Keywords

Overview

  • Definition

    • Chronic, multisystem, autoimmune disease characterized by the production of numerous autoantibodies, mostly targeted against components of the cell nuclei

    • Damage is mediated by immune complex deposition in tissues (lupus nephritis and arthritis) or by direct effects of auto-Ab on cell surface molecules or serum components (hemolytic anemia, thrombocytopenia, antiphospholipid syndrome)

    • Disease severity and prognosis vary widely depending on the extent of organ involvement

  • Symptoms

    • May precede systemic presentation

    • Wide ranging from dry eye symptoms, ocular pain and photosensitivity, to severe loss of vision

  • Laterality

    • Can present unilaterally or bilaterally

  • Course

    • Relapsing and remitting

  • Age of onset

    • Typically late teens to early 40s, but 15% have late onset (late 50s–early 60s)

  • Gender/race

    • F:M = 9:1

    • African Americans, Asians, and Hispanics are more affected

  • Systemic association

    • Skin, joints, and kidneys are classically involved, but practically all organs can be affected, as the autoantibodies target all cellular nuclei

    • Skin (85% of patients): butterfly rash across the nose and cheeks, known as malar flush, is the most common finding. Other findings include discoid rash (erythematous raised areas with adherent keratotic scaling and follicular plugging), cutaneous ulcers, splinter hemorrhages, purpuric skin lesions, and alopecia

    • Musculoskeletal (85%): painful peripheral joints, non-deforming migratory polyarthritis, myalgia, and myositis

    • Renal (50%): the major cause of morbidity and mortality in SLE patients; manifest as nephrotic syndrome, mesangial disease, focal or diffuse proliferative nephritis, and membranous glomerulonephritis

    • Painless oral ulcers (30–40%)

    • Neuropsychiatric (30%): seizures, organic brain syndrome, psychosis; transverse myelitis is rare (4%) but is associated with optic neuritis

    • Raynaud’s phenomenon (20%)

    • Cardiac (20%): pericarditis, myocarditis, Libman-Sacks endocarditis (also known as nonbacterial thrombotic endocarditis + phospholipid antibody)

    • Pulmonary: pleuritis and pneumonitis

    • Hepatosplenomegaly and adenopathy are common despite not being part of diagnostic criteria (see Table 3.1)

    • Hematologic: chronic anemia, hemolytic anemia, leukopenia, lymphopenia, thrombocytopenia, and increased thrombotic risks

    • Secondary antiphospholipid syndrome (APL): deep vein thrombosis, cerebral arterial thrombosis, pulmonary embolism, thrombocytopenia, and recurrent fetal loss (typically in second and third trimesters) in the presence of APL antibodies

Table 3.1 The American College of Rheumatology Criteria for SLE
Full size table

Exam: Ocular

External

  • Discoid rash: erythematosus rash over the eyelids characterized by keratotic scaling and follicular plugging (may coexist with blepharitis and thus be overlooked)

  • Strabismus due to cranial nerve or muscle involvement

Anterior Segment

  • Keratoconjunctivitis sicca

  • Episcleritis: generally benign and self-limiting

  • Scleritis: anterior diffuse or nodular scleritis; necrotizing is rare

  • Recurrent corneal erosions, peripheral keratitis (ulcerative or not), interstitial keratitis, endotheliitis

  • Anterior uveitis is rare, non-granulomatous, and typically mild

Posterior Segment

  • Retinopathy is the most well-recognized ocular manifestation of SLE, observed in 1 out of 10 patients

    • Microangiopathy is an extremely accurate barometer of systemic disease activity: cotton-wool spots (most common), arteriolar attenuation, retinal hemorrhage, microaneurysms

    • Retinal findings are compounded by systemic hypertension as a sequelae of SLE nephropathy: AV nicking, hard exudates, papilledema, and multifocal choroidal infarctions (Elschnig’s spots)

    • Occlusive vasculitis affects the arterioles primarily, causing vascular sheathing and retinal opacification; diffuse non-perfusion leads to neovascular complications such as vitreous hemorrhage, tractional retinal detachment, and glaucoma

    • Venous occlusion is less common and may be due to venous stasis secondary to arterial occlusion

  • Choroidopathy is uncommon

    • Present as single or multifocal serous retinal detachment

    • Associated with CNS vasculitis, nephropathy, and uncontrolled hypertension

    • Very responsive to systemic therapy

  • Vitritis is rare

  • Optic nerve involvement

    • Papillitis due to optic nerve vasculitis

    • Optic neuritis with resultant ischemic optic neuropathy; transverse myelitis is seen in more than half of these patients

    • Papilledema from rare pseudotumor cerebri

Exam: Systemic

  • For clinical research, at least 4 of 11 ACR diagnostic criteria need to be met (Table 3.1). However, in practice, patients with fewer than 4 can still be diagnosed with SLE

Imaging

  • OCT

    • Macular edema

    • Subretinal fluid in choroidopathy

  • FA

    • Microaneurysms

    • Retinal non-perfusion with retinal neovascularization

    • Macular leakage

    • Optic nerve leakage

  • ICG

    • Early, transient hypofluorescence followed by late hyperfluorescence in areas of choroidopathy

    • Multifocal hyperfluorescence during intermediate phase possibly indicative of immune complex staining

Laboratory and Radiographic Testing

  • BMP, CBC, LFTs, and complete urinalysis

  • ANA: nonspecific but present in almost all patients (97–98%); diffuse, peripheral or speckled pattern

  • Anti-dsDNA and anti-Smith antibodies are most SLE-specific

    • Anti-dsDNA Ab: present in 30% of SLE patients, tends to represent a more serious disease state such as nephritis; however, its level cannot be used to monitor disease activity

    • Anti-Sm Ab: present in 20% of SLE patients; does not reflect disease severity

  • Less SLE-specific antibodies: anti-Ro/SSA and anti-La/SSB (30–40%), anti-U1RNP (25%), APL (17%)

  • Anti-histone Abs typically suggests drug-induced SLE, but may also be found in primary SLE

  • Total complement (CH50), C3, C4 can be low due to complement consumption

  • Chest X-ray

  • Echocardiogram

Differential Diagnosis

  • Adamantiades-Behcet’s disease

  • Polyarteritis nodosa

  • Takayasu’s disease

  • Granulomatosis with polyangiitis (Wegener’s)

  • Syphilis

Treatment

  • Oral NSAIDs and aminoquinolines, including chloroquine and hydroxychloroquine, may be appropriate for cutaneous lupus, arthritis, and serositis

  • Systemic corticosteroids are reserved for hematologic, renal, and CNS diseases; long-term steroid-sparing immunosuppression may be necessary in systemic and ocular lupus (ocular flare-up can occur despite systemic quiescence)

  • Plasmapheresis in combination with immunosuppressive therapy has been used in a few severe, recalcitrant cases

  • Laser photocoagulation +/− intravitreal anti-VEGF are used in severe vaso-occlusive disease to prevent ischemic complications

Referral/Co-management

  • Rheumatology

  • Nephrology

  • Other specialists per systemic involvement