Lupus erythematosus: Clinical Guidelines

List of Abbreviations

DNA – deoxyribonucleic acid

ICD – International Classification of Diseases

SLE – systemic lupus erythematosus

Terms and Definitions

Lupus erythematosus is a multifactorial autoimmune inflammatory connective tissue disease affecting various organs and systems with a wide range of clinical manifestations.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Lupus erythematosus is a multifactorial autoimmune inflammatory connective tissue disease affecting various organs and systems with a wide range of clinical manifestations.

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

The etiology of discoid lupus erythematosus is unknown. Important links in the pathogenesis of the disease are exposure to ultraviolet radiation, formation of autoantibodies and development of autoimmune reactions, impaired regulation of T-lymphocyte and dendritic cell functions.

Risk factors for the development of discoid lupus erythematosus include: prolonged exposure to the sun, frost, wind (agricultural workers, fishermen, construction workers), skin phototype I, drug intolerance, and foci of chronic infection.

Factors provoking the development of cutaneous forms of lupus erythematosus include ultraviolet radiation, certain drugs (terbinafine, tumor necrosis factor-α inhibitors, anticonvulsants, proton pump inhibitors, calcium channel blockers, angiotensin-converting enzyme inhibitors, β-blockers, leflunomide**, etc.), viral infections, and skin trauma. About 1/3 of all cases of subacute cutaneous lupus erythematosus are drug-induced. Smoking is associated with an increased risk of developing cutaneous forms of lupus erythematosus and a more severe disease course. Alterations in sex hormone (estrogen) levels also play an important role in predisposition to lupus erythematosus.

1.3 Epidemiology of the Disease or Condition

The incidence of cutaneous forms of lupus erythematosus ranges from 3.0 to 4.2 cases per 100,000 population per year, with patients suffering from discoid lupus erythematosus accounting for 70–80%. Disease onset is most commonly observed between 20 and 40 years of age, and women are affected several times more frequently than men. In children, cutaneous forms of lupus erythematosus are significantly rarer (children under 10 account for 3% of all cases), and gender differences are not pronounced before puberty.

Patients with cutaneous lupus erythematosus are at risk of developing systemic lupus erythematosus. The risk of developing and diagnosing SLE is highest in the first years after the diagnosis of cutaneous lupus erythematosus [66]. In Sweden, the probability of being diagnosed with SLE within 1 year after being diagnosed with cutaneous lupus erythematosus was 12.1%, and within 3 years, 18.1% [67]. In Denmark, the probability of an SLE diagnosis in patients with cutaneous lupus erythematosus was 9.4% in the first 5 years after the diagnosis of cutaneous lupus erythematosus and 12.9% 10 years after the diagnosis of cutaneous lupus erythematosus [66]. Among patients with cutaneous lupus erythematosus, the risk of developing SLE was higher in women and in patients with subacute cutaneous lupus erythematosus. The median time elapsed from the diagnosis of cutaneous lupus erythematosus to the diagnosis of SLE was 2.05 years [66].

1.4 Features of Coding the Disease or Condition

Lupus erythematosus (L93):

L93.0 – Discoid lupus erythematosus

L93.1 – Subacute cutaneous lupus erythematosus

L93.2 – Other local lupus erythematosus

1.5 Classification of the disease or condition

Cutaneous lesions in lupus erythematosus are divided into specific and nonspecific. Specific skin lesions include chronic, subacute, and acute forms of the disease:

1. Acute cutaneous lupus erythematosus:

a. localized;

b. generalized;

c. toxic epidermal necrolysis-like.

2. Subacute cutaneous lupus erythematosus:

a. annular;

b. papulosquamous/psoriasiform;

c. bullous;

d. toxic epidermal necrolysis-like.

3. Chronic cutaneous lupus erythematosus:

a. discoid:

o localized;

o generalized;

b. hypertrophic/verrucous;

c. deep/lupus panniculitis;

d. tumor-like/papulomucinous lupus erythematosus;

e. lupus erythematosus profundus / chillblain lupus;

f. mucosal lupus erythematosus (oral cavity, nose, genitals, conjunctiva);

g. lichenoid discoid lupus erythematosus (lupus erythematosus / lichen planus overlap syndrome).

