A Young Woman With Ulcerative Colitis Presenting With Facial Diplegia, a Variant of Guillain-Barré Syndrome

Introduction

Ulcerative colitis (UC) is a chronic, recurrent inflammatory bowel disease (IBD) characterized by continuous diffuse inflammation of the colonic mucosa, extending from the rectum to the cecum [1]. Guillain-Barré syndrome (GBS) is an acquired immune-mediated inflammatory peripheral neuropathy characterized by acute ascending flaccid paralysis and areflexia [2]. Neurologic complications of inflammatory bowel disease are uncommon [3]. In rare cases, GBS can present as an extraintestinal manifestation (EIM) of UC when in relapse or remission, as they share similar enteric infectious triggers, immunological mechanisms, and genetic background [3]. We report a case of facial diplegia variant GBS presenting during a relapse of UC, a combination which has never been reported before.

Case Report

Three and half months ago, a 22-year-old woman was diagnosed with segmental ulcerative colitis for frequent (2–3/day) loose, bloody bowel movements, which was confirmed by colonoscopy (Figure 1A). She had achieved remission with oral and rectal mesalazine, but during the past month, since stopping the treatment, she experienced a severe relapse, with up to 10 episodes/day of bloody, mucopurulent diarrhea, abdominal pain, and tenesmus. Colonoscopy indicated severe and extensive UC (Figure 1B). She started treatment with intravenous dexamethasone and oral and rectal mesalazine 1 week before. By the time of admission, the bloody stool had disappeared.

She was admitted to our department for sudden onset of bilateral facial weakness, without any antecedent infections. On physical examination, she was unable to close her eyes, raise her eyebrows, puff her cheeks, or purse her lips. Other cranial nerves were preserved. The muscle strength, tendon reflexes, coordination movement, and sensation of all 4 limbs were unremarkable.

Full blood count revealed moderate iron deficiency anemia, and the serum ferritin level was 4.0 ng/ml (reference range 10–291 ng/ml). The erythrocyte sedimentation rate (ESR) was 30 mm/h (reference range 0–20 mm/h). Stool cultures were negative, and Clostridium difficile toxins were not detected. Screening tests for infections by human cytomegalovirus (CMV), Epstein-Barr virus (EBV), Varicella-Zoster virus (VZV), herpes simplex virus (HSV), human immunodeficiency virus (HIV), Treponema pallidum (TP), and Borrelia burgdorferi were all negative. Serum rheumatoid factor (RF), anti-nuclear antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), angiotensin-converting enzyme (ACE), vitamin B12, and tumor markers were all unremarkable. Cerebrospinal fluid (CSF) analysis done 5 days after symptom onset confirmed albuminocytological dissociation with normal cells and albumin of 83.2 mg/dL (reference range 15–45 mg/dl). Serum and CSF anti-ganglioside antibodies were undetectable. Facial nerve conduction studies (NCSs) showed notably decreased amplitude of facial nerve compound muscle action potential (CMAP) bilaterally and prolonged latency of the right side (Table 1). The blink reflex test showed absent ipsilateral R1, R2, and contralateral R2 during bilateral stimulation, which further confirmed a prominent axonal lesion of the bilateral facial nerves. CAMPs and conduction velocity of the motor nerves and sensory nerves of all 4 limbs were within normal range. Brain magnetic resonance imaging (MRI) plain scan and enhanced scan excluded neoplastic lesions and inflammatory disorders. A chest computed tomography (CT) scan showed no remarkable findings, and electrocardiograph (ECG) and echocardiography results were normal.

The diagnosis of facial diplegia variant GBS was established based on clinical presentation, typical albuminocytological dissociation in CSF and electrophysiological findings. The patient was treated with intravenous immunoglobulin 0.4 g/kg/d for 5 days, with partial improvement achieved until 2 weeks after treatment. At the 5-month follow-up visit, she only had partial improvement and still could not close her eyes tightly or inflate her cheeks forcefully. UC was in sustained remission with a prednisolone tapering and mesalazine. Colonoscopy showed complete resolution of colonic inflammation (Figure 1C, 1D).

Discussion

We present a young woman who presented with a relapse of UC subsequently followed by bilateral facial paralysis. By prompt recognition of the clinical presentation, along with comprehensive examinations, we were able to confirm the diagnosis of a facial diplegia variant of GBS, followed by timely and appropriate management. This case demonstrates a rare clinical presentation of co-existent UC with facial diplegia variant of GBS.

