List of Abbreviations
UV rays - ultraviolet rays
CG – clinical guidelines
Terms and Definitions
Erythema - a circumscribed redness of the skin caused by the dilation of blood vessels in the dermis.
Erythemas considered as separate nosological forms differ in etiopathogenetic characteristics, clinical manifestations, and therapeutic approaches.
1. Brief information on the disease or condition
1.1 Definition of the disease or condition
Erythema - a circumscribed redness of the skin caused by the dilation of blood vessels in the dermis.
Erythema is considered:
– as a morphological component in the clinical symptom complex of various skin diseases,
– an obligate body reaction to various exogenous and endogenous factors (mechanical, biological, radiation, temperature, chemical, intoxication, medicinal, psychogenic, etc.),
– a nosological form (erythema exudativum multiforme, Darier's centrifugal erythema, persistent figured erythema, etc.).
1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)
Active and passive erythema are distinguished. Active erythema is characteristic of the acute phase of an inflammatory process, has a bright color, and may be accompanied by edema and discomfort. Passive erythema is associated with the dilation of dermal venules and blood stasis, resulting in a congested blue-red color with a cyanotic tint, and typically develops as a result of prolonged chronic inflammation.
Erythemas considered as separate nosological entities differ in their etiopathogenetic characteristics, clinical manifestations, and therapeutic approaches. As a rule, these diseases are poorly studied [1].
Erythemas Caused by Physical Factors
Persistent solar (ultraviolet; radiation) erythema is a vascular reaction to ultraviolet (UV) radiation. The key event occurring upon exposure of the skin to UV radiation is vasodilation caused by the action of vasoactive mediators on blood vessels [2].
Thermal erythema (erythema of the second degree/burn erythema, erythema ab igne) is a reticular telangiectatic pigmented dermatosis. It occurs in response to repeated and prolonged exposure to weak infrared radiation, the intensity of which is insufficient to cause a burn. Upon initial exposure to subthreshold infrared radiation, transient reticular erythema develops. Repeated exposures lead to more pronounced erythema with hyperpigmentation and, in some cases, superficial epidermal atrophy. As a result of repeated and prolonged exposures, poikiloderma with reticular telangiectasia, melanosis, and diffuse hyperkeratosis develop [3].
Cold erythema is a reaction in response to low temperatures. One of the suspected mechanisms is an innate defect in serotonin metabolism.
Erythema of the Palms and Soles
Palmar erythema (congenital)
Hereditary palmar erythema or Lane's disease ("red palms") is the dilation of numerous capillary anastomoses in the skin of the palms and soles. The familial nature of the disease is almost always traceable.
Palmar erythema (acquired)
"Liver palms" occur in liver diseases, most commonly in patients with cirrhosis, although these manifestations can be idiopathic. Similar changes can be observed during pregnancy and in certain chronic processes (polyarthritis, pulmonary diseases, subacute bacterial endocarditis, etc.). It is hypothesized that palmar erythema in liver pathology and pregnancy develops as a result of hyperestrogenemia and may occur against the background of taking high-dose estrogen contraceptive drugs.
Congenital telangiectatic erythema (Bloom syndrome) is caused by an autosomal recessive inheritance pattern. Males are affected more frequently.
Ulerythema ophryogenes (scarring eyebrow erythema) is a rare dystrophic dermatosis. The disease develops in childhood or adolescence, sometimes manifesting from birth. The etiology and pathogenesis are not studied. Inheritance is presumed to be autosomal dominant. Congenital dystrophy of the follicular apparatus with impaired keratinization is hypothesized. A number of authors consider the disease not as a separate nosology, but as a clinical variant of keratosis pilaris. It is frequently associated with Noonan syndrome [4–9].
Biesiadecki's centrifugal erythema is a superficial variant of the cutaneous form of lupus erythematosus. See clinical guidelines for "Lupus erythematosus".
Paraneoplastic Erythemas
Necrolytic migratory erythema is a marker of glucagonoma (a glucagon-secreting tumor of the pancreas) and also occurs against the background of hereditary multiple endocrine neoplasia syndrome [10, 11].
Erythema gyratum repens of Gammel is a disease from the group of figurate erythemas that is an obligate paraneoplastic process. It occurs in patients aged 40–60 years who have a visceral malignancy. It is observed most often several months (sometimes 2–4 years) before the clinical signs of the malignant neoplasm. It is more common in women suffering from breast adenocarcinoma, gastric adenocarcinoma, lung cancer, brain tumor, sarcoma, multiple myeloma, or genital tumors.
Erythema centrifugale annulare of Darier ("persistent figurate erythema") is a series of chronic annular and figurate eruptions with various localizations, configurations, and evolutionary variants of rash elements. The etiopathogenesis is not established. An infectious and toxic-allergic nature of the disease is hypothesized. A link between erythema and viral infections, fungal diseases, candidiasis, carcinoma, drug intolerance, dysproteinemia, and immune disorders has been proven, but the majority of cases are idiopathic as the cause cannot be identified. Familial cases have been described. Both sexes are affected, slightly more often men, and children are affected in rare cases [12].
Persistent figurate erythema of Wende
The etiology and pathogenesis of Wende's erythema are unknown. A number of authors classify it as a hereditary disease or a variant of Darier's erythema centrifugale annulare.
Erythema dyschromicum perstans (ashy dermatosis of Ramirez, figurate melanodermatosis)
The disease is more common among people with skin types III and IV, aged 10 to 30 years, and more frequently in women. The etiology and pathogenesis are unclear. An association of the disease with the intake of ammonium nitrate, benzodiazepines, or penicillin, contact with pesticides and cobalt, endocrine diseases, and helminthic infestation has been noted. An association with foci of focal infection (carious teeth, chronic sinusitis) has been described. A number of authors classify erythema dyschromicum perstans as a clinical variant of lichen planus, which is confirmed by the similarity of pathohistological changes. A cell-mediated immune reaction to antigens located in keratinocytes of the basal and spinous layers of the epidermis is hypothesized [13].
