3.1. Theoretical questions for the lesson:

1. Etiology and pathogenesis of lupus erythematosus.

2. Classification of lupus erythematosus.

3. Clinical varieties of chronic lupus erythematosus (discoid, disseminated, erythema centrifugum, and lupus erythematosus profundus).

4. Systemic lupus erythematosus.

5. Diagnosis, differential diagnosis of lupus erythematosus.

6. Treatment, prevention and prognosis of lupus erythematosus.

7. Etiology and pathogenesis of scleroderma.

8. Classification of scleroderma.

9. Circumscribed scleroderma (linear scleroderma, white spot disease, and superficial scleroderma).

10. Systemic (diffuse) scleroderma.

11. Diagnosis, differential diagnosis of scleroderma.

12. Treatment and prognosis of scleroderma.

The subject-matter:

DISEASES OF THE CONNECTIVE TISSUE (COLLAGENOSES)

LUPUS ERYTHEMATOSUS (CICATRIZING ERYTHEMATOSIS)

Lupus erythematosus is characterized by a protracted and persistent course and diversity and conspicuousness of the clinical symptoms. It should be admitted that the name of the disease, lupus erythematosus, is not appropriate because it reflects neither the etiology nor the pathogenesis and is not clear not only to patients but to some physicians who identify the disease with lupus tuberculosis (seu vulgaris).

General information. Lupus erythematosus accounts for 0.25-1.0 per cent of the total number of cases with skin diseases; the incidence of systemic lupus erythematosus is one tenth that of the discoid form. Cicatrizing erythematosus incidence is higher in countries with a humid sea climate and cold winds and quite low in tropical countries despite the considerable insolation. Lupus erythematosus is encountered much more frequently among females (mostly in young women and girls) than among males. People with light hair have the disease more often than those with dark hair and persons with a light skin acquire it more often than individuals with a dark skin, because the skin and body of the latter are less susceptible to irradiation. The most vulnerable age is that between 20 and 40. Much less cases of the disease are recorded among older people. Individuals whose occupation involves long-term exposure to sunlight, frost, wind, and great variations in the environmental temperature (fishermen, truck drivers, builders, agricultural workers, etc.) contract the disease more often and the dermatosis is more persistent.

Etiology and pathogenesis. Clinicians are lately focusing main attention on pathogenic factors contributing to the occurrence of the disease. It proved, for instance, that the disease may be precipitated or exacerbated by treatment with antibiotics, the antihypertensive drug hydrallazine, sulphonamides, vaccines, sera, and ultraviolet irradiation and under the effect of stress situations.

Hargraves, Richmond, and Morton discovered the existence of lupus erythematosus cells in 1948 and thus opened the epidemiological era in the study of erythematosus. The blood serum of patients with systemic lupus erythematosus was found to contain an increased amount of gamma globulins among which a peculiar protein, macroglobulin, was detected; it caused damage to the nuclei of the blood cells, the leucocytes and lymphocytes in particular. This protein was isolated by ultracentrifugation with 19S sedimentation constant and was named the antinuclear factor.

This factor attaches itself on the nuclei of neutral leucocytes and lymphocytes and destroys them. The nuclear substance of these cells loses its structure, separates from the protoplasm and is pushed out of the cell and transforms to a foreign body. The intact neutrophils ingest it by ordinary phagocytosis. Neutrophil leucocytes, which have phagocytosed the denaturated nuclei with homogeneous inclusions and antinuclear factors, are called lupus erythematosus cells, LE cells. These LE cells are a valuable diagnostic sign, though it is not absolutely specific. The LE phenomenon, for instance, is sometimes encountered in acute rheumatism, acute leucoses, plasmacytoma, severe affections of the liver and Duhring's disease.

In the direct method for LE cell identification, 3 ml of patient's venous blood is defibrinated by means of glass beads. The defibrinated blood with beads again put into it is then shaken in a shuttle apparatus for 20 minutes, which raises the percentage of positive results. After that, the blood is centrifuged at 1000 rpm for 5 minutes. Smears are prepared from the leucocytic layer and stained by the Romanovsky-Giemsa method. The result is more reliable in the direct method than in the indirect techniques.