GBS is an autoimmune disease of the peripheral nervous system with multiple different variants [2]. Bilateral facial palsy is a rare variant presenting in less than 1% of patients with GBS [4]. The facial diplegia variant GBS rarely presents as pure bilateral facial weakness; it is usually accompanied by limb paresthesia and areflexia or followed by symmetric ascending limb weakness and hyporeflexia [5]. The present case is unique because bilateral facial palsy was the only manifestation. Bilateral facial palsy is a rare clinical entity caused by various conditions. GBS is one of the most common causes, but other relevant factors such as infectious, metabolic, vascular, neoplastic, and immunological diseases should be carefully excluded. Infection or activation of neurotropic virus HSV and VZV can lead to bilateral facial palsy [6], which was ruled out by negative pathogen tests and normal CSF cell counts in our patient. Facial neuritis is the most common neurological manifestation of Lyme disease [7]. Our patient reported no tick bites or typical skin lesions. The serum antibodies against Borrelia burgdorferi tested by ELISA was negative, which made Lyme disease highly unlikely. We also considered sarcoidosis as a differential diagnosis because facial nerve palsy is a cardinal manifestation of neurosarcoidosis [8]. However, our patient had a relatively acute onset, and she did not have other nervous system presentations, skin lesions of any kind, pulmonary nodules, mediastinal lymph node enlargement, or cardiac involvement. Her serum calcium level and ACE activity were normal. Although the soluble IL-2 receptor (sIL-2R) level detection was unavailable, we still considered the diagnosis of sarcoidosis was less likely. There have been a few reported cases of peripheral facial nerve paralysis related to autoimmune disorder such as primary Sjögren’s syndrome (pSS) and systemic lupus erythematosus (SLE) [9,10], but there was no evidence of any systemic autoimmune diseases in our case. Other possible etiological factors, including tumors infiltration and brainstem encephalitis were all excluded by laboratory tests and neuroimaging.

IBD is a systemic disorder that often involves organs other than the gastrointestinal tract, so extraintestinal manifestations are common [3]. As a subgroup of these EIMs, neurological manifestations are well documented in the literature. The overall incidence is unknown, and ranges from 0.25% to 47.5% in various reports because of selection bias or divergent diagnostic criteria [3]. Peripheral neuropathy (PN) is recognized as one of the most common neurological EIMs. However, there are few reports on GBS as an extraintestinal manifestation of UC. In 1985, Zimmerman first described GBS in 2 patients with UC [11]. To date, only 13 cases have been reported (Table 2). The most common type of GBS concomitant with UC is acute inflammatory demyelinating polyradiculopathy(AIDP); other types include acute motor axonal neuropathy (AMAN), acute motor and sensory polyneuropathy (AMSAN), and pharyngeal-cervical-brachial (PCB) [11–22]. We present a bilateral facial diplegia variant of GBS concomitant with UC, which has never been documented before. The relationship between UC activity and the development of GBS is unclear. The course of GBS may be parallel to the course of UC, and may be independent or even antecedent to the occurrence of UC. According to our literature review, only 5 out of 13 UC patients were diagnosed with GBS during an active period. Most cases developed symptoms of polyneuropathy during the remission period of UC, which is consistent with previous research [19]. However, our patient had bilateral facial palsy during the relapse phase of UC, suggesting involvement of an autoimmune inflammation response in the pathogenesis.

The pathogenesis of involvement of peripheral nerves in IBD remains largely unknown. It has been assumed that genetic susceptibility, aberrant autoimmunity, vasculitis, coagulation abnormalities, malabsorption, vitamins deficiency, infective etiology, and direct effects of the treatment (anti-tumor necrosis factor alpha therapy)contribute to development of the peripheral neuropathy [3]. The considerable overlap of genetic risk loci between IBD and EIMs suggests the role of genetic factors [23]. Since both UC and GBS are autoimmune diseases, there may be common autoimmune mechanisms involved in the development of both these diseases. In our patient, no etiological factor could be found for the acute peripheral neuropathy except for the flare of ulcerative colitis. Infection by enteric bacteria, a leaky intestinal barrier, and shared peptide sequences between enteric bacteria and host major histocompatibility complex molecules combine to trigger immune cross-reactivity [24]. For instance, infection by a microbial agent, namely Campylobacter jejuni, is linked to exacerbations of IBD and may increase the risk of GBS. Further research is required to explore the common pathogenic pathways, especially autoimmune mechanisms, in these 2 disorders.

Of the 13 cases of GBS related to UC, 6 were treated with intravenous immunoglobulin, 3 patients were treated with corticosteroids, 2 were treated with intravenous immunoglobulin and corticosteroids, 1 was treated with plasmapheresis, and 1 was treated with intravenous immunoglobulin and plasmapheresis. Upon treatment, 10 patients showed recovery and 3 showed improvement, with no recurrences reported. Our patient had some improvement after intravenous immunoglobulin therapy. Demyelinating and axonal neuropathies in patients with IBD may respond to immunotherapy, but a better treatment outcome is observed in the demyelinating form [25]. This may explain our patient’s poor response to immunological treatment.

Conclusions

GBS is an uncommon group of neurological EIM which can occur during UC relapse or remission. Facial diplegia as a variant GBS has not been previously reported to be concomitant with UC. Our case suggests that UC can be an underling cause or predisposing factor for bilateral facial palsy. We believe that this case report and literature review will encourage prompt diagnosis and accurate treatment of co-existent GBS and UC.