Erythema multiforme exsudativum (See clinical guidelines for "Erythema multiforme").
Erythema marginatum (incl. rheumatic annular erythema of Leiner-Lennhoff) is a reactive inflammatory erythema and is one of the manifestations of acute rheumatic fever; less commonly, it can be observed in hereditary angioedema or psittacosis. The disease occurs predominantly between the ages of 5 and 15 years, without gender differences, and more frequently in developing countries. It is found in 1–18% (on average 6%) of patients with acute rheumatic fever, which is an autoimmune disease caused by group A $\beta$-hemolytic streptococci. Serotypes M3 and M18 of group A $\beta$-hemolytic streptococcus associated with acute rheumatic fever are linked to the formation of type IV anticollagen antibodies, which are responsible for post-streptococcal rheumatic disease. However, cases of erythema occurring in psittacosis and angioedema—both hereditary and acquired due to C1 inhibitor deficiency—have been described. The exact etiopathogenesis of the appearance of erythema is unknown.
Erythema elevatum diutinum is a rare form of leukocytoclastic vasculitis. (See clinical guidelines for "Skin-limited vasculitis").
Fixed erythema is a variant of toxicoderma. (See clinical guidelines for "Toxicoderma").
A group of infectious erythemas is distinguished (infectious erythema - fifth disease; erythema migrans; scarlatiniform desquamative erythema, etc.). Infectious agents play a leading role in the etiopathogenesis of these erythemas, forming an infectious-allergic genesis of the disease. The features of the clinical picture depend on the infectious agent; approaches to the diagnosis and treatment of infectious erythemas are based on the elimination of the etiological factor and are described in the relevant clinical guidelines.
1.3 Epidemiology of the Disease or Condition
Epidemiology has not been studied.
1.4 Features of Coding the Disease or Condition
L53.1 - Erythema annulare centrifugum
L53.2 - Erythema marginatum
L53.3 - Other chronic gyrate erythema
L53.8 - Other specified erythematous conditions
L53.9 - Erythematous condition, unspecified
L59.0 - Thermal erythema [dermatitis ab igne]
1.5 Classification of the disease or condition
There is no universally accepted classification.
1.6 Clinical presentation of the disease or condition
Persistent solar (ultraviolet; radiation) erythema is manifested by the occurrence of immediate erythema (directly after irradiation), which disappears within 30 minutes after the cessation of UV exposure, and delayed erythema, which develops 2–6 hours after irradiation, reaches a maximum in 10–24 hours, and gradually disappears over several days. The severity of ultraviolet erythema depends on the intensity of irradiation: ranging from barely noticeable hyperemia with a minor local temperature reaction to crimson-red burns with edema and blistering elements accompanied by itching and pain. The process resolves within 3–10 days.
Thermal erythema (erythema of burn) — a single exposure to subthreshold infrared radiation leads to the development of transient reticular erythema. Repeated exposures result in more pronounced erythema with hyperpigmentation and occasionally superficial epidermal atrophy. Multiple and prolonged exposures cause a clinical picture resembling poikiloderma with reticular telangiectasia, melanosis, and diffuse hyperkeratosis. The localization of the dermatosis is determined by the site of radiation exposure. Subjective sensations are generally absent, although a burning sensation and pruritus may occasionally occur [14].
Cold erythema — clinically characterized by erythematous rashes without a urticarial component.
Palmar erythema (congenital) — clinically characterized by a bright red, uniform, or reticular coloration of the palms (in some cases also the soles) with clear borders. It is observed throughout life.
Palmar erythema (acquired) occurs in two clinical variants: mottled fine-spotted pink-red coloration of the palms, dorsal surface of the hands, fingers, and nail beds; sharply demarcated hyperemia of the hypothenar area with subsequent spread to the skin of the entire palm.
Congenital telangiectatic erythema (Bloom syndrome) is characterized by facial erythema and short stature. Other components of the syndrome include low birth weight, an elongated dolichocephalic skull, and an asthenic constitution. It develops in infancy or early childhood. Spots and plaques group in a butterfly pattern on the nose and cheeks, but may also appear on the eyelids, forehead, auricles, dorsum of the hands, and forearms. The surface of the elements is slightly scaly. Sun exposure causes exacerbation of the rash, as well as the appearance of blisters, development of hemorrhages, and crust formation on the lips.
Ulerythema ophryogenes (ophryogenes scarring erythema) is characterized by the appearance of symmetrical areas of skin redness, upon which very small follicular papules are located that do not coalesce and create the impression of granularity. The disease is observed in childhood, more often in girls, on the skin of the lateral part of the eyebrows, cheeks, forehead, and chin. The skin is rough to the palpation. The eyebrows thin out, hair in the affected areas falls out, hair follicles atrophy, and the process ends with scarring follicular atrophy. Over the years, the disease stops progressing and barely noticeable areas of reticular atrophy remain on the skin. Subjectively, patients sometimes note burning and itching. Disease progression usually stops during puberty.
Differential diagnosis: lichen planopilaris, seborrheic dermatitis, atrophodermia vermiculata, keratosis follicularis spinulosa decalvans of Siemens, follicular ichthyosis.
Necrolytic migratory erythema most commonly occurs at the age of 19 to 73 years; 85% of affected individuals are women aged 45 years and older. Bright red erythematous lesions are noted, sometimes papulosquamous rashes are simultaneously identified. A rim of desquamating epidermis is characteristic at the periphery of the lesions. Localization is variable, however, the rashes spread rapidly, being most abundant on the skin of the lower abdomen, thighs, genitals, and intergluteal region. The vermilion border of the lips, oral mucosa, and vaginal mucosa are frequently affected. Subsequently, flaccid-roofed blisters and erosions are noted on the surface of the rashes, rapidly forming crusts as they resolve. The rashes tend to resolve from the center with the formation of a spreading annular red crust. The coalescence of individual lesions leads to the formation of large plaques bounded from healthy skin by a scalloped edge. Resolution is usually accompanied by hyperpigmentation. The clinical picture of necrolytic migratory erythema is characterized by pronounced polymorphism: erythematous spots, flaccid blisters, and crusts are noted adjacent to hyperpigmented resolved areas. Patients may present with alopecia, onychodystrophy, cheilitis, atrophic glossitis, stomatitis, as well as urethritis or vaginitis. Skin manifestations of glucagonoma frequently have an atypical psoriasiform appearance.
