Clinical Notes about Systemic Lupus Erythematosus

Inheritance role in ✓ An identical twin of a patient with SLE carries a 25– the development of 50% chance of developing SLE. SLE ✓ A nonidentical twin has a risk of 2–5%, and still being greater than that in the general population. ✓ First-degree relatives of a patient with SLE carry a six times higher risk of SLE. ✓ Inherited deficiencies of early complement components (C1q, C2, C4) increase 5-10 times the risk of SLE development.

Clinical or laboratory • The presence of: manifestations predict that a • malar rash, oral ulcers patient not fulfilling • elevated anti-dsDNA diagnostic criteria will • and decreased serum C4 evolve to SLE complement levels • Individual not fulfilling at that time SLE diagnostic criteria will evolve to SLE within the next 2–5 years, but not necessarily with major organ involvement

The most common autoantibodies encountered in patients with SLE, and their main clinical associations

ANA • ANAs are not specific for SLE • In normal population it is positive in around 10%. • Less than 5% of individuals presenting ANA positivity will develop SLE. • Yet, 100% of systemic lupus erythematosus patients

Anti-dsDNA • Highly diagnostic for SLE • Correlate with disease activity, in particular lupus nephritis.

Anti-Sm (Smith) • Highly diagnostic SLE • Do not correlate with disease activity.

Anti-Ro/SSA • Encountered also in patients with • SCLE, • Sjögren’s syndrome, • Neonatal lupus (especially antiRo52), • Neuromyelitis optica spectrum diseases, • and photosensitivity.

Anti-La/SSB: • Encountered primarily in patients with • Sjӧgren’s syndrome • and patients with SCLE.

Anti-ribosomal P • Highly specific for SLE with psychiatric disease (lupus psychosis, epilepsy).

Antiphospholipid • Associated with • Inhibition of in vitro coagulation tests (lupus anticoagulant), • Thrombosis, • Recurrent fetal loss, • and thrombocytopenia

Anti-histones • Encountered in • SLE and • Drug-induced SLE.

Fever being due to bacterial infection and not to disease exacerbation • White blood cell count: leukocytosis • Elevated serum CRP levels (more than 15–20 times above normal value) • Elevated serum procalcitonin levels

Laboratory • CBC, parameters • serum creatinine, should be • Liver enzymes, periodically • ESR, evaluated to • Urine analysis, follow SLE • Serum C3 and C4 levels, activity • and anti-dsDNA autoantibody levels.

Demographic and clinical findings which predict acute flare will occur in a SLE patient • Young age of SLE onset (<25 years), • Proliferative lupus nephritis at diagnosis, • Oral ulcers, • Increased anti-dsDNA levels >50%, • Leukopenia and thrombocytopenia, • Anti-Sm antibody positivity, • and use of immunosuppressive agents

• The commonest causes of morbidity are: Commonest • Infections, morbidity and • Hypertension, mortality causes • Cardiovascular disease, in patients with • Osteoporosis, SLE • Cytopenia due to immunosuppressive agents, • and malignancies. • The most frequent causes of mortality are • Active SLE, • Cardiovascular disease, thromboses, • And serious infections.

• Microbial septicemia, The most common infections seen in • Pneumocystis carinii immunosuppressed pneumonia, SLE patients • Varicella zoster virus infection, • and tuberculosis.

• First described in patients Jaccoud’s arthropathy with rheumatic fever. • It can be seen in patients with SLE and Sjögren’s syndrome. • Presents with correctable deformities of the MCP and MTP joints • A result of soft tissues abnormalities such as laxity of ligaments, fibrosis of the capsule, and muscular imbalance, rather than joint bony destructions

Lupus band test • It is a diagnostic procedure performed on a skin biopsy specimen that detects, with direct immunofluorescence staining, deposits of immunoglobulins and various complement components along the dermo-epidermal junction in lupus erythematosus patients. • Detection of these deposits in the skin of patients with lupus erythematosus demonstrates a linear band at the basement membrane zone, hence the name lupus band test.

Lupus band test • A positive lupus band test may serve as a prognostic indicator in patients with an established diagnosis of lupus erythematosus. • It correlates with severe extracutaneous disease, mainly lupus nephritis, and with anti-dsDNA antibodies.

