Symptoms of systemic lupus erythematosus

Symptoms of systemic lupus erythematosus are characterized by pronounced polymorphism, but almost 20% of children have monoorgan variants of the disease onset. The course of systemic lupus erythematosus is usually undulating, with alternating periods of exacerbations and remissions. In general, systemic lupus erythematosus in children is characterized by a more acute onset and course of the disease, earlier and more violent generalization, and a less favorable outcome than in adults.

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General symptoms of systemic lupus erythematosus

The first symptoms of the onset of systemic lupus erythematosus or its exacerbation in most children are fever (usually intermittent), increasing weakness, malaise, decreased appetite, weight loss, and increased hair loss.

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Lesions of the skin and its appendages in systemic lupus erythematosus

The skin syndrome observed in children with systemic lupus erythematosus is highly variable.

Lupus "butterfly" is the most typical manifestation of systemic lupus erythematosus, which is observed in 80% of patients, 40% of whom - at the onset of the disease. "Butterfly" is a symmetrical erythematous rash on the skin of the face, located in the malar region and the bridge of the nose, in shape resembling a butterfly with spread wings; the rash can spread beyond the malar region to the skin of the forehead, chin, free edge of the auricle and its lobe.

Lupus "butterfly" can be in the form of:

• erythema, manifested by hyperemia of the skin with clearly defined boundaries, infiltration, follicular hyperkeratosis with subsequent cicatricial atrophy;
• bright erysipelas with infiltration, hyperemia, small necroses covered with crusts, and swelling of the face;
• centrifugal erythema - persistent erythematous-edematous spots with mild follicular hyperkeratosis located in the center of the face;
• vasculitic "butterfly" - unstable diffuse redness with a cyanotic tint in the middle zone of the face, intensifying with excitement, exposure to insolation, etc.

Erythematous rashes can also be observed on exposed areas of the skin: the upper third of the chest and back (the décolleté area), above the elbow and knee joints.

Discoid lesions are erythematous rashes with hyperemic edges and depigmentation in the center, infiltration, follicular hyperkeratosis and subsequent cicatricial atrophy. They are localized mainly on the skin of the scalp, face, neck, and upper limbs. In children, such rashes are usually observed in the chronic course of systemic lupus erythematosus.

Photosensitivity - increased sensitivity of the skin to the effects of solar radiation, typical for patients with systemic lupus erythematosus. Characteristic erythematous rashes on the skin usually appear in children in the spring and summer, their brightness increases after exposure to the sun or treatment with UFO.

Capillaritis is an edematous erythema with telangiectasias and atrophy on the fingertips, palms and plantar surfaces of the feet, observed in most children in the acute period of the disease.

Hemorrhagic rashes in the form of petechial or purpuric elements, usually located symmetrically on the skin of the distal parts of the extremities, primarily the lower ones, are often noted in children with systemic lupus erythematosus as cutaneous vasculitis.

Livedo reticularis (bluish-violet spots forming a mesh on the skin of the lower, less often upper limbs and trunk) and subungual microinfarctions (thrombovasculitis of the capillaries of the nail bed).

Non-specific skin rashes are often observed in patients with high activity of systemic lupus erythematosus; they can be represented by all the main morphological types of skin elements: from maculopapular to bullous.

Raynaud's syndrome (periodically developing ischemia of the fingers caused by vasospasm and structural vascular lesions) is observed in children much less frequently than in adults.

Alopecia is very common in patients with systemic lupus erythematosus. During the active period of the disease, patients experience thinning and increased hair loss, which leads to patchy or diffuse alopecia.

Mucosal lesions in systemic lupus erythematosus

Lesions of the mucous membranes of the oral cavity, observed in more than 30% of children, mainly in the active period of the disease, include:

• lupus enanthem (erythematous-edematous spots with clear boundaries and sometimes with an erosive center, located in the area of the hard palate);
• aphthous stomatitis (painless erosive or, less commonly, deeper ulcerative lesions with a keratotic rim and intense erythema);
• cheilitis - a lesion of the red border of the lips, most often the lower one (emphasis of the rim along the edge of the lip, swelling, hyperemia, formation of cracks, in some cases erosion and ulcers with subsequent development of cicatricial atrophy).