Differential diagnosis: in early stages, the rashes may resemble eczema, seborrheic dermatitis, acrodermatitis enteropathica; differential diagnosis is carried out with pustular psoriasis, subcorneal pustular dermatosis, as well as acquired zinc and biotin deficiency.
Erythema gyratum repens of Gammel is characterized by abundant and widespread annular erythematous spots resembling wood grain. It is accompanied by pruritus. The first elements usually appear on the facial skin and then spread to the trunk and proximal extremities. The peripheral margin is slightly raised and slowly increases in size. Subsequently, a scaly pigmented zone is formed. Palms and soles are not affected. The erythema lesions migrate, frequently moving up to 1 cm per day. Lymphadenopathy may be observed. The combination with ichthyosis and palmoplantar keratoderma has been described. Conditions associated with erythema gyratum repens are presented in Appendix A3.1.
Differential diagnosis: erythema annulare centrifugum of Darier, erythema migrans, urticaria, urticarial phase of bullous pemphigoid, tinea corporis, rheumatic erythema, subacute cutaneous lupus erythematosus, granuloma annulare, secondary syphilis, leprosy, sarcoidosis.
Erythema annulare centrifugum of Darier is characterized by a chronic course and development at any age, but more frequently in young individuals. The average duration of the disease is about 3 years. Primary efflorescences are represented by non-scaly yellowish-pink spots resembling urticarial erythema, which rapidly form into dense annular formations represented at the periphery by arcs, segments, and rings. The central part of the lesions tends to resolve, where barely noticeable pigmentation is noted. A characteristic sign of this type of erythema is the "centrifugal" growth of the rash (at the periphery). The skin of the trunk (73%), lower extremities (55%), upper extremities (32%), and less frequently the face and neck (14%) are most often affected. Subjective sensations may be absent or manifest as moderate pruritus; excoriations are not observed.
The superficial type of Darier's erythema is distinguished by the absence of clear borders of the spots, peripheral desquamation of the lesions, and the presence of pruritus.
The deep type is characterized by pronounced edematous, ridge-like borders of the rash, and the absence of scaling and pruritus (see Appendix A3.2).
Atypical variants of Darier's erythema include: scaly Darier's erythema (scaling of the outer edge of the lesions is noted, while other typical clinical features are present), vesicular erythema (accompanied by rapidly transient vesicular elements at the edges of typical erythema lesions), simple garland-like erythema of Jadassohn (differs from the typical form by the cyclic course of individual rashes that last only a few days, although the process itself is prolonged), persistent microgarland-like erythema (characterized by the small size of individual rash elements (up to 1 cm in diameter); the rashes can exist unchanged for several months), and rarer induced and telangiectatic-purpuric Darier's erythema. The general condition of patients with Darier's erythema and its variants is not impaired.
Differential diagnosis: erythema gyratum repens of Gammel, persistent figurate erythema of Wende, erythema multiforme exsudativum, erythema migrans, rheumatic erythema of Leendertz-Leiner, mycoses, atypical pityriasis rosea of Gibert.
Persistent figurate erythema of Wende is presented by solitary round or oval erythematous spots up to 5-10 cm in diameter, without infiltration, with more intense coloration at the periphery. Over time, insignificant pigmentation and scaling form in the central part. It is predominantly localized on the skin of the trunk and upper extremities. Pruritus is absent. It persists for a long time. Differential diagnosis: erythema gyratum repens of Gammel, chronic erythema migrans, rheumatic erythema of Leendertz-Leiner, Darier's erythema, glucagonoma syndrome.
Erythema dyschromicum perstans (ashy dermatosis of Ramirez, pigmented purpuric lichenoid dermatosis) is characterized by the appearance of erythematous macules that gradually acquire an ashen-gray color with a bluish tint. The peripheral zone may be slightly infiltrated or erythematous. Sometimes, areas of inflammation alternating with post-inflammatory hyperpigmentation appear within the same lesions. In other cases, the macules always remain bluish-gray. The rashes range in size from a few millimeters to several centimeters in diameter, slowly increase in size, and can coalesce, involving extensive areas of the skin. The most frequent localization is the neck, trunk, and proximal upper extremities, and less frequently the face, axillae, and lower extremities. The rashes are usually symmetrical, less often unilateral, and often follow Blaschko's lines. The palms, soles, scalp, and mucous membranes are not affected. Subjective sensations are absent. The erythema persists for many years. In children, in 70% of cases, the rash elements spontaneously regress within 2-3 years.
Differential diagnosis: small-plaque parapsoriasis, pityriasis rosea, fixed drug eruption, mastocytosis (urticaria pigmentosa), pigmented lichen planus, idiopathic eruptive macular pigmentation, post-inflammatory hyperpigmentation, Addison's disease, drug-induced hyperpigmentation, melasma, macular amyloidosis, argyria.
Erythema marginatum (including Landouzy-Leiner rheumatic annular erythema) occurs at the peak of an exacerbation of rheumatic fever, 1-5 weeks (average 19 days) after a streptococcal pharyngitis, against the background of a fever (>38.0 °C). Erythematous macules are noted, characterized by rapid peripheral growth (up to 15-20 mm per 12 hours), forming annular erythemas. The active margin is slightly edematous, while the center of the skin is hyperpigmented or cyanotic. In some cases, the entire lesion has an urticaria-like appearance. In places, the rings coalesce, forming polycyclic, "geographic" outlines. Typical localization is the skin of the trunk, especially the abdomen, less frequently the extremities. After a few days, the rashes disappear without a trace. Relapses are often observed at intervals of several weeks (recurrent marginal erythema). Subjective sensations are absent.
