Erythema anulare centrifugum L53.1

Colcott-Fox 1881; Darier 1916

Chronic recurrent, polyetiologic, inflammatory skin disease, which has its clinical significance as a "reaction cutanée" or "indicator" dermatosis.

It is characterized by centrifugally growing, annular, or more rarely, circular, red "palpable" plaques (no erythema). The entity of the clinical picture is controversial, especially since the conception of this clinical picture has changed several times since its first description by Darier.

Jean Darier originally described the disease as a "self-limited, etiologically unexplained dermatosis, as "érythème papulocirciné migrateur et chronique", with anular, rapidly spreading foci that regress spontaneously after 1-2 weeks. Subsequent literature describes inconsistent, apparently reactive clinical pictures with and without scaling, some urticarial, some eczematous, some vesicular with different histologic patterns presenting with superficial and deep lymphocytic (also eosinophilic?) infiltrate.

Both from a clinical and histological point of view,:

• superficial type
• and
• profound type.

Remark: It is doubtful whether the profound type is an independent entity. It is more likely that variants of other diseases have been described under this term (e.g. lupus erythematodes tumidus or pseudolymphomas). The descriptive term "deep gyriated erythema" chosen by some authors for this clinical picture is not very helpful for its etiopathic classification.

Ultimately, the etiopathogenesis of erythema anulare centrifugum (EAC) is unclear.

The association with:

• Malignant primary diseases (lymphoma, leukemia (especially chronic lymphocytic leukemia), breast carcinoma, ovarian carcinoma, bronchial carcinoma). The acronym "PEACE = paraneoplastic erythema anulare centrifugum" was coined for the paraneoplastic form of EAC (Chodkiewicz HM et al. 2012) .
• Infections (esp. candidiasis of the gastrointestinal tract, HIV, zoster),
• Autoimmunediseases (autoimmune hepatitis, polygandular autoimmune syndrome, Hashimoto's thyroiditis, Crohn's disease; sarcoidosis, polychondritis, lupus erythematosus).
• Medications (including amitriptyline, salicylates, finasteride, chloroquine, penicillin, diuretics, cimetidine)
• Food allergies(tomatoes, fish proteins, moulds contained in cheese).

On average, patients in middle age fall ill (50.-55. LJ). Less frequently occurring in adolescents. Women are slightly more frequently affected (w:m = 5:4).

Affected are mainly trunk (50-60%), proximal limbs, glutaeal region. Face, hands and feet remain free, as well as mucous membranes.

Multiple, initially homogeneous 1.0-2.0 cm red plaques that heal centrally and expand centrifugally. Centrifugal growth of the plaques is several millimeters per day. This results in ring formations up to 6.0 cm in diameter within a few weeks. These may coalesce in multiple arches.Typically, the plaques are smooth on the surface. In some cases, a finely lamellar scale ruff can be found at the inner edge of the ring.

Almost pathognomonic is the palpatory finding: when stroking from the center to the periphery of a focal area, the marginal rim feels like a "wet woolen thread" under the skin.

Notice. The term "erythema" in the naming is misleading, because it is anular or also multi-arched narrow-banded (always palpable) plaques.

Furthermore, scaly - eczema-like, vesicular or teleangiectatic-purpuric, or pseudolymphoma-like special forms are described.

In the profound type, any epidermal involvement is absent. The surface is then smooth and scale-free. Here, a distinction must be made from both lupus erythematosus tumidus and pseudolymphoma.

A superficial type is distinguished from a profound type, and it is increasingly considered that these are 2 distinct entities.

• The superficial type shows a superficial perivascular and interstitial lymphocyte infiltrate with eosinophilic leukocytes in 1/3 of the cases , occasionally also neutrophilic granulocytes. Histoeosinophilia may also dominate the histological picture, and erythrocyte extravasations may be found in isolated cases. Exocytosis with focal spongiosis and parakeratosis is regularly detectable. Intraepidermal blistering is rare.
• The profound type shows dense, usually strictly perivascular infiltrative pods of lymphocytes in the mid and/or deep dermis; eosinophilic leukocytes in varying admixture in 1/3 of cases. The epithelium shows occasional vacuolar degeneration and dyskeratosis. Not infrequently, melanophages are encountered in the upper dermis. Spongiosis and parakeratosis are completely absent in this type. There are some authors who classify the profound type as an independent (deep figurate erythema) clinical picture.

