Idiopathic Intracranial Hypertension as the Initial Manifestation of Systemic Lupus Erythematosus: A Case Report and Literature Review

Introduction

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organ systems, most commonly in women of reproductive age. SLE can manifest with a wide range of symptoms, from mild joint pain to severe conditions, such as lupus nephritis and neuropsychiatric systemic lupus erythematosus (NPSLE), which can affect the central and peripheral nervous systems [1,2].

Neuropsychiatric involvement (NPSLE) in SLE includes seizures, mood changes, cognitive dysfunction, and more severe issues, such as stroke and intracranial hypertension [2].

Idiopathic intracranial hypertension (IIH) is a condition marked by elevated intracranial pressure without an obvious underlying cause, typically presenting with headaches, visual disturbances, and papilledema [3]. Although IIH is rare, about 90% of cases occur in young women with obesity [4]. The connection between SLE and IIH is rare but increasingly recognized. Risk factors for IIH in patients with SLE include active disease, severe renal involvement, a hypercoagulable state, and a history of thrombosis [5].

Although the exact link between SLE and IIH remains unclear, studies suggest that IIH could be an early manifestation of undiagnosed SLE [6]. Potential mechanisms include immune-mediated damage to the arachnoid villi, resulting in reduced cerebrospinal fluid absorption, and thrombotic occlusion of cerebral vessels, due to the hypercoagulable state present in patients with SLE [7]. Diagnosis involves neuroimaging and lumbar puncture to confirm elevated intracranial pressure [3]. Recognizing IIH as a potential manifestation of SLE is crucial for early intervention and preventing complications, such as vision loss [8].

Research suggests that IIH is rare, with an estimated incidence of 0 to 1 per 100 000 in the general population of the United States [9]. In Japan, the incidence among patients with SLE was found to be as low as 0.03 per 100 000 [10]. Hershko et al reported that 1% of hospitalized SLE patients presented with IIH, which is significantly higher than in the general population [5]. The first reported case of IIH in a patient with SLE dates back to 1968, described by Bettman et al [11]. Although the association is uncommon, early diagnosis and treatment of IIH in patients with SLE is essential to prevent serious complications [8]. The purpose of this study is to emphasize the uncommon nature of IIH as an initial sign of SLE and the importance of recognizing atypical presentations to ensure early diagnosis and treatment of SLE.

Additionally, we provide a review of the existing literature (Table 1). Early detection and treatment of IIH in SLE is essential to prevent complications, such as permanent vision loss or serious neurological sequelae.

This case highlights the need for heightened clinical suspicion of autoimmune disease in young women presenting with IIH. Recognizing such atypical presentations is critical to ensuring early diagnosis and prompt treatment of SLE, potentially avoiding irreversible complications, such as vision loss. The significance of this report lies in its geographic context (Saudi Arabia), which adds regional insight to the global spectrum of SLE presentations. Moreover, the patient’s individualized therapeutic journey reflects real-world clinical challenges and decision-making in limited-resource settings.

Case Report

A previously healthy 23-year-old Saudi woman presented to the King Faisal Medical Complex, Department of Medicine with a 1-week history of headache and blurred vision, accompanied by generalized fatigue and bilateral lower limb swelling for 1 month. The headache had a gradual onset, was moderate in intensity, generalized, and throbbing in nature. It occurred intermittently and was mildly relieved by paracetamol. There were no identified aggravating factors. Concurrently, she developed bilateral blurred vision without associated aura, photophobia, phonophobia, diplopia, loss of consciousness, seizures, or sensory disturbances. Additionally, she experienced progressive bilateral lower limb swelling up to the ankles, without joint pain, redness, or deformity. There was no malar rash or change in urine color, shortness of breath, palpitation, chest pain, cough, night sweating, or weight loss.

The symptoms significantly affected her daily activities. She denied prior similar episodes or a family history of autoimmune diseases. The patient had been on oral contraceptive

pills for 6 months, which she discontinued a month before presentation. Other systematic findings were unremarkable.