Erythema marginatum is a clinical diagnosis; its presence is essentially considered one of the major criteria in the diagnosis of acute rheumatic fever. In erythema marginatum, one or more signs of acute rheumatic fever are almost always present: carditis (30-50%); migratory polyarthritis (35-66%) of the knee, elbow, wrist, and ankle joints; Sydenham's chorea (10-30%); rheumatic nodules (0-10%); fever (>38.0 °C); arthralgia.
Differential diagnosis: urticaria, adult-onset Still's disease, erythema centrifugum annulare of Darier, erythema multiforme, infectious mononucleosis, eosinophilic annular erythema, erythema gyratum repens of Gammel, erythema migrans.
Differential diagnosis of figurate erythema is presented in Appendix A3.3, and annular erythema in children in Appendix A3.4.
2. Diagnostics, medical indications and contraindications for diagnostic methods
Diagnostic criteria
The diagnosis is established on the basis of:
1) anamnestic data;
2) physical examination;
3) if clinical diagnosis is difficult, the diagnosis is confirmed by the results of pathomorphological examination of skin biopsy material.
The diagnosis of erythema marginatum is based on anamnestic, clinical, and laboratory data. The direct connection of the rashes with acute rheumatic fever serves as the basis for diagnosis. Evidence of a recent streptococcal infection includes: elevated anti-streptolysin-O (ASO) titer (testing serum anti-streptolysin-O (ASO) levels is a tool for retrospective diagnosis, as it increases only by the 7th-9th day of streptococcal infection and may also reflect previously endured diseases or chronic infection [15]); positive throat swab culture for group A streptococci; positive rapid test for detecting group A streptococcal antigens in a posterior pharyngeal swab. Initial acute rheumatic fever is characterized by the presence of 2 major criteria or 1 major and 2 minor criteria (major criteria: carditis; migratory polyarthritis; chorea; erythema marginatum; rheumatic nodules; minor criteria: fever; arthralgia; leukocytosis, elevated erythrocyte sedimentation rate, and C-reactive protein; prolonged P-R interval on the electrocardiogram) [16,17].
2.1 Complaints and Anamnesis
Complaints and medical history are described in the section "Clinical Presentation".
2.2 Physical Examination
Physical examination findings are described in the section "Clinical Presentation".
2.3 Laboratory Diagnostics
It is recommended that patients with erythema undergo microscopic examination of skin scrapings for fungi (yeasts, molds, dermatophytes) for differential diagnosis and to exclude a fungal infection [18].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
It is recommended that patients with annular erythema undergo a rapid test to detect group A streptococcal antigens in a posterior pharyngeal swab if they present with clinical signs of erythema marginatum (rapid immunochromatographic throat swab test for group A streptococci) [19-21].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
Comments: rapid testing is based on enzyme immunoassay or immunochromatography, providing results within 5-15 minutes. The analysis does not require a specialized laboratory. The average specificity and sensitivity of modern test systems are 94% and 97%, respectively.
2.4 Instrumental Diagnostics
Not applicable.
2.5 Other Procedures
It is recommended to consider pathomorphological examination of skin biopsy material from the lesion site (skin biopsy, pathomorphological examination of skin biopsy/surgical material from the lesion site) in patients with erythema when differential diagnosis with other skin diseases is necessary [14,18,21-24].
GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)
Comments: the histological picture of ulerythema ophryogenes is characterized by follicular hyperkeratosis, atrophy of sebaceous glands and hair follicles, perivascular lymphohistiocytic infiltrates, and perifollicular connective tissue fibrosis. Pathomorphological examination of biopsy material in erythema gyratum repens of Gammel is of low informativeness, showing focal spongiosis, parakeratosis, and a small perivascular infiltrate of lymphocytes and histiocytes in the papillary dermis. In erythema centrifugum annulare of Darier, there are no specific changes in the epidermis and dermis. The epidermis shows acanthosis, parakeratosis, spongiosis, and rarely vesiculation. In the superficial type, the dermis shows a perivascular infiltrate of histiocytes and lymphocytes, sometimes mixed with eosinophils and neutrophils, and edema of the papillary dermis; in the deep type, the infiltrate involves both the superficial and deep vascular networks. Epidermal changes and papillary dermal edema are rarely observed.
The histological picture of erythema perstans figuratum of Wende is characterized by moderate hyper- and parakeratosis and small perivascular inflammatory infiltrates. Pathomorphologically, erythema dyschromicum perstans reveals vacuolar degeneration of basal layer cells with pigment incontinence and dermal macrophages loaded with melanin. In the upper third of the dermis, minor perivascular infiltrates consisting of lymphocytes (CD4+ and CD8+ T cells) and histiocytes mixed with melanophages are observed. Pathomorphological examination of biopsy material in erythema marginatum is nonspecific and includes a perivascular polymorphic infiltrate of neutrophils and mononuclear cells in the papillary dermis and upper reticular dermis [21]. Histological examination of necrolytic migratory erythema reveals necrobiotic changes in the epidermis with the formation of subcorneal or intraepidermal clefts. Subcorneal pustules may form. Pronounced perivascular lymphocytic inflammatory infiltrates are present in the dermis.
Patients with clinical signs of erythema undergo further evaluation to diagnose specific lesions of various organs and systems, as well as comorbid conditions that may influence the course of the disease, establish the etiological factor, and guide therapy selection:
It is recommended to have a consultation (examination, consultation) with a dermatovenereologist/infectious disease specialist/general practitioner/pediatrician/family physician to diagnose infectious pathology in patients with clinical signs of infectious erythema [25-28].
Level of Recommendation CLevel of Evidence 4Level of Recommendation C (level of evidence – 4)
It is recommended that children undergo a consultation (examination, consultation) with a geneticist to diagnose genetic pathology in patients suspected of having Bloom syndrome [29,30].
GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)
It is recommended that adult patients undergo a consultation (examination, consultation) with a geneticist to diagnose genetic pathology in patients suspected of having Bloom syndrome [29,31].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
It is recommended to perform an initial consultation (examination, assessment) by a rheumatologist to diagnose acute rheumatic fever in patients with erythema marginale (including annular erythema of Leiner) [20].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
When diagnosing necrobiotic migratory erythema or Gammel's erythema gyratum repens, taking into account the paraneoplastic genesis of the diseases, it is recommended to have an initial consultation (examination, assessment) with a general practitioner (family physician)/general internist/oncologist for cancer screening [32,33].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
3. Treatment, including drug and non-drug therapies, diet therapy, and pain management
Treatment of erythema in the vast majority of cases consists in eliminating the etiological factor (in case of erythema caused by physical factors, elimination of exposure to ultraviolet rays, infrared radiation, or low temperatures is necessary; in case of paraneoplastic erythema, treatment of the underlying oncological process; in case of infectious erythema, therapy for the infection; therapy for erythema marginale is based on the treatment of acute rheumatic fever if diagnosed). Elimination of the etiological factor leads to the regression of rashes.
3.1 Conservative Treatment
Topical therapy
For erythema annulare centrifugum in adult patients, it is recommended to use topical preparations containing vitamin D3 analogues (ATC D05AX02, other topical antipsoriatic preparations) [34].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
Comments: #calcipotriol 0.005% ointment for topical use, apply to affected skin areas 1 time per day for 12 weeks [34]. For long-term treatment, the daily dose should not exceed 1 g. The drug should not be applied to extensive skin areas exceeding 30% of the body surface. The drug should not be prescribed before UV irradiation, as this leads to inactivation of the drug.
For erythema annulare centrifugum, adult patients are recommended to use topical preparations (ATC D11AH01, dermatological preparations excluding corticosteroids) [35].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
Comments: #tacrolimus** 0.1% ointment is applied in a thin layer to the affected skin areas 2 times a day until the lesions regress [35].
For erythema annulare centrifugum in adult patients, topical glucocorticoids used in dermatology for anti-inflammatory and antipruritic purposes are recommended (D07AB, moderately potent corticosteroids (group II)) [18,36–38].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
Comments: it is possible to use #triamcinolone 0.1% external ointment [37] or #alclometasone 0.05% cream, 0.05% external ointment once daily [38].
Systemic therapy
It is recommended to prescribe oral macrolides for the treatment of patients with idiopathic erythema annulare centrifugum for anti-inflammatory purposes, as well as for the eradication of "occult" infection [39].
Level of Recommendation CLevel of Evidence 4Level of Recommendation C (level of evidence – 4)
Comments: #azithromycin**[39], treatment of children older than 8 years and/or weighing more than 45 kg is carried out in accordance with adult treatment regimens, taking into account contraindications. Available data indicate that low-dose macrolides (#azithromycin** 250 mg per day until resolution of clinical manifestations or for a maximum of up to 3 weeks) can be effective in idiopathic Daria's erythema annulare centrifugum.
It is recommended to use oral systemic triazole derivatives for widespread and idiopathic forms of erythema annulare centrifugum, as well as in cases of ineffectiveness of local therapy [40].
Level of Recommendation CLevel of Evidence 4Level of Recommendation C (level of evidence – 4)
Comments: #fluconazole**[40] - the recommended dose in children ranges from 3 to 6 mg per kg of body weight per day for 2 to 14 weeks orally in the absence of contraindications.
To reduce the intensity of pruritus, it is recommended to prescribe systemic antihistamines (piperazine derivatives) [36,41–42].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
Comments: cetirizine** for children aged 2 to 6 years – 2.5 mg orally 2 times a day or 5 mg orally 1 time a day; for children aged 6–12 years – 5 mg orally 2 times a day or 10 mg 1 time a day; for children over 12 years and adults – 10 mg orally 1 time a day.
It is recommended in severe cases of the disease, involvement of a large skin surface, and lack of effect from topical therapy, to prescribe oral glucocorticoids to relieve this condition [18,43].
Level of Accessibility of Guidelines 5Level of Consensus C (level of evidence – 5)
Phototherapy
It is recommended for adult patients with widespread lesions to undergo ultraviolet skin irradiation. Local narrow-band medium-wave ultraviolet therapy with a wavelength of 311 nm, 15 procedures per course, 3 times a week [18,43–45].
Level of Recommendation CLevel of Evidence 4Level of Recommendation C (level of evidence – 4)
Comments: prior to prescribing phototherapy, a clinical examination of the patient and a set of laboratory tests are advisable to identify contraindications. Narrow-band medium-wave therapy with a wavelength of 311 nm can be used in children from 7 years of age for severe forms and torpid disease course. The initial irradiation dose is determined based on individual skin sensitivity by measuring the minimal erythemal dose during UVB therapy using a Gorbachev biodosimeter, or without determining minimal erythemal doses based on skin phototype (according to T.B. Fitzpatrick's classification). The degree of sun tan, affected area, and severity of the inflammatory skin reaction should also be taken into account. For all phototherapy methods, the main immediate side effects are erythema and pruritus. Blisters, hyperpigmentation, or skin dryness are observed less frequently. Long-term multi-course phototherapy dose-dependently causes symptoms of chronic skin photodamage. To reduce pruritus and skin dryness, patients must use emollients or moisturizers during the course of treatment. In cases of persistent pruritus, anti-pruritic medications, including antihistamines, anesthetics, and others, are prescribed. If skin hyperpigmentation appears, zinc oxide or sun-protection cream is applied to the pigmented areas to protect the skin from further irradiation. When performing phototherapy, the following precautions must be observed: throughout the course of treatment, patients should avoid staying in the sun and protect the skin of exposed body areas with clothing or sun-protection cream; the use of other photosensitizing drugs and cosmetics should be excluded: tetracycline**, griseofulvin, sulfonamides, thiazides, phenothiazine derivatives, aromatic oils, etc.