1.6 Clinical presentation of the disease or condition

Discoid lupus erythematosus is characterized by a triad of symptoms: erythema, hyperkeratosis, and atrophy. Lesions may be localized (primarily affecting the face (malar areas, cheeks, and nasal alae), auricles, scalp) or generalized. Hyperemic spots appear on the skin, which slowly increase in size, become infiltrated, and turn into elevated plaques. Initially, follicular hyperkeratosis appears in the central part of their surface, followed by confluent hyperkeratosis. Scales are difficult to detach, and scraping them causes pain (Bournier-Meshchersky sign). On the underside of the removed scale, horny spikes are found, projecting into the dilated follicular funnels. A zone of active inflammation and hyperpigmentation persist at the periphery of the lesions. Plaques slowly increase in size, and in the central part, the elements resolve with the formation of coarse, depressed, disfiguring scarred skin atrophy, against which telangiectasias may appear.

In the area of the vermilion border of the lips, eruptions present as slightly infiltrated cherry-red spots covered by a small amount of tightly adherent scales. When the scalp is affected, erythema of various shapes with surface desquamation develops, upon resolution of which cicatricial atrophy, telangiectasias, and areas of hypo- and hyperpigmentation remain. A zone of cicatricial alopecia forms in the center of the lesions, with areas of preserved hair typically present within the patches of hair loss.

Deep lupus erythematosus (lupus panniculitis) clinically manifests as one or more deeply situated firm nodules that are mobile, well-demarcated, and not adherent to surrounding tissues. The skin over the nodules has a congested cherry-red color; lesions of erythema and hyperkeratosis typical of discoid lupus erythematosus are frequently observed (a combination of deep and discoid lupus erythematosus). After the resolution of nodules, areas of subcutaneous fat atrophy remain, manifesting as deep depressions. In some cases, nodules may ulcerate, forming coarse retracted scars upon healing. Calcium salt deposition in the skin with the formation of calcifications is possible. Eruptions are usually located asymmetrically in the areas of the face, neck, shoulders, breasts (lupus mastitis), thighs, and buttocks.

Verrucous (hypertrophic) lupus erythematosus is characterized by the development of single plaques protruding sharply above the skin surface with marked hyperkeratosis and a warty surface. The most frequent localization of this form of lupus erythematosus is the face, the dorsum of the hands, and the extensor surfaces of the forearms and arms. Verrucous lupus erythematosus may be combined with discoid lupus erythematosus, which facilitates diagnosis. Eruptions show resistance to ongoing therapy.

Chilblain lupus is a rare form of the disease whose development is induced by low temperatures. The clinical picture is characterized by bluish-red papules and small plaques located on exposed areas of skin and the distal parts of the limbs: the fingers (85%), toes (42%), auricles (9%), and nose (6%). Eruptions persist for a long time, and their evolution does not depend on the season. Ulceration or the formation of verrucous vegetations and telangiectasias is possible. The period between chilblains and the development of lupus erythematosus averages about 3–4 years.

Tumor-like lupus erythematosus is considered by some authors to be a chronic cutaneous form of lupus erythematosus, while others classify it as an intermediate form of the disease. The clinical picture is represented by skin eruptions in the form of firm urticaria-like papules and red plaques (from pink to bluish), round, irregular, or annular in shape, with distinct borders and a shiny surface, located on sun-exposed areas – the upper chest, back, shoulders, neck, and face. Sometimes elements may coalesce, forming polycyclic figures. Exacerbations of the disease are more often observed in the spring-summer period. Eruptions may spontaneously resolve without leaving a trace after several weeks or persist for a long time. Annual exacerbations of the disease after sun exposure with the reappearance of elements in the same places are frequently observed.

Mucosal lupus erythematosus may develop simultaneously with or precede skin involvement. This form of the disease is rarely diagnosed in a timely manner (in 10–50% of cases). Eruptions are more often observed on the oral mucosa, but may be localized in the nasal cavity, on the genitals, or the conjunctiva. Elements present as inflammatory lesions with infiltration at the base, atrophy in the center, and hyperkeratosis in the form of dots and stripes. Bright hyperemia, solitary painful erosions, and ulcers may develop. Resolution of eruptions is often accompanied by the formation of scars or cicatricial atrophy.

