompromised patients but rarely in transplanted hosts. We conclude that, in transplant patients, the mechanism of Guillain-Barre syndrome can be explained by the triggered autoimmunity by an infectious agent in an immunosuppressed host, such as VZV in our case. Posttransplant IRIS is a poorly studied entity; due to its rarity in transplant recipients, a collaborative multicenter effort to advance knowledge in this field is needed. Treatment of these patients with a reduction in the immunosuppressive regimen can lead to a dramatic improvement.

Volume: 19 Issue: 11 November 2021

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