For the treatment of burn erythema in the absence of regression upon elimination of the triggering factor, adult patients are recommended laser treatment of integumentary tissues: Q-switched nanosecond Nd:YAG laser (1064 nm) ("Low-intensity laser skin irradiation") 1 time every 2 weeks for a course of 3 procedures [14,46–48].
Level of Recommendation CLevel of Evidence 4Level of Recommendation C (level of evidence – 4)
For ulerythema ophryogenes in cases of moderate to severe course, it is recommended to prescribe retinoids for acne treatment [49].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
For ulerythema ophryogenes in cases of moderate to severe course in adult patients, it is recommended to use oral #isotretinoin at a dose of 1 mg/kg/day for 16 weeks [50].
Level of Recommendation CLevel of Evidence 4Level of Recommendation C (level of evidence – 4)
Comments: in case of relapse, a repeated course is possible within 8 months.
In persistent dyschromic erythema with a moderate to severe course, it is recommended to prescribe retinoids for acne treatment [51].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
Comments: the choice of the #isotretinoin treatment regimen depends on the severity of the course, individual tolerance, and response to therapy. Adult patients are typically indicated oral #isotretinoin at a dose of 40 mg/day for 1 month, then 20 mg/day for 3 months, then 10 mg/day for 1 month. The drug is a potential teratogen and has side effects (most commonly cheilitis, dry skin, peeling, less commonly alopecia, conjunctivitis, headache, arthralgia, etc.). Isotretinoin safety data: the course of isotretinoin treatment is generally well tolerated and safe; adverse events involving the skin and mucous membranes occur frequently, are reversible, respond well to topical moisturizing therapy, and do not require drug discontinuation; musculoskeletal side effects are rare; clinically insignificant laboratory abnormalities may be observed that do not require drug discontinuation. However, baseline liver function and lipid metabolism parameters must be determined and monitored during treatment; the contraceptive period after treatment is 5 weeks.
For persistent dyschromic erythema, it is recommended to use topical preparations (ATC D11AH, dermatological preparations excluding corticosteroids) [52,53].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
Comments: #tacrolimus** 0.1% ointment is applied in a thin layer to the affected skin areas 2 times a day until the lesions regress [52,53].
For widespread forms of persistent dyschromic erythema, systemic therapy is recommended for adult patients:
#dapsone** 100 mg orally daily for 8 to 12 weeks [54,55].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
Comments: regular monitoring of blood parameters is required during dapsone** therapy. In case of a significant decrease in leukocyte count, platelet count, or bone marrow suppression, treatment with dapsone** should be interrupted. Age under 18 years is a contraindication to prescribing dapsone**.
3.2 Diet therapy
Organization of therapeutic nutrition for patients with acquired keratosis (keratoderma) of the palms and soles during inpatient treatment in medical organizations is carried out in accordance with the orders of the Russian Ministry of Health No. 330 of August 5, 2003 "On measures to improve therapeutic nutrition in healthcare institutions of the Russian Federation", No. 395n of June 21, 2013 "On approval of therapeutic nutrition standards", and No. 1008n of September 23, 2020 "On approval of the procedure for providing patients with therapeutic nutrition" (see Appendix A3).
4. Medical Rehabilitation and Sanatorium-Resort Treatment
Not required.
5. Prevention and Dispensary Observation
All patients should be provided with complete information about causal agents triggering the disease.
Patients diagnosed with persistent dyschromic erythema are advised to use photoprotective agents.
Patients with a prolonged chronic course of erythema annulare centrifugum are recommended to undergo dispensary follow-up by a dermatologist [56].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
6. Organization of Medical Care
Medical care for patients with erythema may be provided outside a medical organization; on an outpatient basis; in a day or round-the-clock inpatient setting.
Primary specialized health care is provided by a dermatologist, or in their absence, by a general practitioner (family physician), general physician, or pediatrician.
Specialized medical care is provided by dermatologists.
Indications for inpatient medical care:
insufficient efficacy of outpatient treatment.
Indications for patient discharge from a medical organization:
partial or complete regression of rashes.
Criteria for Evaluating the Quality of Medical Care
№ | Quality assessment criterion | Performance evaluation |
|---|---|---|
1 | Admission (examination, consultation) by a dermatologist/infectious disease physician/general physician/pediatrician/general practitioner (family physician) for the diagnosis of infectious pathology in patients with clinical signs of infectious erythema | Yes/no |
2 | Treatment administered with dermatitis medications (excluding glucocorticoids) / moderate-potency corticosteroids (group II) (in the presence of medical indications and absence of contraindications) | Yes/no |
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Appendix A1. Working Group Composition
Nikolay N. Potekaev – Doctor of Medical Sciences, Professor, President of the All-Russian Public Organization "National Alliance of Dermatovenereologists and Cosmetologists", Honored Doctor of the Russian Federation, Chief freelance specialist in dermatovenereology and cosmetology of the Russian Ministry of Health, Chief freelance specialist in dermatovenereology and cosmetology of the Moscow City Health Department, Director of the Moscow Scientific and Practical Center for Dermatovenereology and Cosmetology of the Moscow Health Department, Head of the Department of Skin Diseases and Cosmetology at the Faculty of Continuing Professional Education, Pirogov Russian National Research Medical University of the Russian Ministry of Health.
Olga V. Zhukova – Doctor of Medical Sciences, Professor, Executive Director of the All-Russian Public Organization "National Alliance of Dermatovenereologists and Cosmetologists", Chief freelance specialist in dermatovenereology and cosmetology of the Central Federal District of the Russian Ministry of Health, Chief Physician of the Moscow Scientific and Practical Center for Dermatovenereology and Cosmetology of the Moscow Health Department, Head of the Department of Dermatovenereology and Allergology with a Course of Immunology at the Medical Institute, Peoples' Friendship University of Russia.
