¹Fatimetou Ba, ¹Ahlam Almarzooqi, ¹Malaz Soliman, ¹Abdullah Alrammmal

¹EHS- Qassimi Hospital

Purpose Statement: Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease that commonly affects women of childbearing age, and it is the highest in people of African descent. The exact etiology is unknown however multiple risk factors have been identified including genetic, hormonal, and environmental factors. The disease develops as a result of inappropriate activation of the immune system which leads to the formation of several autoantibodies. Multiple phases of remission and relapse characterize SLE. The severity of symptoms varies between patients and any organ is a possible target . The occurrence of neuropsychiatric manifestations ranges between 12% and 95%  . SLE can affect both the central nervous system (CNS) and peripheral nervous system (PNS), along with causing various psychiatric symptoms. The prevalence of myelopathy is relatively rare and accounts for 3.9% of total neuropsychiatric manifestations . In this report, we present a case of a middle-aged South Asian man who presented with weakness and was found later to have transverse myelitis as an initial symptom of SLE.

Method(s): A previously healthy South Asian man in his mid-40s presented to our emergency department complaining of bilateral lower limb weakness with difficulty ambulating. This weakness was gradual and accompanied by periorbital, perioral, and bilateral pedal edema. He also complained of urinary frequency and incontinence. The patient denied constitutional symptoms (fatigue, fever, night sweats, anorexia, and weight loss etc). He had no extra-articular disease manifestation. He also had no history of joint manifestation, oral ulcers, Raynaud’s phenomenon, rashes, nodules, etc. Aside from the associated symptoms, the patient denied having a medical or surgical history or taking any medications. His vital signs were stable, and he was afebrile. His blood pressure was 120/68, and saturation was 98% on room air. He had a temperature of 37.1 and a heart rate of 93. Examination-wise, GCS 15/15, his chest, cardiovascular, and abdominal examinations were unremarkable, and he had no spinal tenderness. The patient needed assistance to mobilize from his wheelchair to the bed. His neurological examination revealed normal eye movement and pupil, no bulbar weakness and no facial asymmetry. Power-wise his muscle power of the neck was grade 3 + in flexion and grade 4 in extension. In the upper limbs, it was grade 4+, while in the lower limbs, it was grade 2 + to 3 in different muscle groups, with the weakness being more appreciable proximally. The patient also had resting right-hand tremors and brisk tendon reflexes in both upper and lower limbs. Sensations for vibration sense and temperature were impaired in the distal feet with no clear sensory level. He had upgoing planters on both sides.

His initial laboratory investigations revealed a low platelet count of 73.00 x10(3)/mcL (normal range 150-450), a slightly increased lymphocyte count of 46.10 % (normal range 20-40), an ESR of 22 (0-15), sodium levels of 128 (136-145), hypokalemia with potassium levels of 2.8 (3.5-5.1). His CRP was <0.5 mg/L. Initial radiological examination of the chest and abdomen was insignificant. Further workup was done as detailed ahead. CT Head and brain were normal, and an MRI of the lumbar and thoracic spine was done as advised by neurology, which showed Bilateral paraspinal erector spinae muscles displaying high T2 and STIR signal intensity more on the right side from D11 to L4/5 level representing skeletal muscle oedema. The Picture was suggestive of erector spinae myositis. MRI brain was normal.  His viral serology workup (HIV, HBV, HCV, EBV, CMV, Influenza, COVID etc) was negative. His thyroid functions and C1 esterase levels were normal. His autoimmune panel workup showed positive ANA), positive SM and SMRNP >200 U/ml for both, low C3 16.8 (Normal range 90-180 mg/dL) and low C4 3.2 (normal range 10-40 mg/dL), myositis panel is normal. The patient also had proteinuria of more than 1.2 g per 24 hours in addition to pyuria and hematuria.