Joint damage in systemic lupus erythematosus

Joint syndrome is observed in almost all children with systemic lupus erythematosus, and in 80% of them already in the initial period of the disease. This syndrome has a migratory nature of the lesion, rarely leads to the formation of persistent deformations, with the exception of symmetrical fusiform deformations of the proximal interphalangeal joints of the II-IV fingers of the hands without impairment of their function.

Arthralgia is typical for the active period of the disease. It is localized in large and small joints of the extremities, most often in the knee, ankle, elbow and proximal interphalangeal joints of the fingers, less often in the shoulder, elbow, wrist, sometimes in the hip joints and cervical spine.

Arthritis. Acute arthritis in systemic lupus erythematosus usually occurs with multiple, often symmetrical joint lesions (primarily the proximal interphalangeal fingers, knees, ankles, elbows), accompanied by pronounced periarticular reactions, pain contractures, but quickly disappears after the start of treatment with glucocorticosteroids. Subacute and chronic polyarthritis is characterized by a longer, wave-like and often progressive course, pain, moderate exudation, and is accompanied by limited function of the affected joints, complaints of short-term morning stiffness. X-ray examination reveals moderate changes in the form of epiphyseal osteoporosis (stage I according to Steinbrocker).

Bone changes in systemic lupus erythematosus

Aseptic necrosis, characterized by osteochondral sequestration with secondary osteosclerosis, occurs much less frequently in children than in adults. It is usually localized in the area of the femoral head epiphysis (rarely in other bones), leading to dysfunction of the affected limb and disability of the patient.

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Muscle damage in systemic lupus erythematosus

Muscle damage is observed in 30-40% of children in the active period of systemic lupus erythematosus. It is expressed by myalgia or polymyositis with the involvement of symmetrically located, more often proximal muscles of the extremities.

In polymyositis, in addition to muscle pain, there is tenderness upon palpation, some decrease in muscle strength, moderate increase in the activity of muscle breakdown enzymes (creatine phosphokinase - CPK, aldolase). The outcome of polymyositis may be the development of moderate hypotrophy. Lupus polymyositis should be differentiated from steroid myopathy, which develops in patients during treatment with glucocorticosteroids.

Damage to serous membranes

Damage to the serous membranes (polyserositis) is a characteristic manifestation of systemic lupus erythematosus and is observed in 30-50% of children.

Pleurisy is usually symmetrical, dry, less often exudative, and rarely has a bright clinical manifestation. Clinically, the development of pleurisy can be manifested by coughing, chest pain that intensifies with deep breathing, and pleural friction noise during auscultation. X-rays show thickening of the costal, interlobar, or mediastinal pleura, as well as pleuro-pericardial adhesions. In some cases, massive accumulation of exudate in the pleural cavities is noticeable.

Pericarditis is observed in children more often than in adults. Typical clinical symptoms of pericarditis include tachycardia, dyspnea, friction rub, but in most cases pericarditis is clinically asymptomatic, it is detected only by echocardiography: thickening and separation of the epi- and pericardial layers are visible on the image. With high activity of the disease, pericarditis is usually accompanied by an accumulation of exudate. Rarely, with the occurrence of massive effusion, a threat of cardiac tamponade may arise. In rare constrictive pericarditis, adhesions are formed in the pericardial cavity up to its obliteration.

In some cases, patients exhibit aseptic peritonitis.

Respiratory system involvement in systemic lupus erythematosus

Observed in 10-30% of children with systemic lupus erythematosus at different stages of the disease.

Acute lupus pneumonitis is occasionally observed with high disease activity, manifesting itself with a symptom complex characteristic of pneumonia (cough, dyspnea, acrocyanosis, weakened breathing and wheezing in the lungs during auscultation, etc.). In these cases, the radiograph usually reveals symmetrically located infiltrative shadows in the lungs, discoid atelectasis.