Baranov Alexander Alexandrovich – Doctor of Medical Sciences, Professor, Academician of the Russian Academy of Sciences, Chief freelance specialist in pediatrics of the Russian Ministry of Health, member of the Union of Pediatricians of Russia.
Leyla S. Namazova-Baranova – Academician of the RAS, Professor, Doctor of Medical Sciences, President of the Union of Pediatricians of Russia; Past-President of EPA/UNEPSA; Head of the Research Institute of Pediatrics and Child Health, Academician V.V. Petrovsky National Medical Research Center of Surgery, Head of the Department of Faculty Pediatrics, Pediatric Faculty, Pirogov Russian National Research Medical University of the Russian Ministry of Health, Chief freelance pediatric specialist in preventive medicine of the Russian Ministry of Health.
Ambarchyan Eduard Tigranovich – Candidate of Medical Sciences, Leading Researcher, Head of the Pediatric Dermatology Department, Research Institute of Pediatrics and Child Health, Petrovsky National Research Centre of Surgery (NC2) of the Ministry of Science and Higher Education of the Russian Federation, member of the Union of Pediatricians of Russia.
Sofya I. Artemyeva – Member of the All-Russian Public Organization "National Alliance of Dermatovenereologists and Cosmetologists", Researcher at the Department of Clinical Dermatovenereology and Cosmetology, Dermatovenereologist at the Department of Specialized Medical Care, Moscow Scientific and Practical Center for Dermatovenereology and Cosmetology of the Moscow Health Department, Assistant at the Department of Dermatovenereology and Allergology with a Course of Immunology at the Medical Institute, Peoples' Friendship University of Russia.
Aida G. Gadzhigoroeva – Doctor of Medical Sciences, Member of the All-Russian Public Organization "National Alliance of Dermatovenereologists and Cosmetologists", Head of the Department of Clinical Dermatovenereology and Cosmetology, Moscow Scientific and Practical Center for Dermatovenereology and Cosmetology of the Moscow Health Department.
Olga V. Dolya – Doctor of Medical Sciences, Member of the All-Russian Public Organization "National Alliance of Dermatovenereologists and Cosmetologists", Deputy Director for Research, Moscow Scientific and Practical Center for Dermatovenereology and Cosmetology of the Moscow Health Department.
Daria D. Evlentyeva – Dermatovenereologist at the Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Medical Research Center of Surgery of the Ministry of Science and Higher Education of the Russian Federation, Member of the Union of Pediatricians of Russia.
There is no conflict of interest.
Appendix A2. Methodology for Developing Clinical Guidelines
Target audience for these clinical guidelines:
1. Dermatovenereologists
2. General practitioners
3. General physicians
4. Pediatricians
5. Trainees of the institute for higher qualification training and additional professional education in the specialties of "Dermatovenereology"
6. Residents training in the specialties of "Dermatovenereology"
Table 1. Scale for assessing levels of evidence (LE) for diagnostic methods (diagnostic interventions)
LoE | Definition |
|---|---|
1 | Systematic reviews of studies with reference standard control or systematic reviews of randomized controlled trials with meta-analysis |
2 | Individual studies with reference standard control or individual randomized controlled trials and systematic reviews of studies of any design, except randomized controlled trials, with meta-analysis |
3 | Studies without consecutive reference standard control or studies with a reference standard not independent of the test method, or non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case report |
5 | Only justification of mechanism of action or expert opinion is available |
Table 2. Rating scale for levels of evidence (LE) for preventive, therapeutic, and rehabilitation methods (interventions)
LoE | Definition |
|---|---|
1 | Systematic review of RCTs with meta-analysis |
2 | Individual RCTs and systematic reviews of studies of any design except RCTs, with meta-analysis |
3 | Non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case reports or case series, case-control studies |
5 | Only justification of the mechanism of action of the intervention (preclinical studies) or expert opinion is available |
Table 3. Rating scale for grades of recommendation (GR) for preventive, diagnostic, therapeutic, and rehabilitation methods (interventions)
GoR | Definition |
|---|---|
A | Strong recommendation (all considered efficacy criteria (outcomes) are important, all studies are of high or acceptable methodological quality, and their conclusions on the outcomes of interest are consistent) |
B | Conditional recommendation (not all considered efficacy criteria (outcomes) are important, not all studies are of high or acceptable methodological quality, and/or their conclusions on the outcomes of interest are inconsistent) |
C | Weak recommendation (lack of adequate quality evidence (all considered efficacy criteria (outcomes) are unimportant, all studies are of low methodological quality, and their conclusions on the outcomes of interest are inconsistent) |
Procedure for updating clinical guidelines.
The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in 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:
Procedure for providing medical care in the profile of "dermatovenereology", approved by Order of the Ministry of Health of the Russian Federation No. 924n of November 15, 2012.
Order of the Ministry of Health of the Russian Federation No. 330 dated August 5, 2003, "On measures to improve therapeutic nutrition in healthcare institutions of the Russian Federation".
Order of the Ministry of Health of the Russian Federation No. 395n of June 21, 2013, "On Approval of Therapeutic Nutrition Standards".
Order of the Ministry of Health of the Russian Federation No. 1008n dated September 23, 2020, "On Approval of the Procedure for Supplying Patients with Clinical Nutrition."
Appendix A3.1. Conditions Associated with Erythema Gyratum Repens (Gammel's Erythema)
Table. Conditions Associated with Erythema Gyratum Repens (Gammel's Erythema) [18]
Malignant neoplasms | Lung, esophageal, breast, and gastric cancer, lymphoma, urogenital malignancies |
|---|---|
Chronic inflammatory skin diseases | Pityriasis rubra pilaris, psoriasis, ichthyoses, hypereosinophilic syndrome |
Idiopathic | |
Autoimmune diseases | CREST syndrome, rheumatoid arthritis |
Systemic infections | Tuberculosis, Helicobacter pylori infection |
Medicinal products | Azathioprine, interferon |
Appendix A3.2. Subtypes of erythema annulare centrifugum
Table. Subtypes of Erythema Annulare Centrifugum [18].
