Cross-manifestations of skin lesions are frequently observed in patients with cutaneous forms of lupus erythematosus (LE). Two or more clinical forms of cutaneous LE are observed in 35% of patients, acute cutaneous LE associated with discoid cutaneous LE in 30%, with subacute cutaneous LE in 14%, and with both discoid and subacute cutaneous LE in 15% of patients.

The likelihood of developing systemic lupus erythematosus (SLE) is up to 90% with acute cutaneous LE, 35-50% with subacute cutaneous LE, approximately 20% with widespread forms of chronic cutaneous LE, and no more than 5% with localized discoid cutaneous LE.

Discoid lupus erythematosus

Characterized by a triad of symptoms: erythema, hyperkeratosis, and atrophy. Lesions may be localized (mainly on the face, including the cheeks, nasal wings and ears, and the hairy part of the scalp) or widespread. Reddish patches appear on the skin that slowly increase in size, become infiltrated, and transforming into elevated plaques. In the central part of these plaques, follicular hyperkeratosis develops initially and then becomes continuous. The scales are difficult to remove and are painful to scrape. On the underside of the removed scale, keratin spicules are found embedded in enlarged follicular openings. A zone of active inflammation remains at the periphery of the lesions, accompanied by hyperpigmentation. The plaques gradually enlarge, and in the central area there is a disintegration of the elements, forming a coarse, indented, disfiguring scarred atrophy of the skin, which may be accompanied by telangiectasias.

In the vermilion border of the lips, eruptions are represented by slightly infiltrated cherry-red spots, covered with a small amount of scales that are difficult to remove.

Deep Lupus Erythematosus (Lupus Panniculitis)

Clinically presents as one or more deep-seated, firm nodules that are mobile, well demarcated, and not adherent to surrounding tissues. The skin overlying the nodules has a congested cherry-red color, often with foci of erythema and hyperkeratosis typical of discoid cutaneous LE (combination of deep and discoid forms). After resolution of the nodules, areas of subcutaneous tissue atrophy remain, manifesting as deep depressions. In some cases, the nodules may ulcerate, forming rough, indrawn scars as they heal. Calcium salts may be deposited in the skin, forming calcinosis cutis. The eruptions are usually asymmetrical and localized on the face, neck, shoulders, breasts (lupus mastitis), thighs, and buttocks.

Hypertrophic lupus erythematosus (verrucous lupus erythematosus)

Characterized by the development of single sharply raised plaques above the skin surface, with pronounced hyperkeratosis and a wart-like appearance. The most common localization for this form of lupus erythematosus is the face, dorsal surfaces of the hands, extensor surfaces of the forearms and arms. Verrucous lupus can coexist with discoid cutaneous lupus, which aids in the diagnosis of the disease. The eruptions are noted to be resistant to the conducted therapy.

Chilblain lupus

Chilblain lupus represents a rare form of the disease induced by low temperatures. The clinical presentation is characterized by purplish-red papules and small plaques located on exposed skin areas and the distal parts of the limbs: fingers of the hands (85%) and feet (42%), earlobes (9%), and nose (6%). Eruptions last for a long time and their development does not depend on the season. Ulceration or the formation of verrucous growths is possible, as well as the appearance of telangiectasias. The average time between frostbite and the development of LE is about 3-4 years.

Lupus tumidus

Considered by some authors as a chronic cutaneous form of lupus erythematosus, while others classify it as an intermediate form of the disease. The clinical picture consists of eruptions on the skin in the form of dense urticaria-like papules and reddish plaques (ranging from pink to bluish), round, irregular, or ring-shaped, with well-defined borders and a shiny surface. These eruptions are localized to areas exposed to sunlight, such as the upper chest, back, shoulders, neck, and face. Sometimes the elements may merge to form polycyclic patterns. Exacerbations are more common in the spring and summer months. The eruptions may disappear spontaneously after a few weeks or they may persist for a long time. Frequent annual exacerbations are often observed after sun exposure, with elements reappearing in the same locations.

Oral lupus erythematosus

May develop simultaneously with or precede skin involvement. This form of the disease is rarely diagnosed in time (10-50% of cases). Eruptions are more commonly observed on the oral mucosa, but may also localize to the nasal cavity, genitalia, and conjunctiva. The eruptions consist of hyperemic macules, bluish-red papules covered with whitish deposits, occasionally forming blisters. Painful erosions and ulcers may develop. Resolution of eruptions often leads to the formation of scars or scar atrophy.