Chronic diffuse interstitial lung disease may develop with a relatively long course of systemic lupus erythematosus. Physical signs of lung damage are scanty or absent. Functional diagnostic methods reveal a decrease in lung function, pulmonary blood flow disorders, and radiographs show an increase and deformation of the vascular-interstitial pattern with loss of clarity of its outlines and expansion of the lumen of the vessels.

Pulmonary (alveolar) hemorrhages, which are very rare in children, can be fatal. Patients show signs of acute respiratory distress syndrome with a rapid decrease in hemoglobin and hematocrit levels and the development of severe hypoxemia.

Pulmonary hypertension in children is observed very rarely; it usually develops with antiphospholipid syndrome (APS).

A characteristic feature is the high position of the diaphragm due to diaphragmatitis, pleurodiaphragmatic adhesions and growths, and decreased tone of the diaphragm muscles.

Heart damage in systemic lupus erythematosus

Heart damage in children with systemic lupus erythematosus is observed in 50% of cases.

Myocarditis in severe cases is characterized by dilated heart borders, changes in the sonority of tones, disturbances in heart rhythm and conductivity, decreased contractility of the myocardium, and the appearance of signs of heart failure. With high disease activity, myocarditis is usually combined with pericarditis. In most cases, myocarditis has scant clinical signs and is diagnosed only with a comprehensive instrumental examination.

The development of myocardial dystrophy in patients is likely.

Endocarditis. In systemic lupus erythematosus, the valvular or parietal endocardium may be affected. In most cases, mitral valvulitis is observed, less often the aortic or tricuspid valves, or its consequences in the form of thickening of the valves, which do not cause hemodynamic disturbances and do not create conditions for the occurrence of organic noises. The formation of heart defects due to endocarditis in systemic lupus erythematosus is not typical and occurs extremely rarely.

Systemic lupus erythematosus is characterized by atypigmentary warty endocarditis of Libman-Sachs with the formation of warty deposits with a diameter of 1-4 mm in areas of small ulcerations of the endocardium and the possible appearance of small perforations of the valve cusps and rupture of the chords.

Coronaritis (vasculitis of the coronary arteries), which causes impaired myocardial perfusion, may be accompanied by pain behind the sternum or in the heart region, but is usually clinically asymptomatic. Isolated cases of myocardial infarction in adolescents have been reported.

Kidney damage in systemic lupus erythematosus

Nephritis is clinically diagnosed in 70-75% of children with systemic lupus erythematosus, in most of them it develops within the first 2 years from the onset of the disease, and in about a third - already at the onset. The prognosis and outcome of the disease as a whole largely depend on the nature of the kidney damage.

Morphological examination of the kidneys reveals signs of immune complex glomerulonephritis of various types.

World Health Organization classification of kidney damage in systemic lupus erythematosus

Type	Description	Clinical and laboratory signs
I	No changes according to light, immunofluorescence and electron microscopy	None
IIA	Mesangial glomerulonephritis with minimal changes (absence of light-optical changes in the biopsy in the presence of immune complex deposits in the mesangium according to immunofluorescence and electron microscopy)	None
IIb	Mesangial glomerulonephritis (variable degrees of mesangial hypercellularity with the presence of immune deposits in the mesangium)	Proteinuria <1 g/day, erythrocytes 5-15 in the field of vision
III	Focal proliferative glomerulonephritis (active or chronic, segmental or total, endo- or extracapillary damage involving less than 50% of the glomeruli)	Proteinuria <2 g/day, erythrocytes 5-15 in the field of vision
IV	Diffuse proliferative glomerulonephritis (same changes as in class III with involvement of more than 50% of glomeruli)	Proteinuria >2 g/day, erythrocytes >20 in the field of view, arterial hypertension, renal failure
V	Membranous glomerulonephritis (uniform thickening of the glomerular basement membrane due to subepithelial and intramembranous deposition of immune complexes)	Proteinuria >3.5 g/day, scanty urinary sediment
VI	Chronic glomerulosclerosis (diffuse and segmental glomerulosclerosis, tubular atrophy, interstitial fibrosis, arteriolosclerosis)	Arterial hypertension, renal failure