• Clinical Differential Diagnoses:
  • Dermatitis herpetiformis: this differential diagnosis should be considered in cases of marginal vesicle formation. In these cases, histological or imunhistological clarification is recommended.
  • Tinea corporis: pruritic, marginal plaques; if not pre-treated marked scaling, palpatory no marked marginal induration. Clinical and histological evidence of the pathogen (e.g. PAS stain).
  • Annular urticaria: Large migratory velocity of urticae (changes in localization are detectable by pen marking and exclusion criterion for erythema anulare centrifugum); prominent to severe pruritus; bright red color. Histology excludes erythema anulare centrifugum.
  • Nummular dermatitis: Eczematized pruritic plaques without prominent margins; usually disseminated. Most chronic course, no volatility.
  • Seborrheic dermatitis: Difficult differential diagnosis with marginalized plaques! Typical for this diagnosis is chronic course of the disease with intensification in the winter months and possibly complete healing under summer, maritime climate.
  • Pityriasis rosea: It can be assumed that a part of the so-called spongiotic type of Eac belongs to this clinical picture. Pityriasis rosea does not tend to anular configuration. Distribution pattern below analogous (truncal). Erythema anulare centrifugum is not cleavage line-betent.
  • Erythema anulare-like psoriasis: Typical (anular) plaque psoriasis is a very important DD. Like erythema anulare centrifugum, anular-configuirated, but always evidence of pustules (The Eac shows no pustularations; exclusion criterion); usually psoriasis history! Histology is diagnostic.
  • Parapsoriasis en plaques: No marginal accentuation, usually no scaling, pseudoatrophy! No itching!
  • Mycosis fungoides (esp. type pagetoid reticulosis): No marginal accentuation; very slow growth over months or years! Little or no itching; histology is diagnostic!
  • Erythema gyratum repens (extremely rare!): Anular, garland-shaped or spirally intertwined (atypical of erythema anulare centrifugum), nonpruritic, slightly indurated plaques. Rapid change of foci.
  • Erythema exsudativum multiforme: Initially high rate of progression (hours and days); argues against erythema anulare centrifugum; shooting target configuration (absolutely atypical of erythema anulare centrifugum); frequent involvement of mucous membranes (exclusion criterion for erythema anulare centrifugum).
  • Bullous pemphigoid: Initially high rate of progression (hours and days); argues against Eac; usually prominent pruritus; laboratory (pemphigoid antibodies), histology and immunohistology are conclusive.
  • Granuloma anulare: color red-brown, plaques usually polyclic bordered (atypical for erythema anulare centrifugum), never scaling, histology proving.
  • Eosinophilic cellulitis (rare): Stage-dependent variability of clinical presentation (erythema anulare centrifugum is morphologically stable).
  • Lupus erythematosus tumidus: Solid, homogeneous plaques, no anular structures, never scaling. DD less necessary from a clinical than from a histological point of view!
  • Erythema migrans (history, usually only single foci, serology...).
• Histological differential diagnoses (often difficult and can only be made in connection with the clinical picture. Good clinical information is important!):
  • Acute and subacute eczema: spongiosis, planar parakeratosis. No strict perivascular accentuation.
  • Urticaria (acute or chronic): Only sparse (never prominent) perivascularly oriented, mixed-cell infiltrate of eosinophils, neutrophils, and few lymphocytes. No epidermotropy; occasionally few perivascular erythrocytes.
  • Pityriasis rosea: Although clinically distinct, the histopathologic changes show extensive indentity. Differentiation only in connection with clinical picture!
  • Lupus erythematosus tumidus: Superficial and deep lymphocyte infiltrate, also in the vascular walls. No epidermal changes (also absent in the profound type of erythema anulare centrifugum). Usually no prominent eosinophilia! Histologically, profound type of erythema anulare centrifugum and lupus erythemaodes tumidus often cannot be differentiated with certainty, but clinically they almost always can!
  • Borrelia-associated pseudolymphoma: Superficial and deep lymphocytic infiltrates, often with characteristic admixture of plasma cells. Possible arragenments of lymphoid follicles. no eosinophilia.
  • Psoriasis vulgaris: Mostly prominent acanthosis, extensive hyper- and parakeratosis with neutrophil inclusions. No eosinophilia!
  • Parapsoriasis en plaques: Fibrosis of the stratum papillare; rather atrophic surface epithelium; the perivascular accentuation of the infiltrate typical of erythema anulare centrifugum is absent.
  • Early syphilis: interface dermatitis with psoriasiform epidermal reaction. Dense, band-like infiltrate in the upper and middle dermis of lymphocytes, histiocytes, and plasma cells). Extension of the infiltrate to the deep vascular plexus.

Focus search and remediation is in the foreground with elimination of gastric and intestinal disorders (including intestinal candidiasis, worm infections), foci of tonsils, teeth, gallbladder and adnexa. Thorough examination for visceral neoplasms (breast, larynx, lung, pancreas, ovary; see also paraneoplasia, cutaneous) and exclusion of myeloid diseases.

Possibly triggering drugs (see above) should be discontinued and foods such as fish or blue cheese should be avoided.