Psoriasiform lupus erythematosus

The eruptions are represented by erythematous papules and small plaques in the shoulder, upper chest, and back area, rarely on the facial skin, earlobes, and the hairy part of the scalp, which may coalesce. On the surface of the patches and plaques there are tightly adherent scales and slight hyperkeratosis, accentuated around the openings of the hair follicles.

Annular Lupus Erythematosus

Characterized by the formation of erythematous patches and rings and polycyclic figures with hyperkeratosis and superficial scaling, primarily on sun-exposed areas of the skin. A combination of papulosquamous and annular forms may occur in the same patient. Eruptions may resolve without scarring, forming long-lasting areas of hypopigmentation with superficial telangiectasias, or they may result in very superficial scar atrophy. Patients in this category often have relatively mild systemic manifestations of red lupus: arthralgia, arthritis, and other symptoms of musculoskeletal involvement without renal, central nervous system, or serous membrane involvement.

Bullous lupus erythematosus

A rare form of the disease that develops due to the autoantibodies targeting type VII collagen fibers in the epidermal-dermal junction. Numerous small blisters or large blisters with a tense roof and serous contents appear on externally unchanged skin or against a background of erythema, primarily on sun-exposed areas (face, neck, extensor surfaces of shoulders, upper back, and chest). The formation of bullous elements on mucous membranes is possible. Upon resolution, secondary hyperpigmented spots or scars may form. The development of the bullous form indicates high disease activity and systemic manifestations.

Poikilodermatous Lupus Erythematosus

Characterized by areas of mottled brown hyperpigmentation, hypopigmentation, and atrophy accompanied by telangiectasias and superficial scaling. It usually occurs after prolonged and intense sun exposure. Localization includes exposed areas of the body such as the face, upper chest, back, forearms, and dorsal surfaces of the hands.

Erythrodermic Lupus Erythematosus

A rare variant of subacute cutaneous lupus erythematous that occurs after prolonged and intense sun exposure and is characterized by the spread of eruptions over a significant part of the trunk and limbs with symptoms of erythroderma.

Pigmented (Melanotic) lupus erythematosus

A rare form of the disease characterized by hyperpigmented spots with mildly pronounced follicular hyperkeratosis, typically on sun-exposed areas such as the face, extensor surfaces of the forearms, and the dorsal sides of the hands.

Comedonal lupus erythematosus

Characterized by the formation of comedones within the infiltrated plaques of red lupus, primarily on the face.

Rowell syndrome

Begins with chills, a rise in body temperature, and the appearance of eruptions on the trunk and limbs of a polymorphic exudative erythema type, while on the face, there is erythema resembling erythema annulare centrifugum or discoid lupus erythematosus. The lesions are annular with a vesicular component in the peripheral part on a background of edematous erythema, bullae and areas of necrosis. The process is resistant to desensitizing and anti-inflammatory therapy, with regression occurring only after 8-10 weeks, after which it assumes a recurrent character (with intervals from 6 months to 2 years). Antinuclear and rheumatoid factors, anti-DNA antibodies, false-positive reactions to syphilis, increased ESR (erythrocyte sedimentation rate), and lymphopenia are detected in the blood of affected individuals.

Lupus mastitis

More common in middle-aged women over 40 years of age, with rare cases reported in men. It occurs in patients with or precedes a confirmed diagnosis of systemic or discoid lupus erythematosus. It is characterized by thickening of the mammary gland, the appearance of focal hyperkeratosis, atrophy, erythema, lipodystrophy, hypertrichosis, and occasionally ulcers on its surface. Both mammary glands may be involved or only one. Ultrasound shows iso- or hyperechoic areas. The disease is characterized by a chronic course with remissions and relapses, which may occur at the same sites.

Overlap syndrome lupus erythematosus/lichen planus

Represents a true combination of lupus erythematosus and lichen planus in which patients have symptoms of both diseases simultaneously. Clinically, eruptions are characterized by large atrophic hypopigmented patches or patches of red or pink color. Over time, the hypopigmentation of the affected areas intensifies with the appearance of desquamation and telangiectasias. Cutaneous eruptions are usually localized on the mid-back and extensor surfaces of the limbs.

A prominent palmoplantar keratosis is characteristic. Atrophy or complete absence of nails is common. Some patients may have scarring alopecia and areas of oral mucosal involvement.

