Ptosis: an uncommon manifestation to autoimmune disease activity in systemic lupus erythematosus

Abstract

Background

Systemic lupus erythematosus (SLE) is an autoimmune disease with diverse manifestations, including rare neuro-ophthalmic complications. Isolated unilateral ptosis as a presenting sign of SLE is uncommon and diagnostic uncertainty often exists.

Case presentation

A 30-year-old woman with a 16-year history of SLE presented with acute right-sided ptosis without other neurological deficits while on stable maintenance immunosuppressive therapy. MRI of the brain and orbits, along with other relevant investigations, excluded common structural causes and showed no abnormalities. Serological testing indicated moderately active SLE, supporting an autoimmune flare as the likely mechanism. Myasthenia gravis–specific testing was not performed, a recognized limitation, but was considered clinically unnecessary given the absence of fatigability, diurnal variation, or generalized weakness. The ptosis resolved completely within 24 h of initiating high-dose systemic corticosteroid therapy.

Conclusions

Isolated unilateral ptosis may represent a rare neuro-ophthalmic manifestation of SLE, though alternative diagnoses cannot be definitively excluded. The rapid steroid response may suggest an inflammatory or autoimmune mechanism, underscoring the importance of considering such etiologies and initiating timely immunosuppressive therapy when appropriate.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12886-025-04384-2.

Introduction

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that affects multiple organ systems, including the nervous system. While neurological involvement is less frequent compared to other systemic autoimmune conditions, it can present with a wide range of symptoms collectively known as Neuro-Psychiatric SLE (NPSLE), including seizures, psychosis, and peripheral neuropathies [1, 2]. Ophthalmic complications, though less common, are also part of NPSLE. Approximately one-third of SLE patients experience some form of eye involvement, ranging from mild symptoms to severe, vision-threatening conditions [3].

Neuro‑ophthalmic manifestations in SLE arise through multiple mechanisms, including immune-complex deposition, vasculitis, microvascular thrombosis, and direct immune-mediated injury to neural and vascular structures. Immune-complex deposition in ocular vasculature has been demonstrated histologically in SLE-related retinopathy, while vasculitic and thrombotic processes, often associated with antiphospholipid antibodies, are implicated in ischemic optic neuropathy, cranial nerve palsies, and ocular motor dysfunction. Optic neuritis (ON) is among the most frequently reported neuro-ophthalmic complications. However, diplopia, extraocular movement (EOM) deficits, internuclear ophthalmoplegia (INO), cranial nerve palsies (ONP), and even myasthenia gravis (MG) have been documented in both early and recent literature [4–6].

In his influential 1979 review, Simons Lessell described a spectrum of neuro-ophthalmic manifestations in SLE, including transient ptosis, diplopia often linked to vertebrobasilar ischemia, and INO, each with notable diagnostic and prognostic implications [7]. Subsequent literature, including a 2014 systematic review, has reinforced these observations, noting that while ON remains the most frequently reported manifestation, other ocular motor disorders such as diplopia and INO continue to be clinically relevant [5]. Considering the rarity and diagnostic challenges of such presentations, we report this case to describe an unusual episode of isolated unilateral ptosis in the context of SLE.

Isolated unilateral ptosis without additional neurologic signs remains particularly rare in SLE and its pathophysiology is not well understood [8]. This report presents a rare case of unilateral ptosis in an SLE patient, which resolved rapidly with escalated steroid therapy.

Case presentation

A 30-year-old woman presented at a tertiary care hospital in Muscat, Oman, in 2023 with a 16-year history of SLE, managed with low-dose oral prednisolone, azathioprine, and hydroxychloroquine. She presented with an acute onset of right upper eyelid drooping (Fig. 1). The ptosis developed over a few hours and was accompanied by mild pain on upgaze, but she denied any changes in vision, diplopia, or generalized muscle weakness. There was no recent history of infections, trauma, or new medication use. Her previous SLE manifestations included musculoskeletal involvement and lymphadenopathy, with no prior neurological complications. Upon the presentation, her symptoms were well controlled and there were no activities on the multi-modal treatment regimen that she was on.