Subacute cutaneous lupus erythematosus has a transitional clinical picture between acute and chronic lupus erythematosus. This form presents with the development of papulosquamous or annular erythematous rashes. In psoriasiform lupus erythematosus, the elements appear as hyperemic papules and small plaques on the shoulders, upper chest, and back, and rarely on the facial skin, auricles, and scalp, which may coalesce. The surface of the spots and plaques shows tightly adherent scales and minor hyperkeratosis, which is intensified around the hair follicle ostia. The annular form of the disease is characterized by the formation of hyperemic spots and erythema in the form of rings and polycyclic figures with hyperkeratosis and scaling on the surface, located predominantly on sun-exposed skin areas. A combination of papulosquamous and annular forms in a single patient is possible. Rashes in subacute cutaneous lupus erythematosus may resolve without scarring, forming long-standing areas of hypopigmentation with superficial telangiectasias, or form a very superficial scarring atrophy. These patients often have relatively mild systemic manifestations of lupus erythematosus: arthralgia, arthritis, and other musculoskeletal symptoms without involvement of the kidneys, central nervous system, or serous membranes.

Bullous lupus erythematosus is a very rare form of the disease that develops as a result of autoantibody-mediated damage to type VII collagen fibers at the dermo-epidermal junction. Numerous small vesicles or large blisters with a tense roof and serous contents appear on outwardly unchanged skin or against a background of erythema, predominantly in sun-exposed areas (face, neck, extensor surfaces of the shoulders, upper back, and chest). Formation of bullous elements on the mucous membranes is possible. Resolution of the rashes results in secondary hyperpigmentary spots or scars. The development of the bullous form of lupus erythematosus indicates high disease activity and systemic manifestations.

Acute cutaneous lupus erythematosus is always a manifestation of systemic lupus erythematosus, presenting with skin lesions in 70–85% of cases. The acute form of lupus erythematosus is characterized by the development of erythema with a cyanotic hue in the center and edema on the skin of the face in the cheekbones, cheeks, and nose area («butterfly rash»). Widespread maculopapular rashes are less common. The rash elements usually appear after sun exposure, persist for several days, and resolve, leaving minor hyperpigmentary spots. A distinct equivalent of the «butterfly» is Biedt's centrifugal erythema, which appears on the cheeks as slightly edematous, bright hyperemic spots that slowly increase in size due to peripheral growth while simultaneously resolving centrally. Involvement of the vermilion border of the lips, development of facial edema, and the appearance of widespread maculopapular rashes on symmetrical skin areas are possible. Lesions of the oral mucosa, hard palate, and nose may present with erosion and ulceration. In rare cases, the clinical picture of the acute cutaneous form of lupus erythematosus may resemble toxic epidermal necrolysis.

Neonatal lupus erythematosus is a rare form of the disease that develops due to transplacental passage of anti-Ro/SS-A and/or anti-La/SS-B antibodies from mother to fetus. Clinically, neonatal lupus erythematosus manifests as rashes similar to the subacute form of lupus erythematosus and the development of heart blocks, which appear in the first days and weeks of the child's life. Involvement of the central facial skin and periorbital areas is characteristic. Newborn infants may also exhibit hemolytic anemia, leukopenia, thrombocytopenia, and hepatomegaly.

Patients with cutaneous forms of lupus erythematosus frequently exhibit overlapping skin manifestations. Two or more clinical forms of cutaneous lupus erythematosus are observed in 35% of patients, acute cutaneous lupus erythematosus associated with discoid lupus erythematosus in 30%, with subacute cutaneous lupus erythematosus in 14%, and with both discoid and subacute cutaneous lupus erythematosus in 15% of patients.

The probability of developing systemic lupus erythematosus is up to 90% in acute lupus erythematosus, 35–50% in subacute lupus erythematosus, about 20% in widespread forms of chronic lupus erythematosus, and no more than 5% in localized discoid lupus erythematosus.

In children, discoid lupus erythematosus is more common (accounting for 73% of all cutaneous forms of the disease). Skin lesions are usually limited in nature and localized to the face, scalp, and neck. Children with generalized discoid lupus erythematosus frequently develop SLE [41].

2. Diagnostics, medical indications and contraindications for diagnostic methods

2.1 Complaints and Anamnesis

Patients complain of rashes, which are usually unaccompanied by subjective sensations.

Solar or ultraviolet radiation may contribute to the appearance of rashes. Exacerbations of the disease are more commonly observed in the spring-summer period.

