Systemic lupus erythematosus (SLE) associated uveitis in India – A case series

Abstract

Purpose:

To report the uveitic manifestations of patients with systemic lupus erythematosus (SLE).

Methods:

This was a retrospective analysis of all SLE cases with ocular manifestations seen by a single ophthalmologist between 2015 and December 2021.

Results:

In total, seven patients with a median age of 40 (range 18–50) years were included in the study. Female (85.7%) predominance was noted. Ocular findings were bilateral in 71% (five patients) of cases. Majority (10 eyes, 83%) of the patients had retinal vasculitis as the common finding. Antinuclear antibodies were positive in all the patients. The vision improved in two (16.6%) eyes, was stable in eight (66%) eyes, and worsened in one (8%) eye. All the patients were treated with oral steroids along with immunosuppressive agents.

Conclusion:

Though SLE is rare cause of uveitis, it can be associated with significant ocular morbidity. Hence, early diagnosis and treatment can salvage vision in many cases.

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory connective tissue disorder involving multiple organs.[1] Although the pathogenesis of SLE is unclear, it occurs as a result of a complex interaction between hormonal, environmental, and genetic factors.[2] One-third of patients with adult-onset SLE have noted ocular involvement, and the prevalence rate varies widely in the literature.[3] SLE can involve any part of the eye, including the orbital, periorbital, and adjacent structures of the eye.[2] Ocular findings include an abnormality of eyelids, keratoconjunctivitis sicca, anterior uveitis, retinal vasculitis, choroiditis, and optic neuropathy.[1,2,3,4] Though rare, few studies reported optic nerve involvement and retinal vasculitis as the first sign of SLE.[2,3,5,6] Studies relating to SLE-associated uveitis are limited in the Indian literature.[7,8,9] This case series enumerates the clinical manifestations and management of SLE-associated uveitis from a tertiary eye care center in southern India.

Methods

This observational case series is from a tertiary eye care center in southern India. The study was approved by the institutional review board and conducted in accordance with the tenets of Declaration of Helsinki. All the patients were examined by a single observer between January 2015 and December 2021 to avoid observer bias. Patients who met the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE were enrolled in our study, which included 15 patients.[10] Eight of 15 patients with a previous history of uveitis, improper documentation, and lesser than 6 months of follow-up were excluded from the study. All the study participants underwent a complete ophthalmic evaluation including a detailed history, best-corrected visual acuity, intraocular pressure measurement by applanation tonometry, slit-lamp examination, and fundus evaluation with indirect ophthalmoscopy. The systemic examination included a complete hemogram, serum angiotensin-converting enzyme (SACE), antinuclear antibody, C-reactive protein, complement (C3/C4), anti-double-stranded DNA antibodies (anti-dsDNA Ab), rheumatoid factor, antiphospholipid antibody, chest X-ray, Mantoux test, high-resolution computed tomography, human leukocyte antigen (HLA) B27, venereal disease research laboratory test, and Treponema pallidum hemagglutination assay, which were done in all cases. Additional evaluation by a rheumatologist was sought in all cases. Topical and oral steroids were the mainstay of the treatment. Immunosuppressives or biologics were added as steroid-sparing agents in recalcitrant uveitis cases. The vision was assessed using the Snellen visual acuity chart and converted to log of minimum angle of resolution (logMAR) values for analysis. In our study, the visual outcome was categorized as “improved” if there was a two-line difference in vision between the first and the final visit, “worsened” if contrary, and “stable” if no change was seen.

All the clinical data were entered in Microsoft Excel and analyzed using Statistical Package for the Social Sciences (SPSS) version 20 (SPSS Inc., Chicago, IL, USA). The Kolmogorov–Smirnov test was used to check the normality assumptions of study parameters. Chi-square Fisher’s exact test was used to compare categorical variables. Wilcoxon signed-rank test was used to check the visual acuity changes between the first and last visits of the patient to the clinic. In our study, continuous variables were represented as median with a quartile range and categorical values as frequency and percentages. A P value less than 0.05 was considered significant in all the statistical tests.

Results

A total of seven (12 eyes) patients who satisfied the inclusion criteria were included in our study. The median age of these patients was 40 years (ranging from 18 to 50 years). Female (85.7%) preponderance was noted in our study. The median age at the time of SLE diagnosis was 36 years. Of all the seven patients, retinal vasculitis was the presenting feature of SLE in three (25%) patients (cases 2, 5, and 7). The other four (57%) patients developed ocular manifestation over a median period of 1 (0.03–7) year. The median duration of follow-up was 14 (10–43) months. In our series, majority (five patients, 71%) of the patients presented with bilateral involvement.

