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Diagnosis of Systemic Lupus Erythematosus - clinical picture & investigations

Here , we are going to discuss a diagnostic approach to Systemic Lupus Erythematosus involving clinical picture , Laboratory investigations and summary of diagnostic criteria .

Clinical picture

• Male: female ratio is 1 : 9
• The presentation and course are highly variable :

1- Fever of unknown origin.
2- Musculoskeletal manifestations :
Systemic_Lupus_Erythematosus

-  Joint involvement is mainly arthralgia with mild morning stiffness.
-  The arthropathy is bilateral and symmetrical. The small joints are
usually affected mimic rheumatoid disease.
-  It is non deforming but tendosynovitis may lead to deformity (Jaccoud's arthropathy), it is due to tendon or ligament laxity.
-  A vascular necrosis of the hip may occur with steroid therapy.


3- The skin


-          Butterfly rash: fixed erythema (flat or raised) on the cheeks of the face and across the bridge of the nose, occurs in a photosensitive distribution that spares the naso-labial folds.

       -   Discoid rash: erythematous raised patches with adherent scaling,
         atrophic scarring may occur. It may lead to scarring alopecia if present on the scalp.

       -  Photosensitivity: skin rash as a result of unusual reaction to sun light.

-          Purpuric lesion due to thrombocytopenia or vasculitis.
      - Leg Ulcers .

Vasculitic lesions :
 • Nail bed and finger bulb infarcts .
 • Purpuric rash with elevated edge.

- Raynaud's phenomenon.
- Urticaria.       -  Alopecia.

-  Panniculitis (Lupus profundus)
-  Lichen plannus like.
-  Livedo reticularis.

4- The Eye
  -  Retinal vasculitis can cause infarcts, cytoid bodies which appear as hard exudates
  -  Episcleritis, conjunctivitis or optic neuritis may occur.
  -  Kerataconjunctivitis sicca with Sjogren's syndrome.

5- The heart
   -  Pericarditis and pericardial effusion.
   -  Myocarditis with heart failure.
   -  Libman sacks endocarditis (affecting mitral or aortic valves causing regurge), It is a sterile endocarditis.
   -  Blood pressure is increased with renal hypertension.
   -  Coronary heart disease (accelerated atherosclerosis).

6- The Kidney
Lupus nephritis (WHO classification)
• Type I       Minimal pathology (Normal glomeruli)
• Type II      Mesangial widening with or without hypercellularity.
• Type III     Focal proliferative G.N.
• Type IV    Diffuse proliferative G.N.
• Type V     Membranous G.N.
• Type VI    Advancing sclerosing G.N.  

7- GIT
   -  Mesenteric vasculitis with acute abdomen. Liver involvement is unusual,     pancreatitis is uncommon.
   -  Nausea, vomiting and diarrhea can occur with an SLE flare.

8- The Lung
   -  Pleurisy and pleural effusion
   -  Interstitial pulmonary fibrosis.
   -  Shrinking lung syndrome with elevation of the diaphragm due to recurrent    pulmonary infarction.
   -  Pulmonary hypertension with antiphospholipid syndrome.
   -  Adult respiratory distress syndrome.

9- Neuro psychiatric manifestations
   -  Psychosis, depression, cognitive dysfunction (difficulties with memory and resoning).
   -  Lymphocytic meningitis, transverse myelitis.
   -  Chorea.
   -  Cerebral vasculitis leading to cerbrovascular stroke.
   -  PolyNeuropathy .
   -  Lupus headache.               -  Seizures .

Psychosis due to lupus must be differentiated from steroid induced psychosis which occurs in the first weeks of steroid therapy at doses of 2 40 mg of prednisone or equivalent, it resolves over several days after steroids are decreased or stopped .


10-Blood
    -  Autoimmune thrombocytopenia and haemolytic anaemia .
    -  Lymphopenia (guide to disease activity).
    -  Antiphospholipid $ leading to thrombo-embolism .

11- Polyserositis affecting:
    - Pleura. - Pericardium. - Peritoneum.
lupus symptoms

Diagnostic Criteria of Systemic Lupus Erythematosus

1. Butterfly rash 50% : Fixed erythema- flat OR - raised
2. Discoid rash 20% : Erythymatous raised patches + scales
3. Photosensitivity 70% : Rash on exposure to sun light
4. Oral Ulcers 40% : Painless, it may be nasopharyngeaL
5- ArthroPathy 95% : Involving 2 or more  peripheral joints.
                                                       
6- Serositis. : Pleuritis, pericarditis
7- Renal  (50%have clinical nephritis) persistent protinuria > 0.5 grn/24h (30-50%) Casts and RBCs .
8. Neurologic  disorders 
Seizures or psychosis in the absence of offending drugs or known metabolic disorders .
  1. Hematological disorders
    • Leukopenia  < 4000 / mm
    • Lymphopenia < 1500 / mm
    • Thrombocytopenia < 100000 / mm
    • Hemolytic anemia

10 . Immunologic disorders
  • Anti DNA        
  • Anti-sm antibody
  • Anti-phospholipid antibody


  1. Abnormal titre of ANA . 
To diagnose patients with SLE, 4 or more criteria must be present serillay or simultaneously or have occurred in the past .

LAB investigations
1- Blood
            • Anemia of chronic disease (normocytic normochromic).
            • Autoimmune hemolytic anaemia (positive coomb's test).
            • Leucopenia, lymphopenia with activity, thrombocytopenia.

2- ESR is High  with activity of the disease.

3- Immunological tests

a- C-reactive protein is low but increases with superimposed infection.
b- Hyper gammaglobulinemia usually IgG and IgM (polyclonal).
c- Low  C3 & C4 as they are consumed during disease activity.
d- ANA + ve (it is positive in almost all cases, 95%), patients with negative ANA are unlikely to have SLE.
e- Anti DNA is the most specific. It is positive in about 60% of cases, it may reflect disease activity .
f- Rheumatoid factor is positive in 30 % of cases.
g- Anti Ro, La antibodies (They are asked if ANA is negative, especially anti-Ro).
Anti Ro is the causal antibody for neonatal lupus and congenital
heart block.
h- Anti-sm Ab (specific for SLE).
4- Kidney function tests and urine analysis for protein, RBCS and casts to detect renal involvement.

Q : Symptoms and signs suggesting active SLE?
• Weight loss, fever, arthritis, seizures, hair loss, anaemia, haematuria, rashes, mouth sores and oliguria.
 Q : Laboratory diagnosis of disease activity?
• -Low  C3 ,  C4
  +ve Anti-DNA (high titre)
Q : Patient with SLE+ fever?
• Disease activity (see above)
• Infection (+ ve C- reactive protein)
 Q : Patients with SLE+ leucocytosis
• Steroid therapy.
- PNL high  -Eosinophils low - Lymphocytes low .
• Infection:
- Toxic granulations within WBCs, presence of staff cells and positive CRP.

Sequence of investigations to diagnose SLE



Subsets of  Lopus

A- Idiopathic
• Systemic lupus.
• Chronic discoid lupus (CDLE) is a benign variant of the disease in which skin involvement is often the only feature, systemic manifestations may occur with time (5%)
 ANA is positive in 30%.
• Subacute cutaneous lupus, -ve ANA, +ve anti Ro, anti La, organ involvement is rare.
• Late onset after 50 years age.
..  Neonatal Lupus with positive Ab to Ro. and La.

B- Drug induced (see before)
C- Overlap syndrome
Diagnosis of Systemic Lupus Erythematosus - clinical picture & investigations
Dr.Tamer Mobarak

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