|Ahead of print publication
Guillain–barre syndrome as a presenting feature of systemic lupus erythematosus in a child and it's complete resolution with rituximab treatment
Rahul Reddy, Anu Punnen, Annie Bella, Sathish Kumar
Department of Pediatrics, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
Department of Pediatrics, Christian Medical College, Vellore - 632 004, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Systemic lupus erythematosus (SLE) can present with varied neurological manifestations in children. Guillain–Barre syndrome (GBS) as a presenting feature of SLE is quite rare in children. We report a 9-year-old girl who presented with acute motor axonal polyradiculoneuropathy and noticed to have features of SLE. She was initially treated with intravenous immunoglobulins and corticosteroids with partial response. After starting rituximab, she showed dramatic recovery, proving the role of rituximab in GBS refractory to first-line medications in SLE. She remained in remission after 12 months of follow-up.
Keywords: Guillain–Barre syndrome, rituximab, systemic lupus erythematosus
|How to cite this URL:|
Reddy R, Punnen A, Bella A, Kumar S. Guillain–barre syndrome as a presenting feature of systemic lupus erythematosus in a child and it's complete resolution with rituximab treatment. Indian J Rheumatol [Epub ahead of print] [cited 2019 Jan 18]. Available from: http://www.indianjrheumatol.com/preprintarticle.asp?id=246307
| Introduction|| |
Several forms of lupus-related polyneuropathy have been reported. However, Guillain–Barre syndrome (GBS) as an initial presentation of systemic lupus erythematosus (SLE) is rare in pediatric age group. Most frequent neuropsychiatric manifestations include seizure disorder, psychosis, mood disorder, anxiety disorder, peripheral nervous system disorder, cerebrovascular disease, chorea, demyelinating syndrome, and myelopathy. There are reports of GBS presenting as the initial manifestation of SLE; however, the variant forms of GBS have been described mainly as late complications. The rarity of association and lack of strong evidence make the treatment options difficult. We describe a 9-year-old girl with GBS and SLE who showed a good outcome after treatment with rituximab.
| Case Report|| |
A 9-year-old girl presented with 4-day history of difficulty in walking and pain over the both legs. She also had double vision and deviation of eye. She also had a history of erythematous rash over the cheeks, excessive hair fall, and intermittent headache for the past 1 month. She did not give a history of recent vaccination, recent symptoms of respiratory or gastrointestinal tract infection, or exposure to toxins or chemical agents.
Her examination revealed a malar rash and hard palate ulcer. Neurological examination showed external ophthalmoplegia with bilateral abducens paresis and absent deep tendon reflexes with power 3/5 in the shoulder and hip joints. Cardiovascular and respiratory examinations were unremarkable.
Laboratory examination revealed a total count of 5600/mm3 with differential of N 68%, L 25%, and M 7% with platelets of 269 × 103. Her erythrocyte sedimentation rate was 48 mm/h. Her liver and renal function tests were within normal limits.
Urine routine analysis showed protein 2+ with no hematuria or casts. Her spot urine protein/creatinine ratio was 0.54. The cerebrospinal fluid revealed a normal cell count, total protein, and glucose (but it was done on day 5 of onset of weakness). C3 was <18.4 mg/dl (normal: 90–180 mg/dl) and C4 was <5.42 mg/dl (normal: 10–40 mg/dl. Antinuclear antibody (ANA) by immunofluorescence was positive (speckled 3+) and DsDNA by ELISA was 310 IU/ml (normal <100 IU/ml) was high. Other antibodies (anticardiolipin, anti-SSA, anti-SSB, and anti-Sm) and lupus anticoagulant were negative. GM2 and GM3 antiganglioside antibodies (AGA) were positive.
Magnetic resonance imaging spine showed mild thickening and enhancement of 3rd, 5th, and 6th nerve on the left side and thickening and enhancement of nerve roots in cauda equina, which were suggestive of acute inflammatory polyradiculoneuropathy. Nerve conduction study (NCS) done showed features suggestive of acute motor axonal radiculoneuropathy.
She was diagnosed to have SLE based on hair loss, oral ulcers and rash over the malar area, neurological manifestations, hypocomplementemia, proteinuria, and ANA positivity fulfilling ACR 1999 criteria for the diagnosis of SLE. Because of the clinical picture of the rapid progression of symmetric proximal limb weakness to total paralysis associated with areflexia, the diagnosis GBS was made.
On day 2 in hospital, she was administered intravenous immunoglobulins (IVIGs) 2 g/kg given over 5 days. Pulse methylprednisolone (30 mg/kg/day) was started and given daily for 5 days and then thrice weekly. Pulse IV cyclophosphamide one dose was given on day 5 in hospital.