Lupus band test Direct immunofluorescence staining of clinically healthy and unexposed to sun skin from systemic lupus erythematosus patient revealed deposits of immunoglobulins and complement components along the dermo-epidermal junction (arrows)



Acute cutaneous systemic lupus erythematosus • Butterfly rash (maculopapular eruption in the central face area around the nose). • Photosensitivity eruptions in sun-exposed areas • Papular erythematous rashes in the arms and legs • Bullous eruptions with erosions and mouth/ hard palate ulcers.

Butterfly rash in a 50-year-old woman with systemic lupus erythematosus

Painless hard palate ulcer in a 40- year-old lady with exacerbating SLE

Subacute cutaneous lupus erythematosus • Annular/polycyclic and psoriasiform/papulosquamous rashes. • The lesions typically occur in photosensitive distribution. • Common locations of SCLE rash include the neck, the shoulders, the upper chest, the upper back, and the extensor surface of the hands. • In most patients, sun exposure exacerbates the disease.

Annular/polycyclic and psoriasiform/papulosquamous rash on the back after sun exposure

Chronic cutaneous manifestations • Discoid rashes which are painless disc-shaped erythematous plaques with areas of follicular hyperkeratosis. • When the lesions progress, they result in cutaneous atrophy, either in loss or increase of skin pigmentation, and depressed scars can develop. • If the discoid lesions are on the scalp, they result in scarring alopecia.

Discoid lupus erythematosus: a 36-year-old female patient with multiple chronic hyperpigmented discoid lesions on the face

Scarring scalp alopecia: a 34-year-old female with systemic lupus erythematosus and multiple discoid scarring scalp lesions

Histopathologic classification lupus nephritis

Class I • Minimal mesangial LN • Normal appearing glomeruli by light microscopy (LM) with immune deposits confined to the mesangium visible by immunofluorescence.

Class II • mesangial proliferative LN • Mesangial proliferation (of any degree) visible by LM and mesangial deposits by IF. • Minute subendothelial or subepithelial immune deposits may rarely be visible by IF or electron microscopy (EM) , but not by LM, whether there is endocapillary proliferation.

Class III • focal LN • focal, segmental, or global endo- or extra capillary glomerulonephritis involving <50% of all glomeruli, typically with focal subendothelial immune deposits, with or without mesangial alterations.

Class IV • diffuse LN • Subendothelial immune deposits visible by LM with or • without mesangial alterations involving ≥50% of all glomeruli. • Class IV is subdivided into diffuse segmental (IV-S, segmental defined as a glomerular lesion that involves less than half of the glomerular tuft) when ≥50% of the involved glomeruli has segmental lesions, and diffuse global (IV-G) when ≥50% of the involved glomeruli have global lesions

Lesions in classes III and IV are further characterized as purely active (A), as purely chronic (C), and as a combination of active and chronic lesions (A/C).

Class V • Membranous LN • Global or segmental subepithelial immune deposits involving ≥50% of the glomerular tuft in ≥50% of glomeruli. • Class V lupus nephritis may occur in combination with class III or IV

Class VI • Advanced sclerosing LN • ≥90% of glomeruli are globally sclerotic with no evidence of ongoing activity.

Adverse • Adverse predictors of remission are: predictors of • severe proteinuria remission and • and delayed initiation of therapy from the time relapse of lupus nephritis was clinically diagnosed. nephritis • Predictors of earlier relapse for patients entering remission include: • a longer time to remission • and a history of central nervous system involvement.

Poor prognostic • Hypertension, factors for lupus • renal failure, nephritis • massive proteinuria, • and high activity score of lupus nephritis on renal biopsy specimen.

Neurologic • Cognitive impairment is the most frequent manifestations manifestation, followed by seizures. can be seen in SLE patients • Additional manifestations include peripheral neuropathies, acute confessional state, headache, and depression. • Central nervous system involvement can also manifest as lupus retinopathy. • Less common manifestations are psychosis, movement disorders, myelopathy, optic neuritis, cerebrovascular accidents, cranial neuropathies, and aseptic meningitis

How common are strokes in systemic lupus erythematosus patients? • Strokes in SLE patients are twice more common compared to the incidence of strokes in the general population. • Usually, strokes occur within the first year after SLE diagnosis. • Thus, as soon as the diagnosis of SLE is established, the physicians should search for stroke risk factors and apply the necessary measures to eliminate them.

Predictors of poor The number of previous neuropsychiatric outcome in SLE events patients with neuropsychiatric and the coexistence of antiphospholipid manifestations syndrome

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