Erythema annulare centrifugum | ||
|---|---|---|
Superficial erythema annulare centrifugum | Deep erythema annulare centrifugum | |
Clinical presentation | Desquamating scales, pruritus | "Cord-like border" (firm, raised, nodular ridge), absence of scales, absence of pruritus |
Histopathological findings | Spongiosis, parakeratosis, superficial perivascular lymphocytic infiltrate | No epidermal changes, mononuclear infiltrate in the mid and lower dermis |
Appendix A3.3. Differential diagnosis of figures of erythema
Table. Differential Diagnosis of Figurate Erythema [18].
Infectious diseases | Dermatophytosis, impetigo, erythema migrans, secondary syphilis, tuberculoid leprosy |
|---|---|
Autoimmune diseases | Bullous pemphigoid, linear IgA bullous dermatosis, lupus erythematosus (subacute cutaneous lupus erythematosus), Sjögren's syndrome, lichen planus, generalized pustular psoriasis (annular erythema-like psoriasis with pustules), subcorneal pustular dermatosis (Sneddon-Wilkinson disease), pityriasis rubra pilaris, dyschromic erythema perstans (ashy dermatosis of Ramirez) |
Neoplastic diseases | Lymphoma, mycosis fungoides |
Metabolic disorders | Necrolytic migratory erythema (glucagonoma) |
Allergic diseases | Urticaria, allergic cutaneous vasculitis, annular erythema, eosinophilic annular erythema, thrombocytopenic purpura, migratory arcuate palpable erythema, seborrheic dermatitis, erythema multiforme exudativum, sarcoidosis, elastosis perforans serpiginosa, Darier's erythema annulare centrifugum, erythema gyratum repens (Gammel's erythema) |
Diagram. Differential Diagnosis of Figurate Erythema Based on Lesion Lifespan [18]
Appendix A3.4. Differential diagnosis of annular erythema in children
Table. Differential Diagnosis of Annular Erythema in Children [57].
Diagnosis | Age | Pathogenesis | Clinical presentation | Clinical examination | |
|---|---|---|---|---|---|
Neonatal period | Neonatal lupus erythematosus | 6–12 weeks | Maternal anti-SSA (95%) and anti-SSB antibodies | Annular macules and plaques, "owl eyes" / "raccoon eyes", photosensitivity. Lesions resolve without scarring within 4–6 months Cardiac manifestations (AV block, cardiomyopathy) | Clinical presentation and serological testing in the infant and mother; histology: interface dermatitis, keratinocyte damage, perivascular and periadnexal lymphocytic infiltrate; direct immunofluorescence (DIF): granular IgG deposition at the dermo-epidermal junction |
Familial annular erythema | Shortly after birth | Autosomal dominant inheritance | Erythema annulare centrifugum, rare disorder, positive family history | Histology: superficial and deep perivascular infiltrate with a significant number of neutrophils, small number of eosinophils and histiocytes | |
Annular erythema of infancy | Usually manifests at 3–11 months of age | Idiopathic | Recurrent annular erythematous plaques, slow centrifugal spread, resolve without sequelae within several weeks | Histology: perivascular lymphocytic infiltrate with eosinophils | |
Preschool age | Eosinophilic annular erythema | After the first year of life | Idiopathic | Annular erythematous eruptions on the trunk and extremities, recurrent and persistent course over many years | Histology: superficial and deep perivascular lymphohistiocytic infiltrate with abundant eosinophils |
Wells syndrome | 1–9 years | Arthropod bites, vaccination | Painful infiltrated plaques with a greenish hue, bullous form, systemic symptoms (fever, arthralgia, malaise) | Peripheral eosinophilia > 50%, elevated eosinophil cationic protein Histology: superficial or perivascular and interstitial eosinophilic infiltrate with "flame figures" | |
Centrifugal annular erythema | Primarily affects adults, rarely seen in children | Idiopathic | A clinical pattern rather than a clinico-pathological entity. Erythematous papules expanding centrifugally at the borders, scaling at the inner edge, individual lesions resolve within weeks, chronic course | Histology: perivascular lymphohistiocytic infiltrate, acanthosis, parakeratosis, and spongiosis | |
School age/adolescents | Chronic migratory erythema of Afzelius-Lipschütz | Children over 2 years of age | Pathogen of tick-borne borreliosis (Borrelia afzelii and Borrelia garnii) | «Bull's-eye» expanding annular erythema with central clearing, often manifesting in the head and neck region in children as multifocal lesions | Serological testing: informative in the early stages of manifestation or for monitoring post-therapy Histology: superficial or deep dermal lymphocytic infiltrate, plasma cells, and eosinophils |
Erythema marginatum (rheumatic) | Schoolchildren, adolescents | Acute rheumatic fever following group A streptococcal infection | Recurrent erythematous annular spots and plaques, Jones criteria for rheumatic fever (others include carditis, polyarthritis, chorea, subcutaneous nodules) | Histology: interstitial and perivascular neutrophilic infiltrate without vasculitis. Erythrocyte extravasation in later stages | |
Annular juvenile lichenoid dermatitis | Over 10 years | Idiopathic | Asymptomatic annular spots with an erythematous rim and a hypopigmented center. Predominant localization in the groin and on the lateral parts of the body (flanks) | Histology: lichenoid dermatitis restricted to epidermal ridges, with intradermal lymphocytic infiltrate |
Appendix B. Physician Action Algorithms
Appendix C. Patient Information
In cases of erythema caused by physical factors, it is extremely important to eliminate the influence of the provoking factor, against which background the clinical manifestations in most cases regress without a trace.
The prophylactic use of moisturizers and sunscreens is important.
In the event of diagnosed comorbid pathology causing clinical manifestations of erythema, a timely referral to allied specialists is necessary to determine the treatment tactics for the underlying disease.
In case systemic treatment methods are prescribed, the doctor's recommendations must be strictly followed.
Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools
No.