Fig. 1.

Picture showing moderate ptosis of the right upper eyelid on presentation

Notably, the patient reported a non-documented prior episode of acute ptosis that occurred after she had independently discontinued systemic steroids; however, this episode was not medically documented, as she did not seek hospital evaluation at the time. According to her recollection, the ptosis resolved spontaneously within 24 h after she resumed steroid therapy on her own.

Her ocular history included LASIK surgery a few years prior, as well as a prophylactic barricade laser procedure for a retinal hole before LASIK treatment.

On examination, she was alert, oriented, and cooperative. Neuro-ophthalmic assessment revealed isolated moderate right-sided ptosis with preserved levator function and no involvement of other extraocular muscles. Fatigue testing yielded negative results. Ocular alignment was normal, with orthophoria demonstrated on alternate cover testing. Pupillary responses were normal, with no afferent pupillary defect. A comprehensive cranial nerve, motor, and sensory examination was unremarkable. Slit-lamp and fundus examination of both eyes showed no abnormalities. MRI contrast-enhanced thin-slice orbital and brainstem imaging with fat suppression was ordered and showed no abnormalities (Fig. 2).

Fig. 2.

MRI orbit and brain with contrast showing no abnormalities

Additional autoimmune and inflammatory markers were reassessed to support the working diagnosis and evaluate for neuropsychiatric lupus involvement. Antinuclear antibody (ANA) remained positive at a titre of 1:320 (≤ 1:40). Notably, there was a significant elevation in anti-dsDNA antibodies: >150 IU/mL (< 25 IU/ml), with concurrently low C3: 0.78 g/L (0.90–1.80 g/l) and lower limit of normal range for C4: 0.10 g/l (0.10–0.40 g/l). The antiphospholipid antibody panel, including lupus anticoagulant, anticardiolipin antibodies, and anti-β2 glycoprotein I, was negative. Extended ENA testing revealed strongly positive anti-RNP and anti-ribosomal P antibodies, and moderately positive anti-Ku, anti-Sm, and anti-nucleosome antibodies. Anti-dsDNA by Crithidia assay was negative. These serologic findings, in the setting of active joint inflammation and leukopenia, supported SLE activity with possible neuropsychiatric involvement.

The SLE Disease Activity Index 2000 (SLEDAI-2 K) was calculated and totaled 9, indicating moderate disease activity. Scoring parameters included arthritis, low complement, rising dsDNA, and leukopenia. While autoantibodies such as anti-ribosomal P and anti-RNP are classically associated with neuropsychiatric lupus, in this case, the isolated ptosis with no other neurological deficits raised the possibility of localized inflammation around the globe.

At presentation, she was already on maintenance prednisolone (5 mg/day). Following consultation with her rheumatologist, she received a three-day course of intravenous methylprednisolone (500 mg/day), which was then transitioned to 40 mg oral prednisolone. Remarkably, the ptosis resolved completely within 24 h of initiating treatment (Fig. 3). The steroid dose was gradually tapered over the following weeks. The patient was reviewed over multiple follow-up visits spanning two years, during which no recurrence was observed.

Fig. 3.

Picture showing complete resolution of ptosis of the right upper eyelid within 24 h of commencing systemic corticosteroid therapy

Discussion

SLE is a complex autoimmune disease with diverse clinical manifestations affecting nearly every organ system [1, 2]. While neurological involvement is less common than other systemic complications, it is a recognized feature and can present as cranial neuropathies, myelitis, or peripheral neuropathies. The isolated nature of ptosis in this case highlights the complexity of neuro-ophthalmic manifestations in SLE [2, 8]. Recent work by De Andrade et al. comprehensively reviewed neuro-ophthalmologic presentations in SLE, spanning optic neuropathies to internuclear ophthalmoplegia, and a case-based review by Voulgari et al. detailed orbital myositis in a cohort of 48 SLE patients, emphasizing the need for high clinical suspicion across varied ocular syndromes [9, 10].