Table 1 details the patients’ demographic, clinical, and laboratory characteristics. Most (71.4%) of the patients presented with the complaint of diminution of vision. Clinical findings included retinal vasculitis [Fig. 1 and 2] in six (10 eyes, 83%) patients and nongranulomatous anterior uveitis in one (two eyes, 16.6%) patient. Associated optic disc pallor was seen in nine (75%) eyes and optic disc edema in one (8.3%) eye. Antinuclear antibodies and antiphospholipid antibodies were positive in all (100%) patients. Malar rashes were seen in four (57%) patients. Anti-dsDNA Ab were detected in one (12.5%) patient. The anti–Sjögren's syndrome related antigen A autoantibodies (SSA RO) ribonucleic protein complex, which is specific to Sjogren’s syndrome and SLE, was positive in two (29%) patients. Leukopenia (one patient, 14%), polycytopenia (one patient, 14%), polyarthralgia (three patients, 43%), myalgia (one patient, 14%), and myositis (one patient, 14%) were seen in our case series.

Table 1.

Summary of demographic, clinical, and laboratory findings of the study participants

		Case 1		Case 2		Case 3		Case 4		Case 5		Case 6		Case 7
Age at presentation (years)		18		50		33		43		40		32		48
Gender		F		F		F		F		M		F		F
Laterality		U/L		B/L		B/L		B/L		B/L		U/L		B/L
Age at the diagnosis of SLE		18		50		32		36		40		28		48
Duration between the diagnosis of SLE and the onset of ocular symptoms		12 days		0 days		6 months		7 years		0 days		4 years		0 days
Ocular complaints		RE: DOV		BE: DOV		BE: DOV		BE: Nil		BE: flashes		LE: DOV, floaters		BE: DOV
Vision at presentation		RE: 3/60		RE: HM+LE: 6/9		RE: HM+LE: 6/24		RE: 6/6 LE: 6/6		RE: 6/6 LE: 6/6		LE: 2/60		RE: NO PL LE: HM+
Vision at the final visit		RE: 3/60		RE: 3/60 LE: 6/36		RE: HM+LE: 6/18		RE: 6/6 LE: 6/6		RE: 6/6 LE: 6/6		LE: 6/9		RE: PL + PR inaccurate LE: 1/24
Vision status at the final follow-up		RE: stable		RE: improved LE: worsened		RE: stable LE: stable		RE: stable LE: stable		RE: stable LE: stable		LE: improved		BE: stable
Clinical signs of SLE		Malar rash, arthritis, leukopenia, positive anti-dsDNA, ANA, D-dimer		Polyarthralgia, skin pigmentation, myalgia, ANA positive		Myositis, pancytopenia, probable lupus nephritis, positive ANA		Positive ANA, SSA RO		Rashes, fever, positive ANA		Polyarthralgia, malar rash, ANA positive, anti-RO, HPE-proven necrotizing histiocytic lymphadenitis presented as cervical lymphadenitis, SLE with Kikuchi’s syndrome		Skin rashes, arthritis, ANA positive, anti-CCP positive
Ocular findings		RE: RV		BE: RV		RE: RV, RD LE: RV		BE: NGAU		BE: RV		LE: RV		BE: RV
Optic disc		RE: pallor		BE: pallor		RE: pallor LE: normal		BE: pallor		RE: pallor LE: edema		LE: normal		BE: pale disc
Treatment		Oral steroids, HCQ, MMF		Oral steroids, HCQ, azathioprine		Oral steroids, MMF		Oral steroids, MMF		Oral steroids, IV cyclophosphamide, oral cyclophosphamide		Oral steroids, MMF, injection rituximab, HCQ		Oral steroids, rituximab, and MMF
Surgery		RE vitrectomy, phacoemulsification, Avastin injection		RE: vitrectomy, phacoemulsification		RE: vitrectomy		Nil		Nil		Nil		PRP three sittings
Complication		RE: cataract, glaucoma		BE: Nil		BE: Nil		BE: glaucoma		BE: Nil		LE: Nil		BE: Nil

ANA=antinuclear antibody, anti-dsDNA=anti-double stranded DNA, BE=both eyes, B/L=bilateral, DOV=diminution of vision, HM+ = hand movements, LE=left eye, MMF=mycophenolate mofetil, NGAU=nongranulomatous anterior uveitis, PRP=panretinal photocoagulation, RD=retinal detachment, RE=right eye, RV=retinal vasculitis, SLE=systemic lupus erythematous, U/L=unilateral, NO PL=No perception of light, PR=projection of rays, HCQ= Hydroxychloroquine

Figure 1.

Fundus photography of right eye (case 5) shows pale disc, multiple cotton wool spots, superficial hemorrhages throughout the fundus before treatment (a) and resolving cotton wool spots and superficial hemorrhages post treatment (b)

Figure 2.