The classification of lupus nephritis in children, based on clinical data (V.I. Kartasheva, 1982), includes:

• severe nephritis with nephrotic syndrome (NS) (characterized by diffuse edema, massive proteinuria, hypoproteinemia, hypercholesterolemia, severe hematuria in most cases with persistent arterial hypertension and hyperazotemia);
• severe nephritis without nephrotic syndrome (characterized by proteinuria with protein loss within 1.5-3 g/day, significant erythrocyturia, often macrohematuria, moderate arterial hypertension and azotemia);
• Latent nephritis (characterized by moderate urinary syndrome: proteinuria <1.3 g/day, hematuria <20 red blood cells in the field of view).

The most unfavorable prognosis is likely in rapidly progressive lupus nephritis, characterized by the presence of nephrotic syndrome, severe (sometimes malignant) arterial hypertension and rapid development of renal failure, leading to an unfavorable outcome within a few weeks or months.

In addition to glomerulonephritis, the spectrum of renal pathology in systemic lupus erythematosus includes tubulointerstitial damage, as well as thrombotic damage to vessels of various calibers within the framework of APS.

Gastrointestinal tract involvement in systemic lupus erythematosus

Gastrointestinal tract lesions are observed in 30-40% of patients with systemic lupus erythematosus. In the acute period, loss of appetite and dyspeptic disorders are usually observed. Endoscopic examination often diagnoses inflammatory lesions of the mucous membrane of the esophagus, stomach and duodenum, sometimes with the formation of erosions and even ulcers.

Intestinal lesions are relatively rare and are mainly caused by lesions of the mesenteric vessels. Vasculitis of the mesenteric arteries with subsequent thrombosis may lead to hemorrhage, infarctions and necrosis with subsequent perforation and development of intestinal bleeding or fibrinous-purulent peritonitis. A symptom complex of malignant Crohn's disease (terminal ileitis) is possible.

Liver damage. Hepatomegaly of varying degrees, often reactive in nature, is diagnosed in most patients with systemic lupus erythematosus. In 10-12% of patients, along with hepatomegaly, a moderate increase in liver enzymes (usually 2-3 times) is noted, caused by thrombotic microangiopathy.

In some cases, hepatitis, liver infarction, and hepatic vein thrombosis (Budd-Chiari syndrome) may develop.

Damage to the pancreas (pancreatitis) may be a consequence of the pathological process within systemic lupus erythematosus or caused by exposure to large doses of glucocorticosteroids.

Nervous system damage in systemic lupus erythematosus

Psychoneurological symptoms in systemic lupus erythematosus are extremely diverse, since any parts of the nervous system can be affected. Manifestations characteristic of the clinical picture of systemic lupus erythematosus are observed in 30-50% of children.

Organic brain syndrome, the development of which is caused by thrombotic vasculopathy or diffuse damage mediated by antineuronal antibodies, is accompanied by a deterioration in cognitive functions (memory, attention, thinking), which can lead to a noticeable decrease in intelligence, and the appearance of emotional and personality disorders (emotional lability, irritability, apathy, depression).

Mental disorders in systemic lupus erythematosus in children are characterized by clinical polymorphism, a tendency to relapse, their severity usually correlates with the severity of somatic disorders. With high activity, acute psychosis may develop with the appearance of productive symptoms in the form of visual and auditory hallucinations, schizophrenia-like disorders, affective syndromes (manic and depressive), motor restlessness, sleep disorders, etc.

Headaches, including migraine-like ones, usually intense, are observed during the active period of the disease, usually in patients with systemic lupus erythematosus with antiphospholipid syndrome.

Convulsive syndrome, usually manifested by generalized epileptiform seizures, is characteristic of highly active systemic lupus erythematosus.

Chorea, similar to chorea minor in rheumatism, can be unilateral or generalized.

Transient cerebrovascular accidents characterized by general cerebral, focal or mixed symptoms that persist for no more than 24 hours and ischemic stroke are observed in children much less frequently than in adults. Their occurrence is due to thrombosis or thromboembolism of intracerebral arteries in the presence of antiphospholipid antibodies.