2.2 Physical Examination

Scope of patient evaluation for lupus erythematosus:

dermatovenereologist – examination of the skin and visible mucous membranes, determination of the Besnier-Meschersky sign, magnified skin examination (dermatoscopy), skin biopsy for pathological anatomical examination of skin biopsy (surgical) material and/or pathological anatomical examination of skin biopsy (surgical) material using immunofluorescence methods, complete blood count (CBC), general biochemical blood test, immunological tests for antinuclear antibodies, precipitation reaction with cardiolipin antigen, and urinalysis;

pediatrician/general practitioner – examination of the skin and visible mucous membranes, complete blood count (CBC), general biochemical blood test, immunological tests for antinuclear antibodies, precipitation reaction with cardiolipin antigen, and urinalysis;

rheumatologist – examination of the skin and visible mucous membranes, skin biopsy for pathological anatomical examination of skin biopsy (surgical) material and/or pathological anatomical examination of skin biopsy (surgical) material using immunofluorescence methods, complete blood count (CBC), general biochemical blood test, immunological tests for antinuclear antibodies, precipitation reaction with cardiolipin antigen, and urinalysis.

Objective clinical manifestations of skin lesions in lupus erythematosus identified during physical examination are described in the «Clinical Presentation» section.

Comments: in patients with discoid lupus erythematosus, scales are difficult to detach, and scraping them causes pain (positive Besnier-Meschersky sign).

2.3 Laboratory Diagnostics

The diagnosis of cutaneous forms of lupus erythematosus is established by a dermatovenereologist based on the clinical picture. Laboratory evaluation is performed to rule out systemic lupus erythematosus, as well as in patients receiving systemic therapy.

complete blood count (CBC) [25, 26, 35, 59-65]:

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)

Comments: the use of a complete blood count (CBC) to monitor the safety of therapy with antimalarial drugs, #dapsone** or #methotrexate** is necessary due to their ability to affect hematopoiesis, causing anemia and/or neutropenia and/or thrombocytopenia [59-65].

general biochemical blood test with determination of the activity of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and investigation of blood urea, creatinine, and serum C-reactive protein levels.

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)

Comments: the use of a general biochemical blood test to monitor the safety of therapy with antimalarial drugs, #dapsone** or #methotrexate** is necessary due to their ability to affect liver function [59-65].

Comments: autoantibodies may be produced in cutaneous forms of LE. Patients with discoid LE show the formation of anti-Ro/SS-A, anti-La/SS-B, and anti-annexin-1 antibodies. The majority of patients with subacute cutaneous LE test positive for anti-Ro/SS-A (70%), ANA (60–80%), and anti-La/SS-B (30–50%) antibodies. When performing differential diagnosis, it is important to consider that systemic LE is characterized by the presence of antibodies to extractable nuclear antigen Sm (Smith) (anti-Sm) and positive anti-dsDNA tests.

2.4 Instrumental Diagnostics

2.5 Other Procedures

Comments: pathomorphological changes in various cutaneous forms of lupus erythematosus may have significant differences. Discoid lupus erythematosus is characterized by epidermal changes in the form of hyperkeratosis, increasing in the area of hair follicle ostia and sweat glands, atrophy, vacuolar degeneration of the basal layer, and thickening of the basement membrane; the dermis shows edema and dilation of papillary vessels, formation of predominantly lymphocytic infiltrates around vessels and skin appendages, basophilic degeneration of collagen, and mucin deposition. In subacute cutaneous lupus erythematosus, changes are less pronounced: in the epidermis, hyperkeratosis is observed only in the area of hair follicle ostia ("follicular plugs"), while atrophy and vacuolization of basal keratinocytes are less prominent; sparse lymphocytic infiltrates are found in the dermis, predominantly in the papillary dermis. In deep lupus erythematosus, the epidermis and dermis may not be involved in the inflammatory process. The main changes are observed in the hypodermis, where the process begins with lobular panniculitis followed by involvement of the septal walls. Histological changes in tumid lupus erythematosus are characterized by the formation of dense dermal perivascular and periadnexal lymphocytic infiltrates, as well as significant mucin deposits between dermal collagen fibers, while the epidermis remains intact.

Comments: direct immunofluorescence examination of a skin biopsy from a LE lesion site reveals macroglobular deposits of IgM/IgG immunoglobulins and complement in the dermo-epidermal junction zone, representing a positive "lupus band" test. In patients with systemic LE, this test may also be positive in uninvolved skin areas. Positive results of direct immunofluorescence skin biopsy examination are not specific for LE and can be observed in other dermatoses, as well as in healthy individuals on areas exposed to prolonged solar radiation.