OCT-A of the left eye in a patient with SLE (case 6) shows gross capillary nonperfusion areas in both superficial (a) and deep (b) capillary plexus. Also, corresponding OCT macula (c) of the same patient shows altered foveal contour and inner retinal thinning. OCT = optical coherence tomography, SLE = systemic lupus erythematosus

In our series, three patients treated with hydroxychloroquine showed decreased macular sensitivity on multifocal retinogram. The presenting visual acuity and final visual acuity were 0.00 (interquartile range [IQR]: 0.10–1.35) log units and 0.00 (0.10–1.00) log units, respectively. Regarding visual outcome, the vision was improved in two (16.6%) eyes, worsened in one (8%) eye, and was stable in eight (66%) eyes. All the patients were treated with oral steroids along with immunosuppressive agents. Among the immunosuppressants, mycophenolate mofetil (75%) was used most commonly. Two (29%) patients required treatment with rituximab due to nonresponsive treatment. Glaucoma (30%) and cataract (10%) were the common complications in our series.

Discussion

We report here a series of cases with SLE-associated ocular manifestations. SLE can involve any part of the eye. Although keratoconjunctivitis sicca is commonly reported in SLE patients, retinal vasculitis occurs in 29% of SLE-diagnosed patients.[11] The exact mechanism of retinal vasculitis is not well understood yet. Theories have been made based on the circulating immune complexes which cause occlusion of vessels as a reason for SLE retinopathy.[12] Furthermore, few studies reported that elevated antiphospholipid antibodies are associated with the development of retinopathy.[13,14,15] In our series, most of the patients had diagnosis of retinal vasculitis. Out of eight patients, three patients had retinal vasculitis as the preceding sign of SLE. Alhassan et al.[3] reported a case of bilateral vasculitis as the first sign of SLE with no involvement of other organs. Another study reported Purtscher-like retinopathy as the initial sign of systemic involvement in a 15-year-old girl, who was successfully treated with oral steroids and hydroxychloroquine.[16] Similarly, a few other authors also reported ocular involvement as the first sign of SLE. In a prospective study of 43 confirmed SLE patients, seven patients developed retinopathy over a period of 5 years.[17] They also reported that detection of retinopathy is associated with exacerbation of SLE, and improvement in ocular condition was noted with control of SLE.[17]

As the disease involves multiple organs, it is imperative to control the systemic involvement of the condition to achieve effective ocular improvement. The mainstay of the treatment for SLE retinal vasculitis is similar to the treatment of SLE in general, including corticosteroids and immunosuppressants.[18,19] Patients with acute SLE retinopathy may require treatment with intravenous pulse steroid therapy and cytotoxic agents such as cyclophosphamide. If the improvement in ocular parameters is noted, the patient can be maintained on low level of corticosteroids with hydroxychloroquine. Hydroxychloroquine is a lysosomotropic agent that inhibits the function of lysosomes, thereby downregulating the immune response against autoantibodies.[20] Many studies have reported the efficacy of hydroxychloroquine in the treatment of SLE.[20,21] However, hydroxychloroquine can be associated with several adverse events. About 10% of patients treated with hydroxychloroquine develop corneal deposits and poor macular functions.[20] In our series, three patients treated with hydroxychloroquine showed decreased macular sensitivity on multifocal retinogram. We strongly suggest frequent macular assessment tests in cases treated with hydroxychloroquine.

Local therapies such as pan-retinal photocoagulation (PRP) can also be beneficial in perivascular leakage SLE-associated retinopathy cases.[22] PRP reduces the metabolic demand of the retinal tissues and prevents the formation of new vessels. In addition, the intravitreal anti-vascular endothelial factor can be useful in cases with cystoid macular edema.[23] Several studies have shown rituximab’s efficacy and relative safety in severe and refractory SLE cases.[23,24] Rituximab is an anti-CD20 chimeric antibody that depletes B-cells, which are crucial in the pathogenesis of SLE.[23] In the case of recalcitrant Bechet’s disease-associated retinal vasculitis, a significant improvement in the disease course was achieved with an intravitreal injection of rituximab.[25] Similarly, another recent study showed a rapid marked improvement in a case of SLE retinal vasculitis following treatment with rituximab.[26] In our series, two patient had recalcitrant inflammation of the retinal vessels, where a marked improvement was seen after a single intravitreal injection of rituximab. We suggest treatment with rituximab in recalcitrant cases, which can salvage vision and rapidly improve the disease course.

Conclusion

Although uveitis in SLE is a rare phenomenon, if present, it can lead to severe vision-threatening complications. Moreover, its presence can be a sign or marker for overall systemic activity. Prompt diagnosis and early recognition is paramount in reducing systemic as well as ocular morbidity. Close collaboration between the treating ophthalmologist and rheumatologists is critical for the effective management of this complex disease.

Financial support and sponsorship:

Nil.

Conflicts of interest:

There are no conflicts of interest.