Mild unilateral ptosis in SLE has been documented in only a few reports. One study identified 11 cases in which ptosis was associated with active disease, though only two patients exhibited overt cerebral involvement. This finding suggests that isolated ptosis may result from localized inflammation rather than central nervous system pathology, emphasizing the importance of differentiating focal manifestations from more extensive neurological complications in SLE [7]. Similarly, another study investigating eye movement abnormalities in SLE mentioned ptosis as one of the observed findings, along with restricted ocular movements, abnormal eye positioning at rest, and spontaneous eye movement disorders [11].

The pathogenesis of ptosis in SLE is likely multifactorial, involving immune‑mediated, inflammatory, or ischemic effects on eyelid elevation structures. The levator palpebrae superioris and Müller’s muscle are innervated by the oculomotor nerve and sympathetic fibers, respectively. In this case, preserved levator function makes significant oculomotor nerve involvement or primary levator myopathy unlikely. Instead, a more plausible mechanism is transient inflammation of Müller’s muscle or periorbital soft tissues, which could impair eyelid elevation through edema or immune-mediated effects, without overt nerve or muscle damage. The patient’s mild pain on upgaze supports this possibility, suggesting local inflammatory irritation around the eye rather than intrinsic muscle pathology. Orbital myositis associated with SLE has been described in several case reports and reviews, where extraocular muscle inflammation occurs without structural nerve injury and typically responds rapidly to corticosteroids. While less frequently reported, perineural inflammation of the sympathetic fibers supplying Müller’s muscle could explain the acute and reversible ptosis via transient dysfunction of the sympathetic innervation, especially in the context of systemic autoimmune activity [12, 13].

Another possible contributor is microvascular ischemia or endothelial dysfunction secondary to antiphospholipid antibodies, which are known to compromise blood flow to neural and muscular structures. This may transiently affect sympathetic innervation to Müller’s muscle or lead to localized edema, both of which can cause mild ptosis [5]. Immune-mediated disruption of neuromuscular transmission is another theoretical mechanism for ptosis in SLE, although it is rarely reported and seems unlikely in this case given the lack of generalized muscle weakness or clinical fatigability. Concomitant MG has been documented in patients with SLE, and ocular MG has presented with ptosis and diplopia that respond to steroids and acetylcholinesterase inhibitors [14]. However, in our patient, the abrupt onset, absence of fatigability, and complete resolution within 24 h of corticosteroid therapy more closely match a focal, reversible inflammatory process rather than neuromuscular junction dysfunction.

The rapid resolution of ptosis following systemic corticosteroid therapy strongly suggests an inflammatory or immune-mediated mechanism. Corticosteroids are well established in SLE management for their potent anti-inflammatory and immunosuppressive effects, which include inhibiting cytokine release, reducing leukocyte infiltration, and downregulating autoantibody production [15]. In neuro-ophthalmic involvement, corticosteroids likely reduce inflammation around the nerves or within the orbital tissues, alleviating compressive or inflammatory neuropathy. The patient’s rapid response within 24 h aligns with the known ability of steroids to control acute inflammation effectively. Notably, neuro-ophthalmic Manifestations in SLE respond well to corticosteroids, with treatment success rates ranging from 60–75% [16, 17]. However, although the rapid resolution of ptosis following systemic corticosteroid therapy supports an inflammatory mechanism, it does not definitively establish SLE as the underlying cause, since spontaneous remission cannot be excluded without further diagnostic confirmation. Furthermore, the absence of confirmatory diagnostic tests such as electromyography or muscle biopsy limits the ability to definitively localize the pathology.

Third nerve palsy and Horner’s syndrome were excluded based on clinical findings and imaging. The patient presented with isolated, unilateral ptosis with preserved levator function, normal pupillary responses, full extraocular movements, and no additional cranial nerve deficits. She reported no symptoms suggestive of intracranial pathology such as headache, diplopia, or facial numbness, making a third nerve palsy or central lesion unlikely [18–20]. Furthermore, contrast-enhanced, thin-slice MRI of the brain and orbits with fat suppression was performed and reported as normal, supporting the exclusion of structural causes.