The physical examination upon admission found the patient was alert, conscious, and hemodynamically stable. She appeared pale but showed no signs of jaundice, cyanosis, or respiratory distress. She had no malar rash, discoid lesions, or oral ulcers.

Neurological examination revealed blurred vision and mild left abducens nerve palsy, evidenced by double vision at extreme lateral gaze (mild left abducens nerve palsy). Other cranial nerves were intact. Neurological examination revealed no facial weakness, dysphagia, or limb weakness. There was no rigidity or spasticity. Muscle power was 5/5 in all limbs, with intact sensation and reflexes. There were no cerebellar or meningeal signs, and gait was normal. Fundoscopic examination showed severe papilledema (Figure 1). Lower limb examination demonstrated bilateral pitting edema up to the ankles, with no signs of deep vein thrombosis.

Musculoskeletal examination showed no joint deformity, swelling, or signs of Raynaud’s phenomenon. Echocardiogram revealed a normal ejection fraction (63%) with mild pericardial effusion. Laboratory investigations at admission (Table 2) showed pancytopenia, including moderate normocytic anemia on peripheral blood smear (hemoglobin: 6.8 g/dL), absolute neutropenia, and lymphopenia. Peripheral blood smear showed ovalocytes, mild agglutination, marked absolute neutropenia, moderate lymphopenia (with no abnormal cells), and large platelets. Urinalysis revealed leukocytosis (22 per high-powered field; reference range: 0–5), proteinuria (+2), and granular casts. Blood and urine cultures were negative, except for the presence of extended-spectrum beta-lactamase-producing bacteria in the urine. The patient was initially started on ciprofloxacin, which was later adjusted based on culture sensitivity results. Serological workup was positive for antinuclear antibody (ANA) and anti-double-stranded (ds)DNA, with low complement levels (C3: 11.10 mg/dL [79–152], C4: 25.80 mg/dL [16–38]), suggestive of SLE. Inflammatory markers were elevated (erythrocyte sedimentation rate [ESR]: 50 mm/h, C-reactive protein [CRP]: 0.03 mg/dL). Anti-cardiolipin antibodies were negative.

Brain magnetic resonance imaging and magnetic resonance venography were performed to rule out mass lesions and venous sinus thrombosis. Both imaging modalities were normal, with no evidence of hydrocephalus, mass effect, or dural venous sinus thrombosis.

The diagnosis of IIH was made clinically based on the modified Dandy criteria, which include signs and symptoms of increased intracranial pressure (eg, headache, papilledema); absence of localizing neurological signs, except for possible abducens nerve palsy; normal neuroimaging; and normal cerebrospinal fluid composition with elevated opening pressure. Although a lumbar puncture was not performed due to patient refusal, clinical and radiological findings supported presumed IIH.

The patient was admitted for further evaluation of pancytopenia and was started on vitamin B12 and folic acid supplementation. Given the positive autoimmune markers, a diagnosis of SLE with lupus nephritis was suspected. However, due to facility limitations, a renal biopsy was not performed. Initially, she was started on oral prednisolone (60 mg daily), which led to an improvement in headache and resolution of lower limb edema. However, she developed new-onset eyelid swelling, prompting further evaluation. A 24-h urine protein test revealed significant proteinuria (0.4 g/day), supporting a diagnosis of Class I lupus nephritis per nephrology assessment.

On post-admission day 12, the patient reported worsening blurred vision, and a lumbar puncture was planned to assess intracranial pressure. However, she declined the procedure. In response to worsening symptoms, oral steroid changes to intravenous methylprednisolone (500 mg for 3 days) were administered, followed by a tapering regimen of oral prednisolone.

Clinical and laboratory improvements were noted, including resolution of pancytopenia and partial recovery of complement levels (C3: 15 mg/dL, C4: 2.03 mg/dL), white blood cells 4.7×109/L, neutrophil count: 2.7, hemoglobin 6.8 g/dL, and platelets 168×109/L. The patient was discharged on oral prednisolone 60 mg once daily; oral hydroxychloroquine 200 mg twice daily; oral mycophenolate mofetil 500 mg twice daily; and oral acetazolamide 250 mg twice daily for presumed IIH. Two weeks after discharge, follow-up investigations showed improved pancytopenia (white blood cells 6.2×109/L, hemoglobin 7 g/dL, platelets 162×109/L), and normalized ESR and CRP levels. However, fundoscopy (Figure 1) revealed persistent grade 3–4 papilledema, and 24-h urine protein increased to 4 g per day, suggesting disease progression.