Intracerebral hemorrhages can be caused by arterial hypertension or thrombocytopenia, subarachnoid hemorrhage and subdural hematoma - by cerebrovasculitis.

Spinal cord damage caused by ischemic necrosis and demyelination of fibers is rarely observed in children. It may be accompanied by symmetrical damage to the thoracic spinal cord. In this case, lower paraparesis, impaired sensitivity in the lower half of the body, pelvic disorders, and severe back pain are diagnosed. The prognosis for "transverse myelitis" is unfavorable.

Damage to the cranial nerves (oculomotor, trigeminal, facial or optic) can be isolated or combined with other brainstem symptoms.

The damage to the peripheral nervous system occurs as a symmetrical distal, predominantly sensory polyneuropathy, rarely - multiple mononeuropathy. In some cases, Guillain-Barré syndrome (acute inflammatory polyradiculoneuropathy) develops.

Damage to the nervous system in systemic lupus erythematosus may be secondary and caused by arterial hypertension, uremia, hypoxemia, infectious diseases, intake of glucocorticosteroids (leading to steroid psychosis), etc. Clarification of the genesis of damage to the nervous system is necessary for pathogenetically based treatment.

Cumulative assessment of damage to various organs in systemic lupus erythematosus

To determine the severity of organ damage in systemic lupus erythematosus, the SLICC/ACR Damage Index is determined. The scoring includes all types of damage from the onset of the disease, caused by systemic lupus erythematosus and developed as a result of the therapy and persisting for 6 months or more.

SLICC/ACR Damage Index

Sign	Score, points
Visual organs (each eye) during clinical assessment
Any cataract	1
Retinal changes or optic nerve atrophy	1
Nervous system
Cognitive impairment (memory loss, difficulty counting, poor concentration, difficulty speaking or writing, impaired performance) or major psychosis	?
Seizures requiring treatment for more than 6 months	1
Strokes ever (score 2 if more than one episode) or cerebral resection not related to neoplasm	1-2
Cranial or peripheral neuropathy (excluding optic)	1
Transverse myelitis	1
Kidneys
Glomerular filtration rate <50 ml/min	1
Proteinuria >3.5 g/day	1
End-stage renal disease (regardless of dialysis or transplant)	3
Lungs
Pulmonary hypertension (bulging of the right ventricle or a ringing second heart sound over the pulmonary artery)	1
Pulmonary fibrosis (physical and radiological)	1
Shrunken lung (radiographic)	1
Pleural fibrosis (radiological)	1
Pulmonary infarction (radiological)	1
Cardiovascular system
Coronary artery bypass grafting	1
Myocardial infarction ever (score 2 points if >1)	1-2
Cardiomyopathy (ventricular dysfunction)	1
Valve disease (diastolic or systolic murmur >3/6)	1
Pericarditis for 6 months (or pericardiectomy)	1
Peripheral vessels
Intermittent claudication for 6 months	1
Minor tissue loss (toe pads)	1
Significant tissue loss ever (loss of finger or limb) (score 2 if in more than one location)	1-2
Venous thrombosis with edema, ulceration or venous stasis	1
Gastrointestinal tract
Infarction/resection of bowel (below duodenum), spleen, liver or gallbladder ever for any reason (score 1 point if in more than one site)	1-2
Mesenteric insufficiency	1
Chronic peritonitis	1
Strictures or upper GI surgery	1
Musculoskeletal system
Muscle atrophy or weakness	1
Deforming or erosive arthritis (including reducible deformities, excluding vascular necrosis)	1
Osteoporosis with fractures or vertebral collapse (excluding avascular necrosis)	1
Avascular necrosis (score 2 points if >1)	1-2
Osteomyelitis	1
Tendon rupture	1
Leather
Chronic cicatricial alopecia	1
Extensive scarring or panniculitis (excluding scalp and fingertips)	1
Skin ulceration (excluding thrombosis) for more than 6 months	1
Reproductive system
Premature gonadal failure	1
Endocrine system
Diabetes mellitus (regardless of therapy)	1
Malignancy
Excluding dysplasia (score 2 points if more than one localization)	1-2

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