Interestingly, the patient also had a normal creatinine kinase level of 147 IU/L (normal range 39-308), and it remained within the normal limits during his stay. He had negative SS-A & SSA-B, c-ANCA & p-ANCA, scl-70 antibody, centromere and JO-1. He started receiving methylprednisolone pulse therapy for five days. Afterwards, he started on oral prednisolone 60 mg and hydroxychloroquine 200mg twice daily. He did an initial nerve conduction study and an electromyogram, which suggest muscle fiber disease of the proximal and the distal muscles rather than inflammatory muscle disease. The patient denied constitutional symptoms (fatigue, fever, night sweats, anorexia, weight loss etc). He had no extra-articular disease manifestation. He also had no history of joint manifestation, oral ulcers, Raynaud’s phenomenon, rashes, nodules, etc

Further workup was sent, which was negative for anti-cardiolipin antibodies. But he had positive Anti-dsDNA >200 and a Rheumatoid Factor of 24 (normal range 0-14). The workup also included tumour markers, which were negative. Pan computer tomography demonstrated minimal amounts of peritoneal free fluid, fat stranding, and subcutaneous diffuse fat stranding and oedema. MRI of his proximal thighs demonstrated oedema in the subcutaneous, intermuscular and muscular compartments extending from the anterior abdominal wall to the buttocks and thighs. His Creatinine Kinase levels were repeated multiple times but were always within the normal range.

After a lumbar puncture, which was unremarkable except for the presence of proteins, the patient was started on cyclophosphamide infusion as per EURO-LUPUS protocol. He was to receive a dose of 500 mg every 2 weeks. He also received 2 doses of IVIG 1gm/kg 75mg daily for 2 consecutive days around the same time. The patient’s second dose of cyclophosphamide was postponed due to UTI, and it was given when it was resolved. During the admission, the patient received a total of 3 doses of cyclophosphamide 2 weeks apart.

The patient had neurological findings, including brisk upper and lower limb reflexes, an upgoing plantar response, weakness in different muscle groups, especially in the proximal lower limbs, in addition to impaired sensations for vibration sense and temperature in the distal feet with no clear sensory level, a diagnosis of peripheral neuropathy was considered which was most probably related to his new diagnosis of SLE .

A repeated nerve conduction study showed normal sensorimotor functions of the upper limbs but totally absent sensory action potentials reflecting a severe sensory lesion that could signify severe sensory neuropathy or sensory neuronopathy in the bilateral sural nerves.

A diagnosis of inclusion body myositis was considered in view of the MRI findings and normal CK levels; however, muscle biopsy couldn’t be done due to several technical and logistical issues. The same was applied to sural nerve biopsy as well, which was recommended in view of the nerve conduction study results. The patient continued receiving his medications in addition to symptomatic treatment and physiotherapy. His lower limb power improved dramatically from ⅖ to ⅘, and he didn’t develop any complications during his stay. He was discharged on hydroxychloroquine 200 mg BID, tapering dose of prednisolone ( starting at 1mg/kg ), a proton pump inhibitor, and folic acid. He was planned to receive a total of 6 doses of cyclophosphamide with rheumatology follow-up appointments. His final working diagnosis was SLE myelitis.

Result(s): In conclusion, this case underscores the diverse clinical spectrum of systemic lupus erythematosus (SLE), emphasizing the significance of recognizing neuropsychiatric manifestations, particularly myelopathy. The diagnostic process involved comprehensive assessments, revealing positive anti-nuclear antibodies, anti-double-stranded DNA antibodies, and low complement levels.

The patient’s unique presentation, marked by normal creatinine kinase and absence of myositis, posed challenges but guided treatment decisions. Following the EURO-LUPUS protocol, the patient responded positively to methylprednisolone, cyclophosphamide, and intravenous immunoglobulin, leading to substantial improvement in lower limb power.

This case highlights the necessity for a multidisciplinary approach to effectively manage SLE-associated neuropsychiatric manifestations. Continued reporting and research contribute to refining diagnostic and therapeutic strategies in the complex landscape of SLE.

Conclusion(s): In conclusion, this case underscores the diverse clinical spectrum of systemic lupus erythematosus (SLE), emphasizing the significance of recognizing neuropsychiatric manifestations, particularly myelopathy. The diagnostic process involved comprehensive assessments, revealing positive anti-nuclear antibodies, anti-double-stranded DNA antibodies, and low complement levels.

The patient’s unique presentation, marked by normal creatinine kinase and absence of myositis, posed challenges but guided treatment decisions. Following the EURO-LUPUS protocol, the patient responded positively to methylprednisolone, cyclophosphamide, and intravenous immunoglobulin, leading to substantial improvement in lower limb power.

This case highlights the necessity for a multidisciplinary approach to effectively manage SLE-associated neuropsychiatric manifestations. Continued reporting and research contribute to refining diagnostic and therapeutic strategies in the complex landscape of SLE.