Treatment adjustments included oral furosemide 20 mg once daily; oral prednisolone 30 mg twice daily for 30 days, followed by tapering; oral hydroxychloroquine 200 mg once daily for 30 weeks; oral acetazolamide 250 mg twice daily for 300 days; oral lisinopril 5 mg once daily (for proteinuria); oral mycophenolate mofetil 1500 mg twice daily for 100 days; and oral calcium carbonate/vitamin D3 (1500 mg/800 IU) once daily for 100 days. The patient was co-managed by a multidisciplinary team, including neurologists, nephrologists, ophthalmologists, and internists. Although no formal multidisciplinary meeting was convened, clinical decisions were made collaboratively across departments.

Cyclophosphamide and rituximab were not initiated, due to the partial response observed with corticosteroids and mycophenolate mofetil, and the absence of life-threatening organ damage. Patient preference and the setting’s resource limitations were also considered. The treatment plan was escalated based on persistent proteinuria and worsening papilledema.

Discussion

SLE is a complex autoimmune illness with a wide range of clinical presentations, including rare neurological manifestations, such as IIH [1]. Our case fits within a discrete subclass of SLE presentations in which IIH is the first manifestation, a pattern we discovered in a literature study of 40 cases spanning from 1968 to 2024.

The pathophysiology of IIH in SLE remains unclear, but proposed mechanisms include immune-mediated damage to the arachnoid villi resulting in impaired cerebrospinal fluid (CSF) absorption, vasculitis, hypercoagulability from antiphospholipid antibodies, and cerebral venous thrombosis—even in the absence of overt thrombotic events [5,18]. Our literature study revealed that IIH was the first presenting symptom of SLE in 18 of the 40 patients, emphasizing its uncommon but noteworthy frequency [6]. Our patient, a woman, fits the demographic description found in the literature, in which all 40 cases were female patients, with a mean age of roughly 24.1 years in bigger series [5]. Symptomatically, our patient had headaches, vision problems, and papilledema, which is consistent with the literature’s findings of headache in 92.5% (37/40), vision troubles in 82.5% (33/40), and papilledema in 85.0% (34/40) of cases [7]. Furthermore, systemic symptoms, such as weariness and lower limb swelling, in our case are consistent with frequent SLE features, such as fever and arthralgia reported in the examined cases. Diagnostically, our patient’s serological markers of positive ANA (95.0% frequency in published cases) and anti-dsDNA (87.5% prevalence) with low complement levels closely reflect the patterns observed in the literature [12].

The normal magnetic resonance venography in our case, which ruled out venous sinus thrombosis, supports an immune-mediated cause for IIH, which is consistent with previous research [3]. Due to logistical constraints, we did not assess CSF opening pressure, despite clinical and imaging data strongly supporting the IIH diagnosis, a limitation also reported in earlier investigations [13].

We started with oral prednisolone and progressed to intravenous methylprednisolone, along with hydroxychloroquine, mycophenolate mofetil (for lupus nephritis), and acetazolamide. This matches the literature, in which corticosteroids were used in 95% of cases, acetazolamide in 75%, and immunosuppressants, such as mycophenolate mofetil, in 30% for concurrent SLE activity [8]. The research generally demonstrated cases of symptom remission, while some cases reported relapses or consequences such as optic nerve injury [14]. Our patient’s pancytopenia improved initially, but papilledema and proteinuria persisted at follow-up, indicating continued disease activity, a pattern typical in instances with incomplete resolution.