Acute cutaneous lupus erythematosus

Always represents a manifestation of systemic lupus erythematosus that manifests with skin involvement in 70-85% of cases. It is characterized by the development of erythema with a cyanotic center and swelling on the skin of the face in the area of the cheeks, cheekbones, and nose ("butterfly rash"). Less commonly, widespread maculopapular eruptions are observed. The rash elements usually appear after sun exposure, last a few days, and resolve, leaving minor hyperpigmented spots.

A unique equivalent of the "butterfly" is centrofacial erythema, which appears in the cheek area as slightly edematous, bright erythematous spots that slowly increase in size due to peripheral growth and simultaneously resolve in the central part. The red border of the lips may be involved, facial swelling may occur, and widespread maculopapular eruptions may occur on symmetrical areas of the skin.

Involvement of the mucous membranes of the oral cavity, hard palate, and nose may result in erosions and ulcerations. Rarely, the clinical picture of acute cutaneous lupus erythematosus may resemble toxic epidermal necrolysis.

Neonatal Lupus Erythematosus

A rare form of the disease that develops as a result of the transplacental transfer of anti-Ro/SS-A and/or anti-La/SS-B antibodies from the mother to the fetus. Clinically, neonatal lupus erythematosus is characterized by rashes similar to subacute cutaneous lupus erythematosus and the development of heart block in the first days and weeks of life. Skin involvement typically affects the central part of the face and periorbital areas. Newborns may also present with hemolytic anemia, leukopenia, thrombocytopenia, and hepatomegaly.

Scarring alopecia

When the scalp is involved, there is erythema of various shapes with scaling on the surface, and after resolution, scarring atrophy, telangiectasias, and areas of hypo- and hyperpigmentation remain. In half of the patients (52%), there are multiple large areas of alopecia with skin changes such as scleroatrophy, telangiectasia, hyperpigmentation, erythema, and follicular hyperkeratosis. The scarred alopecic zone forms in the center of these areas, with the presence of hair remnants within the areas of hair loss. 33% of patients have single focal lesions and 15% have small focal lesions that clinically resemble Brocq's pseudopelade ("footprints in the snow"). The primary site is the crown of the head. In 58% of cases, there are no manifestations of cutaneous lupus erythematosus outside the scalp.

Nail involvement in lupus erythematosus

Severe nail destruction may be seen in acute lupus erythematosus. Gangrene of the fingertips is seen in systemic lupus erythematosus. However, neither of these nail conditions allows the diagnosis of systemic lupus erythematosus without the presence of other cutaneous symptoms or histologic examination. Other signs of lupus erythematosus affecting the nails include pinpoint hemorrhages, abnormal keratinization with leukonychia, red lunula, depressions, Beau lines, onycholysis, and onychomadesis.

The diagnosis of lupus erythematosus is based on the characteristic clinical picture, histological changes, and results of immunological tests.

Blood tests for all cutaneous forms of lupus erythematosus should include:

• Complete blood count (CBC) and urinalysis.
• Determination of blood biochemical markers: ALT, AST, γ-glutamyl transpeptidase, alkaline phosphatase, urea, creatinine, C-reactive protein.
• Immunological tests: antinuclear antibodies (ANA) - if positive, further testing includes antibodies to extractable nuclear antigens (ENA) and double-stranded DNA (anti-dsDNA), antibodies to nucleoproteins - anti-Ro/SS-A and anti-La/SS-B, antiphospholipid antibodies (via enzyme-linked immunosorbent assay), and precipitation reaction with cardiolipin antigen - VDRL.
• In cutaneous forms, autoantibodies may be produced. Patients with the discoid form exhibit the formation of anti-Ro/SS-A, anti-La/SS-B, and anti-annexin-1 antibodies. The majority of patients with subacute cutaneous lupus erythematosus show anti-Ro/SS-A (70%), ANA (60-80%), and anti-La/SS-B (30-50%) antibodies. When performing differential diagnosis, it is essential to consider that systemic lupus erythematosus is characterized by the presence of antibodies to the extractable nuclear antigen Sm (Smith) - anti-Sm and positive tests for anti-dsDNA.

• Polymorphic photodermatosis
• Lymphocytoma cutis (pseudo-lymphoma)
• Pemphigus erythematosus
• Erythema annulare centrifugum
• Rosacea
• Perioral dermatitis
• Seborrheic dermatitis
• Dermatomycoses (ringworm, tinea, favus)
• Granuloma faciale
• Sarcoidosis
• Psoriasis
• Lupus vulgaris
• Pseudopelade of Brocq
• Jessner's lymphocytic infiltrate
• Erysipelas

Treatment Goals:

• The goal is to achieve disease remission.

