Diagnosis of systemic lupus erythematosus

The diagnosis of systemic lupus erythematosus is based on the patient's clinical, instrumental, laboratory and morphological features, which requires a comprehensive examination.

[1], [2], [3], [4], [5], [6], [7],

Laboratory diagnostics of systemic lupus erythematosus

Clinical blood test. The active period of systemic lupus erythematosus is characterized by an increase in ESR, the development of leukopenia with lymphopenia, and less frequently, hemolytic anemia with a positive Coombs reaction. Hypochromic anemia can be a consequence of chronic inflammation and intoxication, hidden bleeding, etc.

Thrombocytopenia (usually mild) is usually diagnosed in patients with secondary AFS. In some cases, autoimmune thrombocytopenia develops, due to the appearance of antibodies to platelets.

General urine analysis. They reveal proteinuria, hematuria, leukocyturia, cylindruria of various degrees of severity, correlating with the type and activity of lupus nephritis.

Blood chemistry. Changes in biochemical parameters are nonspecific, their research is conducted to evaluate the functions of various organs and systems. An increase in the level of C-reactive protein for systemic lupus erythematosus is not typical, it is usually noted when secondary infection is attached.

Immunological diagnosis of systemic lupus erythematosus

ANF (antinuclear antibodies) is a heterogeneous group of antibodies reacting with various components of the nucleus. The sensitivity of this test is very significant (95% of patients with systemic lupus erythematosus), but the specificity is low (it is often determined in patients with other rheumatic and non-rheumatic diseases).

Antibodies to double-stranded DNA are recorded in 20-70% of patients with systemic lupus erythematosus. Highly specific for systemic lupus erythematosus, their level usually correlates with the activity of the disease, especially in the presence of lupus nephritis.

Antibodies to histones are more characteristic for medicinal lupus-like syndrome, with systemic lupus erythematosus associated with the development of arthritis.

Antibodies to Sm-antigen are highly specific for systemic lupus erythematosus, but they are defined only in 20-30% of patients.

Recorded low AT titers to small nuclear ribonucleoproteins in systemic lupus erythematosus are usually associated with Raynaud's syndrome and leukopenia; their high titers are found in patients with mixed connective tissue disease.

Antibodies to SS-A / Ro-antigen, SS-B / La-antigen are less characteristic of systemic lupus erythematosus, associated with lymphopenia, thrombocytopenia, photodermatitis and pulmonary fibrosis. They are found in 60-80% of patients with Sjogren's syndrome, these antigens are also characteristic for subacute skin and drug lupus.

Antibodies to cardiolipin (ACL), antibodies to S ₂ -glycoprotein 1, lupus anticoagulant are determined on average in 60% of children with systemic lupus erythematosus. These are the markers of the secondary AFS.

Rheumatoid factor (autoantibodies of the IgM class reacting with the Fc fragment of IgG) are often noted in children with systemic lupus erythematosus who have a pronounced articular syndrome.

LE cells - polymorphonuclear neutrophils (less often eosinophils or basophils) with the phagocytized nucleus of the cell or its individual fragments, are formed in the presence of antibodies to the DNA-histone complex. These cells are found on average in 70% of children with systemic lupus erythematosus.

Reduction of the total hemolytic activity of the complement (CH50) and its components (C3, C4) usually correlates with the activity of lupus nephritis and in some cases may be a consequence of a genetically determined deficiency.

Instrumental methods of diagnosis of lupus erythematosus

Musculoskeletal: radiography of bones and joints, ultrasound of joints and soft tissues, MRI (in the presence of indications), densitometry.

Respiratory system: radiography of chest organs (at least once a year), chest CT (if there are indications), echocardiography (for the detection of pulmonary hypertension).

Cardiovascular system: ECG, Echocardiography, Holter ECG monitoring (if there are indications).

Gastrointestinal tract: ultrasound of the abdominal cavity, esophagogastroduodenoscopy, CT and MRI (in the presence of indications).

Nervous system: in the presence of indications - electroencephalography, CT, MRI.

To establish the diagnosis of systemic lupus erythematosus, the classification criteria of the American Rheumatology Association are most widely used.