Notably, the fact that our case is from Saudi Arabia adds geographic diversity to the literature, which already includes examples from India, the United States, Japan, and Korea [10]. The concomitant lupus nephritis needed a larger treatment approach, separating our care from IIH-focused regimens in certain studies [10]. The link between SLE and IIH may be due to immune-mediated damage to arachnoid granulations, which impairs CSF absorption, or to a hypercoagulable state that causes microvascular thrombosis [3]. Our case’s lack of venous sinus thrombosis supports the immune-mediated concept, which is consistent with data

that highlight inflammation over structural obstruction in SLE-related IIH [3]. This is consistent with the general setting of neuropsychiatric SLE, which emphasizes autoantibody-driven inflammation [7].

The present case highlights the necessity of screening for SLE in young girls with IIH, particularly if systemic symptoms are present. Early detection, as reported in past research, can avert serious effects, including visual loss [13]. With 18 of 40 literature cases presenting similarly to ours, this underscores the need for increased clinical suspicion [6]. Corticosteroids (95%) and acetazolamide (75%) are widely used in the literature, which is reflected in our approach, indicating their usefulness, while our patient’s ongoing papilledema underscores the necessity for long-term surveillance [8].

Our case report has limitations, particularly the absence of CSF opening pressure measurement; however, this is compensated for by robust clinical and imaging findings. The literature evaluation, which is based on case reports and small series, is not as robust as that of larger studies and includes some missing data, such as antiphospholipid antibody status [12]. Future research should look at larger cohorts to further understand the SLE-IIH link, investigate causes, and standardize management procedures [11].

Our patient improved with high-dose corticosteroids, acetazolamide, and mycophenolate mofetil. However, follow-up fundoscopy showed persistent grade 3–4 papilledema, indicating the need for ongoing monitoring. Treatment in previous reports primarily involved corticosteroids, with acetazolamide frequently used to reduce intracranial pressure [15]. Some cases also required additional therapy, such as mannitol or glycerol [15]. Long-term follow-up in previous studies generally showed resolution or significant improvement in IIH symptoms [16]. Moreover, the persistence of papilledema on follow-up in our patient reflects a chronic course. The case of this patient suggests IIH can be an atypical single presenting sign of SLE. This has implications for clinicians who evaluate patients with IIH and do not regularly consider SLE as part of the differential in the absence of any other signs of a connective disorder. The pathophysiology and etiologic link between SLE and IIH are unclear. The difference between increased IIH being idiopathic or a manifestation of SLE has important implications because the first-line treatment will differ quite a bit. Further prospective studies must be performed in an effort to definitively establish the association and pathophysiology between IIH and SLE.

Notably, this case provides geographic insight from the Gulf region. Previous regional cases, including that of Omer et al [33], highlight that patients in resource-limited or conservative communities may delay investigation or treatment, especially invasive procedures, such as lumbar puncture. This reinforces the need for culturally sensitive care.

The lack of long-term follow-up limits our ability to determine whether IIH fully resolved or transitioned into chronic papilledema. Additionally, the patient’s refusal of lumbar puncture meant we could not directly measure CSF opening pressure. Future studies should focus on longitudinal outcomes and immune biomarker profiles to clarify the role of IIH as an SLE prodrome.

Conclusions

This report demonstrates a case of IIH, an uncommon and unusual early symptom of SLE. While the link between SLE and IIH is uncommon, the prevalence of neuro-ophthalmic symptoms, such as headache, papilledema, and visual disturbances, particularly in young women, should urge doctors to investigate underlying autoimmune etiologies, including SLE. Our patient’s appearance, which was consistent with that of previously reported cases, emphasizes the significance of a thorough systemic assessment when IIH is identified without a clear explanation. Early detection and commencement of immunosuppressive medication, such as corticosteroids and disease-modifying drugs, can drastically influence disease progression and prevent long-term consequences, including vision loss. Persistent papilledema in our case highlights the importance of close monitoring, even after initial treatment response. Further studies are needed to explore the role of IIH as a prodrome of SLE and to guide optimal therapeutic strategies.

This case emphasizes the importance of close long-term monitoring, due to the possibility of persistent or recurrent symptoms. Future studies with larger cohorts are needed to better understand the pathophysiologic relationship between SLE and IIH, as well as to provide uniform diagnostic and treatment criteria for such overlapping symptoms.