Neurological examination showed rapid progression to a complete paralysis of all limbs. She gradually developed difficulty swallowing, loss of gag reflex, decreased speech output, and loss of head control. She was shifted to pediatric intensive care units (PICUs) for monitoring and respiratory support, in view of worsening neurological deficits. A repeat NCS after a week showed reduced compound muscle action potentials and worsening from previous NCS. Plasmapheresis was considered, however, withheld in view of the recent administration of IVIG. On day 10, intubation and mechanical ventilation became necessary, due to respiratory muscle weakness and impending respiratory failure. In PICU, over the next few days, she had paroxysmal tachycardia at times and hypertension intermittently attributed to autonomic dysfunction in GBS, and a centrally acting antihypertensive clonidine was added.
For immunosuppression along with pulse steroids, IV rituximab two doses were given 2 weeks apart (first dose on day 20 in the hospital), following which there was improvement in the power gradually. She needed ventilator support for 32 days. In view of prolonged requirement for ventilation, a tracheostomy was done, and the child was later gradually weaned off the ventilator. Pulse steroids were given tapered and changed to oral prednisolone. After 2 months, tracheostomy was decannulated slowly.
At the time of discharge, she was able to tolerate soft solids; she was ambulant and had Grade 4 power in bilateral upper and lower limbs. Tracheostomy tube was decannulated 2 weeks later, and tracheostomy site was closed. This treatment regimen induced a complete resolution of the GBS and the renal and neurological lupus symptoms. Her proteinuria decreased with treatment, and there was normalization of complement and DsDNA level, which are sensitive markers for lupus-specific disease activity. At follow-up after 12 months, she is doing well on hydroxychloroquine.
| Discussion|| |
The prevalence of SLE in patients with GBS has been reported to be between 0.6% and 1.7%. The precise mechanism of SLE-related acute inflammatory demyelinating polyradiculoneuropathy (AIDP) remains unclear but is probably immune-related. There are variant forms of lupus-related polyneuropathy seen in about 10% to 20% of patients with SLE, which usually present as late complications of lupus. Acquired inflammatory demyelinating polyneuropathy as the initial presentation of SLE is rather rare., Our child had clinical symptoms of SLE before; however, she presented with GBS to us.
Her NCS revealed suggestive of acute motor axonal radiculoneuropathy. Her GM2 and GM3 AGA were positive. Horrillo demonstrated that AGAs have been associated with several peripheral neuropathies, such as Miller–Fisher syndrome, GBS, and multifocal motor neuropathy. They have also been studied in patients with SLE, focusing on neuropsychiatric manifestations, and peripheral neuropathy, but the results are contradictory.
Pathophysiology of AIDP is essentially unknown and probably mediated by the attack of peripheral nerves myelin by the immune system. Nerve biopsies have shown endoneural and epineural infiltrates, predominantly T-cells, and macrophages. Schwann cells are competent to antigen presentation and T-cell activation and can function as nonprofessional antigen-presenting cells. These lymphocytes break down and migrate through the blood–nerve barrier, allowing the access of autoantibodies into the myelin lamellae, resulting in demyelination. After lymphocytes and macrophages accumulation, demyelination and nerve injury can arise either by cellular cytotoxicity or by direct binding of the antibodies on the myelin targets, such as proteins P0, P2, and peripheral myelin protein 22.
No consensus was available for treating demyelinating diseases associated with SLE. Case reports and case series were available in the literature for high-dose steroids, IVIG, cyclophosphamide, and plasmapheresis. Our child was treated with high-dose steroids and IVIG. After the failure of the established therapy of immunoglobulins, she had clinical worsening with deteriorating power in the upper and lower limps and worsening weakness of neck muscles and respiratory muscles. Then, along with pulse steroid intravenous rituximab, two doses were given following which child had improvement in weakness gradually.
Rituximab is a humanized chimeric anti-CD20 monoclonal antibody. Clinical and experimental data show that B-cell depletion by rituximab is associated with several events supposed to be relevant to the therapeutic response, including a decrease in the level of pathogenic autoantibodies produced by short-lived plasma cells, in addition to other less understood effects: a decrease in antigen presentation by B-cells to T-cells and probably effects on T-regulatory cells. Few case reports are available in the literature for rituximab in conventional therapy-resistant cases AIDP with SLE. After starting rituximab the child's clinical symptoms improved markedly and she continued to do well on follow-up.
Therefore, the association of GBS with lupus seems to have implications for both treatment and prognosis. This is the first description of improvement with the use of rituximab in the AIDP with SLE. The clinicians may consider using Rituximab in patients with a GBS which is not responding to IVIG.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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