Criteria for the American Rheumatology Association for the diagnosis of systemic lupus erythematosus (1997)

Criteria	Definition
Rashes in the cheekbone area	Fixed erythema flattened or raised on zygomatic arches with a tendency to spread to nasolabial folds
Discoid rashes	Erythematous raised plaques with keratotic dysfunction and follicular plugs; old foci may have atrophic scars
Photosensitivity	Skin rashes as a result of an unusual reaction to insolation according to anamnesis or doctor's observations
Ulcers of the mouth	Ulcers in the mouth or nasopharynx, usually painless, observed by a doctor
Arthritis	Non-erosive arthritis of 2 or more peripheral joints, characterized by soreness, swelling, or effusion
Serosite	A) Pleurisy (pleural pain in anamnesis, pleural friction noise in auscultation, pleural effusion); B) pericarditis (pericardial friction noise, pericardial effusion, ECG signs)
Renal damage	A) Persistent proteinuria> 0.5 g / day; B) cylindruria (erythrocyte, hemoglobin, granular, mixed cylinders)
Neurological disorders	Convulsions or psychosis that are not associated with medication or metabolic disorders due to uremia, ketoacidosis, electrolyte imbalance
Hematologic disorders	A) Hemolytic anemia with reticulocytosis; B) leukopenia (<4x10 9 / l) with 2 or more determinations; C) lymphopenia (<1.5 × 10 9 / L) with 2 or more studies; D) thrombocytopenia (<100x10 9 / l), not associated with taking medication
Immune disorders	A) Antibodies to native DNA in elevated titers; B) the presence of antibodies to the Sm-antigen; C) presence of AFA: Increased titre of ACL (IgM or IgG); the detection of lupus anticoagulant by a standard method; a false positive Wasserman reaction for at least 6 months in the absence of syphilis, confirmed by the pale treponema immobilization reaction or in the absorption test of fluorescent anti-treponemal antibodies
ANF (antinuclear antibodies)	An increase in the ANP titer in the immunofluorescence test or in another similar one, not related to the intake of drugs capable of inducing lupus erythematosus

If the patient has 4 or more symptoms in any combination, the diagnosis is considered reliable, if there are 3 signs, it is probable.

The sensitivity of these criteria is 78-96%, and the specificity is 89-96%.

Degrees of activity of systemic lupus erythematosus

The activity of systemic lupus erythematosus is determined based on the severity of the patient's condition, taking into account the totality and severity of the available clinical and laboratory signs of the disease.

There are 3 degrees of activity of systemic lupus erythematosus:

With high activity (grade III), high fever, marked changes in the internal organs (nephritis with nephrotic syndrome, endomyocarditis, pericarditis with effusion and / or exudative pleurisy), severe CNS, skin (dermatitis), musculoskeletal (acute polyarthritis and / or polymyositis), and others, accompanied by marked changes in laboratory parameters, including a significant increase in ESR (more than 45 mm / h) and immunological parameters (increase in ANP titres and antibodies to DNA, significantly reduced the total hemolytic activity of the complement and its components C3, C4).

The lupus erythematosus is diagnosed in patients in critical conditions, characterized by the development of functional failure of an organ against the background of an excessively high activity of the pathological process.

With moderate activity (grade II), fever is usually subfebrile, signs of damage to various organs are moderately expressed. Patients may note polyarthralgia or polyarthritis, dermatitis, moderate reaction from serous membranes, nephritis without nephrotic syndrome and impaired renal function, myocarditis, etc. ESR is increased within 25-45 mm / h, increase in titers ANF, antibodies to DNA, circulating immune complexes.

With low activity (I degree), the general condition of patients is usually not disturbed, laboratory parameters are changed little, signs of internal organs lesions determine only with complex instrumental research. Clinically note the soft signs of cutaneous and articular syndromes.

Evaluation of the degree of activity of the pathological process is crucial for determining the tactics of treatment of the patient at each stage of the disease.

The state of remission is ascertained in the absence of clinical and laboratory signs of the activity of the patient.

To more accurately assess the condition of patients with dynamic observation, use different score indices.