Although diagnostic tests for MG, including anti-acetylcholine receptor and anti-MuSK antibody assays, single fiber electromyography, edrophonium testing, and the ice pack test, are typically recommended in cases of isolated ptosis, they were not pursued in this case due to the absence of clinical features suggestive of this disease. The ptosis showed no fatigability or diurnal variation, and the patient exhibited no signs of generalized muscle weakness, making MG less likely. Nonetheless, future similar presentations would benefit from formal testing to conclusively exclude MG.

We acknowledge that a rapid response to corticosteroids is not specific to SLE and can be seen in other inflammatory or autoimmune conditions, such as MG and orbital myositis of different causes. Therefore, this case is presented as a presumed SLE-associated neuro-ophthalmic manifestation, considering the temporal correlation with an SLE flare and systemic response to immunosuppressive therapy, while avoiding definitive attribution of causality. Although MG antibody testing was not performed, the clinical presentation and treatment response supported a benign, self-limited course consistent with SLE [21].

Management of NPSLE remains challenging due to the lack of standardized treatment guidelines. In severe cases, a common approach involves 1 g of intravenous methylprednisolone for three days, followed by oral prednisolone at 1 mg/kg/day, which is then tapered over 3–12 months. Milder cases typically receive an initial dose of 0.5–1 mg/kg/day, with individualized tapering schedules [22]. The dose of 500 mg daily for three days was selected in consultation with the patient’s rheumatologist, considering her stable baseline disease and the aim to provide effective but balanced immunosuppression. This dose is a moderate alternative to the conventional 1 g regimen, tailored to the clinical context. The administration of high-dose intravenous methylprednisolone, followed by oral prednisolone, ensures both an immediate and sustained immunosuppressive effect, which may be critical in preventing permanent neurological damage, particularly if microvascular ischemia or immune-mediated demyelination is involved.

The lack of recurrence of ptosis after steroid tapering suggests a successful resolution of the underlying inflammatory process. However, these findings should be interpreted with caution. We acknowledge that the prior episode of ptosis was based solely on patient recollection without contemporaneous documentation, which may introduce recall bias and limit the certainty of a reproducible steroid-responsive pattern. Long-term stability is also likely supported by the patient’s maintenance immunosuppressive therapy, which continues to modulate disease activity [15].

Additionally, we acknowledge that the available prevalence estimates are largely derived from isolated case reports, which may not accurately reflect the true frequency due to publication bias and underreporting. These factors highlight the need for systematic studies with standardized diagnostic protocols to better understand this association.

Conclusion

This case highlights isolated ptosis as a rare neuro-ophthalmic manifestation potentially associated with SLE, emphasizing the need to consider autoimmune mechanisms in the differential diagnosis of similar presentations. While MG could not be formally excluded due to the absence of specific testing, the lack of clinical features suggestive of MG and the patient’s rapid improvement with systemic corticosteroids support an inflammatory or autoimmune etiology. Clinicians should remain vigilant for autoimmune activity when evaluating unexplained, isolated ptosis, particularly in patients with established SLE. This case provides valuable insights into the possible pathophysiology and management of focal neurological complications in SLE, and further research is needed to clarify diagnostic pathways and optimize therapeutic strategies for such rare manifestations.

Authors’ contributions

All authors attest that they meet the current ICMJE criteria for Authorship. A B designed the original draft and procured data curation, investigation and conceptualization. H G written and reviewed the pre-final version. B L edited and formally analyzed the data. A M reviewed, supervised and finalized the version.

Funding

No funding or grant support.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethical approval and consent to participate

Written informed consent was obtained from the patient for publication of this case report and accompanying images. The need for ethical approval is waived for case reports by my institute.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and accompanying images.

Competing interests

The authors declare no competing interests.