Comments: patients with cutaneous forms of lupus erythematosus may develop systemic lupus erythematosus.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1 Conservative Treatment

Patients with cutaneous forms of lupus erythematosus may receive topical and systemic drug therapy. As first-line topical therapy, corticosteroids used in dermatology or other agents used in dermatology (#tacrolimus** or #pimecrolimus**) are used. For systemic therapy in patients with cutaneous forms of lupus erythematosus, antimalarial drugs (hydroxychloroquine** or #chloroquine) are used as first-line systemic therapy [3, 4]. Hydroxychloroquine** is preferred over #chloroquine due to better tolerability. Due to the potential development of retinopathy when taking antimalarial drugs, patients should undergo ophthalmoscopy and regular laboratory monitoring. In case of acute skin lesions or at the start of therapy with antimalarial drugs or immunosuppressants, short courses of systemic corticosteroids may be prescribed [3, 4]. If antimalarial drugs are insufficiently effective, antileprotic drugs (#dapsone**) or immunosuppressants (#methotrexate**) may be prescribed.

- #betamethasone** 0.1% topical cream, 0.1% topical ointment applied in a thin layer to affected skin areas 2 times a day topically to the lesions [3].

GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)

Comments: #betamethasone** 0.1% topical cream, 0.1% topical ointment are considered optimal for application to lesions on the trunk and limbs [3]. #Betamethasone** 0.1% topical cream and 0.1% topical ointment are contraindicated in children under 6 months of age.

Or

- clobetasol 0.05% topical cream, 0.05% topical ointment applied 1–2 times a day to the lesions [4, 38, 43-45].

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)

Comments: the use of 0.05% clobetasol cream and ointment is considered optimal when rashes are located on the scalp, palms, and soles [3]. Contraindications for prescribing clobetasol 0.05% topical cream and 0.05% topical ointment include children under 1 year of age. In children aged 1 to 18 years, 0.05% clobetasol cream and ointment should be used with caution.

Or

- #methylprednisolone aceponate 0.1% topical ointment for adult patients applied to lesions 1 time per day [48].

GPP CLOE 4Strength of Recommendation C (Level of Evidence – 4)

Or

- #tacrolimus** 0.1% topical ointment applied 2 times a day to the lesions [2, 4, 8, 10].

GCR CLEL 2Grading of Recommendations Assessment, Development and Evaluation C (Level of Evidence – 2)

Comments: the use of #tacrolimus** 0.1% ointment is contraindicated in children under 16 years of age.

Or

- #pimecrolimus** 1% topical cream applied 2 times a day to the lesions [9, 11, 49].

GGR BLOC 2Grade of Recommendation B (Level of Evidence – 2)

Comments: the use of #pimecrolimus** 0.1% cream is contraindicated in children under 3 months of age.

Or

- #tacrolimus** 0.03% topical ointment applied to lesions 2 times a day for adults and children over 6 years of age [50].

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)

Comments: the use of #tacrolimus** 0.03% ointment is contraindicated in children under 2 years of age.

- hydroxychloroquine** for adult patients orally at 5–6 mg/kg of body weight per day (or 2 tablets of 200 mg for an adult of average weight). After achieving a clinical response, the dosage of hydroxychloroquine** may be gradually reduced to 200 mg per day, with therapy continued for at least 2–3 months [39, 52, 53].

GGR BLOC 2Grade of Recommendation B (Level of Evidence – 2)

Comments: administration of the drug may continue for up to 2–3 years. Discontinuation of maintenance doses increases the risk of discoid lupus erythematosus relapse by 2.5 times [8].

Or

- hydroxychloroquine** for pediatric patients orally at 5 mg/kg of body weight per day, but not exceeding 400 mg per day, for no more than 6 months [54, 55].

GPP CLOE 4Strength of Recommendation C (Level of Evidence – 4)

Comments: hydroxychloroquine** is contraindicated under the age of 6 years (200 mg tablets are not intended for children weighing less than 31 kg). Children have an increased risk of toxic effects during long-term therapy [42].

Or

- #chloroquine for adult patients orally at 250 mg 1–2 times a day for 5 days, with 2-day breaks; treatment courses are repeated for 2–3 months [53].

GGR CLEL 3Grade of Recommendation C (Level of Evidence — 3)

Or

- #chloroquine for adult patients orally at 250 mg per day 5–7 days a week for 2 months or more [53].