[8], [9], [10], [11], [12], [13]

Evaluation of the activity of systemic lupus erythematosus according to the ECLAM (European Consensus Lupus Activity Measurement)

1. General symptoms (any of the following x 0.5 points)

Fever	Morning temperature above 37.5 C, not associated with infection
Fatigue	Subjective feeling of increased fatigue

2. Symptoms of joint damage (any of the following x 0.5 points)

Arthritis	Non-erosive arthritis with lesions of 2 or more peripheral joints (wrist, distal or proximal interphalangeal joints, metacarpophalangeal joints)
Arthralgia	Localized pain without objective symptoms of inflammation of 2 or more peripheral joints)

Behind. Symptoms of active skin and mucous membrane damage

Erythematous rash in the zygomatic area	Fixed erythema flat or towering in the zygomatic area with a tendency to spread to the nasolabial region
Generalized rash	Spotted-papular rash, not associated with taking medication. Can be on any part of the body, regardless of exposure to the sun
Discoid rash	Erythematous or depigmented overgrown plaque with adherent keratotic scales or follicular plug
Cutaneous vasculitis	Including digital ulcers, purpura, urticaria, bullous eruptions
Ulcers of the oral cavity	Ulcers in the mouth or nasopharynx, usually painless, detectable by a doctor

3b. Development of symptoms of skin and mucous membrane damage (x 1 point, if the above signs appear again, +1 point, if there is an increase in the severity of symptoms after the last observation)
4. Myositis (x 2 points, if confirmed by elevated levels of CK and / or EMG data or histological examination)
5. Pericarditis (x 1 point, if confirmed by ECG or EchoCG or by listening to pericade friction noise during auscultation)
6. Signs of bowel disease (any of the following x 2 points)
Vasculitis of the intestine	Obvious signs of acute bowel vasculitis
Aseptic peritonitis	Exudation in the abdominal cavity in the absence of infection
7. Symptoms of pulmonary disorders (any of the following x 1 point)
Pleurisy	Adhesive or exudative, auscultatory or radiologically confirmed)
Pneumonitis	Single or multiple shadows on the radiograph, reflecting the activity of the disease and not related to infection
Progressive dyspnea	-
8. Symptoms of psychoneurological disorders (any of the following x 2 points)
Headache / migraine	Recently developed, persistent or persistent, difficult to treat with analgesics and easy to treat with corticosteroids
Epipristupy	Small or large seizures and choreokinetic syndrome, not developed due to side effects of drugs and metabolic disorders
Stroke	-
Encephalopathy	Reduced memory, orientation, perception, ability to count
Psychoses	In the absence of drugs
9a. Symptoms of kidney damage (any of the following x 0.5 points)
Proteinuria	Daily proteinuria> 0.5 g / day
Urinary sediment	Erythrocyturia, cylinduria
Hematuria	Macroscopic or microscopic
Increased creatinine level or decreased creatinine clearance	"
9b. Development of symptoms of kidney damage (x 2 points, if any of the above signs of kidney damage are noted again or observed deterioration compared to the last observation)
10. Signs of hematologic abnormalities (any of the following x 1 point)
Non-hemolytic anemia	Coombs-negative hypochromic or normochromic anemia without reticulocytosis)
Hemolytic anemia	Coombs-positive hemolytic anemia with reticulocytosis
Leukopenia	<3500 or lymphopenia <1500 in μL
Thrombocytopenia	<100 000 VMLL
11. ESR	<25 mm / h in the absence of other causes
12. Hypokomplementemia (any of the following x 1 point)
NW	Radial diffusion or nephelometry
CH50	Standard hemolytic method
12b. Developing hypocompleteemia (x 1 point with a significant decrease in the level of complement (C4) compared with the last observation

[14], [15], [16], [17], [18], [19], [20]

Final score

If myositis, symptoms of psychoneurological disorders and renal lesions are the only ones recorded among points 1-10, 2 points should be added. If the calculation is not an integer, it should be rounded to a smaller one with a value less than 6 and to a larger one - at a value greater than 6. If the final score is more than 10, it must be rounded to 10.

Evaluation of activity of systemic lupus erythematosus according to SLEDAI-2K scale