General Remarks on Therapy

Patients are treated with systemic antimalarials and topical glucocorticosteroids.

In cases of localized skin involvement, topical glucocorticosteroid preparations are prescribed. Creams and ointments are used for lesions on the body skin, and lotions are used for lesions on the scalp.

Antimalarial agents are effective both in combination therapy and monotherapy. Hydroxychloroquine sulfate is preferred due to better tolerability. Ophthalmologic examination is performed before starting antimalarial treatment and at least once every 6 months to monitor the possible development of retinopathy. Regular monitoring of laboratory parameters is also performed. In cases of resistance to antimalarial drugs, back-up drugs such as dapsone, retinoids or methotrexate are used. Systemic retinoids are indicated for severe hyperkeratosis (discoid, verrucous). The bullous form is treated with dapsone, which suppresses neutrophil migration, and systemic glucocorticosteroids.

Indications for Hospitalization

• Severe course of dermatosis.
• Lack of effect from outpatient treatment.

Treatment Regimens

Topical Glucocorticosteroids

For skin lesions localized on the face, it is recommended to use low or moderate potency topical glucocorticosteroids:

• Fluocinolone acetonide, cream, gel, ointment, lotion, applied to the lesions twice a day for 12 weeks.

Moderate potency topical glucocorticosteroids are recommended for lesions on the trunk and extremities:

• Triamcinolone, ointment, applied twice a day under occlusion to the lesions for 1 week, or.
• Betamethasone, cream, ointment, applied twice a day to the lesions for 8 weeks

For eruptions located on the scalp, palms, and soles, high potency topical glucocorticosteroid are recommended:

• Clobetasol propionate, cream, ointment, applied twice a day to the lesions for 4 weeks.

Intralesional injection of glucocorticosteroids may be used for localized refractory lesions. The use of this method is limited due to the risk of persistent atrophy.

• Triamcinolone Acetonide, 5-10 mg per mL, intralesional injection, or
• Betamethasone, 0.2 mL per cm2, intralesional injection, with a weekly dose not exceeding 1 mL.

An interval of no less than 4 weeks between injections is recommended if the need for intralesional injections persists.

Systemic Therapy

Antimalarial Drugs:

• Hydroxychloroquine, 5-6 mg per kg per day orally (or 2 tablets of 200 mg each for an adult of average weight). After achieving a clinical response, the dosage of hydroxychloroquine may be gradually reduced to 200 mg per day, continuing therapy for at least 2-3 months. Treatment with the drug may continue for 2-3 years. A 2.5-fold increase in the risk of recurrence occurs when discontinuing maintenance doses.
• Alternatively, chloroquine, 250-500 mg orally daily for at least 2-3 months. Treatment with the drug may continue for 2-3 years.

Considering the important role of ultraviolet-induced free radical damage to membranes and microcirculation disturbances in the pathogenesis, the inclusion of antioxidants in the treatment regimen is recommended: (Low evidence. Need more investigations)

• Vitamin E, 50-100 mg per day orally in intermittent courses: 1 week of drug intake, followed by 1 week of break, for 4-8 weeks.

Angioprotectors and microcirculation correctors are also recommended: (Low evidence. Need more investigations)

• Pentoxifylline, 200 mg orally 3 times a day for 1 month.
• Nicotinic acid, 0.05-0.1 g orally 2-3 times a day for 21-30 days, or 2-3 ml intramuscularly every other day, with a course of 8-10 injections.

Special Situations

Treatment for pregnant women is limited to topical corticosteroids of class I or II. The use of antimalarial drugs is contraindicated due to the possibility of fetal anomalies.

Approach in the Absence of Treatment Efficacy

Second-line drugs prescribed in the absence of effectiveness of topical glucocorticosteroids are topical calcineurin inhibitors:

• Tacrolimus, 0.1% ointment applied twice a day to the lesions for 4-8 weeks.
• Pimecrolimus, 1% cream applied twice a day to the lesions for 4-8 weeks.

Second-line systemic therapy includes retinoids. Treatment should start with lower doses (10-20 mg per day) and gradually increase based on tolerance and absence of side effects:

• Acitretin, 50 mg per day orally for 8 weeks, or
• Acitretin, 0.2-1.0 mg per kg body weight per day orally for 8 weeks, or
• Isotretinoin, 0.2-1.0 mg per kg body weight per day orally for 8 weeks.

Prevention