Guillian-Barre syndrome as the initial presentation of systemic lupus erythematosus – case report and review of literature

Abstract

A number of neurological entities have been associated with systemic lupus erythematosus (SLE). Gullian-Barre syndrome (GBS) as a presenting feature of SLE remains uncommon with just 9 cases reported in the last half-century with the first case reported in 1964^1–9 (Table 1). We report a young female presenting with GBS in whom SLE and WHO class V lupus nephritis (LN) was subsequently diagnosed. The neurological symptoms partially responded to pulse methylprednisone, intravenous immunoglobulin (IVIG) and plasmapheresis.

A 23-year-old Saudi female with no prior medical illness presented with a new onset of progressive motor weakness of all four extremities in an ascending pattern associated with increasing difficulty in standing up and walking over a period of 3 days. There were no sensory symptoms. Additionally, there was increasing lower limb swelling. Upon admission there was further deterioration of her weakness to profound quadriparesis with areflexia. Fortunately there was no evidence of respiratory muscle involvement and FEV1 was monitored closely with spirometry. History was negative for any recent gastroenteritis, flu-like symptoms, travel or recent immunizations. Family history was negative for renal disease and connective tissue disease. Physical examination was unremarkable except for motor weakness with a power of 1/5 in all four limbs. Deep tendon reflexes were absent and plantar reflexes were flexor. Sensation was intact. Laboratory investigations revealed hemoglobin 96 g/L, white cell count 8.29×10⁹/L, platelets 322×10⁹/L, ESR 68 mm/hr, CRP 1.0 mg/L. Urinalysis showed +2 protein, no casts, 0–3 red blood cells/hpf. 24-hour proteinuria was 6.05 g/24 hours. Serum creatinine 41 μmol/L, urea 7.1 mmol/L, albumin 28 g/L. Liver function tests were normal. Immunologic tests revealed ANA positive with titer of 1:1280 speckled pattern, double stranded DNA antibody of 28.2 U/mL (normal<20), and a border-line positive anti-Smith antibody. Both C3 and C4 were normal. Serum cryoglobulin was absent. CSF revealed a normal cell count, total protein, and lactate. Oligoclonal immunoglobulin bands were not present. Serology was negative for hepatitis B, hepatitis C, cytomegalovirus and HIV. A renal biopsy was performed given the heavy proteinuria, all the glomeruli showed diffuse thickening of the capillary basement membrane associated with mesangial expansion. Some of the glomeruli showed segmental scaring. There was no increase in cellularity, proliferation, crescents or necrosis. A foci of mild tubular loss with replacement by fibrosis was noted. No significant interstitial inflammation was noted. Immunofluorescence 1 to 2+ glomerular capillary wall and mesangial staining for IgG, IgA, C3, C1q, kappa and lambda gave the characteristic full house immunofluorescence for LN. Fibrinogen and IgM were negative. Electron microscopy was not done as there was inadequate tissue. The findings were consistent with membranous nephropathy, suggesting WHO class V lupus nephritis. MRI brain and whole spine were normal. Electromyogram and nerve conduction revealed characteristic findings of a demyelinating polyneuropathy. GBS was diagnosed on the basis of the Asbury criteria¹⁰ and the patient also fulfilled the criteria of the American College of Rheumatology case definitions for GBS.¹¹ The patient received intravenous pulses of methylprednisone 1 g daily for 3 days in addition to 9 cycles of plasmapheresis and IVIG for a total of 2 g/kg. Furthermore, the patient was prescribed prednisone 60 mg daily for 6 weeks and thereafter tapered to a maintenance dose of 5 mg daily. She was discharged on prednisone and physiotherapy. The patient had substantial resolution of weakness regaining motor power to 3 of 5 in all extremities after 6 months, and on the 8-year follow-up her motor power was around 4 of 5. Lupus nephritis was in remission on maintenance mycofenolate mofetil and steroid.

DISCUSSION

The prevalence of SLE with GBS has been reported to be between 0.6% and 1.7%.¹² However, to the best of our knowledge this is the tenth case to be reported in the last 50 years where the initial manifestation of SLE was GBS, thus making it rare and notable. In our patient the diagnosis of SLE was made with the presence of hemolytic anemia, renal involvement, positive ANA and positive ds-DNA antibody, meeting the minimum 4 of 11 criteria for the diagnosis of SLE by the American College of Rheumatology. In addition to these findings renal biopsy consistent with class V LN.¹³ The pathogenesis of GBS as a manifestation of active SLE is not clear, however both cell-mediated and humoral processes may play a significant role.¹⁴ When GBS and LN present concurrently, the efficacy of prednisone as a single agent for therapy is insufficient in about 50% of the cases.⁴ In the setting of GBS alone plasma exchange and IVIG have been established as standard therapy with satisfactory patient outcomes.¹⁵ The mechanism of action of IVIG in autoimmune disease was unclear, but most likely due to binding and neutralization of autoantibodies by anti-idiotypes in the IVIG preparation. IVIG also retards antibody secretion and modifies T cell function.¹⁶ Currently, there is no ideal treatment combination that has been proven to treat GBS in the context of SLE. In our patient the neurological symptoms resolved with plasmapheresis, IVIG and corticosteroid treatment. Cyclophosphamide was not administered, although others have reported success when it was employee.^4,5 Interestingly, our patient did not have evidence of recent or intercurrent infection that may have been the trigger factor for autoantibody cross-reaction. Our case highlights the importance of early diagnosis and prompt institution of therapy in the form of plasmapheresis, IVIG and corticosteroids in this rare clinical presentation, in which a sustained clinical response was achieved.

Table 1.

Guillain-Barre syndrome (GBS) as the presenting symptom of systemic lupus erythematosus.

Case No./Year	Age/Sex	Renal Involvement	Associated neurological manifestation	Treatment	Outcome
1/1964	32/F	none	Anterior radiculopathy	CS	Full but slow recovery, able to return to premorbid functional state
2/1980	22/F	none	Bilateral cranial nerve V, IX, X involvement	CS	Death secondary to tracheostomy
3/1986	23/F	none	Cranial Nerve Involvement, recurrent GBS	ACTH and CS	Slow recovery with recurrence at 2 and 3 years
4/1989	40/M	Membranous GN	Tonic, clonic seizure	CS, IV CYP, PE	Full recovery, able to walk with frame, persistent bilateral foot drop
5/1999	23/M	Membranous lupus Nephritis (WHO class V)	none	PE, CS, IV-CYP	Complete resolution of GBS but recurrence of lupus nephritis and progression to end-stage renal disease
6/2001	20/F	Mesangiocapillary lupus nephritis with a membranous component (WHO class IV.C)	Cranial Nerve Involvement	IVIG, CS, IV CYP	Complete resolution of GBS and lupus symptoms
7/2003	33/F	none	Cranial Nerve Involvement	CS	Complete resolution
8/2009	28/F	none	Paresthesia in distal limbs	CS, PE	Complete resolution
9/2013	20/F	Renal biopsy not done but had proteinuria	Cranial Nerve Involvement	PE, CS, IVIG, IV CYP	Complete resolution
10/2013	23/F	Membranous lupus Nephritis (WHO class V)	none	PE, CS, IVIG	Near complete resolution

CS-Corticosteroid, IV CYP-intravenous Cyclophosphamide, PE-Plasma exchange