The LE cells and the antinuclear factor are found especially often in patients with the systemic form of the disease and much less frequently in cases with the chronic variety. The disappearance of the LE cells as the result of treatment has definite diagnostic importance. Lupus erythematosus is therefore regarded as an autoimmune (autoaggressive, infectious-immunological) disease today, which is precipitated by various drugs (hydrallazine, antibiotics, sulphonamides, vaccines, sera), infectious factors (streptococcal and virus infections) and by exposure to environmental stimuli (ultraviolet and infrared rays, radiation, cooling). The disease is genetically consolidated with hereditary predisposition by the dominant type with non-uniform expressivity. It is caused by mobilization of gamma globulin-bound antibodies and amino acids.

Much importance in the pathogenesis of lupus erythematosus is attached to foci of chronic infection, photosensitization, hypersensitivity to cooling, disorders of central and vegetative nervous regulation, and neuroendocrine disorders.

Classification. Most authors recognize the following forms:

1. Chronic lupus erythematosus (chronic cicatrizing erythematosus);

2. Acute, or systemic, lupus erythematosus (acute erythematosus) in which not only the skin but the internal organs are involved;

3. Subacute lupus erythematosus (subacute erythematosus) the clinical symptoms of which are less manifest than those of the acute form.

Chronic cicatrizing erythematosus. The following four clinical varieties of chronic erythematosus are distinguished: discoid, disseminated, erythema centrifugum (Biett's disease), and the Kaposi-Irgang disease syn. lupus erythematosus profundus.

In many cases there are no subjective signs at the onset of the disease. The chronic discoid form is most common; it may be manifested on any body areas, including the mouth, lips, hands, feet, chest, back, and scalp. The face is the favoured localization; the lesions are circumscribed pink-red scaly spots, which grow on the periphery and coalesce. Infiltrated erythematous patches covered with keratotic tightly sitting scales form later. The infundibuli of the follicular orifices are exposed when the scales are removed (follicular hyperkeratosis) and tiny projections are often found on the undersurface of the scales (the 'ladies' heel' sign). Scraping of the scales is usually painful (Besnier-Meshchersky's sign). Three zones may be discerned in the foci of affection: a zone of cicatricial atrophy in the centre, a zone of hyperkeratosis next to it and a zone of redness on the periphery. Telangiectasia, hyperpigmentation, and depigmentation are found in the region of the foci. There is a typical eruption on the cheeks and the bridge of the nose which resembles a butterfly in shape. Comedones and distended follicular orifices may be found in the foci of affection on the nose and the auricular conchae.

The cicatricial atrophic process on the scalp causes stable alopecia. Leucoplakia, ulcers, and erosions may sometimes form on the oral mucosa, and localized oedema with tumorous thickenings and cracks on the lips.

In the disseminated variety of lupus erythematosus, the eruption on the face, scalp, neck and upper part of the chest (where it is sometimes arranged like a necklace) occurs as numerous foci which are usually small. These patients have in essence disseminated numerous discoid foci. In distinction from systemic lupus erythematosus, the foci are more clearly demarcated and there are infiltration, hyperkeratosis, and atrophy. In disseminated lupus erythematosus, however, erythematous foci with a bluish tinge may also be found on which neither marked hyperkeratosis nor marked infiltration is seen. Such foci are usually found on the fingers, toes, and knees. At the same time, the accompanying severe general symptoms (periods of subfebrile temperature, increased ESR, leucopenia, anemia, pain in the joints, etc.) are much more frequent in disseminated erythematosis than in the discoid form. A localized infection (chronic tonsillitis, sinusitis, purulent otitis, tooth disease, etc.) is found in such patients as a rule. These circumstances provided the grounds for some authors to consider disseminated cicatrizing erythematosis an intermediate form between discoid and systemic lupus erythematosus.

Erythema annulare centrifugum is a superficial variety of chronic erythematosis. Biett described it in 1828. A circumscribed, somewhat oedematous erythema red, pink-red or bluish-red in colour usually occurs on the face and spreads away from the centre. The bridge of the nose and both cheeks are involved (the appearance of a butterfly) or, in some patients, only the cheeks or only the bridge of the nose (a butterfly without wings). The patient has no subjective sensations. Follicular hyperkeratosis and cicatricial atrophy are absent. Biett's disease may herald systemic erythematosis or may be accompanied with involvement of the viscera in the systemic variety of lupus erythematosus (acute or subacute).

Kaposi-Irgang deep disease (lupus erythematosus profundus) is characterized by an infiltrate penetrating the subcutaneous fat in the region of the erythematous spots. Such deep-seated foci of affection are usually localized on the upper half of the trunk, and on the head and arms; they undergo ulceration in some cases.