Points	SLEDAI-account	Symptoms	Definition
8	-	Epileptic seizure	Recently emerged. It is necessary to exclude metabolic, infectious and medicinal causes
8		Psychosis	Violation of the ability to perform actions in normal mode due to a pronounced change in the perception of reality, including hallucinations, restlessness of thinking, a significant decrease in associative abilities, depletion of thinking activity, marked illogicality of thinking, strange disorganized or catatonic behavior. It should be distinguished from similar conditions caused by uremia or medications
8		Organic Brain Syndromes	Violations of mental activity with disregard for orientation, memory, or other intellectual abilities with acute onset and unstable clinical symptoms, including blurred consciousness with reduced focus and concentration, and at least two of the following: impaired perception, incoherent speech, insomnia or drowsiness in the daytime, a decrease or increase in psychomotor activity. It is necessary to exclude the possibility of metabolic, infectious and medicinal effects
8		Visual disorders	Changes in the retina (including cell bodies, hemorrhages, serous exudate or hemorrhages in the choroid) or optic neuritis. It should be distinguished from disorders caused by hypertension, infection, medicinal effects
8	-	Violation of the functions of the cranial nerves	The first appeared sensitive or motor neuropathy of the cranial nerves
8	-	Headache	Expressive persistent headache, not amenable to treatment with narcotic analgesics
8	-	Violation of cerebral circulation	The first occurrence of a disorder of cerebral circulation. It should be distinguished from the disorders that arose as a result of atherosclerosis
8		Vasculitis	Ulcers, gangrene, painful nodules on the fingers, okolonogtevye infarcts, hemorrhages or biopsy data or angiograms that confirm vasculitis
4	-	Arthritis	> 2 painful joints with signs of inflammation (edema or effusion)
4	~	Myositis	Proximal muscle pain / weakness associated with elevated CK / aldolase levels, or EMG data or biopsies confirming myositis
4	-	Cylindreria	Granular or erythrocyte cylinders
4		Hematuria	> 5 erythrocytes in n / sp. It is necessary to exclude hematuria caused by urolithiasis, infections and other causes
4	-	Proteinuria	> 0.5 g / day
4	-	Leucocyturia	> 5 leukocytes in n / sp. It is necessary to exclude the possibility of infectious causes of leukocyturia
2	-	Rashes on the skin	Eruptions of inflammatory nature
2	-	Alopecia	Increased focal or diffuse hair loss
2	-	Ulcers of the mucosa	Ulceration of the mucous membrane of the mouth and nose
2	-	Pleurisy	Pain in the chest with pleural friction noise or effusion or pleural pleasures
2	-	Pericarditis	Pericardial pain with one of the following signs: pericardial friction noise, electrocardiographic or echographic confirmation
2	-	Low complement	The fall in the level of СН50, СЗ or С4 is lower than the lower limit of the norm (according to the testing laboratory)
2	-	Elevated levels of anti-DNA	> 25% Farr binding or excess of the normal values of the testing laboratory
1	-	Fever	> 38 C, infectious causes should be excluded
1	-	Thrombocytopenia	<100x10 7 l, the drug exposure factor should be excluded
1	-	Leukopenia	<3х10 9 / l, it is necessary to exclude the factor of medicinal action

[21], [22], [23], [24], [25], [26], [27], [28],

General SLEDAI-account

In the column of the SLEDAI account, points are made if the symptom is present at the time of the inspection or has occurred during the 10 days preceding the inspection. SLEDAI-1K unlike the SLEDAT scale allows to take into account the persistent activity associated with the presence of skin rashes, ulcers of mucous membranes, alopecia proteinuria. In the SLEDAI scale, only recurrence or primary appearance of such signs as skin rash, alopecia, ulcers of mucous membranes and proteinuria is taken into account, and in the SLEDAI-2K scale any variant of these signs (newly emerged, relapse, persistent activity) is taken into account.

Differential diagnosis of lupus erythematosus

In most children (> 80%), usually a few weeks (less often months) from the moment of appearance of the first symptoms, a polysyndromic clinical picture with signs of involvement of various organs and systems is formed. If the patient has a lupus "butterfly", the diagnosis is usually established in the early period from the moment of onset of the disease. Difficulties in diagnosing systemic lupus erythematosus arise in the absence of a characteristic erythematous rash in a child. Differential diagnosis in such cases should be carried out with diseases that have a polysyndromic clinical picture:

• rheumatic systemic forms of juvenile rheumatoid arthritis, adolescent dermatomyositis, acute rheumatic fever, Shenlaine-Henoch disease, primary antiphospholipid syndrome, nodular polyarteritis, microscopic polyarteritis, etc .;
• hematological diseases: hemolytic anemia, ITP;
• lymphoproliferative diseases: lymphogranulomatosis, lymphoma;
• infectious diseases: borreliosis (Lyme disease), hepatitis B and C with extrahepatic manifestations, tuberculosis, syphilis, iersiniosis, HIV infection, etc .;
• inflammatory bowel diseases: nonspecific ulcerative colitis with systemic manifestations, Crohn's disease;
• kidney diseases: glomerulonephritis, etc .;
• infective endocarditis;
• lupus erythematosus and paraneoplastic lupus-like syndrome.

[29], [30], [31], [32], [33], [34], [35]