Neuropsychiatric lupus: An uncommon presentation of pediatric systemic lupus erythematosus

INTRODUCTION

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a fluctuating course and a wide array of clinical manifestations. Neuropsychiatric involvement in SLE encompasses a spectrum of neurological and psychiatric symptoms that impact both the central and peripheral nervous systems. Approximately 25% of children with SLE have neuropsychiatric manifestations of SLE which significantly contribute to morbidity and mortality.^[1] The variability in clinical presentation and the extensive differential diagnoses pose significant challenges to accurate diagnosis and treatment. A heightened clinical suspicion, in conjunction with laboratory and neuroimaging findings, is essential for confirming the diagnosis. This case report discusses a 16-year-old male who presented with fever, rash, and seizures, diagnosed with neuropsychiatric lupus and treatment with corticosteroids and cyclophosphamide resulted in significant clinical improvement.

CASE REPORT

A 16-year-old boy presented with a low-grade, intermittent fever since 1 year, associated with maculopapular rash over the face, both arms, and palatal ulceration for 1 week and two episodes of generalized tonic-clonic seizures lasting 4-5 minutes and subsiding spontaneously. In addition, there was a history of a 10 kg weight loss over 5 months.

On examination, the child had pallor, palatal ulcer, maculopapular rash across the face and bilateral arms, along with hyperpigmented rash evident on the trunk [Figures 1-3]. The child was normotensive, and without signs of meningeal irritation.

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Figure 1:

Palatal ulcer.

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Figure 2:

Macular rash over face.

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Figure 3:

Macular rash over back.

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Autoimmune conditions, particularly systemic lupus erythematosus (SLE) was considered. Baseline blood investigations revealed hemoglobin of 8.7 mg/dl, total leucocyte count (TLC) of 4,600c/mm³, platelet count of 3.34 lakh, C-reactive protein 1, and erythrocyte sedimentation rate of 49 [Table 1].

Magnetic Resonance Imaging (MRI) brain revealed acute left insular cortex bleed with significant surrounding edema, acute non-hemorrhagic infarct along the left posterior watershed area, and multiple white matter hyperintense lesions in bilateral parietal region – suggestive of central nervous system (CNS) involvement in SLE [Figures 4-6].

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Figure 4:

Axial T2-weighted hyperintense lesion with a central dark area in the left insular cortex with perilesional edema.

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Figure 5:

Axial T1-weighted hypointense lesion in the left insular cortex.

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Figure 6:

Axial fluid-attenuated inversion recovery extension of perilesional edema into left thalamus and posterior limb of internal capsule.

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Diagnosis of systemic lupus erythematous was made in accordance with the American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) criteria as detailed in Table 2.

This child had a score of 25 ( > 10 diagnostic). Renal function tests along with a 24-h urine protein test were normal.

During the hospital stay, child developed abnormal aggressive behavior for which antipsychotic medications were started.

Injection methylprednisolone was administered for 5 days, followed by a single dose of injection cyclophosphamide. Neuropsychiatric complaints improved, no further episodes of seizures were seen, and the patient was discharged on oral steroids (60 mg/m²), tablet hydroxychloroquine, and tablet levetiracetam. In addition, planned for monthly injections of cyclophosphamide for a duration of 6 months. The parents were counseled regarding the disease and the necessity of follow-up.

DISCUSSION

SLE is a multisystemic autoimmune disease with a variety of clinical manifestations and several immune-mediated abnormalities leading to multiple organ dysfunctions. In adult-onset SLE, neurological symptoms and polyarthritis predominate, whereas in children and adolescents, lupus nephritis, hematological disorders, photosensitivity, butterfly rash, and mucosal ulceration are more common.^[2] Neuropsychiatric SLE (NPSLE) comprises the neurologic and psychiatric manifestations of SLE in which other causes have been excluded. Although reported in up to 40% adults with SLE, neuropsychiatric involvement is rare in children, especially as initial presentation. A variety of neuropsychiatric manifestations have been described with SLE and have been classified into 19 syndromes in accordance with the ACR, divided into central and peripheral syndromes^[3,4] [Table 3].

The NPSLE is mainly clinical, based on the EULAR criteria, supported by MRI findings if present. The neuroimaging findings of NPSLE may result from many different pathophysiologic mechanisms such as vasculitis and vasculopathy, thromboembolic, antiphospholipid syndrome, demyelinating syndrome, and autoimmune antibody-mediated encephalitis.^[5,6]

The initial management of NPSLE is focused on symptomatic treatment such as antiepileptics for seizures, anxiolytics or antipsychotics for psychiatric manifestations, antihypertensive drugs for hypertension, and correction of metabolic derangements. In addition, the underlying SLE process of neuropsychiatric manifestations should also be halted, such as thromboembolic disorder and inflammation-driven syndromes with immunosuppressive drugs.^[7,8] Studies of NPSLE in adults have shown that treatment regimens including cyclophosphamide in addition to prednisolone and hydroxyurea are associated with better patient outcomes. Other drugs used in this context are mycophenolate mofetil (MMF), azathioprine, and rituximab.^[9] Studies on the outcome of children with neuropsychiatric symptoms show that 20% of children experience a disease flare during childhood and 25% may experience a permanent neuropsychiatric damage^[10] [Figure 7].

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Figure 7:

Management of neuropsychiatric systemic lupus erythematosus. SLE: Systemic lupus erythematosus, NPSLE: Neuropsychiatric systemic lupus erythematosus, IV: Intravenous, CV: Cardio vascular, LDL: Low density lipoprotein, ACE: Angiotensin converting enzyme, ASA: Acetyi salicylic acid, APS: Antiphospholipid syndrome, IVIG: Intravenous immunoglobulin.

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CONCLUSION

The clinical spectrum of CNS lupus encompasses various neuropsychiatric manifestations, including cognitive dysfunction, mood disorders, headaches, seizures, psychosis, and cerebrovascular events. These manifestations result from a complex interplay of immune-mediated inflammation, vascular damage, and neuronal dysfunction. The backbone of treatment in NPSLE is steroids and cyclophosphamide.