Webinar replay: A discussion on connective tissue disease

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Presented by



Thermo Fisher Scientific


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Dr Ajesh focussed on the following in his presentation:

  • Understand the classification criteria of systemic lupus erythematosus (SLE) ​
  • Clinical features​
  • Assessment​
  • Latest treatment approaches​.

Systemic lupus erythematosus: 1982 classification criteria

If we look at the systemic lupus erythematosus: 1982 classification criteria definitions, we see​ 11 criteria:

  • Malar rash. Fixed erythema, flat or raised, sparing the nasolabial folds​
  • Discoid rash. Raised patches, adherent keratotic scaling, follicular plugging; older lesions may cause scarring​
  • Skin rash from sunlight​
  • Oral or nasopharyngeal ulcers, usually painless​
  • Nonerosive, inflammatory in two or more peripheral joints​
  • Pleuritis or pericarditis​.
  • Renal disorder. Persistent proteinuria or cellular casts​
  • Neurologic disorder. Seizures or psychosis​​
  • Hematologichaemolytic anaemia, leukopenia (<4 000/mm3), lymphopenia (<1 500/mm3), or thrombocytopenia (<100 00/mm3)​
  • Immunologic disorder. Antibodies to double-stranded deoxyribonucleic acid (dsDNA) or SM or positiveantiphospholipid antibodies (IgG or IgM antibodies, lupus anticoagulant, or false-positive serologic test positive serologic test for syphilis)​
  • Antinuclear antibody test: Positive​.

The Systemic Lupus International Collaborating Clinics (SLICC) classification had 17 criteria. According to the SLICC rule for the classification of SLE, the patient must satisfy at least four criteria.

Classification of nephritis

Systemic lupus erythematosus: classification of nephritis​

  • Normal glomeruli​
  • a) Nil by all techniques​
  • b) Normal by light but deposits on electron microscopy or immunofluorescence
  • Mesangial glomerulonephritis​
  • Focal glomerulonephritis​
  • Diffuse glomerulonephritis (this is the worst type)​
  • Diffuse membranous glomerulonephritis​
  • Advanced sclerosing glomerulonephritis.

Systemic lupus erythematosus: nervous system manifestations 

  • Seizures
  • Ataxia​
  • Headache
  • Rigidity, tremor​
  • Stroke syndromes
  • Chorea ​
  • Subarachnoid haemorrhage
  • Hemiballismus​
  • Transverse myelitis
  • Coma​
  • Multiple sclerosis-like disorder
  • Dementia​
  • Optic neuritis
  • Psychiatric disorders​
  • Aseptic meningitis ​
  • Peripheral neuropathy​
  • Cranial neuropathy ​
  • Mononeuritis multiplex​
  • Guillain-Barré syndrome.

If antinuclear factor (ANF) tests positive, please request extractable nuclear antigen antibodies (ENAs) panel.

Drug-induced lupus

Definite drug associations are:

  • Hydralazine​
  • Procainamide​
  • Minocycline​
  • Chlorpromazine​
  • Isoniazid​
  • Penicillamine​
  • Methyldopa​
  • Interferon-alpha.

Possible drug associations include:

  • Anticonvulsants​
  • Quinidine​
  • Propylthiouracil​
  • Sulfonamides​
  • Lithium​
  • Beta-blockers​
  • Nitrofurantoin
  • Sulfasalazine

Clinicians ordering the anti-nuclear antibodies (ANA) test should be aware of the test's low-positive predictive value in settings with a low prevalence of rheumatic disease, particularly among older patients.

Baseline investigations for SLE 

  • Full blood count
  • Urea and electrolytes
  • Complement (C3& C4)​ test
  • ANF with ENAs/ dsDNA/ anti Smith Antibodies
  • Antiphospholipid antibodies/ Anti-cardiolipin antibodies
  • Lupus anticoagulant​
  • Urine for microscopy and sensitivity/urinary creatinine: protein ration​
  • 24-hour urinary protein with creatinine clearance.

Preliminary classification criteria for antiphospholipid syndrome

  • APS is present if more than one clinical and one lab criteria met​
  • Vascular thrombosis​
  • > One arterial, venous, or small-vessel thrombosis and​
  • Thrombosis confirmed by imaging or Doppler or histopathology and​
  • Without evidence of inflammation in vessel wall on histpathologic confirmation​
  • Pregnancy morbidity​
  • > One foetal death > 10th week gestation or​
  • > One premature birth > 34th week with preeclampsia or placental insufficiency or​
  • > Three consecutive spontaneous abortions​
  • < 10th week gestation​
  • Laboratory criteria​
  • Anticardiolipin antibody IgG or IgM present medium or high titers >two times at least six weeks apart or​
  • Lupus anticoagulant present > two times at least six weeks apart.

Antiphospholipid antibody syndrome

Clinical manifestations of this include:

  • Arterial thrombosis​
  • Venous thrombosis​
  • Valvular abnormalities​
  • Pregnancy loss and infertility​
  • Livedo reticularis​
  • Cerebrovascular thrombosis​
  • Chorea

Antiphospholipid antibody syndrome: tests​

  • Partial thromboplastin time (PTT)​
  • Lupus anticoagulant​
  • Anticardiolipin antibodies by ELISA​
  • Anti-B2-glycoprotein one antibody ​
  • False-positive biologic test for syphilis​
  • Russell viper venom test​
  • Platelet count​
  • Antinuclear and anti-DNA antibodies.

Ancillary investigations

  • Chest x-ray
  • Electrocardiogram

Assessment of SLE ​

Mild disease:

  • Constitutional symptoms​
  • Rash: body surface area (BSA) <9% ​
  • Platelets; 50-100 x 109/L.

Moderate disease​:

  • Rheumatoid arthritis like arthritis​
  • Rash: 9%-18% BSA​
  • Cutaneous vasculitis <18% BSA​
  • Platelets; 20-50x 109/L​
  • Serositis​.

Severe disease​:

  • Major organ threatening disease: nephritis, cerebritis, myelitis, pneumonitis, mesenteric vasculitis​
  • Severe thrombocytopenia with platelets <20 x 109/L​
  • Thrombotic thrombocytopenic purpura-like disease
    • Acute haemophagocytic syndrome.

Treatment of non-renal SLE

Generally, chloroquine is accepted as treatment for all forms of mild, moderate, or severe disease. You can use systemic steroids such as glucocorticoids and prednisone, and we generally use a combination of chloroquine and prednisone. Prednisone is generally started at 1mg per kilogram depending on what the severity of the disease is, especially if they have kidney involvement, brain involvement, lung involvement or heart involvement, it’s generally pulse glucocorticoids systemic corticosteroids and then once we get them under control, we can use methotrexate as a steroid-sparing agent. In patients with moderate to severe disease we use belimumab, which is not available in South Africa, but it is available on Section 21 if it is needed in patients. We don’t have calcineurin inhibitors, but we have mycophenolate mofetil, which we can use for moderate to severe disease.

In patients with severe lupus, we can use cyclophosphamide generally administered as a pulse cyclophosphamide, as a monthly dose and if everything else fails in a patient with lupus after having put them on chloroquine, prednisone, azathioprine, methotrexate, mycophenolate mofetil and cyclophosphamide we then use rituximab which is a biologic for the treatment of lupus and is registered in SA for the treatment of systemic lupus erythematosus. This is generally reserved as a last treatment option, and it is done by a rheumatologist.

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