GGR CLEL 3Grade of Recommendation C (Level of Evidence — 3)

- #chloroquine for pediatric patients orally at 3.5 mg/kg of body weight per day [42].

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)

- #prednisolone** for adult patients 10–40 mg orally (maintenance dose 5–10 mg/day) per day orally (maintenance dose 5–10 mg per day); the duration of therapy is determined individually [38, 68, 70].

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)

- #dapsone** for adult patients orally at 25–150 mg per day in 1–2 doses [4, 52, 56].

Level of Recommendation CLevel of Evidence 4Level of Recommendation C (level of evidence – 4)

Comments: therapy with #dapsone** is initiated at a minimal dose of 25–50 mg per day, increasing it every week by 25 mg until the minimum effective dose is reached, but not exceeding 200 mg per day [3, 52]. During treatment with #dapsone**, monitoring of the complete blood count and liver function tests is necessary [3]. #Dapsone** is contraindicated in children under 18 years of age.

Or

- #methotrexate** 10–25 mg for adult patients once a week orally until remission is achieved [12, 13, 57, 58].

GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)

Comments: To monitor the safety of therapy with #methotrexate**, it is necessary to perform a complete blood count, general clinical biochemical blood test, and urinalysis.

3.2 Surgical Treatment

Not applicable.

3.3 Other Treatment

Diet therapy is not used.

Pain management is not used.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Rehabilitation of patients with lupus erythematosus is achieved in local resort settings. Physiotherapy and resort treatment in the southern regions of the country involving sun exposure are contraindicated for patients with lupus erythematosus. They should refrain from bathing in hot, steamy bathhouses, steam rooms, and saunas, and prolonged stay near a hot stove is discouraged. Optimal working conditions for patients are employment in dry, warm industrial premises [17].

5. Prevention and Dispensary Observation

6. Organization of Medical Care

Indications for hospitalization:

- in severe cases of lupus erythematosus;

- in the absence of an effect from outpatient treatment within 1 month.

Indications for patient discharge:

- cessation of disease progression has been achieved.

7. Additional Information

Long-term remission in cutaneous lupus erythematosus is rarely achieved; it is most likely to be achieved in discoid lupus erythematosus [69].

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Kubanov Aleksey Alekseevich – Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, President of the Russian Society of Dermatovenereologists and Cosmetologists.

2. Samtsov, Alexey Viktorovich – Doctor of Medical Sciences, Professor, Member of the Russian Society of Dermatovenereologists and Cosmetologists.

3. Khayrutdinov, Vladislav Rinatovich – Doctor of Medical Sciences, Professor, Member of the Russian Society of Dermatovenereologists and Cosmetologists.

4. Vadim V. Chikin – MD, Senior Researcher at the Department of Dermatology, State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, member of the Russian Society of Dermatovenereologists and Cosmetologists.

Conflict of Interest: The authors declare no conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Medical specialists: dermatovenereologists, rheumatologists.

2. Residents and trainees of continuing professional education cycles in the specialty "Dermatovenereology".

Table 1. Levels of Evidence (LoE) grading scale for diagnostic methods (diagnostic interventions)

Table 2. Levels of Evidence (LoE) grading scale for prevention, treatment, and medical rehabilitation methods, including those based on natural therapeutic factors (preventive, therapeutic, and rehabilitation interventions)

Table 3. Scale for assessing grades of recommendation (GR) for prevention, diagnostic, treatment, and medical rehabilitation methods, including those based on natural therapeutic factors (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The clinical guidelines update mechanism provides for their systematic revision—at least once every three years, as well as upon the emergence of new evidence-based data regarding the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

These clinical guidelines were developed taking into account the following regulatory legal documents:

Order of the Russian Ministry of Health No. 924n dated November 15, 2012, "On Approval of the Procedure for Providing Medical Care to the Population in the Profile 'Dermatovenereology'."

Appendix B. Physician Action Algorithms

Flowchart 1. Patient Management Algorithm

Appendix C. Patient Information

1. Worsening of skin conditions in lupus erythematosus can be triggered by solar or ultraviolet radiation. Therefore, patients must follow sun-protection measures: wearing hats, long-sleeved clothing, clothing covering the neckline, trousers, and long skirts, as well as regular application of sunscreens with a high SPF index (> 50).

2. Skin lesions in lupus erythematosus may be one of the manifestations of systemic lupus erythematosus, which requires a rheumatologist consultation to rule out systemic involvement.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Scales are not used.