Typical, however, is a long-lasting, sometimes years-long relapsing tactvity. Overall, the duration of the disease varies from months to years. In the vast majority of cases, however, final healing occurs after 9-12 months.

Rarer are seasonal courses with occurrence in the summer months and spontaneous healing in the cold season (Haiges 2016).

Case report 1) The 65-year-old female patient noticed for about 3 weeks, first on the neck, later on the décolleté and the upper extremities, initially filled, slightly pruritic, red plaques, which enlarged centrifugally and faded centrally, so that anular and by confluence also polycyclic formations developed. Marginal parchment-like scaling was demonstrable.

The anamnesis was not very productive (no previous infections, no new medication in the last 3 months, no known tumor diseases). Significant nicotine abuse.

Laboratory: Orientation laboratory o.B.

Histology: superficial perivascular and interstitial lymphocyte infiltrate with eosinophilic leukocytes; sporadic neutrophilic granulocytes and erythrocyte extravasations. Focal exocytosis with spongiosis and parakeratosis.

Further examination findings: striking CT thoracic findings with a suspicious mass in the left lobe of the lung.

Ther: The patient strictly refused further therapeutic measures.

____________________________________________

Case History 2: A 46-year-old Caucasian woman suffered from recurrent self-healing annular eruptions on the extremities that recurred every year for the past 12 years. Physical examination revealed multiple erythematous and purplish annular plaques on both legs and arms. The eruptions began as small, markedly pruritic, scaly in places, erythematous papules that developed into annular plaques with central fading and centrifugal spread. The face, hands, feet, trunk, and mucous membranes were spared. The lesions occurred each year during the summer months and regressed spontaneously in the fall.

The rest of the physical examination revealed no abnormalities.

Her medical history was unremarkable; negative drug screening. Laboratory: Routine laboratory examination, including immunological tests (immunoglobulins, rheumatoid factor, antinuclear factor, and organ-specific antibodies) were within normal range. Borrelia burgdorferi antibodies and viral serological tests yielded negative results. Mycological examinations were negative. A gynecologic screening was normal. Chest radiography and mammography were normal.

Skin biopsy revealed a moderately intense superficial perivascular dermal lymphohistiocytic infiltrate with few eosinophils, focal epidermal spongiosis. DIF: negative.

1. Batycka-Baran A et al (2015) Erythema annulare centrifugum associated with ovarian cancer. Acta Derm Venereol 95:1032-1033
2. Bottoni U (2002) Erythema annulare centrifugum: report of a case with neonatal onset. J Eur Acad Dermatol Venereol 16: 500-503.
3. Chander R et al (2014) Systemic lupus erythematosus presenting as erythema annulare centrifugum. Lupus 23:1197-200
4. Chodkiewicz HM et al.(2012) Paraneoplastic erythema annulare centrifugumeruption: PEACE. Am J Clin Dermatol 13:239-246.
5. Darier (1916) De l'érythème annulaire centrifuge (érythème papulo-circineé migrateuse et chronique) et de quelques éruptions analogues. Annales de dermatologie et de syphilographie (Paris) 5: 57-58.
6. Gniadecki R (2002) Calcipotriol for erythema annulare centrifugum. Br J Dermatol 146: 317-319.
7. Haiges D et al (2016) Recurrent or excercising erythema anuare centrifugum in the summer months. Skin 16: 12-14
8. Halevy S (2002) Autoimmune progesterone dermatitis manifested as erythema annulare centrifugum: confirmation of progesterone sensitivity by in vitro interferon-gamma release. J Am Acad Dermatol 47: 311-313.
9. Ilkit M et al.(2012)Cutaneous id reactions: a comprehensive review of clinical manifestations, epidemiology, etiology, and management. Crit Rev Microbiol 38:191-202.
10. Imafuku K et al. (2015) Erythema annulare centrifugum-like mycosis fungoides after unrelated bone marrow transplantation. Br J Haematol 170:140

11. Mandel VD et al (2015) Annually recurring erythema annulare centrifugum: a case report. J Med Case Rep 9:236.

12. Ohmori S et al (2012) Erythema annulare centrifugum associated with herpes zoster. J UOEH 34:225-229.
13. Vocks E (2003) Erythema annulare centrifugum-type psoriasis: a particular variant of acute-eruptive psoriasis. J Eur Acad Dermatol Venereol 17: 446-448.
14. Yaniv R et al (1993) Erythema annulare centrifugum as the presenting sign of Hodgkin's disease. Int J Dermatol 32: 59-61
15. Weyers, W et al (2003) Erythema anulare centrifugum. Am J Dermatopathol 25: 451-462.
16. Ziemer M et al (2010) Erythema anulare centrifugum. Dermatologist 61: 967-972